https://www.explorationpub.com/Journals/edd Most Recent Articles : Exploration of Digestive Diseases. en-us Tue, 26 May 2026 23:46:25 GMT https://www.explorationpub.com/Journals/edd/Article/10051 Not applicable. Editorial Wed, 16 Mar 2022 00:00:00 GMT Jose C.Fernandez-Checa, Wed, 16 Mar 2022 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/10051 https://www.explorationpub.com/Journals/edd/Article/10052 The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is increasing rapidly worldwide due to the obesity epidemic. Advanced stages of the MAFLD, such as non-alcoholic steatohepatitis (NASH) with advanced fibrosis or cirrhosis are affecting global health. Extracellular vesicles (EVs) are released by all cell types and are important in cell-to-cell communication and maintaining homeostasis, but they also play a role in the pathogenesis of various diseases. EVs contain biological information such as lipids, proteins, messenger RNAs (mRNAs), small RNAs, and DNA, and they act on (distant) target cells. The cargo of EVs is dependent on the type and the state of the releasing cell. EVs have been proposed as biomarkers, prognostic, and even therapeutic agents, also in the context of liver diseases. This review aims to give an overview of the current knowledge on EVs in MAFLD, including the role and interaction of EVs with different cell types in the liver. Several aspects of EVs, including their origin, characteristics, cargo, and functions are reviewed. Moreover, the potential of EVs as targets for the treatment of MAFLD is discussed. Review Wed, 13 Jul 2022 00:00:00 GMT ZongmeiWu, MengmengXia, Sandra SernaSalas, Maria CamilaTrillos-Almanza, Magnolia MartinezAguilar, Johanna C.Arroyave-Ospina, JunyuWang, MarcoArrese, SvenjaSydor, Lars P.Bechmann, Frederike GIvan Vilsteren, HansBlokzijl, HanMoshage, Wed, 13 Jul 2022 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/10052 https://www.explorationpub.com/Journals/edd/Article/10053 Hepatocellular carcinoma (HCC) is considered one of the most aggressive tumors worldwide. The consumption of lipid-enriched diets, mainly high cholesterol, induces oxidative stress and chronic inflammation, leading to HCC progression. Moreover, fatty acids and cholesterol could display differential responses on immune cells inside the tumor immune microenvironment (TIME). Tumor-associated macrophages (TAMs) represent one of the most critical leukocytes in the tumor microenvironment (TME) displaying pro-tumoral responses and one of the mainly cholesterol donors to cancer cells. Immunotherapy or cholesterol regulators, alone or combined, would represent an effective strategy for HCC treatment. Nonetheless, steatotic etiology from non-alcoholic fatty liver disease (NAFLD)-HCC tumors has been unexpectedly resulting in highly aggressive behavior. Review Fri, 29 Jul 2022 00:00:00 GMT AlejandroEscobedo-Calvario, LisetteChávez-Rodríguez, ArturoSimoni-Nieves, VerónicaSouza-Arroyo, Roxana U.Miranda-Labra, Luis E.Gomez-Quiroz, María ConcepciónGutiérrez-Ruíz, Fri, 29 Jul 2022 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/10053 https://www.explorationpub.com/Journals/edd/Article/10054 Aim: Cholestasis remains a partially characterized disease. Evidence has been gained that it is a systemic disease that begins in the liver but significantly impacts other organs and systems such as the kidney, heart, and intestine, among others. One of the primary damage mechanisms is the generation of reactive oxygen species (ROS), which eventually leads to oxidative stress, impacting canalicular morphology and actin cytoskeleton changes that could worsen the problem. These characteristics are also observed in the kidney and intestine. The work focused on addressing the intestine effects of intrahepatic cholestasis induced by α-naphthyl isothiocyanate (ANIT) and the protective response of the hepatocyte growth factor (HGF). Methods: The 10- to 12-week-old CD1 male mice were treated with ANIT and then treated or not with HGF; intestine damage was addressed by histology, immunohistochemistry (IHC) of specific markers, oxidative stress, and apoptosis. Results: Results show changes in the intestine histology, particularly the colon and ileum, induced by the cholestasis. HGF treatment restored the histology presentation and reverted the oxidative damage, clearly indicating a healing response. This observation was supported by an increment in anti-inflammatory macrophages (CD163+) in the HGF treatment. Conclusions: The data prove that HGF induces a protective and repairing response in the intestine under cholestatic challenges. Original Article Fri, 12 Aug 2022 00:00:00 GMT JocelynLópez-Ramirez, RobertoLazzarini-Lechuga, MonserratGerardo-Ramírez, AlejandroEscobedo-Calvario, LisetteChávez-Rodríguez, SorayaSalas-Silva, NataliaNuño-Lámbarri, FelipeMassó, VerónicaSouza-Arroyo, Roxana U.Miranda-Labra, María ConcepciónGutiérrez-Ruiz, Luis E.Gomez-Quiroz, LeticiaBucio-Ortiz, Fri, 12 Aug 2022 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/10054 https://www.explorationpub.com/Journals/edd/Article/10055 Worldwide the number of individuals being overweight or obese has dramatically increased during the last decades, which is also associated with a similar dramatic increase of individuals afflicted with metabolic disorders like dyslipidemia, hypertension, and non-alcoholic fatty liver disease (NAFLD). Genetic predisposition may account for some of the increases in body weight and the development of metabolic disorders; however, much is probably also related to the changes in physical activity and dietary pattern. Indeed, results of epidemiological studies suggest that a ‘western-type dietary pattern’ composed of highly processed foods, sweetened foods, and beverages, all adding to a low fiber but high sugar and saturated fat intake, may increase the odd of developing overweight and metabolic disorders. Consumption of sugar, and especially, fructose has repeatedly been discussed to be a key contributor to the development of health disturbances including hypertension, dyslipidemia, insulin resistance as well as NAFLD. However, despite intense research effort, the question if and how (high) dietary fructose intake interferes with human health has not yet been fully answered also as findings are sometimes contradictory. In the present narrative review, results of recent studies assessing the effect of fructose consumption on the development of metabolic disorders including hypertension, dyslipidemia, cardiovascular diseases (CVDs), hyperinsulinemia, and NAFLD as well as underlying molecular mechanisms are reviewed, thereby, aiming to further address the question if (high) fructose intake is a trigger of metabolic diseases. Review Mon, 29 Aug 2022 00:00:00 GMT AnjaBaumann, AnnetteBrandt, InaBergheim, Mon, 29 Aug 2022 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/10055 https://www.explorationpub.com/Journals/edd/Article/1005104 Pediatric cirrhosis differs significantly from adult liver disease in terms of etiology, progression, and management. The unique physiological, nutritional, and developmental needs of children require specialized diagnostic and therapeutic strategies. This review underscores the distinct challenges in diagnosing and managing pediatric cirrhosis, focusing on its complications, management, and outcomes. Unlike adults, where cirrhosis often results from viral hepatitis or alcohol use, pediatric cases are predominantly cholestatic, with biliary atresia being the most common cause. Complications mainly involve portal hypertension and impaired liver function, leading to malnutrition and neurodevelopmental delay. Nutritional management is complex and requires increased caloric and protein intake, supplementation with fat-soluble vitamins, and the use of medium-chain triglycerides. Although hepatocellular carcinoma is rare in children, it remains a severe complication with a higher incidence in certain genetic and metabolic disorders. Surveillance is challenging due to diagnostic limitations and the lack of standardized pediatric screening protocols. Treatment is further complicated by constraints related to size and developmental stage, particularly in the management of portal hypertension. Pediatric cirrhosis requires an individualized multidisciplinary approach to address the interplay between growth, nutrition, and liver function. Early diagnosis, nutritional optimization, malignancy surveillance, and timely referral for liver transplantation are crucial. Ongoing research on pediatric-specific therapies and outcomes is essential for improving prognosis and quality of life. Review Mon, 08 Dec 2025 00:00:00 GMT Guillermo AlejandroCostaguta, FernandoÁlvarez, Mon, 08 Dec 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005104 https://www.explorationpub.com/Journals/edd/Article/10056 The surface of intestinal epithelial cells is covered by the brush border, which consists of densely packed cellular extrusions called microvilli. Until recently, microvilli have not been known to be interconnected. In 2014, a protein complex, called the intermicrovillar adhesion complex (IMAC) which is located at the tips of the microvilli and responsible for the regular spatial organization of the brush border, was identified. Deletion of IMAC components such as cadherin-related family member-2 (CDHR2) in mice resulted in microvillus disorganization and fanning, a structural aberration that is also found in the brush border of patients with inflammatory bowel disease. The etiology of inflammatory bowel disease has been primarily associated with dysfunctional mucosal immunity, but the discovery of the IMAC may encourage theories of an epithelial origin. Here, possible effects of the brush border on the gut barrier function and intestinal inflammation are discussed proposing that the IMAC protects against inflammation through its microvillus cross-linking function. Perspective Tue, 11 Oct 2022 00:00:00 GMT BernadetteMödl, KatySchmidt, DorisMoser, RobertEferl, Tue, 11 Oct 2022 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/10056 https://www.explorationpub.com/Journals/edd/Article/10057 Caspases are key factors in the regulation of the apoptotic and/or inflammatory responses, both crucial in the pathogenesis of diverse diseases. Caspase-2 is the most evolutionary conserved albeit functionally poorly defined member of the caspase family. The precise role of caspase-2 as an initiator or effector caspase is still unknown, but it has been involved in a wide variety of functions, from apoptosis to genomic stability, oxidative stress, metabolism, and cancer. However, many conflicting results render the exact function of this protease still unresolved. Although caspase-2 has several hundred substrates, the activation, processing, and activity on specific substrates remain poorly described. Recent evidence indicates that caspase-2 has a role in metabolic homeostasis and is required for lipotoxicity-induced apoptosis in hepatocytes, contributing to non-alcoholic steatohepatitis (NASH) progression towards hepatocellular carcinoma (HCC). Caspase-2 protein expression strongly localizes to injured/ballooned hepatocytes, correlating with NASH severity. Also, mice lacking caspase-2 showed protection from western diet-induced obesity, dyslipidemia, and insulin resistance. Although there are no effective therapies for NASH and HCC, the evaluation of a pan-caspase inhibitor has reached a phase I/II in clinical trials for advanced liver disease. Nevertheless, a better understanding of caspase functions with the identification of specific proteolytic substrates is essential for future therapeutic developments. Bearing in mind the pressing need to identify new targets for NASH-HCC and its metabolic-related comorbidities, and the favorable effect of caspase-2 genetic inhibition in animal models, pharmacological caspase-2 inhibition arises as a promising strategy that should be further investigated. Review Mon, 31 Oct 2022 00:00:00 GMT AmayaLopez-Pascual, MarcCusachs, MaríaArechederra, CarmenBerasain, CarmenHerrero, Matías A.Ávila, Maite G.Fernández-Barrena, Mon, 31 Oct 2022 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/10057 https://www.explorationpub.com/Journals/edd/Article/10058 Normal hepatobiliary function depends on an adequate bile flow from the liver through the biliary tree to the gallbladder, where bile is stored and concentrated, and from the gallbladder to the duodenum when it is required for the digestive process. Interruption of this secretory function results in partial or complete cholestasis, which is accompanied by important repercussions due to the lack of bile acids in the intestine and their regurgitation from hepatocytes to blood together with potentially toxic compounds that are normally eliminated in bile. The presence of active and selective transporter proteins located at both poles of the plasma membrane of hepatocytes, cholangiocytes, and epithelial cells of the ileal mucosa, together with the ability of hepatocytes to synthesize bile acids from cholesterol, enables the so-called bile acid enterohepatic circulation, which is essential in liver and gastrointestinal tract physiology. The presence in the ducts of the biliary tree of agents reducing their luminal diameter by external compression or space-occupying obstacles, either in the duct wall or its lumen, can result in total or partial obstructive cholestasis. The clinical impact and management of cholestasis are different depending on the intrahepatic or extrahepatic location of the obstacle. Thus, surgical interventions can often be helpful in removing extrahepatic obstructions and restoring normal bile flow to the duodenum. In contrast, hepatocyte or cholangiocyte damage, either global, restricted to subcellular compartments, or more specifically affecting the elements of the canalicular secretory machinery, may result in hepatocellular cholestasis or cholangiopathies. In these cases, bile flow interruption is usually partial and, except for extremely severe cases when liver transplantation is required, these patients often treated with pharmacological agents, such as ursodeoxycholic acid (UDCA) and rifampicin. The present review gathers updated information on the etiopathogenesis and pathophysiological aspects of different types of cholestasis. Review Mon, 31 Oct 2022 00:00:00 GMT MaitaneAsensio, SaraOrtiz-Rivero, AnaMorente-Carrasco, Jose J. G.Marin, Mon, 31 Oct 2022 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/10058 https://www.explorationpub.com/Journals/edd/Article/10059 Aim: Probiotic bacteria consumption for improving human health and for disease prevention is still controversial. There is a need to develop functional probiotic bacteria with proven efficacy for the human gastrointestinal (GI) system. The novel bacteria will lower the steady state of constant Ethanol production may lead to gut microbiota dysbiosis and liver injuries. Methods: Herein engineered probiotic bacterium B. subtilis to enhance the secretion of human alcohol dehydrogenase-4 (ADH4) by fusion of signal peptides (SPs) was constructed. As a result, higher ADH4 secretion and Ethanol removal rates were observed in phoB SP transformant SP-64, compared to other transformants. The engineered ADH4 expressing probiotic B. subtilis was delivered as spores to evaluate various physiological, biochemical, and immuno-histochemical parameters of mice under a high-fat diet (HFD)-induced obesity and metabolic impairment. Results: The treatment ameliorated significantly weight gain, improved glucose utilization, and prevented HFD-induced pancreatic damage. Lastly, SP-64 inoculation altered the gut microbiota, and increased the Firmicutes/Bacteroides ratio, supporting better fitness under HFD. Conclusions: SP-64 emerged as a potential probiotic that opens a new avenue for interventions against over-nutrition-induced metabolic disorders. Original Article Tue, 01 Nov 2022 00:00:00 GMT Rajnish PrakashSingh, MaxKolton, MayanBoker, Noy BarDavid, StefanGreen, AharonHelman, OrenTirosh, ZviHayouka, Tue, 01 Nov 2022 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/10059 https://www.explorationpub.com/Journals/edd/Article/100510 Several metabolic pathways are involved in the biotransformation of C27 neutral cholesterol to C24 primary bile acids (BAs), mainly cholic acid (CA) and chenodeoxycholic acid (CDCA), which are then conjugated with glycine or taurine. This process can start with the modification of the steroid ring or the shortening of the side chain and involves enzymes present in different subcellular compartments. Inborn errors affecting the biogenesis of organelles, such as peroxisomes, or the expression or function of specific enzymes of these convergent routes result in: i) the lack of mature C24-BAs, with the subsequent impairment in digestion and absorption of dietary fat and liposoluble vitamins, such as vitamin K, which may account for a deficient hepatic synthesis of several coagulation factors; ii) the accumulation of intermediate metabolites, which may affect hepatocyte physiology, causing cholestasis as a commonly shared alteration besides other deleterious hepatic events; and iii) extrahepatic clinical manifestations due to accumulation of toxic metabolites in other territories, such as the nervous system, causing neurological disorders. In general, diseases whose primary alteration is a genetic defect in BA synthesis are diagnosed in children or young individuals with a very low incidence. The symptomatology can markedly vary among individuals, ranging from mild to severe conditions. Oral therapy, based on the enrichment of the BA pool with natural C24-BAs, such as CA, CDCA, glyco-CA, or ursodeoxycholic acid (UDCA), depending on the exact deficiency causing the disease, may be beneficial in preventing life-threatening situations. In contrast, in other cases, a liver transplant is the only option for these patients. This review describes the updated information on the genetic and molecular bases of these diseases and the current approaches to achieve a selective diagnosis and specific treatment. Review Wed, 07 Dec 2022 00:00:00 GMT RicardoEspinosa-Escudero, ElisaHerraez, AnabelSanchez-Martin, PaulaSanchon-Sanchez, Jose J. G.Marin, Maria J.Monte, Wed, 07 Dec 2022 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100510 https://www.explorationpub.com/Journals/edd/Article/100511 During liver injury and cholestasis, the mechanisms allowing the organ to protect itself with the aim of maintaining biliary homeostasis are not completely understood. Central to their biological roles, bile acids (BAs) and their receptors constitute a signaling network with multiple molecular and cellular impacts on both liver repair and protection from BA overload. BA signal through nuclear [mainly farnesoid X receptor (FXR)] and membrane [mainly G protein-coupled BA receptor 1 (GPBAR-1), aka Takeda G protein-coupled receptor 5 (TGR5)] receptors, in which activation elicits a wide array of biological responses. So far, most of the studies have been focused on FXR signaling as hepato-protective, TGR5 being less explored to this regard. While the liver faces massive and potentially harmful BA overload during cholestasis, it is crucial to understand that BAs induce also protective responses contributing not only to reduce the inflammatory burden, but also to spare liver cells and their repair capacities. Based on the available literature, the TGR5 BA receptor protects the liver in the cholestatic context and counteracts BA overload with the aim of restoring biliary homeostasis mainly through the control of inflammatory processes, biliary epithelial barrier permeability, and BA pool composition. Mouse experimental models of cholestasis reveal that the lack of TGR5 was associated with exacerbated inflammation and necrosis, leaky biliary epithelium, and excessive BA pool hydrophobicity, resulting in biliary cell and parenchymal insult, and compromising optimal restoration of biliary homeostasis and liver repair. There are thus widely opened translational perspectives with the aim of targeting TGR5-related signaling or biological responses to trigger protection of the cholestatic liver. Review Fri, 30 Dec 2022 00:00:00 GMT GrégoryMerlen, ValeskaBidault-Jourdainne, IsabelleDoignon, IsabelleGarcin, ThierryTordjmann, Fri, 30 Dec 2022 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100511 https://www.explorationpub.com/Journals/edd/Article/100512 Metabolic zonation in the liver carries out the maintenance of organ and body homeostasis. Hypoxia is an inherent physiological feature of the liver and contributes to the zonal properties of the hepatic parenchyma. As a master regulator of hypoxia, the transcription factor hypoxia-inducing factor (HIF) is stabilized primarily by oxygen availability, and it is thought to contribute to steatohepatitis due to alcohol-related (ASH) and non-alcohol-related liver disease (NASH). Cholesterol has emerged as an important player in both diseases, and hypoxia increases hepatic cholesterol levels. Steroidogenic acute regulatory protein 1 (STARD1) is a mitochondrial outer membrane protein that transfers cholesterol to mitochondrial inner membrane for metabolic processing and acts as the rate-limiting step in the alternative pathway of bile acid synthesis in hepatocytes. STARD1 expression increases in ASH and NASH and determines the accumulation of cholesterol in mitochondria, which impacts the physico-chemical mitochondrial membranes properties and as a consequence impairs the activity of specific mitochondrial solute carriers, such as the 2-oxoglutarate carrier (2-OGC), limiting the exchange between cytosolic glutathione and mitochondrial 2-oxoglutarate (2-OG). Although HIF-1 is stabilized in hypoxia largely due to the requirement of prolylhydroxylases (PHDs) for oxygen to signal HIF degradation, PHDs are also dependent on 2-OG, and therefore it is conceivable that impairment of 2-OGC by STARD1-mediated cholesterol accumulation may contribute to HIF-1 stabilization due in part to decreased availability of cytosolic 2-OG. In this perspective, this review explores the interplay between HIF-1 stabilization and STARD1 induction and the potential contribution of this functional relationship to ASH and NASH. Perspective Fri, 30 Dec 2022 00:00:00 GMT SandraTorres, Jose C.Fernandez-Checa, CarmenGarcia-Ruiz, Fri, 30 Dec 2022 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100512 https://www.explorationpub.com/Journals/edd/Article/100513 Lysosomal hydrolases were once considered effectors of the waste disposal system of the cell, the endo-lysosomal system. However, they are now recognized as highly selective enzymes, which can modulate the function of several substrates, contributing to essential homeostatic and pathological cellular processes. There are more than 50 different lysosomal hydrolases that display optimal activity in the pH present in the acidic cellular compartment but can also be found in other cellular locations. They can work alone or in cooperation with other proteases building signaling pathways or amplification cascades. In the context of liver fibrosis lysosomal hydrolases, especially cysteine cathepsins have been described to participate in several fundamental cellular events contributing to the development, progression, perpetuation, and resolution of liver fibrosis. This paper comprehensively reviews the current knowledge on the contribution of lysosomal hydrolases to liver fibrosis. Review Wed, 22 Feb 2023 00:00:00 GMT MaríaFernández-Fernández, PalomaRuiz-Blázquez, JúliaCacho-Pujol, AnnaMoles, Wed, 22 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100513 https://www.explorationpub.com/Journals/edd/Article/100514 Not applicable. Editorial Sat, 25 Feb 2023 00:00:00 GMT AmedeoLonardo, Sat, 25 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100514 https://www.explorationpub.com/Journals/edd/Article/100515 Evaluation of the hepatobiliary function is critical for the clinicians, not only for the diagnosis of a large variety of liver diseases but also in the follow-up and management of some patients, for instance, those with different degrees of cholestasis suffering from a drug-induced liver injury (DILI) or scheduled for liver resection. Currently, the determination of global liver function mainly relies on laboratory tests, clinical scores, and data from images obtained with ultrasonography, computed tomography (CT), or magnetic resonance. Nuclear medicine scanning, displaying either planar or three-dimensional spatial distribution of liver function, is enhanced when using hepatotropic tracers based on classical radioisotopes such as technetium-99m (99mTc) and with higher resolution using metabolized probes such as those based on monosaccharide derivatives labeled with 18F. Other cholephilic compounds, and hence selectively secreted into bile, have been proposed to visualize the correct function of the liver parenchyma and the associated secretory machinery. This review aims to summarize the state-of-the-art regarding the techniques and chemical probes available to monitor liver and gallbladder function, in some cases based on imaging techniques reflecting the dynamic of labeled cholephilic compounds. Review Tue, 28 Feb 2023 00:00:00 GMT Beatriz Sanchezde Blas, Alvaro G.Temprano, Jose J. G.Marin, Marta R.Romero, Tue, 28 Feb 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100515 https://www.explorationpub.com/Journals/edd/Article/100516 Hereditary cholestasis comprises a broad spectrum of clinical phenotypes of varying severity. Severe forms such as progressive familial intrahepatic cholestasis (PFIC) mostly affect children with disease onset within their first years. Nevertheless, late-onset PFIC forms are increasingly diagnosed. Most adults present with less severe forms of hereditary cholestasis, often suffering from pruritus, gallstone disease, jaundice, or elevated liver enzymes. To identify the underlying genetic background and to rule out potential differential diagnoses, a broad genetic analysis like whole exome sequencing (WES) is recommended. Knowledge of the affected gene may have an impact not only on patient surveillance due to risk for disease progression or tumor development but also on potential therapeutic strategies. This case of the adult patient illustrates the importance of broad genetic analysis, which brought up the potentially relevant rare multidrug resistance protein 3 (MDR3) missense variant p.(Asn489Tyr) underlying the patient’s clinical phenotype of low phospholipid-associated cholelithiasis (LPAC). Patients with MDR3 disease may have an increased risk for cholangiocarcinoma (CCA) development and therefore need an individualized surveillance strategy. Most MDR3-affected patients benefit from life-long therapy with ursodeoxycholic acid (UDCA), which is well tolerated. Bezafibrate treatment can reduce pruritus, one of the main symptoms affecting the quality of life. Whether the administration of ileal bile acid transporter (IBAT) inhibitors is beneficial in adult patients with MDR3 disease is so far unknown. Case Report Fri, 21 Apr 2023 00:00:00 GMT CarolaDröge, TobiasGötze, AnnikaBehrendt, HolgerGohlke, VerenaKeitel, Fri, 21 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100516 https://www.explorationpub.com/Journals/edd/Article/100517 Zebrafish as a preclinical drug induced liver injury (DILI) model provides multiple advantages ranging from ease of breeding and maintenance, availability of different strains and transgenic fish amenable to study liver function, and highly conserved liver structure and function with the human liver. In this review, the authors have aimed to provide an account of the metabolic enzymes that take roles in drug detoxification in both human and zebrafish in a comparative manner and exemplify several recent models in studying liver functionality. Moreover, the authors emphasize the difficulties associated with studying idiosyncratic DILI in preclinical models and propose that zebrafish could be an important complement to mice in testing functions of genes that are associated with DILI with respect to different drugs in human genome-wide association studies (GWAS) Catalog. Finally, this review highlights the state-of-the-art in the development of novel transgenic reporter strains that can be used to study degree and molecular mechanisms of hepatotoxicity caused by drugs in zebrafish. All of these will help researchers to use effectively the available resources in the zebrafish DILI models, while advocating potential leads that can be taken to provide advancements in a better understanding and treatment of DILI. Review Thu, 27 Apr 2023 00:00:00 GMT GulcinCakan-Akdogan, Abdul MoizAftab, Muazzez CelebiCinar, Khalid A.Abdelhalim, OzlenKonu, Thu, 27 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100517 https://www.explorationpub.com/Journals/edd/Article/100518 The late event onset of a fraction of idiosyncratic drug-induced liver injury (DILI) cases and the link observed by genome-wide association studies (GWASs) of certain human leucocyte antigen (HLA) alleles with DILI due to specific drugs support the crucial role of the immune system (both innate and adaptive) in the pathogenesis of DILI. Recent advances in both flow and mass cytometry have allowed the profiling of all major immune cell types in a given sample. Therefore, determining the lymphocyte populations in samples from patients with DILI would facilitate the development of specific biomarkers for DILI diagnosis and prognosis. To date, a few studies have explored the immune landscape in DILI. In a recent study of leukocyte immunophenotyping using flow cytometry from the Spanish DILI Registry, an important role of adaptive immune response in DILI is suggested. DILI patients had significantly higher levels of T helper 1 (Th1) cells and activated helper and cytotoxic T cells than healthy controls. Furthermore, the increased expression of negative immune checkpoints and ligands in DILI patients could reflect a restoration of the immune homeostasis. Differences in the profile of cytokines in DILI patients from the Drug-Induced Liver Injury Network (DILIN) also suggest an involvement of both innate and adaptive immune systems in DILI development and prognosis. Moreover, several studies based on immunophenotyping of liver infiltrates showed a distinctive pattern of cellular infiltrates in patients with immune checkpoint inhibitors (ICIs)-DILI, with lower levels of plasma cells, CD20+ B cells and CD4+ T cells than in autoimmune hepatitis (AIH) patients. These pioneering studies highlight the importance of immunophenotyping for the mechanistic understanding of DILI. In this review, available data on immunophenotyping in DILI are gathered, and the potential clinical applications of cutting-edge, novel immunophenotyping techniques are discussed. Review Thu, 27 Apr 2023 00:00:00 GMT AlejandroCueto-Sánchez, Daniel E. DiZeo-Sánchez, AntonioSegovia-Zafra, GonzaloMatilla-Cabello, AnaBodoque-García, María IsabelLucena, MarinaVillanueva-Paz, Thu, 27 Apr 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100518 https://www.explorationpub.com/Journals/edd/Article/100519 The word “Kampo medicine” means the traditional Japanese herbal medicine. Even “natural herb” can cause drug-induced liver injury (DILI). In this review, the characteristics of Kampo medicine-induced liver injury (KMILI) are reported. The main causative herb involved in Kampo medicine is Scutellariae Radix. KMILI is based on certain hypersensitivity reactions. A small amount of Kampo medicine can cause liver injury, and KMILI can develop after a short latency period. The incidence of liver injury related to Scutellariae Radix is about 1%. KMILI is usually mild and not fatal. The latency period usually lasts 4 weeks to 24 weeks. Fatigue and loss of appetite are sometimes observed. Eosinophilia is not frequently observed. All three types of liver injuries are observed in KMILI: cholestatic, hepatocellular, and mixed types. In Japan, lymphocyte transformation test (LTT) has been generally used for the diagnosis of DILI; however, LTT is likely to yield false-positive result for Kampo medicines, and thus often leads to misdiagnosis in many cases. Recently, researchers reported that a specific human leukocyte antigen (HLA) genotype is possibly associated with KMILI. This hypothesis needs to be examined further. Although Kampo medicine is based on rich knowledge and experience that occurred over a period of thousands of years, much is still unknown about KMILI. Review Tue, 27 Jun 2023 00:00:00 GMT NaokiMantani, Tue, 27 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100519 https://www.explorationpub.com/Journals/edd/Article/100520 The pathogenesis of drug-induced liver injury (DILI) is still in an early stage of research. However, investigators have shown that both oxidative stress and endoplasmic reticulum (ER) stress play a significant role in the pathological mechanism. However, there is little in-depth literature about these two mechanisms. In order to prevent and improve the clinical symptoms of DILI, it is particularly important to study its pathogenesis. In this review article, the role of ER and oxidative stress in DILI is thoroughly discussed. Review Wed, 28 Jun 2023 00:00:00 GMT HanghangWu, XiyuanBao, Alejandro H.Gutierrez, Yulia A.Nevzorova, Francisco JavierCubero, Wed, 28 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100520 https://www.explorationpub.com/Journals/edd/Article/100592 This article evaluates contemporary and evolving surgical techniques in diverticulitis management. A comprehensive literature search was conducted using PubMed on guidelines for articles on surgical interventions for diverticulitis. The relevant data were extracted and synthesized to identify trends, advancements, and gaps in the current understanding of surgical interventions for diverticulitis. Many patients with uncomplicated diverticulitis can achieve favourable outcomes through conservative management strategies. Surgical interventions are increasingly tailored based on individual risk profiles and disease severity. Recent methods for managing diverticulitis highlight the significance of personalized treatment, which can lead to faster recovery times and better overall quality of life. More patients are now considered appropriate candidates for primary anastomosis, with or without a stoma in place of Hartmann’s procedure, where reversal is often tricky. Additionally, minimally invasive surgical techniques are being employed more frequently. Mini Review Thu, 18 Sep 2025 00:00:00 GMT KaushalYadav, SagirAhamed, Thu, 18 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100592 https://www.explorationpub.com/Journals/edd/Article/100521 Aim: This is a Chinese population-based study aimed to determine the causes and clinical features of drug-induced liver injury (DILI) from traditional Chinese medicines (TCMs) and current Western medicines (WMs) and identify the risk factors of drug-induced liver failure (DILF) and chronic DILI for early recognition and better management. Methods: The medical records of patients who were diagnosed with DILI for at least six-month follow-up between January 2018 to December 2020 were reviewed and investigated. The risk factors of DILF and chronic DILI were identified by univariate and multivariate logistic regression analysis. Results: TCMs (47.5%) including herbal medicine (83.0% in TCM-induced DILI) and some Chinese patent drugs were the leading cause of DILI in the present study. Cholestatic type was more associated with severe and chronic DILI. Pre-existing gallbladder disease, initial total bilirubin (TBIL), initial prothrombin time (PT), initial antinuclear antibodies (ANA), and clinical classification are independent risk factors for DILF. Prolonged T0.5AST and T0.5GGT were independent risk factors for chronic DILI [area under the curve (AUC) = 0.812, 95% confidence interval (CI): 0.748–0.876, P < 0.001] with cut-off values of 8.5 days and 29.5 days, respectively. Conclusions: TCMs especially herbal medicine were the leading causes of DILI, and the risk of developing severe DILI was associated with pre-existing gallbladder disease, clinical classification, initial TBIL, PT, and ANA. T0.5AST and T0.5GGT might serve as indicators for chronicity. Original Article Fri, 30 Jun 2023 00:00:00 GMT QianWei, LeiLi, XiaoqingZeng, JieYin, JinshengGuo, Fri, 30 Jun 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100521 https://www.explorationpub.com/Journals/edd/Article/100522 Excessive alcohol intake is still among the leading causes of chronic liver diseases. Epidemiological studies suggest that per capita consumption of alcohol from various alcohol beverages e.g., beer, wine, or spirits, differs markedly between different areas of the world. Studies further suggest that different alcoholic beverages may impact the development of alcohol-related liver diseases (ALD) differentially. Specifically, results of several more recent epidemiological studies suggest that consumption of wine and herein especially of red wine may be less harmful in relation to the development of liver diseases than the intake of hard spirits. Results of studies evaluating the effects of beer on the development of ALD in humans are rather contradictory. Here, results of studies assessing the impact of wine, beer, and spirits on the development of ALD as well as possible underlying mechanisms are summarized and discussed. Review Sat, 01 Jul 2023 00:00:00 GMT FinnJung, VictorSánchez, AnnetteBrandt, InaBergheim, Sat, 01 Jul 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100522 https://www.explorationpub.com/Journals/edd/Article/100523 A high consumption of ultra-processed food (UPF) is a hallmark of Western diets that has been related to increased risk of non-communicable diseases. As an underlying mechanism, UPF may promote non-alcoholic fatty liver disease (NAFLD) which is a key driver of metabolic impairment with extra-hepatic manifestations like type 2 diabetes, cardiovascular disease, chronic kidney disease, and osteoporosis among others. The present review provides an overview of UPF properties that may promote NAFLD and are thus potential targets for reformulation of UPF. Such approaches should address improvements in the quality of carbohydrates and fat, changes in food texture that lower eating rate as well as ingredients that prevent excess caloric intake or avoid dysbiosis and leaky gut syndrome. Promising strategies are enrichment with fiber, prebiotics, phytochemicals, and protein with a concurrent reduction in glycemic load, energy density, saturated fatty acids (FA; SFA), emulsifiers, fructose, and non-caloric sweeteners. Future studies are needed to examine the interactive and protective effects of such modifications in the composition of UPF on prevention and treatment of NAFLD. Review Thu, 24 Aug 2023 00:00:00 GMT Franziska A.Hägele, JannaEnderle, GeraldRimbach, AnjaBosy-Westphal, Thu, 24 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100523 https://www.explorationpub.com/Journals/edd/Article/100524 Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is a rare chronic autoimmune cholestatic liver disease, affecting mostly females. With PBС develops chronic cholangiopathy, this is accompanied by the development of gradually progressive liver fibrosis, which leads to intrahepatic cholestasis. Defects in autoimmune tolerance are critical factors in the emergence of the disease. Biochemical signs in PBС appear already in the asymptomatic stage of the disease and they are associated with a disturbance of the secretion of bile acids. Understanding the pathophysiological mechanisms of these signs is essential to both the early diagnosis and treatment of PBC. Early diagnosis of the disease contributes to its more effective treatment. There are many scientifically based modern data on the pathophysiology of clinical and laboratory signs developing in PBС. The purpose of this review is to summarize the data available in the literature and those obtained by the authors on the mechanisms for the development of biochemical criteria for PBC and their diagnostic significance. The opportunity to present the pathophysiological mechanisms of the development of biochemical signs in patients with PBC is associated with the success in the development of modern research methods in biochemistry, molecular biology, and genetics. Review Mon, 28 Aug 2023 00:00:00 GMT Vasiliy IvanovichReshetnyak, Igor VeniaminovichMaev, Mon, 28 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100524 https://www.explorationpub.com/Journals/edd/Article/100525 Aim: Modifications in long non-coding RNA (lncRNA) expression are associated with inflammation and fibrosis in chronic liver diseases. It has been recently demonstrated that human liver stem cells (HLSCs) and their extracellular vesicles (EVs) can effectively reduce inflammation and fibrosis in a murine model of non-alcoholic steatohepatitis (NASH). Now it has been evaluated whether EVs can modify the expression of inflammation-related lncRNAs in NASH liver. Methods: To induce NASH, severe combined immunodeficient mice were fed with a methionine-choline-deficient diet for 4 weeks. After 2 weeks of diet, 2.5 × 109 EVs were intravenously injected twice a week. An array of 84 inflammation-related lncRNAs was performed on the RNA isolated from NASH livers, and the expression of 14 selected lncRNAs was then validated by real-time polymerase chain reaction (PCR) analysis. Expression levels of maternally expressed gene 3 (Meg3) were further evaluated in vitro, in an activated human hepatic immortalized stellate cell line (LX-2) stimulated with EVs. Results: The screening showed an altered lncRNA expression profile in the liver of NASH mice, in respect to control healthy mice. EV treatment modulated several inflammation-related lncRNAs in NASH livers. Real-time PCR validation of array results indicated that EVs restored to normal levels the expression of 10 lncRNAs altered in NASH. In particular, EV stimulation reduced Meg3 expression levels, which were increased in NASH as well as in activated LX-2. Conclusions: HLSC-EVs regulate the expression of inflammation-related lncRNAs impaired in NASH livers and in an in vitro model of liver fibrosis. Original Article Wed, 30 Aug 2023 00:00:00 GMT GiuliaChiabotto, ElenaCeccotti, ChiaraPasquino, Maria BeatrizHerrera Sanchez, MassimoCedrino, GiovanniCamussi, StefaniaBruno, Wed, 30 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100525 https://www.explorationpub.com/Journals/edd/Article/100526 Nonalcoholic fatty liver disease (NAFLD) is an umbrella definition that describes the ectopic deposition of fat within the liver that occurs in the absence of inciting factors other than the metabolic syndrome and its individual features. NAFLD has a multi-factorial pathogenesis which determines heterogeneous clinical phenotypes and variable natural course spanning from liver-related (steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma) to extrahepatic outcomes (cardio-metabolic and cancer). This narrative review article leverages the key aspects of disease natural history as the background information to discuss studies that may inform strategies to risk-stratify NAFLD patients. Evaluation of hepatic fibrosis with non-invasive tools, including blood-based biomarkers and imaging-based elastometry techniques, seemingly retains the core information useful to predict the heterogeneous outcomes listed above. Additionally, genetic testing and metabolomic profiles may also be utilized to this end. In conclusion, a comprehensive understanding of the variable hepatic, cardio-metabolic and cancer outcomes of NAFLD may enable physicians and researchers to risk-stratify and accurately identify the multilayered prognosis of NAFLD individuals while also defining homogeneous patient subsets to enroll in clinical trials. Review Wed, 30 Aug 2023 00:00:00 GMT AmedeoLonardo, Wed, 30 Aug 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100526 https://www.explorationpub.com/Journals/edd/Article/100527 Drug-induced liver injury (DILI) is an adverse reaction to drugs and other xenobiotics that can have serious consequences and jeopardise progress in pharmacological therapy. While DILI is predominantly hepatocellular, a non-negligible percentage of patients who present with cholestatic damage. Mixed damage is typically lumped together with cholestatic damage in the literature. Drug-induced cholestasis is often caused by the use of some non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics (i.e., amoxicillin-clavulanic acid), statins, and anabolic agents, among others. Drug-associated cholestasis tends to have a more chronic course and mostly affects older population. There is also a genetic predisposition to toxic cholestasis caused by some drugs (amoxicillin-clavulanic acid, statins, etc.). Recently, anatomical alterations of the biliary tract induced by drugs (especially immunotherapy drugs) have been described. Bile duct injury is one of the histopathological findings that have prognostic significance in DILI. A correct differential diagnosis with other causes of cholestasis is mandatory to reach an accurate diagnosis. Ursodexycholic acid, corticosteroids, and replacement therapies have been used as a therapeutic arsenal, although more evidence is needed to establish them as a routine therapeutic management in clinical practice. The breakthrough and validation of biomarkers of cholestasis and bile duct injury is an urgent need for drug development and post-marketing phase. Review Mon, 18 Sep 2023 00:00:00 GMT Jose M.Pinazo-Bandera, Juan PedroToro-Ortiz, Raúl J.Andrade, MirenGarcía-Cortés, Mon, 18 Sep 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100527 https://www.explorationpub.com/Journals/edd/Article/100528 The pathogenesis of primary biliary cholangitis (PBC) is particularly complicated as both intrinsic and extrinsic factors are implicated. Several forms of cellular death, both programmable and non-programmable, operate leading biliary epithelial cells (BECs) to elimination. The precise role of critical pathways like autophagy, apoptosis, senescence, and their interplay has not been fully clarified. Therefore, in this review, data on these important mechanisms are presented and their implication in PBC is discussed. The interplay of the three mechanisms is examined and the factors that drive them are analyzed. Moreover, the upstream drivers of autophagy, apoptosis, and senescence are presented. They include the loss of the protective bicarbonate umbrella in BECs due to the reduction of activity of the anion exchanger 2 (AE2) with the resultant activation of the intracellular soluble adenylyl cyclase (sAC). The role of toxic bile acids is also presented. A sequence of events is proposed including involvement of the gut-liver axis and the possible role of ferroptosis. Finally, a brief account of the initial trigger of the disease is given. Review Mon, 16 Oct 2023 00:00:00 GMT EliasKouroumalis, IoannisTsomidis, ArgyroVoumvouraki, Mon, 16 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100528 https://www.explorationpub.com/Journals/edd/Article/100529 Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease worldwide, with a progressive form of non-alcoholic steatohepatitis (NASH). It may progress to advanced liver diseases, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD/NASH is a comorbidity of many metabolic disorders such as obesity, insulin resistance, type 2 diabetes, cardiovascular disease, and chronic kidney disease. These metabolic diseases are often accompanied by systemic or extrahepatic inflammation, which plays an important role in the pathogenesis and treatment of NAFLD or NASH. Metabolites, such as short-chain fatty acids, impact the function, inflammation, and death of hepatocytes, the primary parenchymal cells in the liver tissue. Cholangiocytes, the epithelial cells that line the bile ducts, can differentiate into proliferative hepatocytes in chronic liver injury. In addition, hepatic non-parenchymal cells, including liver sinusoidal endothelial cells, hepatic stellate cells, and innate and adaptive immune cells, are involved in liver inflammation. Proteins such as fibroblast growth factors, acetyl-coenzyme A carboxylases, and nuclear factor erythroid 2-related factor 2 are involved in liver metabolism and inflammation, which are potential targets for NASH treatment. This review focuses on the effects of metabolic disease-induced extrahepatic inflammation, liver inflammation, and the cellular and molecular mechanisms of liver metabolism on the development and progression of NAFLD and NASH, as well as the associated treatments. Review Thu, 26 Oct 2023 00:00:00 GMT ChunyeZhang, YuxiangSui, ShuaiLiu, MingYang, Thu, 26 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100529 https://www.explorationpub.com/Journals/edd/Article/100530 Aim: Familial achalasia (FA) is a very rare condition. This work aims to evaluate its prevalence, characterize its clinical profile in a large series, and assess the efficacy and safety of pneumatic dilation (PD) in this context. Methods: A total of 817 patients with achalasia were collected over a period of 20 years (1990–2010). All cases of FA: isolated or associated to Allgrove syndrome, were looked for in both parents and siblings. Results: In this study, 18 families with FA were identified n = 41 patients (5%). Two members were affected in each family, in 14 families, three members per family in three others, and for the remaining family 04 members. All cases of achalasia were observed in siblings and parent to child transmission was unfound. Achalasia was associated to Allgrove syndrome in 15 families. It was isolated in 3 families. Consanguinity was found in 89% of patients, and death at a young age in the siblings was recorded in 27% of cases. Achalasia was present before the age of 5 years in 75% of cases. There was no difference between the two groups for age, age at onset, sex and the presence of the cardinal signs of achalasia. A total of 102 dilations were performed. Only one session in 31% of cases, two in 38%, three in 17% and more than three sessions in 14%. The long-term success rate of PD was low. Conclusions: FA manifests almost exclusively in childhood. It is rarely isolated; most often falls under Allgrove syndrome. Alacrima is the earliest sign that should lead to the diagnosis. The long-term success rate of PD is rather low. This requires recourse to multiple sessions of PD or Heller’s cardiomyotomy which may be the best initial approach. Original Article Fri, 27 Oct 2023 00:00:00 GMT AmarTebaibia, FaroukBenmediouni, Mohamed El AmineBoudjella, MustaphaLahcen, NadiaOumnia, Fri, 27 Oct 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100530 https://www.explorationpub.com/Journals/edd/Article/100535 Not applicable. Correction Fri, 12 Jan 2024 00:00:00 GMT , Fri, 12 Jan 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100535 https://www.explorationpub.com/Journals/edd/Article/100531 Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most common chronic liver diseases. Over time, there has been a significant increase in the prevalence of MASLD. It has become one of the leading causes of hepatocellular carcinoma (HCC) in the United States, France, and the United Kingdom. Globally, the incidence of HCC related to MASLD may further increase with the growing prevalence of obesity. Non-alcoholic steatohepatitis (NASH) is an important stage of MASLD, which is more likely to cause cirrhosis and even HCC. And patients with NASH cirrhosis have a much higher incidence of hepatocellular cancer than patients with non-cirrhotic MASLD. As a result, it is critical to investigate the targets of MASLD therapy in HCC. This article reviews therapeutic targets of MASLD, such as farnesoid X receptor (FXR), peroxisome proliferator activated receptor (PPAR), fibroblast growth factor-21 (FGF-21), etc., and introduces the drugs related to these targets and their mechanisms of action in HCC. In addition, the developmental process and pathogenesis of MASLD, as well as risk factors for HCC development, are discussed. These are of great significance for the prevention and treatment of HCC. Review Wed, 13 Dec 2023 00:00:00 GMT ChenyuWei, JianingWu, ChaoyangZhang, YinshenZhao, ChunzhengLi, XianguangYang, Wed, 13 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100531 https://www.explorationpub.com/Journals/edd/Article/100532 Aim: In Switzerland, the first access to interferon-free direct-acting antivirals (DAAs) for hepatitis C virus (HCV) treatment was in 2014. This study aimed to analyze the effects of DAAs on the yearly listed numbers of HCV RNA-positive (RNA+) patients and their mortality on the Swiss organ transplantation waiting list (SOWL). Methods: In this retrospective secondary time series analysis of yearly aggregated data on listed and delisted patients from a subset of HCV RNA+ patients on the SOWL, listed patients were grouped by the requested organ, and delisted patients by reason. Time series were split into two periods of equal length, the phases before and after DAA implementation, and the mean difference was tested using the Mann-Whitney U test. Results: From 2008 to 2019, 328 HCV RNA+ patients were listed on SOWL, 86.6% requesting liver, 11.6% kidney, and 1.8% other organ transplantations. A total of 285 RNA+ patients were delisted from SOWL: 14.7% died, 75.4% had been transplanted, and 9.8% were delisted without surgery. There were significant reductions of patients listed for requesting any organ (–21.7, P = 0.004), liver (–18.3, P = 0.004), or kidney (–3.0, P = 0.031) comparing the periods before and after DAA launch. The mean number of delistings after transplantation (–11.2, P = 0.010), or death (–4, P < 0.001) show a significant reduction. Conclusions: With DAAs, the rising trend of HCV RNA+ people waiting for organs was broken, as was the increasing trend of mortality on the SOWL among HCV RNA+ individuals. Original Article Mon, 25 Dec 2023 00:00:00 GMT LuisFalcato, SimoneTemperli, PhilipBruggmann, FranzImmer, Mon, 25 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100532 https://www.explorationpub.com/Journals/edd/Article/100533 Aim: This study aims to determine the significance of chronic hyperglycemia for the reduced efficacy of eradication therapy in patients with type 2 diabetes mellitus (T2DM) and Helicobacter pylori (H. pylori)-associated upper gastrointestinal tract pathology as well as for H. pylori survival. Methods: A prospective randomized study with the participation of 180 patients (87 men and 93 women) with H. pylori-associated upper gastrointestinal pathology was carried out. Ninety of these patients were with T2DM and 90 were without diabetes mellitus (DM). The patients were divided into 4 groups of 45 patients: the group 1 included non-diabetic patients treated with the classical triple eradication scheme; the group 2 included patients with T2DM treated with the classical triple eradication scheme; the group 3 included non-diabetic patients treated with bismuth quadro-therapy; the group 4 included patients with T2DM treated with bismuth quadro-therapy. The presence of H. pylori and evaluation of eradication efficacy was carried out using the Helix breath test. Results: The effectiveness of 1st line anti-Helicobacter therapy was higher (88.2%) in patients without diabetes in comparison with the group of patients with concomitant T2DM (74.7%). The efficacy of classical triple eradication therapy in patients with concomitant T2DM was 69.1%, and quadro-therapy was 80.5%. There was significantly lower effectiveness (P < 0.017) of eradication therapy in patients with T2DM and glycated hemoglobin (HbA1c) level ≥ 7.0% as compared with the group of patients in whom the target (≤ 6.5%) level of HbA1c was achieved. Conclusions: Chronic hyperglycemia has a favorable effect on the viability of H. pylori bacteria in patients with T2DM. A hypothesis explaining the reduced efficacy of eradication therapy in patients with hyperglycemia has been proposed. Original Article Wed, 27 Dec 2023 00:00:00 GMT Luiza GilmanovnaBektemirova, Igor VeniaminovichMaev, Diana TodorovnaDicheva, Vasiliy IvanovichReshetnyak, Wed, 27 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100533 https://www.explorationpub.com/Journals/edd/Article/100534 Drug-induced liver injury (DILI) poses a complex and heterogeneous clinical challenge, which often resembles non-drug related acute or chronic liver diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). Furthermore, certain drugs can induce hepatic steatosis, which is considered a rare variant of hepatotoxicity. Additionally, the detection and diagnosis of DILI in patients with non-alcoholic liver disease present additional challenges that require attention. The importance of achieving an accurate diagnosis is highlighted by the different therapeutic approaches needed for each of these diseases. Nonetheless, as definitive diagnostic tests and distinct biomarkers often remain elusive, the differential diagnosis must rely on a combination of clinical, biochemical, histological, and immunophenotypic profiling. The diagnosis of hepatotoxicity is predicated upon the temporal nexus between the administration of a potentially hepatotoxic drug and the onset of hepatic injury, concomitantly excluding alternative hepatic pathologies. More frequently, this condition presents an acute course, with a more pronounced elevation of cytolytic and cholestatic parameters as compared to fatty liver disease. Advances in elucidating the underlying mechanisms hold promise for bolstering the diagnosis and management of these conditions. This article aims to thoroughly examine and emphasize the currently available scientific evidence to provide valuable insights into the diagnostic strategies for DILI, metabolic-associated liver disease, and drug-induced steatosis (DIS). Review Wed, 27 Dec 2023 00:00:00 GMT MirenGarcía-Cortés, Juan PedroToro-Ortiz, AlbertoGarcía-García, Wed, 27 Dec 2023 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100534 https://www.explorationpub.com/Journals/edd/Article/100536 Not applicable. Editorial Thu, 18 Jan 2024 00:00:00 GMT MicheleGhidini, Thu, 18 Jan 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100536 https://www.explorationpub.com/Journals/edd/Article/100537 Hunting for tumoral material in body fluids, traditionally in blood, the so-called liquid biopsy is set to revolutionize the diagnosis and management of oncological patients. However, other biofluids can also be considered as alternative sources of biomarkers to provide clinically valuable information for multiple diseases. This is the case of bile, a fluid produced in the liver, stored in the gallbladder, and excreted to the duodenum, which complex composition is known to change in different pathological conditions. Remarkably, different works have demonstrated that the identification of mutations in bile cell-free DNA (cfDNA) can outperform blood analysis for the early diagnosis of biliopancreatic tumors causing biliary strictures. Here, the literature in which bile has been tested as a liquid biopsy matrix where lipids, metabolites, proteins, and cfDNA among other analytes were measured is reviewed. Moreover, the clinical situations and procedures where bile can be available, discussing the possible applications and limitations of bile analysis are summarized. The scientific relevance and clinical potential of bile harvesting, biobanking, and analysis are put forward. All this evidence supports the value of bile as a liquid biopsy matrix for the management of patients beyond cancer, and perhaps also beyond “blood, sweat, and tears”. Review Mon, 05 Feb 2024 00:00:00 GMT MariaArechederra, MariaRullán, DanielOyón, Matias A.Ávila, Jesús M.Urman, CarmenBerasain, Mon, 05 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100537 https://www.explorationpub.com/Journals/edd/Article/100538 Chronic liver diseases (CLDs), which are typically characterized by fibrogenic progression towards liver cirrhosis and related complications eventually leading to organ failure and can also lead to the development of primary liver cancers, represent a major burden for human health on a worldwide basis. Although the present knowledge on the pathogenesis of CLDs progression and primary liver cancers development has remarkably increased in the last decades, critical molecular mediators remain incompletely understood, and approved antifibrotic therapies to efficiently counteract CLDs progression and liver cancer are lacking. In the present review, this study will specifically analyse the putative contribution of SERPINB3, a member of the superfamily of serine-protease inhibitors (SERPINs), which has been shown to exert significant pro-inflammatory and pro-fibrogenic roles in progressive CLDs as well as to be involved in the development of primary liver cancers, including hepatocellular carcinoma (HCC), cholangiocarcinoma, and hepatoblastoma. Review Wed, 28 Feb 2024 00:00:00 GMT PatriziaPontisso, MaurizioParola, Wed, 28 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100538 https://www.explorationpub.com/Journals/edd/Article/100539 Mitochondria are present in all mammalian cells except matured red blood cells. Mitochondria consist of several metabolic pathways for glucose, fatty acids, amino acids, and bioenergetic pathways for ATP synthesis, membrane potential, and reactive oxygen production. In the liver, hepatic mitochondria play a key role in hepatic steatosis because mitochondrial metabolism produces acetyl-CoA which is the building block for synthesis of lipids and cholesterol. Mitochondria inner membrane is impermeable of metabolites, reducing equivalents, and small molecules such as phosphate, and sulfate. Thus, mitochondrial shuttles and carriers function as the routes of influx and efflux of these metabolites and molecules across the inner membrane. The signal regulation of these shuttles and mitochondrial enzymes could play a key role in coordinating the mitochondrial metabolism to adapt the cytosolic part of metabolic pathways in liver metabolic stress. Intriguingly, the interaction of mitochondria protein SH3 domain-binding protein 5 (SAB/SH3BP5) and c-Jun N-terminal kinase (JNK) was found as a pivotal role in sustained activation of JNK and phosphorylated-JNK (P-JNK) mediated activation of lipogenic pathway in nutritional excess. Knockout or knockdown of SAB prevented or reversed the hepatic steatosis, inflammation, and fibrosis, and improved metabolic intolerance and energy expenditure. Moreover, blocking the SAB peptide prevents palmitic acid-induced P-JNK interaction with SAB and inhibition of mitochondrial bioenergetics, implying the P-JNK effect on mitochondrial metabolism. This review focuses on the flow of mitochondrial metabolites in metabolic stress conditions and the contribution of mitochondria and mitochondrial stress signals in hepatic steatosis. Review Thu, 29 Feb 2024 00:00:00 GMT SandaWin, Tin AungThan, NeilKaplowitz, NicoleWong, AlizaArya, Zin ThandarWin, Shwe HlaingWin, Ei HninPhyu, ChristinaKuemerle, JakeSuh, SonaAvanesyan, Pujan PrakashDobaria, Hnin WaiLwin, SeanWong, ShannonKaw, SamuelWong, Kyaw KhaingSoe, GarmaniKyaw, Filbert Win MinAung, Thu, 29 Feb 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100539 https://www.explorationpub.com/Journals/edd/Article/100540 The liver, characterized by a unique metabolic and immunosuppressive environment, is also the organ to which invasive malignant cells of many different cancer types most frequently metastasize. The reasons for this organ-specific metastatic process have been investigated for decades. This review first provides an overview of recent breakthroughs in this field, introducing intercellular communication between circulating tumor cells and the heterogeneous cell populations of the liver, and modifications to the extracellular matrix (ECM). Subsequently, to improve the understanding of the molecular mechanisms involved in the metastasis of colorectal cancer to the liver, the second leading cause of cancer-related mortality, the recent literature on this question was analyzed. Among the various parameters involved, the mechanisms behind the activation of hepatic stellate cells, proteins inducing ECM remodeling, specific genomic features of liver metastases, metabolic rewiring, and characteristics of stromal-enriched microenvironments were discussed. To provide more insights into the molecular determinants of liver metastatic colonization, important findings reported on a set of mitochondrial proteins were addressed, the relative abundance of which changed in the liver during the progression stage of an aggressive experimental model of peritoneal malignant mesothelioma in immunocompetent rats. Based on previous studies cross-comparing the liver proteomes from curcumin-treated tumor-bearing rats/untreated tumor-bearing rats/normal rats, data from the literature were reviewed for 25 mitochondrial proteins of interest. Their role in lipid metabolism, heme biosynthesis, the electron transport chain, small molecule transport, mitochondrial dynamics, the tricarboxylic acid cycle, and protection against oxidative stress were analyzed in the context of both cancer and non-malignant liver diseases. Review Fri, 22 Mar 2024 00:00:00 GMT Daniel L.Pouliquen, Fri, 22 Mar 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100540 https://www.explorationpub.com/Journals/edd/Article/100541 This is a case of remarkable alpha-fetoprotein in a female patient with known cryptogenic liver cirrhosis. Both ultrasound and triphasic computed tomography (CT) abdomen cannot diagnose or exclude hepatocellular carcinoma (HCC). It turns out to be a case of portal vein thrombosis and hepatic pseudo-infarction. It is better to postpone the therapeutic intervention, whether surgical or chemotherapeutic, in cases not confirmed to be HCC for at least 3 months to avoid misdiagnosis of hepatic pseudo-infarction. Case Report Fri, 29 Mar 2024 00:00:00 GMT Maged TharwatElghannam, Moataz HassanHassanien, Yosry AbdelrahmanAmeen, Gamal MohammedELattar, Ahmed AlyELRay, Mohammed DarwishELTalkawy, Fri, 29 Mar 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100541 https://www.explorationpub.com/Journals/edd/Article/100542 Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology that can lead to end stage liver disease if left without treatment. Corticosteroids with or without azathioprine (AZA) are considered the recommended standard first-line treatment option for the induction and maintenance of remission. The aim of treatment is to achieve complete biochemical response (CBR), defined by normal transaminases and immunoglobulin G (IgG) within 6–12 months after treatment initiation. However, response rates to standard treatment vary widely as approximately 10–25% of cases develop intolerance, insufficient response, or rarely non-response to AZA. Mycophenolate mofetil (MMF) is an effective and safe alternative first-line treatment in AIH, based on its high rates of CBR among treatment-naive patients, but can also be considered as second-line drug in patients with poor response or intolerance to AZA. However, even after the administration of second line treatment there is a small proportion of patients with refractory disease that bear the highest probability of developing decompensated cirrhosis and hepatocellular carcinoma. For this difficult to treat subgroup of patients third-line treatments are warranted. Therefore, the aim of this review is to summarize the current evidence on second- and third-line therapies for AIH, as well as, to set the background for future perspectives on safer and more efficient treatment strategies. Review Wed, 10 Apr 2024 00:00:00 GMT PinelopiArvaniti, IgnasiOlivas, SergioRodriguez-Tajes, George N.Dalekos, Maria-CarlotaLondoño, Wed, 10 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100542 https://www.explorationpub.com/Journals/edd/Article/100543 It is generally accepted that eradication of Helicobacter pylori (H. pylori) infection may reduce the risk of the development of gastric cancer. Recommendations for global generalized tests and treat all individuals detected positive for H. pylori infection are currently proposed. However, the bacterium is commensal and harmless for the vast majority of the infected population. Moreover, eradication may have detrimental consequences in several groups of patients. In the present review, the current epidemiological data and recommendations for eradication in connection with the possible beneficial effects of the colonization with H. pylori in diseases such as asthma and allergies or chronic gastro-intestinal disorders such as inflammatory bowel disease and Barrett’ esophagus are presented the problems with increasing antibiotic resistance were also examined. Specific groups of patients where eradication of H. pylori may be necessary and endoscopic surveillance is advised were identified. Finally, based on the paradox of high H. pylori prevalence and low gastric risk as reported for areas of Africa, Asia, South America, and Greece, alternatives that may replace the widespread eradication of H. pylori with equal if not better results and more prudent use of the available financial resources are proposed. Mediterranean diets and alcohol and smoking reduction are among the well documented alternatives. Review Tue, 16 Apr 2024 00:00:00 GMT EliasKouroumalis, IoannisTsomidis, ArgyroVoumvouraki, Tue, 16 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100543 https://www.explorationpub.com/Journals/edd/Article/100544 Aim: Extracellular vesicles (EVs) have gained significant attention for their diagnostic and therapeutic potential in various diseases, including liver disorders. This study focuses on optimizing the isolation and characterization of small EVs from plasma and serum samples in patients with liver diseases, aiming to advance our understanding and potential clinical applications of EVs. Methods: Blood samples were collected from patients with end-stage liver disease (ESLD) enlisted in the TransplantLines Cohort and Biobank Study, and healthy donors. We employed differential ultracentrifugation (DUC) to evaluate three distinct protocols: a 3-step DUC, a washing step omitted [samples without washing (WW)], and a contaminant-depleted plasma (CDP) protocol. RNA isolation methodologies were compared, involving the use of TRI-reagent or the commercial AllPrep DNA/RNA kit. Further insights into EV composition were obtained through proteomic analyses, comparing samples subjected to traditional cell lysis (L) with those processed without lysis (NL). Results: We successfully isolated EVs from both plasma and serum samples as confirmed by the presence of specific EV markers, including CD9, CD63, CD81, and tumor susceptibility gene 101 (TSG-101). While some contaminants remained, such as albumin and lipoproteins, the protocol selected to continue EVs analysis was the 3-step protocol. Transmission electron microscopy (TEM) and nanotracking analysis (NTA) further confirmed EVs presence. RNA extraction was achieved using TRI-reagent, but not with the commercial kit highlighting the importance of selecting an appropriate method for RNA isolation. Finally, proteomics analysis showed that lysed samples were significantly more enriched in proteins compared to non-lysed samples, although protein variability was still present in both groups. Conclusions: Optimizing EV isolation techniques is essential for harnessing their potential in liver disease diagnosis and therapy. Further refinement of purification methods, a deep characterization of our cohort and understanding the variability and cargo within EVs will be crucial for future biomarker discovery and therapeutic applications in liver-related diseases. Original Article Sun, 28 Apr 2024 00:00:00 GMT MagnoliaMartínez-Aguilar, María CamilaTrillos-Almanza, Justina C.Wolters, ManonBuist-Homan, , Frederikevan Vilsteren, HansBlokzijl, HanMoshage, Sun, 28 Apr 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100544 https://www.explorationpub.com/Journals/edd/Article/100545 The most common type of liver cancer is hepatocellular carcinoma (HCC) causes a lower survival rate even after systemic treatment. Previous studies have shown evidence that various molecular and epigenetic mechanisms are involved in the transition of HCC from normal liver cells. Epigenetics plays an important role in maintaining genomic stability in normal liver cells. Apart from the mutation of genes, epigenetic factors are involved in HCC progression. miRNA tends to be a major epigenetic factor involved in regulating major cell cycle pathways. miRNA regulates the HCC progression by inhibiting the major apoptotic pathways and favors angiogenesis and tumor microenvironment. Apart from regulating major pathways, miRNA appears to regulate tight junction integrity. Tight junction proteins appear to be strong barrier proteins involved in cell adhesion and integrity. Disturbance in cell adhesion and integrity leads to the major dysregulation of cell cycle resulting in cancer progression. Moreover, dysregulation of tight junction integrity was observed in the pathogenesis of HCC. The regulation of tight junction proteins via miRNA were studied in various diseases. Here, we discussed the regulation of tight junction proteins via miRNA in HCC progression. This review may focus on the significance of miRNA in cellular function and its role in regulating tight junction proteins that impact in HCC progression which opens a new approach to develop a new diagnostic marker for an early detection of HCC and novel therapeutic approach against HCC. Review Sat, 11 May 2024 00:00:00 GMT SivaBala Subramaniyan, BalasubramaniyanVairappan, Sat, 11 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100545 https://www.explorationpub.com/Journals/edd/Article/100546 Hepatitis B surface antigen (HBsAg) seroclearance is considered the functional cure and the optimal treatment endpoint for chronic hepatitis B (CHB). Patients with CHB who cleared HBsAg generally have a favorable clinical course with minimal risk of developing hepatocellular carcinoma (HCC) or cirrhotic complications. Nevertheless, a minority of patients still develop HCC despite HBsAg seroclearance. While patients with liver cirrhosis are still recommended for HCC surveillance, whether other non-cirrhotic patients who achieved HBsAg seroclearance should remain on HCC surveillance remains unclear. This review provides an overview of the incidence of HBsAg seroclearance, the factors associated with the occurrence of HBsAg seroclearance, the durability of HBsAg seroclearance, the risk of developing HCC after HBsAg seroclearance, the risk factors associated with HCC development after HBsAg seroclearance, the role of HCC risk scores, and the implications on HCC surveillance. Existing HCC risk scores have a reasonably good performance in patients after HBsAg seroclearance. In the era of artificial intelligence, future HCC risk prediction models based on artificial intelligence and longitudinal clinical data may further improve the prediction accuracy to establish a foundation of a risk score-based HCC surveillance strategy. As different novel hepatitis B virus (HBV) antiviral agents aiming at HBsAg seroclearance are under active development, new knowledge is anticipated on the natural history and HCC risk prediction of patients treated with new HBV drugs. Review Sat, 11 May 2024 00:00:00 GMT Jimmy Che-ToLai, Vicki Wing-KiHui, Grace Lai-HungWong, Vincent Wai-SunWong, Terry Cheuk-FungYip, Sat, 11 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100546 https://www.explorationpub.com/Journals/edd/Article/1005111 Herpes simplex esophagitis (HSE) is a viral infection of the esophagus caused by the herpes simplex virus (HSV), most commonly HSV-1. It predominantly presents among immunosuppressed individuals. Eosinophilic esophagitis (EoE) is a chronic, inflammatory, immune-mediated disease characterized by significant eosinophilic infiltration in the esophageal mucosa. It is often associated with atopic diseases, including asthma, food allergies, and eczema. Coexistence of HSE and EoE is rare and may be underdiagnosed due to challenges in diagnosing both conditions simultaneously. A major diagnostic dilemma can be traced to their histopathological similarities and differences. HSE is typically characterized by multinuclear giant cells containing intranuclear inclusions, while EoE involves eosinophilic infiltration in the esophageal epithelium. This report highlights the rare but remarkable coexistence between HSE and EoE secondary to a unique patient case. Although each condition may cause esophagitis individually, together—particularly in immunocompetent individuals—they do present a different diagnostic and therapeutic challenge. Case Report Fri, 13 Feb 2026 00:00:00 GMT SahilSabharwal, BrandynYoung, DeepakSabharwal, Sarat C.Sabharwal, TerrylOrtego, Fri, 13 Feb 2026 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005111 https://www.explorationpub.com/Journals/edd/Article/100547 Aim: This study aimed to develop and evaluate an in-house enzyme-linked immunosorbent assay (ELISA) based on autochthonous antigens to detect immunoglobulin G (IgG) antibodies against Helicobacter pylori (H. pylori) in adult sera. Methods: Whole-cell antigens from three genetically characterized clinical isolates of H. pylori were mixed and used as coating antigens. This assay was validated with a panel of human sera samples of H. pylori seropositive and seronegative patients. Likewise, sera samples from patients with uninvestigated dyspepsia, who were also evaluated by invasive and noninvasive tests (i.e., histopathology, rapid urease test, and stool antigen test), blood donors and patients with confirmed viral and parasitic diseases were also collected. The IgG response against H. pylori was detected by the in-house assay using the commercial ELISA IBL (Germany), as a reference test. Statistical analysis was performed with GraphPad Prism version 5.01. Results: The in-house ELISA showed high repeatability and reproducibility. Sensitivity was 91.1%; 95% confidence interval (CI): 87.2–94.0, specificity was 94.8% (95% CI: 85.0–94.8), and accuracy was 91.6% (95% CI: 88.5–94.6). The in-house ELISA showed an excellent area under the curve (0.96; 95% CI: 0.93–0.98) and a better IgG detection by the inverse cumulative distribution. The frequency of seropositivity in patients with dyspepsia (76.0%) was significantly higher (P < 0.05) than in healthy individuals (57.7%) and patients with other infectious diseases resembling H. pylori infection symptoms (54.4%). The H. pylori seroprevalence was estimated to be 62.7%. A good correlation was found between IgG seropositivity and H. pylori infection diagnosed by histopathology, rapid urease test, and stool antigen test in Cuban adults with dyspepsia. Conclusions: The in-house ELISA demonstrated good diagnostic accuracy and potential usefulness for estimating H. pylori exposure in the adult population, henceforward, this method could be used as an alternative for H. pylori diagnosis in the Cuban setting. Original Article Fri, 31 May 2024 00:00:00 GMT RosabelCorrales, RosabelFalcón, SusanaVázquez, OnelkisFeliciano, ReinaldoMederos, AmílcarDuquesne, OderayGutierrez, RafaelLlanes, Fri, 31 May 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100547 https://www.explorationpub.com/Journals/edd/Article/100548 Hepatocellular carcinoma (HCC) is the most common type of liver cancer and its death rate is rising faster than that of any other cancer, while we still lack effective treatments. The increasing incidence of liver cancer in western countries is closely associated with the growing prevalence of metabolic dysfunction-associated steatohepatitis (MASH) linked to metabolic diseases. While the contribution of lipids in the progression of MASH pathogenesis and its progression to HCC is well recognized, the specific contribution of cholesterol is subject to controversy. The liver plays a central role in cholesterol metabolism, where the majority of its biosynthesis, storage, excretion, recycling, and conversion into bile acids occur. Moreover, cholesterol is implicated in numerous hepatocyte cellular processes, encompassing endoplasmic reticulum function, formation of lipid microdomains in the plasma membrane, metabolism of lipoproteins, and mitochondrial function and performance. Therefore, it is not surprising that cholesterol plays key roles in initiation, promotion, and survival of HCC cells and there are several lines of evidence pointing to that cancer cells are subverting cholesterol metabolism to foster their proliferation and survival through various mechanisms. This narrative review provides a concise overview of the physiological and pathological roles of cholesterol in the transition from healthy hepatocytes to HCC, in the context of MASH. Gaining further understanding of how hepatic cancer cells disrupt cholesterol homeostasis and how these perturbations impact cancer progression will facilitate the identification of novel and more effective cancer treatment strategies in this complex and devastating disease. Review Fri, 14 Jun 2024 00:00:00 GMT VicentRibas, Fri, 14 Jun 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100548 https://www.explorationpub.com/Journals/edd/Article/100595 Primary liver cancer, particularly hepatocellular carcinoma, remains a major global health challenge due to its multifactorial etiology, late-stage detection, and high mortality. This review proposes a precision prevention framework that (i) categorizes risk factors into biological (e.g., HBV/HCV, aflatoxins), environmental (e.g., air pollution, occupational/waterborne toxins), and host-related domains (e.g., obesity, diabetes, genetic susceptibility); and (ii) aligns interventions to three complementary strategies: elimination of dominant risk (HBV vaccination, aflatoxin control, alcohol/tobacco reduction), early warning and targeted management (life-course immunization, MAFLD screening and control, metformin in diabetics), and chemoprevention (e.g., oltipraz, chlorophyllin, sulforaphane). We further articulate “green” prevention as a scalable, diet-centered approach that can be tailored to risk tiers and local food systems. Advances in multi-omics, microbiome science, and AI-enabled risk models—together with cohort evidence from East Asia, sub-Saharan Africa, and Western populations—support stratified surveillance and earlier interventions. Finally, we discuss generalizability and implementation challenges (regional dietary diversity, resource access) and outline pragmatic solutions to improve uptake across diverse settings. Review Tue, 30 Sep 2025 00:00:00 GMT Jian-GuoChen, Tue, 30 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100595 https://www.explorationpub.com/Journals/edd/Article/100549 Hepatitis C viral infections present a significant global health challenge, carrying substantial economic implications. These infections manifest in various clinical forms, including acute and chronic hepatitis, liver cirrhosis, hepatic failure, and hepatocellular carcinoma (HCC). Liver cirrhosis and HCC emerge as the primary contributors to mortality in hepatitis virus-induced liver diseases. To alleviate the public health impact of this disease, it is imperative to enhance the diagnosis and treatment rates among hepatitis C virus-infected individuals. The advent of direct-acting antivirals (DAAs), especially pan-genotypic regimens such as a combination of sofosbuvir and velpatasvir, has shown remarkable progress in achieving hepatitis C cure. However, potential obstacles, such as drug adverse effects and resistance-associated substitutions (RASs), warrant attention. Managing chronic hepatitis C (CHC) requires tailored treatment plans, vigilant monitoring, and judicious re-treatment strategies. Review Wed, 19 Jun 2024 00:00:00 GMT HaoXiong, JinshengGuo, Wed, 19 Jun 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100549 https://www.explorationpub.com/Journals/edd/Article/100550 Transabdominal ultrasound is a valuable diagnostic approach for evaluating the gastrointestinal tract and related disorders. This dynamic examination provides real-time visualization of the digestive tube and surrounding structures, assessment of peristaltic movements, estimation of compressibility of intestinal loops, and recognition of painful spots requiring specific attention. Since ultrasound imaging is non-invasive, painless, reproducible, inexpensive and requires no special preparation, it is used as a major diagnostic tool in emergency settings and in outpatient follow-up of several disorders. Costs, encompassing both accessibility and actual procedural expenses, are lower than those associated with other diagnostic techniques. However, the incorporation of gastro-intestinal ultrasound (GIUS) in clinical practice has not been widely used on a global scale. The purpose of this paper is to provide an overview of the execution techniques as well as the main areas of application for GIUS. Through illustrative iconographic representation, emphasis was placed on its potential within the diagnostic and therapeutic pathway of various acute and chronic gastrointestinal disorders. Perspective Fri, 05 Jul 2024 00:00:00 GMT CristinaFelicani, AliceTrovati, ElenaFranchi, FilippoZanni, FrancescaVerzelloni, AmedeoBianchini, ElenaMazzotta, PietroAndreone, Fri, 05 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100550 https://www.explorationpub.com/Journals/edd/Article/100551 With the rising prevalence of chronic liver disease worldwide, the incidence and prevalence of acute-on-chronic liver failure (ACLF) are increasing and attribute to higher morbidity, mortality, and healthcare costs. Many of such patients die without being considered for the lifesaving treatment option of liver transplantation. The underutilization of liver transplantation as a therapeutic option in the setting of ACLF, is due to multiple reasons; with the heterogeneity of ACLF and the lack of universal definition being the key players. Liver transplantation listing and allocation are based on MELD score. As of now, we do not know where MELD score stands in regard to defining ACLF and the prognostication of such patients. This insight is very important for the efficient identification of potential liver transplantation candidates in the setting of ACLF. This review paper investigates the role of liver transplantation in the setting of ACLF. In light of recent evidence, MELD score is not the perfect model in the setting of ACLF either. The safety of liver transplantation, either deceased donor or living donor, among ACLF patients has been debated. The short-term mortality rate of ACLF patients has created a need for a standard liver transplant selection criterion for these patients. Based on published literature, we find that three commonly used ACLF definitions may be used in combination to define the sensitivity, specificity, and futility of ACLF and we propose an algorithm to best identify patients for urgent liver transplantation in the setting of ACLF. Moreover, we discuss the data on the safety of liver transplantation in the setting of ACLF. Future validation of this multifaceted approach could bridge the gap between ACLF patients and appropriately guided medical intervention. Review Tue, 23 Jul 2024 00:00:00 GMT AndrewJohnson, ShahidHabib, Tue, 23 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100551 https://www.explorationpub.com/Journals/edd/Article/100552 Acute decompensation is defined as the development of ascites, bleeding due to portal hypertension, jaundice, or hepatic encephalopathy in the presence of known or unknown chronic liver disease. Acute-on-chronic liver disease is defined as a clinical entity reflecting acute worsening in liver function along with extrahepatic organ failure with significantly higher 28-day mortality. In the common pathogenesis, severe systemic inflammation and portal hypertension and varying degrees of reaction to these conditions play a major role. Triggering factors act as accelerators in the development of acute decompensation and acute-on-chronic liver failure. The extrahepatic organ failure in acute-on-chronic liver failure is mainly due to tissue hypoxia due to decreased perfusion and cellular edema. The number of organ failure in acute-on-chronic liver failure is considered to be the most important prognostic indicator. Liver transplantation remains the most appropriate treatment option for selected patients, even though supportive therapies based on the severity of the disease and the clinical findings that have developed are at the forefront. Review Wed, 24 Jul 2024 00:00:00 GMT SencanAcar, Wed, 24 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100552 https://www.explorationpub.com/Journals/edd/Article/100553 Patients with advanced chronic liver disease can develop specific pulmonary complications related or unrelated to pre-existing lung disease. The three major pulmonary complications in this patient population include hepatopulmonary syndrome (HPS), portopulmonary hypertension (PoPH), and hepatic hydrothorax (HH). These entities are most often revealed by increasing dyspnea together with signs of portal hypertension. The prevalence of these complications remains underestimated due to the lack of routine screening of the cirrhotic population. The pathophysiology of HH is better understood than that of HPS and PoPH. The clinical features, diagnosis, and therapeutic options of these pulmonary complications are extensively discussed in this chapter. Liver transplantation may offer a curative therapy in highly-selected cases and MELD exception points allow priority access to liver transplantation, thus avoiding potential deterioration while awaiting transplant and providing a better post liver transplant survival. The complexity of managing these pulmonary complications requires a multidisciplinary team approach, especially when liver transplantation is indicated. Review Thu, 25 Jul 2024 00:00:00 GMT ThierryThevenot, SarahRaevens, AvinashAujayeb, Bubu A.Banini, Jean François D.Cadranel, Hilary M.DuBrock, Thu, 25 Jul 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100553 https://www.explorationpub.com/Journals/edd/Article/100554 Chronic hepatitis B (CHB) disease caused by persistent infection with hepatitis B virus (HBV) is a global health problem affecting almost 300 million people worldwide, resulting in up to 1 million deaths each year. The factors contributing to HBV mediated liver disease are yet to be fully resolved, however, multiple studies have suggested that HBV splice variants may be a contributing factor. Recent studies have indicated that novel fusion proteins encoded by splice variants, or the splice-derived RNA itself, may impact replication of wild-type HBV, although the direct mechanisms for these interactions are largely unknown. This review explores the latest knowledge regarding the contribution of splice variants to liver disease and their impact on HBV replication. Review Wed, 07 Aug 2024 00:00:00 GMT Laura C.McCoullough, MargaretLittlejohn, Peter A.Revill, Wed, 07 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100554 https://www.explorationpub.com/Journals/edd/Article/100555 One of the primary complications of cirrhosis and portal hypertension is the occurrence of hepatocellular carcinoma (HCC), which is among the most common malignancies worldwide. There is limited availability of predictive non-invasive markers for primary HCC development in compensated advanced chronic liver disease (cACLD) patients. The reference standard method of assessing prognosis for cACLD patients, beyond liver fibrosis assessed by histology, is the measurement of the hepatic venous pressure gradient (HVPG). HVPG ≥ 10 mmHg is associated with an increased risk of HCC in these patients. However, these methods are expensive and invasive and are available only at referral centers. In the last decade, several studies have focused on the evaluation of several, simple, non-invasive tests (NITs) as predictors of HCC development. Among these methods, attention has particularly been paid to the elastographic techniques for the assessment of liver and spleen stiffness. We have reviewed the current literature about vibration-controlled transient elastography (VCTE), magnetic resonance elastography (MRE), and other ultrasound-based elastographic techniques (e.g., SWE) in predicting primary HCC occurrence and recurrence. Despite promising results, the overall heterogeneity resulting from the variability in the populations analyzed, the differences in the elastographic techniques used, the design and methodological quality of the available studies, prevented us from drawing definite conclusions on the liver and spleen stiffness role for predicting HCC occurrence and recurrence in chronic liver disease patients. Review Thu, 22 Aug 2024 00:00:00 GMT AnnaFichera, MirellaFraquelli, Thu, 22 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100555 https://www.explorationpub.com/Journals/edd/Article/100556 Ascites is a frequent complication in patients with cirrhosis, associated with a bad prognosis. Ascites is associated with severe complications, such as spontaneous bacterial peritonitis and kidney dysfunction, which must be diagnosed and managed rapidly. First-line management is based on diuretics use. Beta-blockers role remains debated but an early administration could probably decrease complications associated with portal hypertension. Albumin infusion is validated in large volume paracenteses, spontaneous bacterial peritonitis, or kidney dysfunction, but is debated in other situations. Technical progresses allow the worldwide use of TIPS (transjugular intrahepatic portosystemic shunt), but patient selection must be rigorous because of potential severe complications. An alternative treatment, automated low-flow ascites pump, can be offered in patients without TIPS possibility: It is a recent technique, whose patients’ selection and installation conditions were improved, with interesting results. Liver transplantation remains the gold standard, but the lack of grafts, and specific side effects, lead to prefer other methods. In case of acute kidney injury due to hepatorenal syndrome, terlipressin remains the standard of care; continuous infusion is associated with fewer side effects. Review Mon, 26 Aug 2024 00:00:00 GMT PaulCarrier, VéroniqueLoustaud-Ratti, MarilyneDebette-Gratien, LaureElkrief, Mon, 26 Aug 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100556 https://www.explorationpub.com/Journals/edd/Article/100557 Lipids are intricate biomolecules responsible for the building up of biological membranes. Besides this structural function, they also display crucial roles in signaling, acting as second messengers that activate specific pathways. Mitochondria are fundamental for cells as they participate in several pivotal functions, such as ATP synthesis, cell survival, metabolic pathways, and calcium homeostasis. Thus, the lipid composition of mitochondrial membranes can affect specific proteins and impact vital functions of mitochondria, such as oxidative phosphorylation and dynamics. The liver possesses a critical function in lipid homeostasis, involving the generation, oxidation, and trafficking of free fatty acids (FFA), triglycerides (TG), cholesterol, and bile acids (BAs). Mitochondria play a key role in lipid storage regulation in hepatocytes, which can control liver function. Their diverse tasks are affected by the lipid composition of mitochondrial membranes, characterized by low cholesterol content and enrichment of specific lipids such as cardiolipin. As mitochondria determine the bioenergetic status of cells and are key regulators of cell viability, alterations of mitochondrial lipid composition can contribute to the induction and progression of chronic diseases, including alcohol-related liver disease (ARLD) and metabolic dysfunction-associated steatotic liver disease (MASLD), two of the most common forms of liver diseases characterized by steatosis, necroinflammation, and fibrosis, which can progress to hepatocellular carcinoma (HCC). Thus, the disruption of lipid metabolism and membrane composition of mitochondria are characteristic features of cancer cells, and altered mitochondrial lipid composition may be a critical player in the progression of chronic liver diseases toward HCC. This review will address the mechanisms whereby alterations of mitochondrial lipid composition lead to the onset and progression of chronic liver diseases. Thus, a better characterization of the alterations of lipid composition in mitochondria may be a crucial step to design strategies and novel therapeutic opportunities for the treatment of MASLD and ARLD. Review Tue, 10 Sep 2024 00:00:00 GMT LauraFàbrega, José C.Fernández-Checa, LauraConde de la Rosa, CarmenGarcia-Ruiz, Tue, 10 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100557 https://www.explorationpub.com/Journals/edd/Article/100558 The formation of metabolic changes is based on many factors. In particular, the infectious theory of the development of metabolic “breakdowns” has not lost its relevance. In this regard, many scientists are investigating the role of various microorganisms in the pathogenesis of metabolic syndrome. The review provides the results of current research on the role of Helicobacter pylori (as one of the most well-known and widespread bacterial pathogens) in the pathogenesis of metabolic syndrome. However, the results of scientific work are sometimes contradictory, which dictates the need for novel further research to clarify the characteristics of the influence Helicobacter pylori on the formation of various components of the metabolic syndrome. Review Tue, 10 Sep 2024 00:00:00 GMT Natalia V.Baryshnikova, Elena I.Ermolenko, Galina F.Leontieva, Yury P.Uspenskiy, Alexander N.Suvorov, Tue, 10 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100558 https://www.explorationpub.com/Journals/edd/Article/100559 Metabolic-associated steatotic liver disease (MASLD) and its pathological version, metabolic dysfunction-associated steatohepatitis (MASH), are becoming the main leading causes of chronic liver disease almost worldwide and are the fastest growing aetiology of hepatocellular carcinoma (HCC), especially in the Western countries. The combination of high incidence and morbidity with limited treatment options for both MASH and HCC highlights an urgent need for the discovery of novel therapeutic candidates to inform drug development. The importance of lysosomes and cathepsins, their most abundant hydrolases, has been overlooked for decades. They were considered organelles only involved in the recycling of macromolecules, with cathepsins simply being their effectors. Contrary to this traditional view, recent findings have shed new light on the lysosome and its enzymes as drivers of essential cellular processes, such as apoptosis and autophagy. Bringing lysosomal activity and the regulation of cathepsins into the spotlight of MASH and HCC research can open new avenues for the development of novel drugs based on targeting cathepsin-driven lysosomal activity and its associated pathological processes. This review comprehensively summarises the current knowledge on the role and contribution of lysosomal cathepsins to MASLD/MASH and HCC progression. Review Tue, 10 Sep 2024 00:00:00 GMT Alejandrodel Castillo-Cruz, MariaFernández-Fernández, AnnaMoles, Tue, 10 Sep 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100559 https://www.explorationpub.com/Journals/edd/Article/100560 Hepatitis B virus (HBV) infection affects 262 million people worldwide, leading to over 820,000 deaths annually. The reason HBV has been a persistent issue for decades is that it is a non-cytopathic, liver-specific virus with the ability for persistent infection, which cannot be completely eliminated by drugs, eventually progressing to cirrhosis and hepatocellular carcinoma (HCC). Although HBV seems to induce little innate immune activation, adaptive immune responses can mediate viral clearance and liver disease. Here, we review the epidemiology, natural history, lifecycle, and modes of transmission of HBV. We also pay particular attention to the adaptive and innate immune responses to HBV and the research progress on therapeutic vaccines, which may provide new insights for targeted HBV treatment. Review Mon, 14 Oct 2024 00:00:00 GMT ChunzhengLi, ChenyuWei, XianguangYang, Mon, 14 Oct 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100560 https://www.explorationpub.com/Journals/edd/Article/100562 Mitochondria are essential organelles responsible for intracellular energy production and play crucial roles in cellular metabolism, inflammation, and apoptosis. Reactive oxygen species (ROS) are primarily produced in the mitochondria and endoplasmic reticulum of hepatocytes due to the activity of cytochrome P450 enzymes. Under ideal conditions, cells have specific molecular mechanisms that manage oxidative stress levels, thus ensuring a balance between oxidants and antioxidants. The interplay between ROS-induced mitochondrial dysfunction and the activation of the NLRP3 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3) inflammasome in the context of liver diseases has been extensively studied. However, the exact mechanisms by which mitochondria promote the activation of the NLRP3 inflammasome and contribute to the onset of liver disease remain unclear. This review aims to elucidate the recently discovered mitochondrial regulation of the NLRP3 inflammasome in liver disorders, including alcohol-related liver disease (ALD), metabolic-associated steatotic liver disease (MASLD), and hepatocellular carcinoma (HCC). Finally, it summarizes various natural and pharmaceutical agents that can mitigate liver damage by modulating the activation of the NLRP3 inflammasome through mitochondrial pathways. This work serves as an important resource for identifying new therapeutic approaches and provides further support for advancing the understanding of liver diseases. Review Tue, 10 Dec 2024 00:00:00 GMT Hala SaeedJaara, SandraTorres, Tue, 10 Dec 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100562 https://www.explorationpub.com/Journals/edd/Article/100563 Liver inflammation, injury, and hepatic cell death are caused by external agents (viruses, bacteria, drugs, alcohol, etc.) along with the genetic susceptibility of an individual. Persistent activation of the fibrogenic response in cells leads to liver fibrosis which in turn progresses to cirrhosis and cancer. The dysregulation of the immune system generates reactive oxygen species which in turn induce necrosis of hepatocytes. This process activates hepatic stellate cells and myofibroblasts to produce a huge quantity of collagens, alpha-smooth muscle actin, and extracellular matrix deposition in liver parenchyma. Due to the multifactorial nature of this disease, conventional therapies increasingly attempted combinatorial therapy or polytherapy to target multiple mechanistic sites in order to prevent entry into further complicated irreversible stages. Despite advancements in conventional therapy, several cases aggravate fibrosis (grade 3 to 4) and cirrhosis. The inconsistency in treatment outcomes and limited organ donors for liver transplantation have led to an ever-increasing and challenging demand for alternative therapies. In this review, we analyze the mechanism and causative factors of liver diseases, conventional mode, and alternative therapeutic options. The central to liver diseases are immune dysregulation, hence bioactive agents with immunomodulatory properties should be searched and exploited to meet therapeutic needs. Mesenchymal stem cells (MSCs) with their specialized anti-inflammatory and immunomodulatory properties could be utilized as an effective alternative therapeutic candidate in treating inflammatory liver diseases. MSC-derived exosome further provides an additional immunomodulatory option that could work in tandem with MSC in a synergistic form. In this series, we have reviewed preconditioned and genetically edited MSCs to augment homing, proliferation, and differentiation. Importantly, all the clinical challenges should be noted and addressed before stem cell cytotherapy should be considered safe and effective for patients with liver diseases. Published literature indicated that MSC therapy has the potential to substitute conventional options in the treatment of high-grade fibrosis and cirrhosis. Review Wed, 15 Jan 2025 00:00:00 GMT ZahidHussain, Wed, 15 Jan 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100563 https://www.explorationpub.com/Journals/edd/Article/100565 Hepatitis B virus (HBV) infection is a major risk factor of cirrhosis and hepatocellular carcinoma (HCC) worldwide. Pathogenesis of HBV-induced cirrhosis and HCC involves viral factors and virus-triggered local inflammatory and immune responses, the latter leading to progressive fibrosis, cirrhosis and carcinogenesis. Antiviral therapeutics suppress HBV replication and reduce the risks of cirrhosis and HCC. We discuss the current knowledge on the pathogenesis of HBV-induced cirrhosis and HCC, focusing on mechanisms of current and emerging antiviral therapeutics. Review Fri, 21 Feb 2025 00:00:00 GMT JuntianYao, JinshengGuo, YouhuaXie, Fri, 21 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100565 https://www.explorationpub.com/Journals/edd/Article/100564 Microsatellite unstable (MSI) colorectal cancer (CRC) tumors have a high mutational load (particularly frame-shift mutations) that creates numerous neoantigens that are presented to major histocompatibility complex molecules and recognized by T cells. Consequently, MSI tumors have a higher presence of tumor-infiltrating lymphocytes than mismatch repair-proficient tumors. Colorectal cancer patients with MSI constitute a rare group of immune checkpoint inhibitor (ICI)-responsive patients. Nonetheless, complete radiological responders comprise between 3% and 16% of MSI advanced CRC patients, which compares poorly with the 45% to 87% rate of pathological complete response in early MSI CRC patients treated with ICIs. In this review, we address the efficacy of current ICIs and the biological differences between early and advanced MSI CRC to potentially increase the efficacy of ICIs in both settings. Review Wed, 19 Feb 2025 00:00:00 GMT MariamRojas, ClaraRodrigo, ReinaldoMoreno, MartaCascante, JoanMaurel, Wed, 19 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100564 https://www.explorationpub.com/Journals/edd/Article/100561 Steatotic liver disease (SLD) has been known for a long time, but our understanding of this disease has remained poor until the past decade. Despite extensive research, our ability to comprehend the etiopathogenesis and natural course of SLD is far from the desired level of comprehension. This is required to develop a universally effective novel therapeutic agent. This review aims to concisely elaborate the conceptual approach and advancement in the understanding of global disease burden and etiopathogenic process, identifying the gaps and the pathophysiologic mechanism behind developing novel therapeutic agents. We searched two major databases, PubMed and Google Scholar, to identify publications related to the abovementioned topics. All publications, including original papers, reviews, and commentaries, were reviewed. Findings: Metabolic dysfunction-associated steatotic liver disease (MASLD) is not limited to obese individuals, rather, it may develop in any individual independent of weight. Visceral adiposity is strongly associated with MASLD and subsequent risks of cirrhosis, hepatocellular carcinoma, and cardiovascular disease. MASLD is associated with diabetes mellitus independent of underlying pathogenic mechanisms, and there is a bidirectional connection between MASLD and diabetes mellitus, making the situation quite challenging. Not all patients with MASLD exhibit atherogenic dyslipidemia and thus do not have a higher risk of cardiovascular disease. The overlap of these metabolic risk factors is not straightforward. There is a differential contribution of these risk factors based on age, gender, race, ethnicity, alcohol consumption, and microbiota composition. Poor dietary habits and lifestyle directly affect the microbiota, modulators, and mediators, thereby affecting the final biochemical processes leading to steatosis, steatohepatitis, fibrosis, and oncogenesis. In conclusion, MASLD is a complex and pathogenically heterogeneous disease with significant interpatient variation in the natural course and outcome. Understanding the precise mechanism of variability is the key gap and a limiting factor in the development of a novel therapeutic agent. Review Mon, 11 Nov 2024 00:00:00 GMT ShahidHabib, AndrewJohnson, Mon, 11 Nov 2024 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100561 https://www.explorationpub.com/Journals/edd/Article/100566 The epidemic of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly growing worldwide. Thus, there is an urgent need for novel, non-invasive, and reliable biomarkers to replace liver biopsy for the diagnosis and prognosis of MASLD. Circulating peripheral blood mononuclear cells (PBMCs) are highly responsive to various stimuli and physiological changes. Beyond their immunomodulatory role, PBMC may act as metabolic sensors in several cardiometabolic disorders, including MASLD, with their metabolic programs shifting accordingly. Recent evidence suggests a link between impaired mitochondrial bioenergetics in PBMC and MASLD. Additionally, impaired mitochondrial respiration is intricately linked to the intracellular depletion of the oxidized form of nicotinamide adenine dinucleotide (NAD+) in various cell types. Accumulating preclinical and clinical data show that NAD+-increasing strategies may protect against MASLD by restoring intracellular NAD+ pools and improving mitochondrial performance. This review will focus on [i] the relevance of mitochondrial dysfunction, including impaired bioenergetics, in PBMC as a marker for the diagnosis and prognosis of MASLD, and [ii] the potential benefits of NAD+ precursors in MAFLD and their relationship with improved mitochondrial respiration in blood immune cells. Review Thu, 27 Feb 2025 00:00:00 GMT JuliaNiño-Narvión, JoanaRossell, Marina IdaliaRojo-López, EstefaníaMoreira, EderMateus, Antonio JoséRuiz-Alcaraz, BrunoRamos-Molina, ElizabethMartínez-Rojo, Laurent O.Martinez, MariaGalán, JosepJulve, Thu, 27 Feb 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100566 https://www.explorationpub.com/Journals/edd/Article/100567 Not applicable. Letter to the Editor Thu, 20 Mar 2025 00:00:00 GMT JannisKountouras, ChristosZavos, Ioannis S.Papanikolaou, Stergios A.Polyzos, ElisabethVardaka, DimitriosChatzopoulos, MariaTzitiridou-Chatzopoulou, Thu, 20 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100567 https://www.explorationpub.com/Journals/edd/Article/100568 Aim: Selecting patients for immunotherapy in metastatic gastric cancer (mGC) in second and subsequent lines remains challenging. The aim of our study is to assess the feasibility of anti-programmed death-ligand 1 (anti-PD-L1) inhibitors in pretreated patients with mGC, and to determine prognostic and predictive biomarkers. Methods: We retrospectively analyzed data of 122 patients treated in five oncology centers in Moscow between 2018 and 2023, who received nivolumab or pembrolizumab for advanced gastric cancer. The primary end-point of our study was 6-month progression-free survival (PFS). For multivariate analysis, variables with a value of p < 0.05 obtained in a univariate analysis were selected. The optimal threshold value of the neutrophil-lymphocyte ratio (NLR) as a predictor of the effectiveness of immunotherapy was determined using receiver operating characteristic (ROC) curve analysis. Results: Patients with mGC who received immune checkpoint inhibitors (ICIs) were included. 6-month PFS rate was 31.6%. The median PFS (mPFS) and overall survival (mOS) in patients in the high NLR group (NLR ≥ 1.8) were 2 and 4 months; mOS and mPFS in the low NLR group were not achieved (p < 0.001). The presence of ascites (p < 0.001), the administration of ICIs in III–IV lines (p = 0.004), and NLR ≥ 1.8 (p = 0.006) were independent prognostic factors, associated with decrease of OS. The median OS of patients in favorable and unfavorable prognostic groups were 13 months and 2 months, respectively (p < 0.001). Conclusions: Ascites, NLR level of ≥ 1.8, and administration of anti-PD-L1 inhibitors were associated with low efficacy of immunotherapy in patients with microsatellite stable mGC. Further research should be planned including patients who did not receive ICIs to determine the prognostic significance of our model. Original Article Fri, 28 Mar 2025 00:00:00 GMT AnastasiaRays, МikhailFedyanin, DmitriyPopov, IlyaPokataev, МarinaLyadova, LyudmilaZhukova, DaniilStroyakovskiy, МikhailVolkonskiy, NatalyaBesova, АlexeyTryakin, Fri, 28 Mar 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100568 https://www.explorationpub.com/Journals/edd/Article/100569 Acetaminophen (APAP)-induced liver injury and acute liver failure is a significant clinical problem worldwide; in addition, APAP overdoses in animals or in cell culture are used as popular models to study drug-induced liver injury mechanisms and test therapeutic interventions. Early assumptions that APAP toxicity is caused by a single mechanism resulting in a defined mode of cell death in hepatocytes had to be questioned when over the years many different mechanisms and modes of cell death were reported. Although many of the contradictory results and conclusions reported over the years can be attributed to lack of understanding of established mechanisms, methodological problems, and misinterpretation of data, it is increasingly recognized that some of the reported differences in signaling mechanisms and even a switch in the mode of cell death can be caused by variations in the experimental conditions. In this review, examples will be discussed how experimental conditions (dose, solvent, etc.), the experimental system (species, strain, and substrain in vivo, cell type, and in vitro conditions), and also adaptive responses and off-target effects of genetic manipulations and chemical interventions, can impact the mechanisms of cell death. Given that the conditions will determine the results, it is therefore of critical importance to keep in mind the translational aspect of the experiments, i.e., the conditions relevant to the human pathophysiology. Only the full appreciation of these issues will lead to reproducible and clinically relevant results that advance our understanding of all facets of the human pathophysiology and identify clinically relevant therapeutic targets. Review Mon, 07 Apr 2025 00:00:00 GMT HartmutJaeschke, AnupRamachandran, Mon, 07 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100569 https://www.explorationpub.com/Journals/edd/Article/100570 Diverticular disease of the colon is a very important digestive disease and its management depends on the characteristics of the disease and the patient and the resources available. There are benefits and harms of open and laparoscopic Hartmann’s procedure, laparoscopic peritoneal lavage, sigmoidectomy, and primary anastomosis. There are many gaps to be eliminated in the future, such as real risks, benefits, and cost-effectiveness in the application of each one. The decision to be made for each case of complicated diverticulitis often depends on the interaction and competence of the multidisciplinary team in charge. Perspective Fri, 11 Apr 2025 00:00:00 GMT Valter NiltonFelix, Fri, 11 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100570 https://www.explorationpub.com/Journals/edd/Article/100571 Pancreatic cystic lesions are frequently found incidentally on cross-sectional imaging and are broadly classified into mucinous and non-mucinous cysts. While some exhibit benign behavior, others have a malignant potential and are considered noninvasive precursors of pancreatic ductal adenocarcinoma. Guidelines from various societies propose risk stratification based on morphologic features and cyst fluid analysis. Fluid analysis through EUS-guided fine needle aspiration contributes to improved classification and recently, targeted DNA or RNA-based next generation sequencing is emerging as a critical investigation tool for diagnostic confirmation and risk stratification of pancreatic cysts. Each of these modalities has specific strengths and limitations, highlighting the need for a multi-modal approach for comprehensive assessment to guide clinical decision making. In this perspective, we aim to provide a thorough clinicopathologic framework for diagnosing and risk stratifying pancreatic cysts encompassing imaging findings, cyst fluid analyses, and next generation sequencing. Perspective Mon, 14 Apr 2025 00:00:00 GMT RudyEl Asmar, NazihBizri, Nikhil VaishnavTirukkovalur, AdamTcharni, NavyaDasyam, SamerAlMasri, Mon, 14 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100571 https://www.explorationpub.com/Journals/edd/Article/100572 Aim: Fructose is a highly lipogenic compound related to the onset of steatosis, its progression to steatohepatitis, and the eventual initiation of hepatocellular carcinoma (HCC). One of the cancer hallmarks is the metabolic adaptation to the environmental sources; however, this characteristic could be exploited to manipulate the HCC tumor’s response to therapies. Due to the high prevalence in the consumption of diets enriched with fructose and the unclear results in the literature, it is pertinent to characterize the effects of fructose on the biology of HCC as a possible beneficial player in the aggressiveness of this cancer. We focused on investigating the metabolic effect of fructose on the aggressiveness of liver cancer cells and chemotherapy response. Methods: We treated Huh-7 and HepG2 liver cancer cell lines with 1 mM fructose to address the metabolic reprogramming and its fructose-induced effects. Results: Cancer cells use fructose as an alternative fuel source in glucose-starved conditions, ensuring tumorigenic properties and cell survival in both cell lines. The metabolic effect differed depending on cell line origin and aggressiveness. Conclusions: HCC cells showed a metabolic adaptation under fructose treatment, enhancing the pentose phosphate pathway to fuel anabolism. Metabolic rewiring also improves the tumorigenic properties and chemoresistance of cancer cells in vitro and in vivo, contributing to chemotherapy failure and the aggressiveness of liver cancer cells. Original Article Mon, 21 Apr 2025 00:00:00 GMT LisetteChávez-Rodríguez, AlejandroEscobedo-Calvario, VerenaJendrossek, JohannMatschke, MaikeBusch, NicoleDünker, MoisésVergara-Mendoza, VerónicaSouza-Arroyo, LeticiaBucio-Ortiz, Roxana U.Miranda-Labra, AraceliPáez-Arenas, María ConcepciónGutiérrez-Ruiz, Diego F.Calvisi, Luis E.Gomez-Quiroz, Mon, 21 Apr 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100572 https://www.explorationpub.com/Journals/edd/Article/100573 Hepatitis D virus (HDV), a satellite virus requiring hepatitis B surface antigen (HBsAg) for propagation, is a hepatotropic virus implicated in acute and chronic viral hepatitis, with an accentuated risk of cirrhosis and hepatocellular carcinoma. The epidemiology of HDV infection is underestimated owing to underdiagnosis and low screening rates. Being inherently defective, HDV depends on HBsAg, the envelope protein of the hepatitis B virus (HBV), for hepatocyte entry and exit. However, viral replication is then HBV-independent but dependent on the host cell RNA polymerases. Infection can either be a coinfection with HBV or superinfection in individuals with pre-existing HBV, with the latter exhibiting a higher propensity for progression to chronicity. Clinical manifestations could range from acute hepatitis to acute flares in chronic hepatitis to rapidly progressive chronic liver disease. For decades, the treatment of HDV infection relied heavily on conventional and pegylated interferons (PEG-IFNs), which, despite limited efficacy and high relapse rates, continue to be a therapeutic option in patients with compensated liver disease. The past decade witnessed an advanced understanding of HDV virology and pathogenesis, which led to the development of multiple specific and targeted therapeutic agents, most notably the HDV viral entry inhibitor, bulevirtide, and the prenylation inhibitor, lonafarnib. In 2020, bulevirtide became the first drug approved in the European Union to treat chronic HDV with compensated liver disease. The emergence of lambda interferons, nucleic acid polymers, RNA silencers, and immune modulators further expands the therapeutic landscape. Combination regimens leveraging complementary mechanisms are promising but require further validation to optimize dosing and treatment durations. While novel therapies provide hope, significant unmet needs remain, especially for patients with decompensated cirrhosis. Future research must prioritize comprehensive strategies to enhance treatment efficacy and accessibility, offering a brighter prognosis for those affected by this devastating virus. Review Fri, 09 May 2025 00:00:00 GMT George SarinZacharia, AnuJacob, Fri, 09 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100573 https://www.explorationpub.com/Journals/edd/Article/100575 Metabolic associated steatotic liver disease (MASLD) stands as the most common hepatic disorder in both developed and developing countries. The global increasing rates in obesity rates are fuelling an increase in MASLD cases. Fibroscan, a transient elastography device, is a research-based, noninvasive method for assessing liver fibrosis. Accurately measuring the extent of fibrosis presents difficulties in a cohort of individuals who are severely obese with a body mass index (BMI) ≥ 40 kg/m2, particularly regarding the reliability and applicability of the XL probe. This study’s objective is to evaluate the precision of fibroscan in morbidly obese individuals with a BMI ≥ 40 kg/m2. We explored Google, PubMed, and Medline to gather information on fibroscan and its application for measuring fibrosis levels in morbidly obese patients ≥ 40 kg/m2 who have MASLD. The fibrosis levels obtained from the fibroscan do not consistently correlate with the clinical or histopathological data, which are essential for accurately determining liver stiffness measurement (LSM) cutoff values and/or ranges for these patients with either significant or advanced fibrosis. Additional prospective multicenter studies are necessary to better establish LSM cutoff values and/or ranges for patients suffering from significant or advanced fibrosis due to morbid obesity. Review Mon, 19 May 2025 00:00:00 GMT Maged TharwatElghannam, Moataz HassanHassanien, Ahmed AlyELRay, Hoda MohamedAbu-Taleb, Yosry AbdelrahmanAmeen, Gamal MohammedELattar, Emad AbdelwahabTurky, Mohammed DarwishELTalkawy, Mon, 19 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100575 https://www.explorationpub.com/Journals/edd/Article/100574 Aim: Our previous study provided evidence that systemic zonula occludens (ZO) 1 levels are elevated in cirrhotic and hepatocellular carcinoma (HCC) patients. Here, we aimed to evaluate serum ZO-1 levels in patients with decompensated alcoholic cirrhosis (DCAC) with hepatorenal syndrome (HRS) and compare its diagnostic potential with the well-established HRS biomarker, cystatin C. Methods: A total of 36 DCAC patients with HRS and 40 healthy volunteers were recruited. Serum ZO-1, cystatin C, and clinical chemistry parameters were analysed. Results: Compared to control subjects, DCAC patients with HRS exhibited significantly higher ZO-1 levels (7.059 ± 0.29 vs. 0.788 ± 0.11; p < 0.0001) and cystatin C levels (2.97 ± 0.24 vs. 1.59 ± 0.04; p < 0.0001). Serum ZO-1 correlated positively with cystatin C (r = 0.561, p < 0.0001), serum creatinine (r = 0.779, p < 0.0001), and MELD-Na (r = 0.850, p < 0.0001). Moreover, ZO-1 demonstrated a higher area under the curve (AUC) than cystatin C, indicating a better diagnostic potential for HRS in DCAC patients. Conclusions: These findings suggest that ZO-1 may serve as a valuable biomarker for HRS in DCAC patients. However, further validation in a larger cohort is necessary to confirm its clinical utility. Original Article Mon, 19 May 2025 00:00:00 GMT BalasubramaniyanVairappan, RajKumar, MuktaWyawahare, Mon, 19 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100574 https://www.explorationpub.com/Journals/edd/Article/100576 Background: Esophageal varices (EV) and gastric varices (GV) are the most common portal hypertension complications in liver cirrhosis patients. Esophagogastroduodenoscopy (EGD) is the main standard procedure for variceal screening and treatment. Nonetheless, luminal evaluation sometimes cannot accurately evaluate the size of varices. Recently, endoscopic ultrasound (EUS) has been studied for EV and GV evaluation. Methods: Literature search was performed from PubMed, Scopus, and Cochrane Library databases until December 2022. Two independent reviewers (C.R.A.L. and T.P.) independently obtained and evaluated the selected studies according to pre-determined eligibility criteria. Results: Ten studies (four observational studies, three randomized controlled trials, and three retrospective reviews of case series) describing 593 patients met our eligibility criteria. Eight out of ten studies evaluated utilization of EUS for coil embolization and/or cyanoacrylate injection. All studies demonstrated excellent technical success rate of the procedure with good therapeutic efficacy, in terms of lowering the risk of recurrent bleeding. Significantly better findings were observed from groups treated with combination of coil and cyanoacrylate glue injection in comparison to monotherapy. One study also highlighted the higher possibility of developing pulmonary embolism in groups treated with conventional cyanoacrylate injection. Discussion: EUS-guided combination therapy appears to be a safe and effective modality for treating patients with gastric variceal bleeding with high number of complete obliteration and low risk of gastric variceal rebleeding. Further meta-analysis large-scale randomized clinical trials are still required to confirm these findings. Systematic Review Wed, 28 May 2025 00:00:00 GMT Cosmas Rinaldi AdithyaLesmana, Maria SatyaParamitha, TrevinoPakasi, Rino AlvaniGani, Wed, 28 May 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100576 https://www.explorationpub.com/Journals/edd/Article/100577 Yu JW et al. (World J Gastroenterol. 2025;31:105188. DOI: 10.3748/wjg.v31.i16.105188) used male Sprague-Dawley rats fed a high-fat diet for 8 weeks to recapitulate metabolic dysfunction-associated steatotic liver disease (MASLD) experimentally. MASLD rats were randomized to receive either the duodenal mucosal ablation (DMA) using irreversible electroporation (IRE) during laparotomy or sham DMA. Data have shown that DMA was associated with duodenal thickening compared to the control group, crypts were narrower and shallower crypts and villi slimmer than sham DMA group. Moreover, the DMA group exhibited improved liver histology compared to the sham group though accompanied by inconsistent variations in blood lipid values and statistically non-significant variations in surrogate indices of MASLD. Thirdly, DMA rats had lower serum concentrations of gut hormones with crucial metabolic functions, lower lipopolysaccharide serum level, increased duodenal expression and immunofluorescence staining intensity of gut hormones expression, and higher expression of zonula occludens-1 and claudin than sham-rats. The study by Yu, et al. has innovative findings and is properly designed to illustrate the pathomechanisms underlying improved MASLD histology after DMA with IRE. However, this paper also has some methodological limitations that prompt additional studies in animal models and, ideally, in humans to be conducted as soon as safety and feasibility are demonstrated. Commentary Wed, 18 Jun 2025 00:00:00 GMT AmedeoLonardo, Ming-HuaZheng, Wed, 18 Jun 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100577 https://www.explorationpub.com/Journals/edd/Article/100578 The changing management paradigm of acute complicated diverticulitis and the elective indications for surgery have evolved in the last decade based on reported evidence-based data. Recently, it has been demonstrated that randomized controlled trials (RCTs), the highest trial format in the hierarchy of evidence-based reporting, suffer from a ‘crisis of replicability’. The development of a fragility index (FI) quantitatively defines the robustness of an RCT by shifting the number of participants in a trial into a different binary group in an effort to influence reported statistical significance (the lower the FI the greater the study fragility). The only available report on FI in diverticular management showed that in an eclectic range of RCT’s comparing intervention and non-intervention, two-thirds of the studies had an FI ≤ 1 where statistical recalculation using Fisher’s Exact test rendered one-quarter of previously positive studies non-significant. Comparisons between studies and units are still dependent upon sample sizes and the numbers lost to follow-up even when some of the FI progeny (including a reverse FI, a fragility quotient dividing the FI by the sample size, or other incidence or generalized FI metrics) are utilized in assessment. Future analyses need to define all comparisons rather than cherry-picking examples where a p value approaches significance. Despite the fact that no FI value defines the strength of a RCT, its use attempts to link the reported p value with the sample size and the statistical power of the study. Positive findings in diverticular trials are then considered not so much definitive as rather provocateurs encouraging further similarly designed studies in different environments. Minimizing patient loss in treatment arms and reporting the reasons for drop-out, strictly adhering to randomization, consistent blinding, and group allocation concealment can all improve the logistical running of an RCT initially designed to evaluate some potentially important new treatment. Review Fri, 27 Jun 2025 00:00:00 GMT Andrew P.Zbar, NirHoresh, Fri, 27 Jun 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100578 https://www.explorationpub.com/Journals/edd/Article/100579 As the most prevalent hepatic disorder worldwide, metabolic dysfunction-associated steatotic liver disease (MASLD) afflicts over one-third of the global population, representing a significant public health challenge. The multifactorial pathogenesis of this condition is principally rooted in metabolic dysregulation. It is notable that emerging evidence highlights a critical role for gut microbiota (GM) in disease initiation and progression. This comprehensive review elaborates some representative GM species that influence hepatic lipid metabolism and elucidates the mechanisms through which GM dysbiosis exacerbates MASLD pathogenesis. Importantly, the positive or negative effects of intestinal bacterial communities on MASLD are largely dependent on their special metabolites, such as short chain fatty acids, ethanol, and trimethylamine N-oxide. Current therapeutic strategies targeting GM modulation, including prebiotics, probiotics, fecal microbiota transplantation, specific medicines, and bacteriphages, demonstrate promising efficacy that partially restores microbial equilibrium and mitigates hepatic steatosis. Although limitations still persist in achieving sustained clinical remission, the expanding frontier of microbiome research continues to refine our understanding of host-microbiota crosstalk in MASLD. Future investigations integrating multiple approaches and longitudinal clinical data hold potential to unravel complex microbial networks, paving the way for innovative therapeutic breakthroughs in metabolic liver disease management. Review Mon, 30 Jun 2025 00:00:00 GMT WenchuQian, LingHe, ChenxueFu, TiantianZeng, HanyuWang, HaifangLi, Mon, 30 Jun 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100579 https://www.explorationpub.com/Journals/edd/Article/100580 The liver operates as a highly coordinated microsystem, where various liver cell types engage in dynamic interactions to maintain homeostasis. This intercellular cooperation resembles sociological models of sustainable cooperation, encompassing mechanisms such as resource sharing, communication networks, and conflict resolution. However, both in biology and sociology, cooperation can break down due to external pressures and self-serving behaviors. In metabolic dysfunction-associated steatotic liver disease (MASLD), chronic metabolic stress disrupts this equilibrium, leading to endothelial dysfunction, immune overactivation, and fibrosis—akin to sociological models of systemic collapse. A common model in sociology, Hardin’s Tragedy of the Commons, describes how individuals overexploit shared resources when acting in self-interest, ultimately leading to resource depletion. Similarly, under metabolic stress, hepatic cells prioritize short-term survival by increasing lipid storage, inflammatory signaling, and extracellular matrix (ECM) production. This self-serving response, much like free-riding in societal systems, exacerbates dysfunction, reinforcing a cycle of fibrosis and organ failure. Moreover, the failure in MASLD extends beyond the liver itself. The liver’s cooperative role is integral to its participation in inter-organ axes, including those with the cardiovascular, gut, brain, and kidney systems. While the analogy has limitations—cells do not possess intent as humans do—the fundamental principle of cooperation breakdown leading to systemic instability holds across disciplines. An interdisciplinary approach integrating biological and sociological insights offers novel perspectives for therapeutic innovation. Sociological frameworks provide concepts such as incentive structures and collective action, which can be applied to cellular behavior. By restoring cooperative cellular networks, therapies like extracellular vesicle (EV) treatment, ECM remodeling, and receptor (ant)agonists mimic interventions in social systems that rebuild trust and sustainability. This review explores how biological and sociological models of cooperation breakdown align and how regenerative medicine can leverage these insights to develop strategies that restore cellular equilibrium and halt disease progression. Review Tue, 08 Jul 2025 00:00:00 GMT JunyuWang, JingtingLei, Martin C.Harmsen, HanMoshage, Tue, 08 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100580 https://www.explorationpub.com/Journals/edd/Article/100581 Aim: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a widespread chronic liver condition associated with liver inflammation, fibrosis, and various metabolic disorders. Although cholic acid (CA), a primary bile acid (BA), is known to reduce steatosis when added to a high-fat diet, it may exacerbate hepatocellular injury by promoting oxidative stress and inflammation. Therefore, regulating BA-induced liver toxicity is crucial. Dimethyl fumarate (DMF) is an FDA-approved drug known to activate the nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2), a transcription factor that induces cytoprotective genes involved in cellular stress. The present study aimed to investigate whether DMF supplementation could attenuate CA-induced liver injury in high-fat diet-fed mice. Methods: To induce liver injury, high-fat diet with and without CA were compared for liver damage and liver fat gain. Following the establishment of the toxic but antisteatotic effect of CA, C57BL/6j mice were fed a high-fat diet supplemented with 0.5% CA (HFDCA) with or without DMF (0.3 mg/mL or 0.6 mg/mL), which was administered via drinking water for 7 weeks. Results: CA was found to be an accelerator of high-fat diet to induce liver damage, but prevented liver fat accumulation. HFDCA mice showed signs of liver damage, including elevated liver enzymes and liver enlargement. However, DMF treatment activated the Nrf2 pathway and partially mitigated the hepatotoxic effect of CA/high-fat diet, although some doses exhibited pro-oxidant effects. Conclusions: The findings suggest that DMF, as an activator of Nrf2, has potential as a therapeutic agent for liver diseases related to high-fat diets and BA-induced injury, though careful dosage management is crucial to maximize its benefits and mitigate BA toxicity. Original Article Thu, 10 Jul 2025 00:00:00 GMT DianaAbu-Halaka, EinatRauchbach, HaimZeigerman, OrenTirosh, Thu, 10 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100581 https://www.explorationpub.com/Journals/edd/Article/100582 Minimal hepatic encephalopathy (MHE) is often the least recognized form of hepatic encephalopathy, affecting up to 80% of people living with liver cirrhosis. While the signs can be quite subtle, MHE can seriously disrupt cognitive functions such as attention and memory. This disruption can impact daily life, potentially leading to an increased risk of accidents. Unfortunately, many health care providers might overlook the diagnosis because the symptoms can be vague, and identifying MHE usually requires specific tests like the psychometric hepatic encephalopathy score (PHES). Several factors contribute to MHE, including elevated ammonia levels, systemic inflammation, and issues with the gut-brain connection. It’s crucial to identify and treat MHE quickly, as it can progress to overt hepatic encephalopathy (OHE), which presents much more severe symptoms and is associated with higher mortality rates. Current treatment approaches often include medications like lactulose and rifaximin, along with cognitive rehabilitation and dietary changes. Emerging treatments that focus on gut health, such as probiotics, are showing potential in helping to lower ammonia levels. This review brings together the latest research on MHE, pointing out significant gaps in how we diagnose it and the potential of new therapies like synbiotics. By looking at recent multicenter studies, we aim to offer practical insights that could help prevent the progression to OHE, ultimately improving patient outcomes. Review Thu, 24 Jul 2025 00:00:00 GMT MahtabGhaemi, Thu, 24 Jul 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100582 https://www.explorationpub.com/Journals/edd/Article/100583 Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease worldwide. Its prevalence is increasing due to its close relationship with obesity, insulin resistance, and other metabolic disorders. In this context, the gut-liver axis has been identified as a fundamental regulator in the progression of MASLD, integrating metabolic, immunological, and inflammatory signals that influence hepatic homeostasis. This article reviews the interconnection between the intestine and the liver in the onset and progression of MASLD, highlighting the roles of cholesterol and its metabolism, intestinal barrier permeability, microbiota, and hepatic signaling pathways. We analyze how intestinal dysbiosis and alterations in the enterohepatic circulation of bile acids affect cholesterol absorption and metabolism. Furthermore, we address the influence of endotoxin translocation, activation of the innate immune system, and the interaction of key transcription factors on disease progression from steatosis to advanced fibrosis and hepatocellular carcinoma (HCC). Finally, therapeutic strategies, including pharmacological, dietary, and immunomodulation-based approaches, are discussed to regulate cholesterol metabolism, modulate the intestinal microbiota, and restore gut-liver axis homeostasis. Integrating this knowledge could open new perspectives for treating and preventing MASLD, addressing the disease from a broader and multidisciplinary viewpoint. Review Wed, 06 Aug 2025 00:00:00 GMT Luis A.Rodríguez-Rojas, LeticiaBucio-Ortiz, VerónicaSouza-Arroyo, María ConcepciónGutiérrez-Ruiz, Luis E.Gómez-Quiroz, Roxana U.Miranda-Labra, Wed, 06 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100583 https://www.explorationpub.com/Journals/edd/Article/100584 Celiac disease is an immune-mediated disorder with significant metabolic implications. Several factors have been proposed to explain the association between celiac disease in patients following a gluten-free diet and metabolic disorders, including metabolic syndrome. Growing evidence suggests a pivotal role of gut microbiome dysbiosis in the onset of celiac disease and its associated metabolic disturbances. The present narrative review examines (i) the connections between celiac disease and metabolism-related comorbidities, including metabolic syndrome and metabolic dysfunction-associated steatotic liver disease; (ii) the role of the gut microbiome in celiac disease, including the outcomes of gut microbiome dysbiosis in celiac children and adults; and (iii) the potential of microbial therapeutic strategies within the context of personalized medicine for patients with celiac disease and comorbid metabolic conditions. A synthesis of existing studies highlights several protective factors and interventions for future celiac disease prevention research. Adopting plant-based, health-promoting dietary patterns such as the Mediterranean or vegetarian diet within the first two years of life reduces celiac disease risk. These fiber- and phytochemical-rich diets support beneficial gut microbiota growth and short-chain fatty acid production, which maintain intestinal barrier integrity by enhancing mucus and tight junction proteins. Short-chain fatty acids also modulate immunity by inducing Tregs that secrete IL-10, suppressing pro-inflammatory Th1 responses and autoantibody production. Precision probiotics offer diverse therapeutic benefits in celiac disease by reducing inflammation, restoring beneficial microbes, and degrading immunogenic gliadin peptides. Postbiotics complement these effects by reinforcing barrier integrity and counteracting gliadin-induced inflammation. Thus, integrating clinical models with microbial biomarkers promises to improve celiac disease diagnosis and monitoring, enabling better risk stratification, earlier detection, and personalized management of this heterogeneous disease. Review Thu, 07 Aug 2025 00:00:00 GMT AlejandroBorrego-Ruiz, Juan J.Borrego, Thu, 07 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100584 https://www.explorationpub.com/Journals/edd/Article/100585 This article addresses the current understanding of the bidirectional relationship between iron metabolism and the gut microbiota. Both iron deficiency and iron overload in the gut can negatively affect the composition and function of the intestinal microbiota. Conversely, beneficial members of the colonic microbiota play a key role in enhancing systemic iron absorption. Particular attention is given to the potential use of microbiota-modulating agents for the correction of colonic dysbiosis as part of a comprehensive therapeutic approach to iron deficiency/overload conditions. Therefore, these interventions, by supporting microbiota restoration and reduction of intestinal inflammation, may also offer novel therapeutic avenues for disorders of iron metabolism. Review Fri, 08 Aug 2025 00:00:00 GMT NataliaBaryshnikova, YuryUspenskiy, ValeriaNovikova, Fri, 08 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100585 https://www.explorationpub.com/Journals/edd/Article/100586 Here, the history of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis nomenclatures is summarized. Metabolic dysfunction-associated fatty liver disease (MAFLD) was coined in 2020, and metabolic dysfunction-associated steatotic liver disease (MASLD) was proposed in 2023. With this backset, the present article aims at reviewing the similarities and differences between MAFLD and MASLD through a systematic analysis of published comparative studies. MAFLD and MASLD have a complex disease spectrum comprising, further to all-cause mortality, hepatic (fibrosis, cirrhosis, and primary liver cancer) and extrahepatic outcomes (major adverse cardiovascular events, chronic kidney disease, extrahepatic cancers, type 2 diabetes, and vascular dementia). Comparative studies document that—due to its superior ability to identify liver fibrosis—MAFLD better captures mortality owing to all-causes, hepatic and extrahepatic outcomes, which are strongly associated with the severity of liver fibrosis. Moreover, MASLD is inappropriate in pediatric care, lacks specificity, tends to overdiagnosis, does not consider coexistent viral hepatitis or lean subjects, and amplifies disease heterogeneity. Collectively, the evidence presented in this narrative review supports an urgent need for the development of evidence-based guideline statements. This novel developmental process should involve not only a systematic review of the evidence, with equal contribution from all the world’s regions of stakeholders and clinical panelists, but also should use quantitative data to identify an objective-level consensus to guarantee wide adoption of the process outcomes. Review Fri, 15 Aug 2025 00:00:00 GMT AmedeoLonardo, Ming-HuaZheng, MohammedEslam, Fri, 15 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100586 https://www.explorationpub.com/Journals/edd/Article/100587 Brazil ranks second globally in absolute liver transplants and leads pediatric transplantation in Latin America. This scoping review aims to map the results and perspectives of pediatric liver transplantation in Brazil from 2000 to 2022. A scoping review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews Checklist (PRISMA-ScR) guidelines, using PubMed, Virtual Health Library (VHL), and ScienceDirect. From 293 records, 26 studies were included based on predefined criteria. The review focused on clinical indications, techniques, outcomes, and regional disparities. Results: Of the 26 included studies, 10 (38%) reported survival rates, showing 1-, 5-, and 10-year survival of 89.3%, 78.1%, and 68.5% for deceased donors and 93.1%, 85.7%, and 67.5% for living donors, respectively. Eleven studies (42%) discussed living donor liver transplantation (LDLT), which accounts for 53.4% of pediatric transplants. Eight studies (31%) detailed postoperative complications, such as vascular (up to 19%) and biliary (15.7%) issues, rejection (~ 50%), and infections. The COVID-19 pandemic led to a 20.6% reduction in transplant activity and increased waiting list mortality from 8.4% to 11.9%. Despite Brazil’s leadership in pediatric liver transplants, challenges persist, including donor shortages, diagnostic delays, geographic concentration in São Paulo (66%), and limited data systematization. These factors hinder equitable access and optimal outcomes across the country. To improve pediatric liver transplantation in Brazil, actions are needed to strengthen donor registration systems, decentralize services, enhance team training, and adopt techniques like split liver transplantation. Expanding national databases and prognostic tools will help address disparities and improve care. Review Wed, 20 Aug 2025 00:00:00 GMT Julia RibeiroKormann, KamilaRecarcati, Mayara MayerAlves, Ariel Pamelada Silva Lopes, JoséSampaio-Neto, Izabel Cristina Meister MartinsCoelho, Camila Aparecida MoraesMarques, Wed, 20 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100587 https://www.explorationpub.com/Journals/edd/Article/100588 Hepatocellular carcinoma (HCC) ranks as the sixth most diagnosed cancer and the third most common cancer-related death globally. The underlying precise molecular mechanisms for its progression remain poorly understood. Interestingly, approximately 90% of HCC-related deaths are not due to the primary tumor itself but rather to its difficult-to-treat metastatic spread. Despite sorafenib being the first-line therapy for HCC, challenges such as drug resistance, frequent recurrence, and metastasis contribute to poor prognosis. In this context, alternative therapeutic strategies are urgently needed. A broad spectrum of phytochemicals, including polyphenolic derivatives, flavonoids, carotenoids, alkaloids, terpenes, lignans, and saponins, has shown considerable promise as potential anti-cancer agents, both in vitro and in vivo. These natural plant-derived compounds exhibit distinct and overlapping mechanisms of action, characterized by their antioxidant, anti-inflammatory, and anti-cancer properties, offering a novel approach to HCC treatment. An extensive literature search was conducted from 2010 to 2024 using reputable electronic databases such as MEDLINE, Embase, Google Scholar, Science Direct, and other reliable sources using different keywords, including HCC, medicinal plants in HCC, HCC metastasis, and mechanism of action of medicinal plants in HCC, among others. This comprehensive review aims to summarize the potential role of plant-based bioactive components in combating HCC through various cellular mechanisms, highlighting their therapeutic potential in the management of both primary and metastatic disease. Review Mon, 25 Aug 2025 00:00:00 GMT Manoj KumarNagar, DeepthiSudha, BalasubramaniyanVairappan, Mon, 25 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100588 https://www.explorationpub.com/Journals/edd/Article/100589 Amyloidosis is a rare disease, corresponding to a deposition of proteins in various tissues. Amyloid light-chain (AL) amyloidosis can involve the liver in 17% to 45% of patients. Diagnosis of liver disease is based on specific criteria, coupling alkaline phosphatases and hepatomegaly. Liver stiffness is altered in cases of heart involvement, and overall, in cases of liver involvement. Liver biopsy is generally avoided due to an important bleeding risk. Treatment is essentially based on stem cell transplantation and chemotherapy, with large progress during the last decade. Liver involvement recovery is generally diagnosed with a reduction in alkaline phosphatases and in liver size. Review Fri, 29 Aug 2025 00:00:00 GMT PaulCarrier, MarilyneDebette-Gratien, JulieAbraham, AnneCypierre, Jean-FrançoisCadranel, ArnaudJaccard, VéroniqueLoustaud-Ratti, Fri, 29 Aug 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100589 https://www.explorationpub.com/Journals/edd/Article/100590 Peroxisome proliferator-activated receptors (PPARs) comprise three isoforms: PPARα, PPARβ/δ, and PPARγ, which regulate the expression of genes involved in fatty acid uptake, β-oxidation, adipogenesis, gluconeogenesis, and insulin sensitivity. Type 2 diabetes (T2D), often accompanied by other features of metabolic syndrome, contributes to vasculopathy, end-stage organ failure, and cancer. Metabolic dysfunction-associated steatotic liver disease (MASLD) refers to steatotic liver disease in the presence of cardiometabolic risk factor(s) and without excessive alcohol consumption. MASLD is prevalent among adults with T2D and carries a high risk of liver fibrosis, metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis and incident T2D. In MASLD, the liver becomes a hub of lipid toxicity, oxidative stress, and fibrotic signalling whenever T2D disrupts hormonal and adipokine signalling, increases free fatty acid flux, and promotes chronic inflammation. MASLD, therefore, results from an impairment of the protection physiologically offered by PPARs through fatty acid oxidation, lipid storage in the adipose tissue, and mitigation of insulin resistance and pro-inflammatory cascades. By examining the molecular mechanisms of PPARα, PPARβ/δ, and PPARγ, as well as their interactions with cofactors like PGC-1α, and their crosstalk with pathways like sterol regulatory element-binding protein (SREBP), NF-κB, AMP-activated protein kinase (AMPK), and adipokines, researchers and clinicians can better understand how T2D-related MASLD can be prevented or treated. Single PPAR agonists, such as fibrates and glitazones, have limited clinical efficacy in achieving hard liver histology endpoints like MASH resolution and fibrosis regression in humans. However, the Pan-PPAR agonist Lanifibranor at the highest doses shows promise in ameliorating these outcomes in subjects with non-cirrhotic MASH. This suggests that activating all three PPAR isoforms together enhances their therapeutic effects on various cells and target organs, restoring insulin resistance, improving gluco-lipidic homeostasis, while inhibiting pro-inflammatory and pro-fibrogenic pathways. Analysis of unresolved issues should dictate the research agenda. Review Tue, 02 Sep 2025 00:00:00 GMT AmedeoLonardo, RalfWeiskirchen, Tue, 02 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100590 https://www.explorationpub.com/Journals/edd/Article/100591 Aim: The current state of the problem of stomach and duodenal diseases presupposes a mandatory examination of patients for the presence of Helicobacter pylori infection. Highly specific and sensitive diagnostic methods are known and applied, however, the problem of removal from clinical laboratories, isolation, including during a pandemic, dictates the search for new solutions. Methods: Mobile diagnostic solutions based on portable devices with highly sensitive quartz piezoelectric sensors were investigated using a variety of devices (1–8 sensor elements) and data processing algorithms. Results: A three-year volunteer monitoring study demonstrated that sensor arrays are informative for exhaled air and volatile skin compound analysis, enabling both point diagnostics and long-term tracking. Conclusions: The study demonstrates the significant potential of sensor libraries in non-invasive diagnostics, particularly through the innovative application of facial skin projection for volatile marker detection. Three diagnostic approaches have been presented for assessing stomach and esophageal conditions via non-invasive monitoring of exhaled air composition and volatile skin compounds. The authors’ extensive experience in breath urease testing for both adults and children enabled purposeful modifications of diagnostic devices and data processing algorithms. A three-year volunteer monitoring study during anti-Helicobacter therapy and dietary interventions revealed high stability and informativeness of the urease test utilizing chemical sensor arrays. Notably, this research represents the first demonstration of facial organ projection as a method for stomach condition assessment and volatile molecule monitoring without sample collection, showcasing promising prospects for future diagnostic applications. Original Article Mon, 15 Sep 2025 00:00:00 GMT Tatyana AnatolievnaKuchmenko, DariaMenzhulina, RuslanUmarkhanov, ArinaKopaeva, Mon, 15 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100591 https://www.explorationpub.com/Journals/edd/Article/100594 Aim: Hepatocellular carcinoma (HCC) poses a significant global health threat. The pregnane X receptor (PXR) is a central regulator of xenobiotic metabolism and plays a key role in mediating cellular resistance to anti-tumor drugs in HCC. Indeed, the precise role of PXR in HCC pathogenesis remains unclear. This study aimed to investigate blood and hepatic PXR levels and their association with inflammation in HCC patients. Additionally, we assessed the diagnostic potential of PXR in HCC patients compared to control subjects. Methods: Following approval by the Institute Ethical Committee, 40 HCC patients and 40 healthy volunteers were enrolled in this study. Baseline patient characteristics, serum alpha-fetoprotein (AFP), and biochemical parameters were analyzed. Serum levels of PXR, tumor necrosis factor alpha (TNF-α), and interleukin (IL)-1β were measured using ELISA. The hepatic expression of phosphorylated nuclear factor kappa B (NFκB) and PXR proteins was analyzed by western blotting. Results: When compared to control subjects, serum PXR levels were increased in HCC cases (1.34 ± 0.16 vs. 4.09 ± 0.33; P < 0.0001). Similarly, hepatic PXR expression was increased in HCC tissues. Moreover, HCC patients exhibited elevated inflammatory cytokines and a deranged hepatobiliary profile compared to controls. Conclusions: Elevated serum PXR levels in HCC patients were positively correlated with inflammation. Notably, serum PXR demonstrated greater sensitivity and specificity in diagnosing HCC. These findings suggest that PXR may serve as a plausible biomarker in the diagnosis of HCC. Original Article Fri, 26 Sep 2025 00:00:00 GMT BalasubramaniyanVairappan, TanyaMishra, BijuPottakkat, Fri, 26 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100594 https://www.explorationpub.com/Journals/edd/Article/100593 Hepatitis A virus (HAV) is a spherical, non-enveloped, linear-positive single-stranded RNA virus that belongs to the Picornaviridae family. The virus attacks the liver, which leads to inflammation and the onset of jaundice. It represents a disease of the pediatric population and, in most cases, it causes an acute self-limited illness, but rarely a fulminant condition. HAV spreads from person to person through the fecal-oral route and ingestion of contaminated food or drink. It is highly endemic in large geographical areas of the world, including the Indian subcontinent, where most of the population is exposed to the virus in childhood. Most of the viral infections at this age cause asymptomatic disease that provides lifelong protection against HAV. However, our recent study showed an increased incidence of HAV infection in the adult population. This signifies a change in the pattern of age-specific seroprevalence of antibodies for hepatitis A and a huge number of non-immune susceptible individuals. Molecular epidemiological studies define various aspects of viral infection and transmission. Sequence characterization based on the VP1/P2A junction region confirmed IIIA and IA as the predominant genotypes circulating in the Indian subcontinent. The duration of the viremia is dependent on the host, and viral genotypes have no role in the severity of the disease. A mutational study confirmed the lack of genetic variations among Indian strains. Due to the high endemicity of this disease in the Indian subcontinent, vaccination is not recommended. However, individuals who are susceptible and seronegative for HAV-IgG should be targeted for vaccination. It will be a rational and cost-effective approach. Review Wed, 24 Sep 2025 00:00:00 GMT ZahidHussain, IzharShaikh, SohebKhan, RajivSinh, KrutikaPatel, VivekPatel, Wed, 24 Sep 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100593 https://www.explorationpub.com/Journals/edd/Article/100597 Hepatic encephalopathy (HE) is a debilitating neuropsychiatric complication of liver dysfunction that spans a continuum from subtle cognitive impairment to deep coma. While historically attributed to hyperammonemia, current insights reveal a multifactorial pathogenesis involving systemic inflammation, astrocyte dysfunction, blood-brain barrier (BBB) disruption, and altered neurotransmission. Central to this complex network is the gut-liver axis—a bidirectional system that links the gut microbiota, intestinal barrier integrity, bile acid metabolism, and hepatic immune responses. In cirrhosis, dysbiosis and increased intestinal permeability facilitate the translocation of microbial products—such as endotoxins and ammonia—that trigger hepatic and systemic immune activation, amplifying neurotoxicity through the gut-liver-brain axis. Experimental and clinical evidence has shown that ammonia and bilirubin synergistically promote neuroinflammation, mitochondrial dysfunction, and glial activation. Multiomics data further support the role of the microbiota as an active modulator of liver-brain homeostasis. Microbiota-targeted therapies—including rifaximin, probiotics, synbiotics, and fecal microbiota transplantation (FMT)—demonstrate efficacy in reducing HE recurrence, improving cognition, and restoring microbial balance. Novel receptor-based strategies targeting the farnesoid X receptor (FXR), Takeda G-protein-coupled receptor 5 (TGR5), and aryl hydrocarbon receptor (AhR) show promise for modulating bile acid pathways and mitigating neuroinflammation. Emerging approaches also focus on dietary interventions, the reinforcement of epithelial barrier function, and artificial intelligence (AI)-driven tools for personalized monitoring. Despite these advances, challenges persist regarding FMT standardization, long-term safety, and the integration of digital diagnostics into routine care. Review Tue, 14 Oct 2025 00:00:00 GMT Arnulfo E.Morales-Galicia, Mariana N.Rincón-Sánchez, Mariana M.Ramírez-Mejía, NahumMéndez-Sánchez, Tue, 14 Oct 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100597 https://www.explorationpub.com/Journals/edd/Article/100596 Aim: Functional defecatory disorder (FDD) is associated with impaired defecation not only due to abnormalities in recto-anal coordination, but also due to abnormalities in anal tone and rectal sensation. This study aimed to characterize the spectrum of anorectal motor and sensory abnormalities in patients with FDD using the London classification. Methods: In this single-center prospective study, 100 consecutive patients fulfilling Rome IV criteria for FDD were included. Secondary causes of constipation were excluded. High-resolution anorectal manometry, rectal sensory testing, and a balloon expulsion test were performed as per the International Anorectal Physiology Working Group (IAPWG) protocol. Patients were classified using the London classification, which identifies multiple subtypes of anorectal dysfunction. Results: The median age was 34 years (range: 18–78), with 64% males and 36% females. Among the cohort, 85% had abnormal expulsion with dyssynergia, while 15% had abnormal expulsion with poor propulsion and dyssynergia. Anal hypotension with normal contractility was seen in 9%, while 4% had anal normotension with hypocontractility. Rectal hyposensitivity and borderline rectal hyposensitivity were noted in 4% and 5% of patients, respectively. Conclusions: This study highlights that dyssynergic defecation is frequently accompanied by additional anorectal dysfunctions. Applying the London classification enhances the recognition of coexisting abnormalities, which may have therapeutic implications. Future research should investigate whether addressing these additional dysfunctions improves treatment outcomes in FDD. Original Article Sat, 11 Oct 2025 00:00:00 GMT StephanBenny, RajeebJaleel, Ashis KumarChoudhury, Amit KumarDutta, Noble VargheseMathews, Sat, 11 Oct 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100596 https://www.explorationpub.com/Journals/edd/Article/100598 This review explores recent advancements in the management of Helicobacter pylori infection, a widespread bacterial pathogen associated with various gastrointestinal disorders. The paper discusses improved diagnostic techniques, including molecular methods and non-invasive tests, which have enhanced detection accuracy and antibiotic resistance profiling. New treatment strategies, such as individualized therapy based on antimicrobial susceptibility testing (AST) and the use of probiotics as adjunctive therapy, are examined. The review also addresses the challenges of antibiotic resistance, highlighting the importance of surveillance and monitoring strategies. Novel antibiotic combinations and non-antibiotic therapies, including antibiofilm agents, are presented as potential solutions. The paper concludes by discussing post-treatment follow-up, management of persistent infections, and considerations for special patient populations. Future directions in Helicobacter pylori management, including emerging technologies and global eradication efforts, are briefly outlined. Review Wed, 22 Oct 2025 00:00:00 GMT SurbhiDumra, AbhishekRay, Wed, 22 Oct 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100598 https://www.explorationpub.com/Journals/edd/Article/100599 Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a multisystem disorder in which iron acts as both a metabolic “spark” and an accelerant of liver injury. This integrates emerging evidence that iron-driven oxidative stress and low-grade inflammation are mutually reinforcing processes in metabolic liver disease. In this perspective article, epidemiological evidence, molecular insights, and emerging clinical data are integrated to clarify how hyperferritinemia, often dismissed as a mere inflammatory marker, maps onto genuine iron redistribution and overload in the metabolic liver. Physiological iron homeostasis and its disruption by adiposity-related inflammation, hyperinsulinemia, sex hormones, and common HFE variants, creating a labile catalytic iron pool that fuels Fenton chemistry in lipid-laden hepatocytes. Population studies and expert-panel criteria are summarized that define “metabolic hyperferritinemia” and stratify dysmetabolic iron accumulation into three magnetic resonance imaging (MRI)-based grades, each linked to stepwise increases in steatosis, fibrosis, and clinical events. Mechanistically, excess Fe2+ triggers lipid peroxidation, mitochondrial dysfunction, ferroptosis, Kupffer cell activation, endoplasmic reticulum stress, and hepatic stellate cell sensitization to TGF-β, thereby accelerating the transition from steatosis to steatohepatitis and fibrosis. Finally, the diagnostic algorithms, iron-modulating therapies (phlebotomy, hepcidin agonists, diet), and prospective data supporting ferritin-based triage in clinics are discussed. Collectively, the outlined evidence positions iron not only as a biomarker but also as a modifiable driver of MASLD progression, underscoring the need for randomized trials that test whether targeted iron reduction improves hard hepatic outcomes. Perspective Wed, 29 Oct 2025 00:00:00 GMT RalfWeiskirchen, Wed, 29 Oct 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/100599 https://www.explorationpub.com/Journals/edd/Article/1005100 Recent studies demonstrate that peripheral innervation and Schwann cells (SCs) activity within the tumor microenvironment (TME) have a significant influence on liver cancer, specifically hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Even though the role of SCs in HCC behavior is only hypothetical, neurotrophic factors like brain-derived neurotrophic factor (BDNF) and artemin (ARTN) enhance tumor growth, angiogenesis, and metastasis. Thus, targeting these pathways has a promising therapeutic potential. Conversely, receptors such as glial cell line-derived neurotrophic factor family receptor α-1 (GFRα1) and factors like neurotrophin-3 (NTF3) exhibit tumor-suppressive roles, indicating a context-dependent, dual impact of neurotrophic signaling in liver cancer. In iCCA, perineural invasion (PNI) correlates with poor prognosis, with SCs promoting tumor progression through the secretion of neurotrophic factors such as nerve growth factor (NGF) and BDNF, which activate signaling pathways downstream. These pathways facilitate epithelial-mesenchymal transition (EMT), invasion, and neural infiltration. This review emphasizes the complex roles of neurotrophic factors in hepatic tumors and their future potential as biomarkers and therapeutic targets via disruption of tumor-nerve interactions. Review Wed, 12 Nov 2025 00:00:00 GMT LorenzoMainardi, FabioMarra, ChiaraRaggi, Wed, 12 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005100 https://www.explorationpub.com/Journals/edd/Article/1005101 Females are more susceptible to alcohol-related liver disease (ALD) owing to increased risk of alcohol dependence; decreased gastric first-pass effect and increased risk of producing hepatotoxic metabolites, higher alcohol bioavailability, and hormonal fluctuations affecting ethanol metabolism. Male sex is independently associated with hepatitis B virus (HBV) infection and hypertransaminasemia in HBV chronic infection. Compared to women, men have higher risks of being hepatitis B surface antigen (HBsAg) carriers, exhibit higher non-response and lower long-term immunity after prophylactic vaccination, have a higher risk of chronic hepatitis, and fibrotic and hepatocellular carcinoma (HCC). Females have higher spontaneous hepatitis C virus (HCV) clearance and reduced risk of fibrosis, cirrhosis, and HCC than men. However, post-menopausal women experience more rapid progression of hepatic fibrosis and HCC development and lower response rates to antiviral regimens compared to younger women. Hormonal and immunological mechanisms explain these sex differences observed in chronic viral hepatitis B and C. Sex and reproductive status affect the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) development and progression. Genetic sex and sex hormones are involved in the pathogenesis of sex differences in MASLD by differential effects on body fat distribution, insulin sensitivity, and oxidative stress. HCC may arise as a complication of ALD, HBV, HCV, and MASLD and has a definite prevalence in the male sex because of the most robust inflammatory response of the male sex and the anti-inflammatory activity of estrogens. We conclude that those major sex differences which are identifiable in the epidemiology and clinical course of ALD, viral hepatitis owing to HBV and HCV, MASLD, and HCC. These sex disparities are explained by biological sex and sex hormones affecting metabolism, immunity, fibrogenesis, and cancer, and are the foundations for precision medicine approaches in these common hepatological conditions. Review Wed, 26 Nov 2025 00:00:00 GMT AmedeoLonardo, AyakoSuzuki, Wed, 26 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005101 https://www.explorationpub.com/Journals/edd/Article/1005103 Interleukin-17 inhibitors (IL-17i) are used for dermatologic and rheumatologic immune-mediated inflammatory diseases (IMIDs), yet paradoxical inflammatory bowel disease (IBD) can occur. Although trials report low incidence, recognition and management remain difficult outside tertiary care centers. A 54-year-old woman treated with ixekizumab (IXE) for presumptive psoriatic arthritis (PsA) without definitive confirmation developed anorexia, weight loss, abdominal pain, rectal urgency, and hematochezia 16 weeks after IXE initiation. Limited access to gastroenterology contributed to the delayed workup. Catastrophic complications, including bowel perforation, postoperative abscesses, and severe malnutrition, resulted from the cumulative effects of longstanding, inadequately treated disease; excessive immunosuppression with high-dose corticosteroids and infliximab; and concurrent use of opioids and antidiarrheals, among other factors. On transfer to a center skilled in IBD, care included withdrawal of excessive immunosuppression, targeted antimicrobials, and nutrition rehabilitation. Histopathology of the surgical specimen was most consistent with features of Crohn’s disease (CD). After recovery, she achieved clinical, endoscopic, and histologic remission. On rheumatologic reassessment at an independent practice, she did not meet classification criteria for PsA. With continued specialty follow-up, the patient has remained in sustained clinical, laboratory, and endoscopic remission for 16 months, underscoring that timely recognition and disciplined, evidence-based care grounded in the principles used for severe IBD and drug-induced colitis can deliver favorable long-term outcomes. This case highlights the need for structured, accessible clinical guidance, not only to support non-IBD specialists in managing IL-17i-associated complications but also to guide clinicians during the pre-therapy phase in selecting appropriate candidates for treatment and assessing potential gastrointestinal risks before initiating therapy. We present an evidence-informed framework for resource-limited settings that addresses screening, early recognition, diagnostic workup, and therapeutic decision-making to guide safer IL-17i use and improve outcomes. Case Report Tue, 02 Dec 2025 00:00:00 GMT Taylor L.Spiewak, Ted A.Spiewak, AnishPatel, Tue, 02 Dec 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005103 https://www.explorationpub.com/Journals/edd/Article/1005102 Not applicable. Editorial Thu, 27 Nov 2025 00:00:00 GMT Vincenzo GiorgioMirante, Thu, 27 Nov 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005102 https://www.explorationpub.com/Journals/edd/Article/1005105 Liver cirrhosis is a condition characterized by scarring of liver tissue resulting from impaired liver function and systemic complications. It shows symptoms like jaundice, ascites, and hepatic encephalopathy. It has significant mortality and morbidity worldwide. As the study of microbial dysbiosis grows, it investigates how an imbalance in gut bacteria can speed up the progression of liver cirrhosis by spreading bacteria, endotoxins, and inflammation all over the body. Dysbiosis damages the gut–liver axis and eventually the liver. The study aims to analyze the therapeutic potential of bacteriophage therapy in liver cirrhosis. Bacteriophage treatment is a new focused method for treating microbial dysbiosis. Bacteriophages are viruses that target and attack harmful pathogens without affecting the helpful ones or causing an imbalance in the gut microbiota’s equilibrium. Since broad-spectrum antibiotics can affect the gut microbiota and lead to antibiotic resistance, phages are a better alternative due to their selectivity. According to preclinical research conducted in animal models, bacteriophage therapy can lower the bacterial load, enhance liver function tests, and decrease the systemic inflammatory indicators. Bacteriophage safety, as well as potential effectiveness in balancing gut microbiota, reducing systemic inflammation, and relieving symptoms such as hepatic encephalopathy, has been shown by preliminary clinical trials and case reports. However, issues like phage-resistant bacteria, patient-specific gut microbiota variation, and lack of clinical trials continue to prevent general use. Additional research is required to determine if it can be used in clinical practice, including large clinical trials and individualized strategies. Bacteriophage therapy is a promising and new technique for improving liver cirrhosis outcomes. Review Tue, 09 Dec 2025 00:00:00 GMT SaralaGudla, Isha SenthilVelmurugan, DanaSamardali, Sreethu SreekantanGeetha, Hitanshi NareshkumarPanchal, Srijamya, Tue, 09 Dec 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005105 https://www.explorationpub.com/Journals/edd/Article/1005106 Gastric cancer (GC) is one of the most common malignant tumors, ranking fifth in incidence and third in mortality worldwide. China also bears a high burden of GC, second only to lung cancer. With the advancement of clustered regularly interspaced short palindromic repeats (CRISPR) technology, the mechanisms underlying the development and progression of various tumor types have been elucidated. This article summarizes the application of CRISPR technology in the functional genomics identification and target screening of GC genes, explores the use of chimeric antigen receptor T (CAR-T) cell therapy for solid gastric tumors, and discusses the progress and significance of CRISPR technology in constructing GC models using organoids. Review Tue, 09 Dec 2025 00:00:00 GMT MengmengZhang, QihangSu, QianZhang, XianguangYang, Tue, 09 Dec 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005106 https://www.explorationpub.com/Journals/edd/Article/1005107 Diverticulitis is one of the most common gastrointestinal causes of hospitalization in Western society. While previously characterized as a disease of older patients, new literature highlights an increasing incidence among the younger population. Over the past few decades, the understanding of etiology and management of diverticulitis has changed drastically. New data refute past beliefs while promoting other novel recommendations to mitigate incidence and subsequent complications. Data now confirms the safety and possible protective benefit of particulate food, while highlighting evidence-based approaches for the use of diagnostic imaging and antibiotics. We recognize modifiable and non-modifiable risk factors that are commonly seen throughout the literature and play a significant role in the management and prevention of diverticulitis. Emerging evidence also links chronic inflammation with subsequent microbial dysbiosis and alterations in the neuroendocrine system, leading to visceral hypersensitivity and perturbation of the gut-brain axis. This review provides a comprehensive update on acute uncomplicated diverticulitis according to the most recent evidence-based literature, encompassing the risks, diagnostic modalities, and management treatment regimens. Review Thu, 25 Dec 2025 00:00:00 GMT Nicholas B.D’Alessandro, TarunVippa, Edward C.Oldfield IV, David A.Johnson, Thu, 25 Dec 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005107 https://www.explorationpub.com/Journals/edd/Article/1005108 Aim: Hepatocellular carcinoma (HCC) accounts for 90% of liver tumors and is the fourth leading cause of cancer-related deaths worldwide. Current treatments have poor outcomes for HCC, highlighting the urgent need for new and effective therapies. Growth differentiation factor 11 (GDF11), a member of the TGF-β superfamily, regulates differentiation, proliferation, and migration processes, effects observed in cancer, including HCC. In this study, we aimed to investigate the chemosensitizing effects on human liver cancer cells. Methods: We pre-treated Huh7 and Hep3B cells with GDF11 50 ng/mL for 72 h in the presence of sorafenib (Sfb) or cisplatin (CDDP) and evaluated cellular response. Results: Pre-treatment with GDF11 lowered the IC50 of CDDP and Sfb in Huh7 cells. Similar effects were observed in Hep3B cells. Additionally, combining GDF11 with CDDP or Sfb significantly reduced cell viability and decreased the size and number of spheroids. Furthermore, we found that the chemosensitizing effect is initiated by GDF11 binding to the type I receptor ALK5. Inhibition of ALK5 abolished SMAD2 activation, impacting the chemosensitizing effects. Finally, GDF11, combined with Sfb or CDDP, reduced the activity of drug transporters MRP2, MRP3, and MRP4, which explains its chemosensitizing properties. Conclusions: GDF11 increases the sensitivity of HCC-derived cell lines to Sfb and CDDP by modulating the drug-efflux transporters MRP2, MRP3, and MRP4. Original Article Tue, 30 Dec 2025 00:00:00 GMT NatanaelGerman-Ramirez, MonserratGerardo-Ramírez, Guadalupe I.Domínguez-Gómez, FelipeMasso-Rojas, AraceliPaez-Arenas, BenjaminPerez-Aguilar, LeticiaBucio-Ortiz, VeronicaSouza-Arroyo, Roxana U.Miranda-Labra, María ConcepciónGutierrez-Ruiz, ArturoSimoni-Nieves, Luis E.Gomez-Quiroz, Tue, 30 Dec 2025 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005108 https://www.explorationpub.com/Journals/edd/Article/1005109 Interventional radiology (IR) is an ideal domain for artificial intelligence (AI) due to its data-intensive nature. This review provides a targeted guide for clinicians on AI applications in liver interventions, specifically focusing on hepatocellular carcinoma and portal hypertension. Key findings from recent literature demonstrate that AI models achieve high accuracy in predicting the response to transarterial chemoembolization and in non-invasively estimating the hepatic venous pressure gradient. Furthermore, emerging deep learning architectures, such as Swin Transformers, are outperforming traditional mRECIST criteria in longitudinal treatment monitoring. Despite these technical successes, the transition from “code to bedside” is hindered by limited external validation and the “black box” nature of complex algorithms. We conclude that the future of IR lies in the “AI-augmented” interventional radiologist paradigm, in which AI serves as a precision tool for patient selection and procedural safety rather than as a replacement for clinical judgment. Review Mon, 19 Jan 2026 00:00:00 GMT HyeonYu, Mon, 19 Jan 2026 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005109 https://www.explorationpub.com/Journals/edd/Article/1005110 Digestive diseases comprise a diverse range of illnesses, which are prevalent worldwide and represent an important health issue. This is particularly relevant for the impact of metabolic dysfunction-associated steatotic liver disease (MASLD) due to its close association with the obesity pandemic, contributing to the escalation of MASLD as the most common form of chronic liver disease, and the main cause of liver cancer. Not only does MASLD reflect the deterioration of liver health, but it also has far-reaching consequences for the development of extrahepatic digestive diseases. Along with the progression of liver and digestive diseases to liver, colorectal and pancreatic cancer, the onset of inflammation in diseases of the digestive tract, drug-induced liver injury, and cholestasis, drives and contributes to the rise of these diseases in the future, which merit the attention of clinical and translational research to increase our understanding of the pathogenic mechanisms underlying these disorders in order to improve the diagnosis, management, and treatment. With this goal in mind, the current collaborative review gathers experts in a wide range of liver and digestive diseases to provide an up-to-date overview of the mechanisms of disease and identify novel strategies for the improvement of these important health issues. Review Mon, 09 Feb 2026 00:00:00 GMT InaBergheim, Jean FrancoisCadranel, Jian-GuoChen, Wen-XingDing, RobertEferl, CarmenGarcia-Ruiz, HartmutJaeschke, FirouzehKazerouni, AmedeoLonardo, Derek A.Mann, NahumMéndez-Sánchez, CameliaMokhtari, HanMoshage, ChiaraRaggi, PavelStrnad, OrenTirosh, Honoré TegwendeZougmore, Jose CFernandez-Checa, Mon, 09 Feb 2026 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005110 https://www.explorationpub.com/Journals/edd/Article/1005112 This review goes over the impact of caffeine consumption in inflammatory bowel disease (IBD), examining epidemiology, clinical outcomes, mechanistic studies, and translational research. Caffeine, a widely consumed methylxanthine, exerts diverse physiological effects on the gastrointestinal tract. Mechanistic and preclinical data offer plausible biological pathways by which caffeine could influence the IBD course. Caffeine’s antagonism of adenosine receptors may modulate immune cell activation and cytokine release; its effects on gut motility and secretion can alter symptom perception, and caffeine-mediated changes in intestinal epithelial barrier function, oxidative stress, and the gut microbiome have been demonstrated. These effects make it a lucrative investigational option, and various studies have demonstrated that caffeine intake may reduce the incidence of IBD and may even have disease-modifying effects in regular consumers. However, differences in caffeine source (coffee, tea, soda), dose, concurrent dietary patterns, and disease subtype (Crohn’s disease versus ulcerative colitis) limit definitive causal inference. Clinical implications remain cautious: while moderate caffeine intake may be tolerable and even helpful for many patients, individualized assessment is advisable, particularly for those with symptom-triggering sensitivity or overlapping functional bowel disorders. Future research should target mechanistic links and clinically meaningful outcomes to inform evidence-based dietary guidance for people with IBD. Review Fri, 27 Feb 2026 00:00:00 GMT Mohamed AhmedMohamed, DimaChokr, HariniSundaram, ShameelahHafeez, ZainabAreebah, SubishwarSanthalingam, FaithBishop, Fri, 27 Feb 2026 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005112 https://www.explorationpub.com/Journals/edd/Article/1005113 Gangliocytic paraganglioma (GP) is a rare tumor that involves the gastrointestinal system and often occurs in the second portion of the duodenum. This is the case of a 73-year-old female presenting for an unintentional 10-pound weight loss over the previous year and a computed tomography (CT) scan of the abdomen and pelvis showing a mass in the second portion of the duodenum with omental nodules. She had no other symptoms. An upper endoscopy revealed a pedunculated 5 cm polypoid mass that was endoscopically resected and found to be a GP on pathology. GP is the third most frequent histopathologic type of gastrointestinal neuroendocrine tumors (NET) after gastrinomas and somatostatinomas. Clinical presentations vary from asymptomatic patients to those having gastrointestinal bleeding, melena, anemia, and abdominal pain. GP presents as a single solid well-demarcated mass that is polypoid, pedunculated, or sessile. Histological features of GP show three cell types: spindle cells, ganglion or ganglion-like cells, and epithelioid cells. Biopsy specimens might not contain all 3 characteristic cell types; thus, definitive diagnosis could be challenging. Periampullary GP should be considered as a tumor with malignant potential. The optimal treatment has not been clarified, but endoscopic resection remains the most common treatment of choice. En bloc resection with negative margins for a pedunculated lesion is possible. This is a rare case of GP in a female patient presenting with weight loss only. It highlights the importance of considering GP in the differential diagnosis for duodenal masses, while keeping a broad differential due to the low rates of diagnostic biopsies. More research is needed to establish standardized management protocols for GP and improve patient care. Case Report Fri, 06 Mar 2026 00:00:00 GMT ChloeLahoud, MarkTawfik, HarikaKandlakunta, AhmedElfiky, OlisaemekaChukwudebe, Jean M.Chalhoub, Fri, 06 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005113 https://www.explorationpub.com/Journals/edd/Article/1005114 In the context of the various management options available for obesity, intragastric balloons (IGBs) represent a solution for patients at high surgical risk. Swallowable IGBs are devices that can be ingested orally and then inflated within the stomach to aid in weight loss. Although generally well tolerated, these devices may migrate and cause gastrointestinal obstructive symptoms. Here we report on two cases where these obstructive complications of swallowable IGBs were promptly and non-invasively diagnosed with ultrasonography (US), which also permitted conservative management via US-guided percutaneous aspiration of the impacted balloons. These cases demonstrate that the US may provide a rapid and effective tool for managing IGBs migration, potentially reducing the need for surgical intervention. Case Report Fri, 06 Mar 2026 00:00:00 GMT GiampieroFrancica, CristianoGiardiello, Fri, 06 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005114 https://www.explorationpub.com/Journals/edd/Article/1005115 Metabolic dysfunction-associated steatotic liver disease (MASLD) is a systemic metabolic disorder closely related to insulin resistance, obesity, and type 2 diabetes mellitus. While sustained hyperglycemia and insulin resistance are central to the pathogenesis of MASLD, there is growing evidence suggesting that glucose dysregulation in this condition is heterogeneous and dynamic. Glycemic variability (GV), which reflects fluctuations in glucose levels over time, has emerged as a complementary dimension of glucose homeostasis and has been increasingly explored in relation to hepatic steatosis, fibrosis, and cardiometabolic risk. Experimental data indicate that recurrent glucose oscillations promote oxidative stress, inflammatory signaling, and fibrogenic activation, while observational studies have reported associations between short- and long-term GV and MASLD-related phenotypes in diverse populations. The aim of this review is to describe the mechanistic links between insulin resistance, GV, and MASLD, summarize the current clinical and population evidence evaluating GV in this context, and identify key methodological and conceptual gaps that should inform future research. Review Fri, 13 Mar 2026 00:00:00 GMT Fernanda M.Martínez-Díaz, Elsie A.Jiménez-Cuevas, Mariana M.Ramírez-Mejía, SaraiGómez-Camacho, NahumMéndez-Sánchez, Fri, 13 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005115 https://www.explorationpub.com/Journals/edd/Article/1005116 Microbial metabolites are now recognized as central mediators of host–microbe communication that shape intestinal immune homeostasis and influence the development of inflammatory gastrointestinal diseases. The objective of this review is to synthesize current mechanistic evidence on how microbiota-derived metabolites regulate epithelial and immune functions in the gut, with a focus on metabolite-driven inflammatory pathways. In the healthy intestine, short-chain fatty acids (SCFAs), indole derivatives, secondary bile acids, and polyamines support epithelial integrity, regulate mucosal immunity, and maintain metabolic balance. SCFAs, particularly butyrate, attenuate inflammation by serving as an energy source for colonocytes, inhibiting histone deacetylases, activating G protein-coupled receptors (GPCRs; GPR41, GPR43, GPR109A), and reinforcing epithelial barrier function. In parallel, microbial tryptophan metabolites such as indole-3-propionic acid and indole-3-aldehyde activate aryl hydrocarbon receptor signaling, promoting IL-22 production, antimicrobial peptide expression, and Th17–Treg balance. In inflammatory bowel disease, dysbiosis disrupts these protective pathways, leading to depletion of SCFA- and indole-producing taxa and accumulation of pro-inflammatory metabolites such as succinate. These metabolic shifts impair epithelial-immune crosstalk, amplify NF-κB-dependent inflammation, and compromise mucosal repair. Therapeutic strategies targeting microbial metabolites, including precision prebiotics, next-generation probiotics, engineered microbial consortia, and postbiotics, show translational promise. However, their clinical application remains constrained by interindividual variability, incomplete causal resolution, and challenges in targeted delivery. Integrative multi-omics approaches and mechanistically informed models are therefore essential to advance metabolite-based diagnostics and therapies for gut inflammation. Review Fri, 27 Mar 2026 00:00:00 GMT Neelakanta SarvashivaKiran, AgnikHaldar, AnkitaChatterjee, Fri, 27 Mar 2026 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005116 https://www.explorationpub.com/Journals/edd/Article/1005117 Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic immune-mediated condition typically requiring invasive endoscopy for monitoring. The bidirectional oral-gut axis suggests that saliva may serve as a non-invasive diagnostic fluid for studying gut inflammations. Studies of salivary biomarkers have shown varying results. Inflammatory biomarkers such as IL-6 are the most robust salivary biomarker, consistently correlating with endoscopic activity. In contrast, salivary calprotectin lacks the reliability of its fecal counterpart, showing diagnostic value primarily in pediatric cases with oral manifestations. Microbial analysis indicates reduced salivary diversity, specifically an enrichment of Prevotella and Veillonella alongside a depletion of core commensals like Streptococcus. While oxidative stress markers such as advanced oxidation protein products (AOPPs) can distinguish disease severity, they lack long-term prognostic utility. Conversely, recent shifts toward exosome-based transcriptomic analysis have improved the stability of salivary microRNAs, offering high precision in differentiating IBD phenotypes. Despite these advancements, clinical integration is currently hindered by small cohort sizes, the confounding effects of local oral health, and a lack of standardized collection protocols. To establish saliva as a reliable tool in the IBD clinical toolkit, future research must prioritize multi-panel biomarker approaches and longitudinal studies to validate diagnostic accuracy across diverse patient populations. Review Fri, 03 Apr 2026 00:00:00 GMT AntoineChrabie, CelineAl Kazzi, DaliaBerjass, AliceGerges Geagea, LauraDosh, Lavinia GiovannaLeone, Sahar AlKattar, NaimOuaini, FrancescoCappello, AngeloLeone, AbdoJurjus, Fri, 03 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005117 https://www.explorationpub.com/Journals/edd/Article/1005118 Exploring long non-coding RNAs (lncRNAs) in liver diseases, particularly liver fibrosis, presents significant opportunities for augmenting our understanding and treatment of these conditions. The rapid advancement of high-throughput sequencing technologies has revealed the complex networks of lncRNAs, highlighting their crucial functions in liver fibrosis. Identifying dysregulated lncRNAs offers promising diagnostic and prognostic biomarkers, as well as potential therapeutic targets. Extracellular vesicles contribute to the relevance of lncRNAs by protecting them from degradation and maintaining their activity in circulation, as exemplified by the role of lncRNA H19 in liver fibrosis. LncRNAs are vital in liver pathology, influencing fibrosis and cirrhosis by modulating responses to liver injury from ethanol. They affect inflammation, oxidative stress, and apoptosis through interactions with pathways like NF-κB and microRNA networks. LncRNAs also control hepatic stellate cells, the production of extracellular matrix, and the activation of stem cells, which opens up new ways to treat fibrosis. Ethanol modulates lncRNA expression, impacting liver fibrosis and cirrhosis development. LncRNAs also influence hepatocellular carcinoma progression by affecting cell proliferation, immune response, and tumor growth. Despite these insights, the regulatory networks and molecular mechanisms of lncRNAs in liver disorders are not entirely understood. In this review, we focus on unraveling these complexities and identifying effective lncRNAs that could revolutionize liver disease treatment, offer novel diagnostic and therapeutic avenues, and improve patient outcomes. Review Wed, 08 Apr 2026 00:00:00 GMT Sangeetha P.Kademani, Krishna S.Nallagangula, PrabhudasNelaturi, Wed, 08 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005118 https://www.explorationpub.com/Journals/edd/Article/1005119 Acute mesenteric ischemia (AMI) is a rare but highly lethal vascular emergency resulting from the abrupt interruption of intestinal blood flow. In advanced stages, extensive bowel necrosis may require near total enterectomy, leading to short bowel syndrome and permanent dependence on parenteral nutrition. An 86-year-old woman with atrial fibrillation and multiple cardiometabolic comorbidities presented with acute abdominal pain, nausea, and vomiting. Initial laboratory findings revealed marked leukocytosis and severe systemic inflammation (CRP: 21.0 mg/L). Computed tomography (CT) angiography demonstrated impaired perfusion of the superior mesenteric artery. Emergency laparotomy confirmed extensive jejunoileal ischemic necrosis, necessitating near total enterectomy with stapled jejunoileal anastomosis. Second-look surgery revealed progressive ischemia of the ileocecal region and right colon, requiring extended right hemicolectomy. Postoperatively, the patient was managed with total parenteral nutrition and intensive supportive care. Despite temporary stabilization and discharge on home parenteral nutrition, she died six months later. AMI complicated by short bowel syndrome is associated with poor prognosis in elderly patients. Persistent systemic inflammation, progressive organ dysfunction, and intestinal failure remain major determinants of adverse long-term outcomes, highlighting the critical importance of early diagnosis, prompt surgical intervention, and multidisciplinary postoperative management. Case Report Fri, 10 Apr 2026 00:00:00 GMT EmineYildirim, Ahmet SezerSezgin, KudretKirsan, CaglaFeyzioglu, Asude NurSay, AbdulhalimSenyigit, OmerOzyigit, HafizeUzun, Fri, 10 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005119 https://www.explorationpub.com/Journals/edd/Article/1005120 Hepatocellular carcinoma (HCC) functions as a major cancer-related death factor around the world. Research indicates that long non-coding RNAs (lncRNAs) play essential roles during HCC onset and development because they belong to the novel RNA subclass that extends beyond 200 nucleotides without protein-coding capability. LncRNAs regulate the expression of downstream target genes and cancer-related signaling pathways, thereby promoting the proliferation, migration, invasion, autophagy, and apoptosis of tumor cells. The study of lncRNA function has been substantially facilitated by the emergence of lncRNA-specific microarrays and the increased accessibility of next-generation sequencing technologies. The function of lncRNAs can be predicted using computational and molecular methodologies. LncRNAs have the potential to function as repressors, scaffolds, regulators of super-enhancers, or molecular decoys. Proliferation, invasion, survival, DNA damage response (DDR), and chromatin dynamics can all be influenced by lncRNAs. Additionally, they can affect stemness/differentiation. The recurrence of tumors may be facilitated by the aberrant expression of these transcripts, which may result in therapy resistance. LncRNAs have the potential to function as innovative prognostic or theranostic biomarkers in HCC and other malignancies. In addition, RNA-based therapeutics may be implemented to target lncRNAs as a novel treatment approach for primary or recurrent HCC. In this review, we investigate the functions of lncRNAs in the pathophysiology of HCC and suggest their potential for novel therapeutic application in the treatment of HCC. Review Mon, 13 Apr 2026 00:00:00 GMT MuhammadSulaiman, YiminNie, ZiyiChen, Umm EHani, FaisalRaza, Mussa MussaYahya, ZhiboZhang, MujahidSher, MeiYang, ShengtaoYuan, ChunyuSun, Mon, 13 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005120 https://www.explorationpub.com/Journals/edd/Article/1005121 Aim: Chronic liver disease (CLD) is characterized by progressive impairment of hepatic function and frequent lipid metabolism abnormalities, with reductions in high-density lipoprotein cholesterol (HDL-C) and other lipoprotein fractions shown to parallel worsening liver dysfunction and predict adverse clinical outcomes such as decompensation and mortality. Established prognostic scores like Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) capture aspects of disease severity, but composite lipid indices such as the non-HDL/HDL-C ratio (NHHR), which balance atherogenic and protective lipoproteins, have emerged as potentially informative biomarkers in metabolic and liver disorders. This study evaluated the association of NHHR with clinical decompensation in CLD. Methods: This cross-sectional study included 220 adults with CLD of mixed etiologies. Baseline demographics, liver disease severity scores, and fasting lipid profiles were obtained. NHHR was calculated, and patients were categorized into tertiles. Spearman correlation coefficients were calculated to examine relationships between NHHR and clinical severity markers. Multivariable logistic regression was used to evaluate the association between NHHR and clinical decompensation. Model performance was compared using receiver operating characteristic curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results: Among 220 patients with CLD (mean age 54.5 ± 11.9 years, 63% male), 96 (43.6%) had decompensated disease. Higher NHHR tertiles were associated with increasing MELD-3.0 scores (P = 0.028) and lower serum albumin (P < 0.001). NHHR correlated positively with MELD-3.0, bilirubin, and international normalized ratio (INR) and inversely with albumin and platelet count. Decompensation prevalence rose across NHHR tertiles (31.1% to 53.4%, P < 0.001). NHHR was independently associated with decompensation (adjusted OR 1.55, 95% CI 1.21–1.98, P < 0.001) and improved model discrimination (AUC 0.79 vs. 0.73). Conclusions: NHHR is independently associated with clinical decompensation in CLD and provides incremental prognostic value beyond traditional predictors, suggesting its potential utility in clinical risk assessment and stratification. Original Article Mon, 27 Apr 2026 00:00:00 GMT RajeshChetiwal, AmitKumar, Binay KumarSingh, AmanDubey, ShwetaTanwar, Mon, 27 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005121 https://www.explorationpub.com/Journals/edd/Article/1005122 Janus kinase (JAK) inhibitors represent a major advancement in the management of immune-mediated inflammatory diseases. A balanced approach that carefully weighs therapeutic benefits against potential risks is essential. Through appropriate patient selection, close monitoring, and open physician–patient communication, the clinical potential of JAK inhibitors can be optimized while minimizing adverse outcomes. Nine JAK inhibitors have demonstrated utility in hepatogastrointestinal disorders; however, only two have FDA approval. JAK inhibitors are classified into reversible (competitive) and irreversible (covalent) inhibitors according to their chemical binding with amino acids. This review discusses the safety profile, adverse effects, and molecular selectivity of JAK inhibitors, and highlights their therapeutic roles in hepatogastrointestinal diseases, including inflammatory bowel disease, hepatic fibrosis, hepatocellular carcinoma, autoimmune diseases associated with cancer therapy in post-transplant patients, eosinophilic esophagitis, metabolic syndrome, and metabolic dysfunction-associated steatotic liver disease, and acute graft-versus-host disease following liver transplantation. Mini Review Mon, 27 Apr 2026 00:00:00 GMT Maged TharwatElghannam, Moataz HassanHassanien, Yosry AbdelrahmanAmeen, Emad AbdelwahabTurky, Gamal MohammedElattar, Ahmed AlyElray, Mohammed DarwishEltalkawy, Mon, 27 Apr 2026 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005122 https://www.explorationpub.com/Journals/edd/Article/1005123 Aim: Recent studies suggest an association between sleep patterns and metabolic dysfunction-associated steatotic liver disease (MASLD) among American adults. Despite established sex-specific disparities in MASLD prevalence, the potential influence of sex on the sleep-MASLD relationship is not well defined. Our research aims to elucidate the sex-specific associations of sleep with MASLD by utilizing a nationally representative cohort from the United States. Methods: Data from United States adults aged 20 and older in the 2017–2020 NHANES were analyzed in this cross-sectional study. Sleep parameters were assessed via interviewer-administered questionnaires, while MASLD was defined using vibration-controlled transient elastography (VCTE). Sex-specific associations were investigated with sex-stratified multivariable logistic regression models, and their robustness was tested through subgroup and sensitivity analyses. Results: This study included 5,243 participants (51.2% female). A significant association was observed between sleep disorders and a greater likelihood of MASLD among male participants (OR = 1.50; 95% CI: 1.08–2.10). After full adjustment for covariates, the association remained significant in females (OR = 1.51; 95% CI: 1.06–2.16). Conversely, high sleep debt remained significantly associated with MASLD in both sexes (males: OR = 1.64; 95% CI: 1.14–2.37; females: OR = 1.51; 95% CI: 1.06–2.15). Subgroup analyses confirmed that sex did not modify these relationships. Conclusions: Sleep disorders and sleep debt were significantly associated with MASLD in both sexes. These findings suggest that sleep health may represent an important modifiable target in MASLD prevention strategies. Original Article Fri, 22 May 2026 00:00:00 GMT Mu-LanCai, Hua-binQiu, Dong-pingLiao, Hong-BinChen, Fri, 22 May 2026 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005123 https://www.explorationpub.com/Journals/edd/Article/1005124 Immunotherapy is a promising treatment strategy for treating colorectal cancer (CRC). Despite significant advances in this field, resistance and low efficacy of immunotherapy remain a principal problem. One of the most important factors affecting the response to immunotherapy is the tumor microenvironment (TME). Among the components of the TME, tumor-associated macrophages (TAMs) are key immune cells involved in cancer progression by stimulating tumor cell proliferation, angiogenesis, epithelial-mesenchymal transition, metastasis, and tumor immune evasion. This review presents currently investigated combination therapy based on the immune checkpoint inhibitors and inhibitors of diverse components of the TME, including TAMs, that can potentially increase the effectiveness of CRC treatment. Therapeutic efficacy, together with the functional activity of TAMs, is estimated in multiple preclinical data obtained with diverse in vitro and in vivo models. Ongoing clinical trials demonstrated the association of treatment effectiveness with TAM phenotypes and functions. Review Mon, 25 May 2026 00:00:00 GMT TatianaSudarskikh, KseniiaShalygina, ElenaShmakova, PavelIamshchikov, AlexeyDobrodeev, IrinaLarionova, JuliaKzhyshkowska, Mon, 25 May 2026 00:00:00 GMT https://www.explorationpub.com/Journals/edd/Article/1005124