Exploration of Digestive Diseases

Table 1. Some chemopreventive agents for liver cancer prevention in populations, with supporting evidence (references).

Agent	Source	Proposed Mechanism	Evidence	Reference
Oltipraz	Synthetic dithiolethione	Enhances phase II detox enzymes, inhibits phase I activation	Human RCT in Qidong reduced aflatoxin biomarkers	Jacobson et al., 1997 [59]
Chlorophyllin	Semi-synthetic chlorophyll	Binds aflatoxins, reduces absorption	Human RCT in Qidong reduced aflatoxin-DNA adducts by 55%	Egner et al., 2001 [61]
Sulforaphane	Broccoli sprouts	Induces phase II enzymes, antioxidant activity	Pilot trial reduced aflatoxin & benzene metabolites	Kensler et al., 2005 [62]
Metformin	Antidiabetic drug	Improves insulin sensitivity, reduces inflammation	Meta-analysis: 48% reduced HCC risk in diabetics	Ma et al., 2017 [58]
SSRI	Antidepressant	Modulates serotonin pathways, reduces inflammation	NHIRD study: 69% reduced HCC risk in alcohol use disorder	Chen et al., 2021 [65]

Return to article view

RCT: randomized controlled trial; SSRI: selective serotonin reuptake inhibitors; HCC: hepatocellular carcinoma.

Declarations

Author contributions

JGC: Conceptualization, Writing—original draft, Writing—review & editing. The author has read and approved the final version of the manuscript.

Conflicts of interest

Jian-Guo Chen, who is the Editorial Board Member and Guest Editor of Exploration of Digestive Diseases, had no involvement in the decision-making or the review process of this manuscript.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229–63. [DOI] [PubMed]

Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol. 2019;16:589–604. [DOI] [PubMed] [PMC]

Barouki R, Samson M, Blanc EB, Colombo M, Zucman-Rossi J, Lazaridis KN, et al. The exposome and liver disease—how environmental factors affect liver health. J Hepatol. 2023;79:492–505. [DOI] [PubMed] [PMC]

Kao YT, Liu YC, Cheng YT, Wen YW, Hsieh YC, Hsu CE, et al. Hepatocellular Carcinoma Incidences and Risk Factors in Hepatitis C Patients: Interferon versus Direct-Acting Agents. Viruses. 2024;16:1485. [DOI] [PubMed] [PMC]

Wild CP, Montesano R. A model of interaction: aflatoxins and hepatitis viruses in liver cancer aetiology and prevention. Cancer Lett. 2009;286:22–8. [DOI] [PubMed]

Colditz GA, Wolin KY, Gehlert S. Applying what we know to accelerate cancer prevention. Sci Transl Med. 2012;4:127rv4. [DOI] [PubMed] [PMC]

Lynch SM, Wiese D, Ortiz A, Sorice KA, Nguyen M, González ET, et al. Towards precision public health: Geospatial analytics and sensitivity/specificity assessments to inform liver cancer prevention. SSM Popul Health. 2020;12:100640. [DOI] [PubMed] [PMC]

Chen JG, Kensler TW, Zhu J, Zhu YR, Wang JB, Lu JH, et al. Profound primary prevention of liver cancer following a natural experiment in China: A 50-year perspective and public health implications. Int J Cancer. 2025;156:756–63. [DOI] [PubMed]

El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118–27. [DOI] [PubMed]

10.

Ringelhan M, McKeating JA, Protzer U. Viral hepatitis and liver cancer. Philos Trans R Soc Lond B Biol Sci. 2017;372:20160274. [DOI] [PubMed] [PMC]

11.

Gouas DA, Shi H, Hautefeuille AH, Ortiz-Cuaran SL, Legros PC, Szymanska KJ, et al. Effects of the TP53 p. Carcinogenesis. 2010;31:1475–82. [DOI] [PubMed]

12.

Dyson J, Jaques B, Chattopadyhay D, Lochan R, Graham J, Das D, et al. Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team. J Hepatol. 2014;60:110–7. [DOI] [PubMed]

13.

Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73–84. [DOI] [PubMed]

14.

Thomas JA, Kendall BJ, El-Serag HB, Thrift AP, Macdonald GA. Hepatocellular and extrahepatic cancer risk in people with non-alcoholic fatty liver disease. Lancet Gastroenterol Hepatol. 2024;9:159–69. [DOI] [PubMed]

15.

Qu LS, Jin F, Guo YM, Liu TT, Xue RY, Huang XW, et al. Nine susceptibility loci for hepatitis B virus-related hepatocellular carcinoma identified by a pilot two-stage genome-wide association study. Oncol Lett. 2016;11:624–32. [DOI] [PubMed] [PMC]

16.

Hassan MM, Li D, Han Y, Byun J, Hatia RI, Long E, et al. Genome-wide association study identifies high-impact susceptibility loci for HCC in North America. Hepatology. 2024;80:87–101. [DOI] [PubMed] [PMC]

17.

Attia AM, Rezaee-Zavareh MS, Hwang SY, Kim N, Adetyan H, Yalda T, et al. Novel Biomarkers for Early Detection of Hepatocellular Carcinoma. Diagnostics (Basel). 2024;14:2278. [DOI] [PubMed] [PMC]

18.

O’Rourke A. A systematic review of the effects of hepatitis B and C virus on the progression of liver fluke infection to liver cancer. Trop Dis Travel Med Vaccines. 2024;10:6. [DOI] [PubMed] [PMC]

19.

Groopman JD, Smith JW, Rivera-Andrade A, Alvarez CS, Kroker-Lobos MF, Egner PA, et al. Aflatoxin and the Etiology of Liver Cancer and Its Implications for Guatemala. World Mycotoxin J. 2021;14:305–17. [DOI] [PubMed] [PMC]

20.

Chen JG, Zhu YR, Qian GS, Wang JB, Lu JH, Kensler TW, et al. Fifty Years of Aflatoxin Research in Qidong, China: A Celebration of Team Science to Improve Public Health. Toxins (Basel). 2025;17:79. [DOI] [PubMed] [PMC]

21.

Jiang Y, Han Q, Zhao H, Zhang J. The Mechanisms of HBV-Induced Hepatocellular Carcinoma. J Hepatocell Carcinoma. 2021;8:435–50. [DOI] [PubMed] [PMC]

22.

Guo X, Jin Y, Qian G, Tu H. Sequential accumulation of the mutations in core promoter of hepatitis B virus is associated with the development of hepatocellular carcinoma in Qidong, China. J Hepatol. 2008;49:718–25. [DOI] [PubMed]

23.

Qiu S, Jin L, Yang D, Zhang D. Clinical application value of hepatitis B virus basal core promoter 1762/1764 and GGTII and GGT in patients with HBV-DNA-positive primary liver cancer. Medicine (Baltimore). 2023;102:e35699. [DOI] [PubMed] [PMC]

24.

Sun CA, Wu DM, Lin CC, Lu SN, You SL, Wang LY, et al. Incidence and cofactors of hepatitis C virus-related hepatocellular carcinoma: a prospective study of 12,008 men in Taiwan. Am J Epidemiol. 2003;157:674–82. [DOI] [PubMed]

25.

Fujino Y, Mizoue T, Tokui N, Yoshimura T. A prospective study of blood transfusion history and liver cancer in a high-endemic area of Japan. Transfus Med. 2002;12:297–302. [DOI] [PubMed]

26.

Hang D, Yang X, Lu J, Shen C, Dai J, Lu X, et al. Untargeted plasma metabolomics for risk prediction of hepatocellular carcinoma: A prospective study in two Chinese cohorts. Int J Cancer. 2022;151:2144–54. [DOI] [PubMed]

27.

Qian GS, Ross RK, Yu MC, Yuan JM, Gao YT, Henderson BE, et al. A follow-up study of urinary markers of aflatoxin exposure and liver cancer risk in Shanghai, People’s Republic of China. Cancer Epidemiol Biomarkers Prev. 1994;3:3–10. [PubMed]

28.

Zhou X, Li T, Xie H, Huang H, Yang K, Zeng X, et al. HBV-induced N6 methyladenosine modification of PARP1 enhanced AFB1-related DNA damage and synergistically contribute to HCC. Ecotoxicol Environ Saf. 2025;298:118254. [DOI] [PubMed]

29.

Lai H, Mo X, Yang Y, He K, Xiao J, Liu C, et al. Association between aflatoxin B1 occupational airway exposure and risk of hepatocellular carcinoma: a case-control study. Tumour Biol. 2014;35:9577–84. [DOI] [PubMed] [PMC]

30.

So R, Chen J, Mehta AJ, Liu S, Strak M, Wolf K, et al. Long-term exposure to air pollution and liver cancer incidence in six European cohorts. Int J Cancer. 2021;149:1887–97. [DOI] [PubMed]

31.

Thongsak N, Chitapanarux T, Chotirosniramit A, Chakrabandhu S, Traisathit P, Nakharutai N, et al. Air pollutants and primary liver cancer mortality: a cohort study in crop-burning activities and forest fires area. Front Public Health. 2024;12:1389760. [DOI] [PubMed] [PMC]

32.

Wu X, Zhang X, Yu X, Liang H, Tang S, Wang Y. Exploring the association between air pollution and the incidence of liver cancers. Ecotoxicol Environ Saf. 2025;290:117437. [DOI] [PubMed]

33.

Wang Z, Zhou Y, Xiao X, Liu A, Wang S, Preston RJS, et al. Inflammation and cardiometabolic diseases induced by persistent organic pollutants and nutritional interventions: Effects of multi-organ interactions. Environ Pollut. 2023;339:122756. [DOI] [PubMed] [PMC]

34.

Melaram R. Environmental Risk Factors Implicated in Liver Disease: A Mini-Review. Front Public Health. 2021;9:683719. [DOI] [PubMed] [PMC]

35.

McGlynn KA, Watling CZ, Hernandez BY, Groopman JD. Environmental risk factors for liver cancer. Hepatology. 2025;[Epub ahead of print]. [DOI] [PubMed]

36.

Liu YL, Patman GL, Leathart JBS, Piguet AC, Burt AD, Dufour JF, et al. Carriage of the PNPLA3 rs738409 C >G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma. J Hepatol. 2014;61:75–81. [DOI] [PubMed]

37.

Yang J, Trépo E, Nahon P, Cao Q, Moreno C, Letouzé E, et al. A 17-Beta-Hydroxysteroid Dehydrogenase 13 Variant Protects From Hepatocellular Carcinoma Development in Alcoholic Liver Disease. Hepatology. 2019;70:231–40. [DOI] [PubMed]

38.

Li D, Yuan X, Dong S, Al-Dhamin Z, Du J, Fu N, et al. Heme oxygenase-1 prevents non-alcoholic steatohepatitis through modulating mitochondrial quality control. Acta Physiol (Oxf). 2023;237:e13918. [DOI] [PubMed]

39.

Toh MR, Wong EYT, Wong SH, Ng AWT, Loo LH, Chow PKH, et al. Global Epidemiology and Genetics of Hepatocellular Carcinoma. Gastroenterology. 2023;164:766–82. [DOI] [PubMed]

40.

Campbell PT, Newton CC, Freedman ND, Koshiol J, Alavanja MC, Freeman LEB, et al. Body Mass Index, Waist Circumference, Diabetes, and Risk of Liver Cancer for U. Cancer Res. 2016;76:6076–83. [DOI] [PubMed] [PMC]

41.

Kanwal F, Kramer JR, Duan Z, Yu X, White D, El-Serag HB. Trends in the Burden of Nonalcoholic Fatty Liver Disease in a United States Cohort of Veterans. Clin Gastroenterol Hepatol. 2016;14:301–8.e1. [DOI] [PubMed] [PMC]

42.

Clifford RJ, Zhang J, Meerzaman DM, Lyu MS, Hu Y, Cultraro CM, et al. Genetic variations at loci involved in the immune response are risk factors for hepatocellular carcinoma. Hepatology. 2010;52:2034–43. [DOI] [PubMed] [PMC]

43.

Zhou GQ, He FC, Zhang HX. Susceptibility genes of hepatocellular carcinoma in Chinese population. SCIENTIA SINICA Vitae. 2011;41:785–9. [DOI]

44.

Liu Y, Pan S, Liu L, Zhai X, Liu J, Wen J, et al. A genetic variant in long non-coding RNA HULC contributes to risk of HBV-related hepatocellular carcinoma in a Chinese population. PLoS One. 2012;7:e35145. [DOI] [PubMed] [PMC]

45.

Urias E, Tedesco NR, Burkholder DA, Moran IJ, Miller MJ, Jasty VSJ, et al. PNPLA3 risk allele is associated with risk of hepatocellular carcinoma but not decompensation in compensated cirrhosis. Hepatol Commun. 2024;8:e0441. [DOI] [PubMed] [PMC]

46.

Chen JG, Zhang YH, Lu JH, Kensler TW. Liver Cancer Etiology: Old Issues and New Perspectives. Curr Oncol Rep. 2024;26:1452–68. [DOI] [PubMed]

47.

Wang J, Qiu K, Zhou S, Gan Y, Jiang K, Wang D, et al. Risk factors for hepatocellular carcinoma: an umbrella review of systematic review and meta-analysis. Ann Med. 2025;57:2455539. [DOI] [PubMed] [PMC]

48.

Huang DQ, El-Serag HB, Loomba R. Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2021;18:223–38. [DOI] [PubMed] [PMC]

49.

Argenziano ME, Kim MN, Montori M, Di Bucchianico A, Balducci D, Ahn SH, et al. Epidemiology, pathophysiology and clinical aspects of Hepatocellular Carcinoma in MAFLD patients. Hepatol Int. 2024;18:922–40. [DOI] [PubMed]

50.

Johnson PJ, Pirrie SJ, Cox TF, Berhane S, Teng M, Palmer D, et al. The detection of hepatocellular carcinoma using a prospectively developed and validated model based on serological biomarkers. Cancer Epidemiol Biomarkers Prev. 2014;23:144–53. [DOI] [PubMed]

51.

Kim SC, Kim DW, Cho EJ, Lee JY, Kim J, Kwon C, et al. A circulating cell-free DNA methylation signature for the detection of hepatocellular carcinoma. Mol Cancer. 2023;22:164. [DOI] [PubMed] [PMC]

52.

Mi K, Ye T, Zhu L, Pan CQ. Risk-stratified hepatocellular carcinoma surveillance in non-cirrhotic patients with MASLD. Gastroenterol Rep (Oxf). 2025;13:goaf018. [DOI] [PubMed] [PMC]

53.

Veronese P, Dodi I, Esposito S, Indolfi G. Prevention of vertical transmission of hepatitis B virus infection. World J Gastroenterol. 2021;27:4182–93. [DOI] [PubMed] [PMC]

54.

Viviani S, Jack A, Bah E, Montesano R. Hepatocellular carcinoma: a preventable cancer. Epidemiol Prev. 1997;21:129–36. [PubMed]

55.

Sun Z, Zhu Y, Stjernsward J, Hilleman M, Collins R, Zhen Y, et al. Design and compliance of HBV vaccination trial on newborns to prevent hepatocellular carcinoma and 5-year results of its pilot study. Cancer Detect Prev. 1991;15:313–8. [PubMed]

56.

Chen DS, Hsu HM, Bennett CL, Pajeau TS, Blumberg B, Chang PY, et al. A program for eradication of hepatitis B from Taiwan by a 10-year, four-dose vaccination program. Cancer Causes Control. 1996;7:305–11. [DOI] [PubMed]

57.

Wong GLH, Hui VWK, Yip TCF, Liang LY, Zhang X, Tse YK, et al. Universal HBV vaccination dramatically reduces the prevalence of HBV infection and incidence of hepatocellular carcinoma. Aliment Pharmacol Ther. 2022;56:869–77. [DOI] [PubMed]

58.

Ma S, Zheng Y, Xiao Y, Zhou P, Tan H. Meta-analysis of studies using metformin as a reducer for liver cancer risk in diabetic patients. Medicine (Baltimore). 2017;96:e6888. [DOI] [PubMed] [PMC]

59.

Jacobson LP, Zhang BC, Zhu YR, Wang JB, Wu Y, Zhang QN, et al. Oltipraz chemoprevention trial in Qidong, People’s Republic of China: study design and clinical outcomes. Cancer Epidemiol Biomarkers Prev. 1997;6:257–65. [PubMed]

60.

Zhang BC, Zhu YR, Wang JB, Wu Y, Zhang QN, Qian GS, et al. Oltipraz chemoprevention trial in Qidong, Jiangsu Province, People’s Republic of China. J Cell Biochem Suppl. 1997;28–29:166–73. [PubMed]

61.

Egner PA, Wang JB, Zhu YR, Zhang BC, Wu Y, Zhang QN, et al. Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer. Proc Natl Acad Sci U S A. 2001;98:14601–6. [DOI] [PubMed] [PMC]

62.

Kensler TW, Chen JG, Egner PA, Fahey JW, Jacobson LP, Stephenson KK, et al. Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a randomized clinical trial in He Zuo township, Qidong, People’s Republic of China. Cancer Epidemiol Biomarkers Prev. 2005;14:2605–13. [DOI] [PubMed]

63.

Niu C, Zhang J, Okolo PI 3rd. Liver cancer wars: plant-derived polyphenols strike back. Med Oncol. 2024;41:116. [DOI] [PubMed]

64.

Zhang W, Shu XO, Li H, Yang G, Cai H, Ji BT, et al. Vitamin intake and liver cancer risk: a report from two cohort studies in China. J Natl Cancer Inst. 2012;104:1173–81. [DOI] [PubMed] [PMC]

65.

Chen VCH, Lee MJ, Yang YH, Lu ML, Chiu WC, Dewey ME. Selective serotonin reuptake inhibitors use and hepatocellular carcinoma in patients with alcohol use disorder. Drug Alcohol Depend. 2021;219:108495. [DOI] [PubMed]

66.

Egner PA, Chen JG, Wang JB, Wu Y, Sun Y, Lu JH, et al. Bioavailability of Sulforaphane from two broccoli sprout beverages: results of a short-term, cross-over clinical trial in Qidong, China. Cancer Prev Res (Phila). 2011;4:384–95. [DOI] [PubMed] [PMC]

67.

Fahey JW, Kensler TW. The Challenges of Designing and Implementing Clinical Trials With Broccoli Sprouts… and Turning Evidence Into Public Health Action. Front Nutr. 2021;8:648788. [DOI] [PubMed] [PMC]

68.

Immunization coverage [Internet]. World Health Organization; c2023 [cited 2025 Jul 25]. Available from: https://www.who.int/news-room/fact-sheets/detail/immunization-coverage

69.

Zhu L, Kim EJ, González E, Fraser MA, Zhu S, Rubio-Torio N, et al. Reducing Liver Cancer Risk through Dietary Change: Positive Results from a Community-Based Educational Initiative in Three Racial/Ethnic Groups. Nutrients. 2022;14:4878. [DOI] [PubMed] [PMC]

70.

Inoue M, Yoshimi I, Sobue T, Tsugane S; JPHC Study Group. Influence of coffee drinking on subsequent risk of hepatocellular carcinoma: a prospective study in Japan. J Natl Cancer Inst. 2005;97:293–300. [DOI] [PubMed]

71.

Botteri E, Peveri G, Berstad P, Bagnardi V, Hoff G, Heath AK, et al. Lifestyle changes in middle age and risk of cancer: Evidence from the European Prospective Investigation into Cancer and Nutrition. Eur J Epidemiol. 2024;39:147–59. [DOI] [PubMed]

72.

Hsu WH, Sue SP, Liang HL, Tseng CW, Lin HC, Wen WL, et al. Dipeptidyl Peptidase 4 Inhibitors Decrease the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis C Infection and Type 2 Diabetes Mellitus: A Nationwide Study in Taiwan. Front Public Health. 2021;9:711723. [DOI] [PubMed] [PMC]

73.

Lee C, Mak LY, Tang EHM, Lui DTW, Mak JHC, Li L, et al. SGLT2i reduces risk of developing HCC in patients with co-existing type 2 diabetes and hepatitis B infection: A territory-wide cohort study in Hong Kong. Hepatology. 2023;78:1569–80. [DOI] [PubMed]

74.

Ross SA, Emenaker NJ, Kumar A, Riscuta G, Biswas K, Gupta S, et al. Green Cancer Prevention and Beyond. Cancer Prev Res (Phila). 2024;17:107–18. [DOI] [PubMed] [PMC]

75.

Zhang W, Xiang YB, Li HL, Yang G, Cai H, Ji BT, et al. Vegetable-based dietary pattern and liver cancer risk: results from the Shanghai women’s and men’s health studies. Cancer Sci. 2013;104:1353–61. [DOI] [PubMed] [PMC]

76.

Shimizu M, Shirakami Y, Sakai H, Kubota M, Kochi T, Ideta T, et al. Chemopreventive potential of green tea catechins in hepatocellular carcinoma. Int J Mol Sci. 2015;16:6124–39. [DOI] [PubMed] [PMC]

77.

Kasai F, Eshak ES, Tamakoshi A, Iso H; JACC Study Group. Dietary Manganese Intake and Risk of Liver Cancer in Japanese Men and Women: The JACC Study. Nutr Cancer. 2023;75:154–63. [DOI] [PubMed]

78.

Yu J, Liang D, Li J, Liu Z, Zhou F, Wang T, et al. Coffee, Green Tea Intake, and the Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis of Observational Studies. Nutr Cancer. 2023;75:1295–308. [DOI] [PubMed]

79.

Rahmani S, Asgary S, Askari G, Keshvari M, Hatamipour M, Feizi A, et al. Treatment of Non-alcoholic Fatty Liver Disease with Curcumin: A Randomized Placebo-controlled Trial. Phytother Res. 2016;30:1540–8. [DOI] [PubMed]

80.

Hung CH, Kee KM, Chen CH, Tseng PL, Tsai MC, Chen CH, et al. A Randomized Controlled Trial of Glycyrrhizin Plus Tenofovir vs. Clin Transl Gastroenterol. 2017;8:e104. [DOI] [PubMed] [PMC]

81.

Ehambarampillai D, Wan MLY. A comprehensive review of Schisandra chinensis lignans: pharmacokinetics, pharmacological mechanisms, and future prospects in disease prevention and treatment. Chin Med. 2025;20:47. [DOI] [PubMed] [PMC]

82.

Gao LL, Li YX, MaM J, Guo YQ, Li L, Gao QH, et al. Effect of Lycium barbarum polysaccharide supplementation in non-alcoholic fatty liver disease patients: study protocol for a randomized controlled trial. Trials. 2021;22:566. [DOI] [PubMed] [PMC]

83.

Zhang J, Feng Q. Pharmacological Effects and Molecular Protective Mechanisms of Astragalus Polysaccharides on Nonalcoholic Fatty Liver Disease. Front Pharmacol. 2022;13:854674. [DOI] [PubMed] [PMC]

84.

Nie Q, Li M, Huang C, Yuan Y, Liang Q, Ma X, et al. The clinical efficacy and safety of berberine in the treatment of non-alcoholic fatty liver disease: a meta-analysis and systematic review. J Transl Med. 2024;22:225. [DOI] [PubMed] [PMC]

85.

Wang H, Chen Y, Wang L, Liu Q, Yang S, Wang C. Advancing herbal medicine: enhancing product quality and safety through robust quality control practices. Front Pharmacol. 2023;14:1265178. [DOI] [PubMed] [PMC]

86.

Noviana E, Indrayanto G, Rohman A. Advances in Fingerprint Analysis for Standardization and Quality Control of Herbal Medicines. Front Pharmacol. 2022;13:853023. [DOI] [PubMed] [PMC]

87.

Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, Abdelmalek MF, Caldwell S, Barb D, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77:1797–835. [DOI] [PubMed] [PMC]

88.

European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol. 2024;81:492–542. [DOI] [PubMed]

89.

Kennedy OJ, Roderick P, Buchanan R, Fallowfield JA, Hayes PC, Parkes J. Coffee, including caffeinated and decaffeinated coffee, and the risk of hepatocellular carcinoma: a systematic review and dose-response meta-analysis. BMJ Open. 2017;7:e013739. [DOI] [PubMed] [PMC]

90.

Trisha AT, Shakil MH, Talukdar S, Rovina K, Huda N, Zzaman W. Tea Polyphenols and Their Preventive Measures against Cancer: Current Trends and Directions. Foods. 2022;11:3349. [DOI] [PubMed] [PMC]

91.

Ma J, Li J, Jin C, Yang J, Zheng C, Chen K, et al. Association of gut microbiome and primary liver cancer: A two-sample Mendelian randomization and case-control study. Liver Int. 2023;43:221–33. [DOI] [PubMed]

92.

Shinde S, Bigogno CM, Simmons A, Kathuria N, Ghose A, Apte V, et al. Precision oncology through next generation sequencing in hepatocellular carcinoma. Heliyon. 2025;11:e42054. [DOI] [PubMed] [PMC]

93.

Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med. 2015;372:793–5. [DOI] [PubMed] [PMC]

94.

Shiina S, Maikhuu J, Deng Q, Batsaikhan T, Canseco LM, Tobari M, et al. Liver disease trends in the Asia-Pacific region for the next 50 years. Clin Mol Hepatol. 2025;31:671–84. [DOI] [PubMed] [PMC]

95.

Bianco C, Jamialahmadi O, Pelusi S, Baselli G, Dongiovanni P, Zanoni I, et al. Non-invasive stratification of hepatocellular carcinoma risk in non-alcoholic fatty liver using polygenic risk scores. J Hepatol. 2021;74:775–82. [DOI] [PubMed] [PMC]

96.

Thomas CE, Diergaarde B, Kuipers AL, Adibi JJ, Luu HN, Chang X, et al. NAFLD polygenic risk score and risk of hepatocellular carcinoma in an East Asian population. Hepatol Commun. 2022;6:2310–21. [DOI] [PubMed] [PMC]

97.

Sanchez JI, Fontillas AC, Kwan SY, Sanchez CI, Calderone TL, Lee JL, et al. Metabolomics biomarkers of hepatocellular carcinoma in a prospective cohort of patients with cirrhosis. JHEP Rep. 2024;6:101119. [DOI] [PubMed] [PMC]

98.

Li ZY, Shen QM, Wang J, Tuo JY, Tan YT, Li HL, et al. Prediagnostic plasma metabolite concentrations and liver cancer risk: a population-based study of Chinese men. EBioMedicine. 2024;100:104990. [DOI] [PubMed] [PMC]

99.

John BV, Dang Y, Kaplan DE, Jou JH, Taddei TH, Spector SA, et al. Liver Stiffness Measurement and Risk Prediction of Hepatocellular Carcinoma After HCV Eradication in Veterans With Cirrhosis. Clin Gastroenterol Hepatol. 2024;22:778–88.e7. [DOI] [PubMed] [PMC]

100.

Moreno-Grau S, Vernekar M, Lopez-Pineda A, Mas-Montserrat D, Barrabés M, Quinto-Cortés CD, et al. Polygenic risk score portability for common diseases across genetically diverse populations. Hum Genomics. 2024;18:93. [DOI] [PubMed] [PMC]

101.

Martin AR, Kanai M, Kamatani Y, Okada Y, Neale BM, Daly MJ. Clinical use of current polygenic risk scores may exacerbate health disparities. Nat Genet. 2019;51:584–91. [DOI] [PubMed] [PMC]

102.

Zhang Y, Yang FJ, Jiang QR, Gao HJ, Song X, Zhu HQ, et al. Association between gut microbiota and hepatocellular carcinoma and biliary tract cancer: A mendelian randomization study. World J Clin Cases. 2024;12:3497–504. [DOI] [PubMed] [PMC]

103.

Best J, Bechmann LP, Sowa JP, Sydor S, Dechêne A, Pflanz K, et al. GALAD Score Detects Early Hepatocellular Carcinoma in an International Cohort of Patients With Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol. 2020;18:728–35.e4. [DOI] [PubMed]