Primary biliary cholangitis (PBC) is an autoimmune cholangiopathy that affects mainly women and, if untreated, can evolve into biliary cirrhosis. Its prevalence varies worldwide, depending on race, and accounts for 22.27 cases/100,000 habitants in Europe. To establish the diagnosis of PBC according to the European Association for the Study of the Liver (EASL) guidelines, two criteria must be satisfied among alkaline phosphatase (ALP) alterations, autoantibody positivity, and histologic abnormalities. Early treatment is effective in prolonging survival. Current guidelines do not suggest hepatic biopsy in patients with autoantibody positivity without cholestasis alterations. However, many patients with these characteristics have been diagnosed with PBC disease only histologically, mainly patients with normal ALP and elevated gamma-glutamyl transferase (GGT), whose normalization has been used as a marker for the follow-up. In contrast, this is the case of a patient with autoantibody positivity and both ALP and GGT within the range, diagnosed for PBC by histology. The manuscript wants to propose the re-evaluation of the role of liver biopsy in PBC diagnosis and the need for a serological or histological biomarker in the follow-up of patients without cholestatic alterations.

Reactivation of hepatitis B virus (HBV; RHBV) is a significant concern during immunosuppressive therapy, as it can lead to severe hepatitis and liver failure. The article reports a case of RHBV during treatment with guselkumab, an interleukin-23 inhibitor in a patient with inactive HBV infection and psoriasis. This report highlights the importance of screening for HBV prior to immunosuppressive therapy and initiating prophylactic therapy when necessary to prevent reactivation and its complications.

Thrombocytopenia is one of the most frequent implications of liver cirrhosis. This condition, when present in the severe form [platelet count (PLT) less than 50 × 10⁹/L] correlates, with an increased risk of bleeding during the main diagnostic-therapeutic procedures which cirrhotic patients usually undergone. In these cases, generally, an infusion of platelets is performed, albeit in recent years has been replaced by a cycle of second generation thrombopoietin receptor (TpoR) agonists. This article reports two different cases concerning respectively an 83-year-old female patient suffering from arterial hypertension, aneurysm of the sub-renal aorta, hepatitis C virus (HCV)-positive liver cirrhosis responsive to treatment with antiviral drugs, and a 2.0 cm diameter hepatocellular carcinoma (HCC) nodule localized in the hepatic segment III and a 53-year-old female patient with HCV-positive liver cirrhosis complicated by portal hypertension with splenomegaly, thrombocytopenia, and F3 esophageal varices at high risk of bleeding. Both of them, eligible for invasive procedures such as HCC transarterial chemoembolization (TACE) and for esophageal variceal band ligation, were prescribed prophylaxis with TpoR agonists due to their severe and persistent thrombocytopenia. These two cases show how a short course of lusutrombopag allows to safely perform one or more invasive procedures and how the administration of the drug can be repeated without losing efficacy. Furthermore, this drug shows an excellent safety profile and avoids the risks of platelet transfusion. In conclusion, second generation TpoR agonists can be considered the prophylactic treatment of choice to reduce the risk of bleeding in patients with liver cirrhosis and severe thrombocytopenia.

Nonalcoholic fatty liver disease (NAFLD), its more rapidly progressive steatohepatitic variant [nonalcoholic steatohepatitis, (NASH)], and the recently defined metabolic dysfunction-associated fatty liver disease (MAFLD) may be collectively alluded to as “metabolic fatty liver syndromes” (MFLS). MFLS is a common clinical complaint for which no licensed drug treatment is available and a public health issue posing a heaven burden on healthcare systems. Iron plays a key role in many of the key pathogenic steps concurring in the development and progression of MFLS, notably including genetics, intestinal dysbiosis, adipositis, insulin resistance, metaflammation, oxidative stress and ferroptosis, endoplasmic reticulum stress, and hepatic fibrosis. This notion raises the logical expectation that iron depletion, which can easily be implemented with venesection, might improve several aspects of MFLS. However, few published studies have globally failed to support these expectations. In conclusion, venesection in MFLS exhibits a strong biological rationale and possible metabolic benefits. However, confronted with failures in hepato-histological outcomes, data call for additional studies aimed to reconcile these inconsistencies.