REFERENCES
1. Bray F, Laversanne M, Sung H, 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.
2. Lugari S, Baldelli E, Lonardo A. Metabolic primary liver cancer in adults: risk factors and pathogenic mechanisms. Metab Target Organ Damage. 2023;3:5.
3. Wu C, Targher G, Byrne CD, et al. Global, regional, and national burden of primary liver cancer attributable to metabolic risks: an analysis of the global burden of disease study 1990-2021. Am J Gastroenterol. 2025;120:2280-90.
4. Bengtsson B, Widman L, Wahlin S, Stål P, Björkström NK, Hagström H. The risk of hepatocellular carcinoma in cirrhosis differs by etiology, age and sex: a Swedish nationwide population-based cohort study. United European Gastroenterol J. 2022;10:465-76.
5. Alarcón-Sánchez BR, Pérez-Carreón JI, Villa-Treviño S, Arellanes-Robledo J. Molecular alterations that precede the establishment of the hallmarks of cancer: an approach on the prevention of hepatocarcinogenesis. Biochem Pharmacol. 2021;194:114818.
6. Zhou J, Wang W, Li Q. Potential therapeutic targets in the tumor microenvironment of hepatocellular carcinoma: reversing the protumor effect of tumor-associated macrophages. J Exp Clin Cancer Res. 2021;40:73.
7. National Cancer Institute. Definition of chemoprevention - NCI dictionary of cancer terms - NCI. Available from: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/chemoprevention. [Last accessed on 5 Aug 2026].
8. Singh S, Singh PP, Roberts LR, Sanchez W. Chemopreventive strategies in hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2014;11:45-54.
9. Athuluri-Divakar SK, Hoshida Y. Generic chemoprevention of hepatocellular carcinoma. Ann N Y Acad Sci. 2019;1440:23-35.
10. Schwenk S, Kaplan DE. Chemoprevention of hepatocellular carcinoma. Hepatol Commun. 2025;9:e0836.
11. Hepatitis B Foundation. Prevention hepatitis B foundation. Available from: https://www.hepb.org/research-and-programs/liver/prevention-of-liver-cancer/. [Last accessed on 7 Aug 2026].
12. Chang MH. Impact of hepatitis B vaccination on hepatitis B disease and nucleic acid testing in high-prevalence populations. J Clin Virol. 2006;36:S45-50.
13. Alqahtani SA, Colombo M. Treatment for viral hepatitis as secondary prevention for hepatocellular carcinoma. Cells. 2021;10:3091.
14. Ali B, Samuel R, Kramer JR, et al. Evolving burden of metabolic dysfunction-associated steatotic liver disease and its complications in a US nationwide healthcare system. Hepatol Commun. 2026;10:e0878.
15. Ding Z, Wang L, Sun J, Zheng L, Tang Y, Tang H. Hepatocellular carcinoma: pathogenesis, molecular mechanisms, and treatment advances. Front Oncol. 2025;15:1526206.
16. Chen H, Huang M, Zhang D, et al. Metformin’s effect on metabolic dysfunction-associated steatotic liver disease through the miR-200a-5p and AMPK/SERCA2b pathway. Front Pharmacol. 2024;15:1477212.
17. Tsai PC, Kuo HT, Hung CH, et al. ; T-COACH Study Group. Metformin reduces hepatocellular carcinoma incidence after successful antiviral therapy in patients with diabetes and chronic hepatitis C in Taiwan. J Hepatol. 2023;78:281-92.
18. Lee TY, Hsu YC, Tseng HC, et al. Association of daily aspirin therapy with risk of hepatocellular carcinoma in patients with chronic hepatitis B. JAMA Intern Med. 2019;179:633-40.
19. Simon TG, Duberg AS, Aleman S, Chung RT, Chan AT, Ludvigsson JF. Association of aspirin with hepatocellular carcinoma and liver-related mortality. N Engl J Med. 2020;382:1018-28.
20. Abdelmalak J, Tan N, Con D, et al. The effect of aspirin use on incident hepatocellular carcinoma-an updated systematic review and meta-analysis. Cancers. 2023;15:3518.
21. Goh MJ, Sinn DH. Statin and aspirin for chemoprevention of hepatocellular carcinoma: time to use or wait further? Clin Mol Hepatol. 2022;28:380-95.
22. Wang J, Qiu K, Zhou S, et al. Risk factors for hepatocellular carcinoma: an umbrella review of systematic review and meta-analysis. Ann Med. 2025;57:2455539.
23. Zeng RW, Yong JN, Tan DJH, et al. Meta-analysis: chemoprevention of hepatocellular carcinoma with statins, aspirin and metformin. Aliment Pharmacol Ther. 2023;57:600-9.
24. Zisis M, Chondrogianni ME, Androutsakos T, et al. Linking cardiovascular disease and metabolic dysfunction-associated steatotic liver disease (MASLD): the role of cardiometabolic drugs in MASLD treatment. Biomolecules. 2025;15:324.
25. Kaplan DE, Ripoll C, Thiele M, et al. AASLD Practice Guidance on risk stratification and management of portal hypertension and varices in cirrhosis. Hepatology. 2024;79:1180-211.
26. Gao SX, Décarie-Spain L, Gu C, Mazzini G, Kanoski SE, Borner T. GLP-1 at the metabolic-cognitive interface: reward, affect, and memory. Compr Physiol. 2026;16:e70129.
27. Weiskirchen R, Lonardo A. How ‘miracle’ weight-loss semaglutide promises to change medicine but can we afford the expense? Br J Pharmacol. 2025;182:1651-70.
28. Pirola CJ, Sookoian S. Semaglutide in MASH with F2-F3 fibrosis: a holistic perspective on the ESSENCE phase 3 trial. Metab Target Organ Damage. 2026;6:17.
29. Dalbeni A, Vicardi M, Natola LA, et al. Glucagon-like peptide-1 receptor agonists and hepatocellular carcinoma prevention: a meta-analysis and clinical decision framework. Cancer Med. 2025;14:e71434.
30. Hansen HH, Pors S, Andersen MW, et al. Semaglutide reduces tumor burden in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH-HCC with advanced fibrosis. Sci Rep. 2023;13:23056.
31. Francque SM, Bedossa P, Ratziu V, et al. ; NATIVE Study Group. A randomized, controlled trial of the Pan-PPAR agonist lanifibranor in NASH. N Engl J Med. 2021;385:1547-58.
32. Harrison SA, Bedossa P, Guy CD, et al. ; MAESTRO-NASH Investigators. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. N Engl J Med. 2024;390:497-509.
33. Petta S, Targher G, Romeo S, et al. The first MASH drug therapy on the horizon: Current perspectives of resmetirom. Liver Int. 2024;44:1526-36.
34. Tsai PC, Huang CF, Yeh ML, et al. ; T-COACH Study Group. Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy. Clin Mol Hepatol. 2024;30:468-86.
35. Dickinson A, Dinani A, Wegermann K. Chemoprevention of hepatocellular carcinoma associated with metabolic dysfunction-associated steatotic liver disease: an updated review. Hepatoma Res. 2024;10:37.
36. Islam MM, Poly TN, Walther BA, Yang HC, Jack Li YC. Statin use and the risk of hepatocellular carcinoma: a meta-analysis of observational studies. Cancers. 2020;12:671.
37. Chang Y, Liu Q, Zhou Z, et al. Can statin treatment reduce the risk of hepatocellular carcinoma? A systematic review and meta-analysis. Technol Cancer Res Treat. 2020;19:1533033820934881.
38. Wang Y, Wang W, Wang M, Shi J, Jia X, Dang S. A meta-analysis of statin use and risk of hepatocellular carcinoma. Can J Gastroenterol Hepatol. 2022;2022:5389044.
39. Singh S, Singh PP, Singh AG, Murad MH, Sanchez W. Statins are associated with a reduced risk of hepatocellular cancer: a systematic review and meta-analysis. Gastroenterology. 2013;144:323-32.
40. Li Z, Li Y, Li X, et al. Statins in hepatitis B or C patients is associated with reduced hepatocellular carcinoma risk: a systematic review and meta-analysis. Turk J Gastroenterol. 2022;33:136-44.
41. Choi J, Nguyen VH, Przybyszewski E, et al. Statin use and risk of hepatocellular carcinoma and liver fibrosis in chronic liver disease. JAMA Intern Med. 2025;185:522-30.
42. Facciorusso A, Abd El Aziz MA, Singh S, et al. Statin use decreases the incidence of hepatocellular carcinoma: an updated meta-analysis. Cancers. 2020;12:874.
43. Zou B, Odden MC, Nguyen MH. Statin use and reduced hepatocellular carcinoma risk in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2023;21:435-44.e6.
44. Tarar ZI, Farooq U, Inayat F, et al. Statins decrease the risk of hepatocellular carcinoma in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis. World J Exp Med. 2024;14:98543.
45. Kim SG, Kang JH, Park SJ, et al. Statin use and risk of hepatocellular carcinoma in metabolic dysfunction-associated steatotic liver disease: a national retrospective cohort study. Cancer Prev Res. 2026;19:303-12.
46. Simon TG, Wilechansky RM, Stoyanova S, et al. Aspirin for metabolic dysfunction-associated steatotic liver disease without cirrhosis: a randomized clinical trial. JAMA. 2024;331:920-9.
47. Memel ZN, Arvind A, Moninuola O, et al. Aspirin use is associated with a reduced incidence of hepatocellular carcinoma: a systematic review and meta-analysis. Hepatol Commun. 2021;5:133-43.
48. Kim MN, Park GU, You SC, et al. Aspirin use and risk of HCC and gastrointestinal bleeding in patients with HBV-related cirrhosis: a landmark analysis. J Gastroenterol Hepatol. 2025;40:2750-7.
49. Chen WM, Ng HJ, Jao AT, Wu SY, Soong RS. GLP-1 receptor agonists and risk of hepatocellular carcinoma and all-cause mortality in patients with MASLD and type 2 diabetes: a propensity score-matched population-based cohort study. Diabetes Res Clin Pract. 2025;227:112407.
50. Sanyal AJ, Newsome PN, Kliers I, et al. ; ESSENCE Study Group. Phase 3 trial of semaglutide in metabolic dysfunction-associated steatohepatitis. N Engl J Med. 2025;392:2089-99.
51. Tungekar B, Echevarria Cruz EC, Dodrill J, et al. Impact of glucagon-like peptide-1 agonists on hepatocellular carcinoma risk and management in type 2 diabetes mellitus: a scoping review. Cureus. 2025;17:e100252.
52. Issachar A, Razi T, Borochov I, Duskin Bitan H, Arbel R. Association of semaglutide treatment with liver cirrhosis and hepatocellular carcinoma in type 2 diabetes: a population-based cohort study. Diabetes Obes Metab. 2026;28:5704-14.
53. Kan R, Wang S, Meng X, Guo Y, Li D, Yu X. The impact of semaglutide on liver outcomes in patients with or at risk of MASH: a dose and duration response meta-analysis of randomized trials. Diabetol Metab Syndr. 2025;17:439.
54. Zhu Y, Cai B. Mechanisms and therapeutic insights into MASH-associated fibrosis. Trends Endocrinol Metab. 2026;37:402-17.
55. Zhang VX, Suoangbaji T, Tsui YM, et al. Repurposing Resmetirom suppresses MASH-associated hepatocellular carcinoma, with mechanistic implications of MDK/LRP1-mediated metabolic reprogramming and immunosuppression. Hepatology. 2026;Epub ahead of print.
56. Lonardo A, Zheng MH, Weiskirchen R. Repurposing Resmetirom to suppress MASLD/MASH-HCC in the dysmetabolic era. Oncol Ther. 2026;14:437-48.
57. Barone M, Viggiani MT, Losurdo G, Principi M, Leo AD. Systematic review: renin-angiotensin system inhibitors in chemoprevention of hepatocellular carcinoma. World J Gastroenterol. 2019;25:2524-38.
58. Crouchet E, Bandiera S, Fujiwara N, et al. A human liver cell-based system modeling a clinical prognostic liver signature for therapeutic discovery. Nat Commun. 2021;12:5525.
59. Crouchet E, Li S, Sojoodi M, et al. Hepatocellular carcinoma chemoprevention by targeting the angiotensin-converting enzyme and EGFR transactivation. JCI Insight. 2022;7:e159254.
60. Noureddin M, Abdelmalek MF. ACE inhibitors: the secret to prevent cirrhosis complications and HCC in NAFLD? Hepatology. 2022;76:295-7.
61. Zhang X, Wong GL, Yip TC, et al. Angiotensin-converting enzyme inhibitors prevent liver-related events in nonalcoholic fatty liver disease. Hepatology. 2022;76:469-82.
62. Noh SW, Ryu HS, Kim YH, Oh BC. SGLT2 inhibitors as systemic metabolic modulators: linking glucose excretion to liver function restoration. Endocrinol Metab. 2025;40:851-65.
63. Bea S, Ko HY, Bae JH, et al. Risk of hepatic events associated with use of sodium-glucose cotransporter-2 inhibitors versus glucagon-like peptide-1 receptor agonists, and thiazolidinediones among patients with metabolic dysfunction-associated steatotic liver disease. Gut. 2025;74:284-94.
64. Slović N, Mishra S, Paul S, et al. Chemoprevention of hepatocellular carcinoma by next-generation antipsychotic aripiprazole. Hepatology. 2026;Epub ahead of print.
65. Toniutto P, Shalaby S, Mameli L, et al. ; Special Interest Group Gender in Hepatology of the Italian Association for the Study of the Liver (AISF). Role of sex in liver tumor occurrence and clinical outcomes: a comprehensive review. Hepatology. 2024;79:1141-57.
66. Yu MW, Chang HC, Chang SC, et al. Role of reproductive factors in hepatocellular carcinoma: impact on hepatitis B- and C-related risk. Hepatology. 2003;38:1393-400.
67. Wang CH, Lin RC, Hsu HY, Tseng YT. Hormone replacement therapy is associated with reduced hepatocellular carcinoma risk and improved survival in postmenopausal women with hepatitis B: a nationwide long-term population-based cohort study. PLoS One. 2022;17:e0271790.
68. Grossman DC, Curry SJ, Owens DK, et al. ; US Preventive Services Task Force. Hormone therapy for the primary prevention of chronic conditions in postmenopausal women: US preventive services task force recommendation statement. JAMA. 2017;318:2224-33.
69. Singal AG, Llovet JM, Yarchoan M, et al. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023;78:1922-65.
70. Wang L, Berger NA, Kaelber DC, Xu R. Association of GLP-1 receptor agonists and hepatocellular carcinoma incidence and hepatic decompensation in patients with type 2 diabetes. Gastroenterology. 2024;167:689-703.
71. Shimizu M, Shirakami Y, Hanai T, et al. Pharmaceutical and nutraceutical approaches for preventing liver carcinogenesis: chemoprevention of hepatocellular carcinoma using acyclic retinoid and branched-chain amino acids. Mol Nutr Food Res. 2014;58:124-35.
72. Sakai H, Shirakami Y, Shimizu M. Chemoprevention of obesity-related liver carcinogenesis by using pharmaceutical and nutraceutical agents. World J Gastroenterol. 2016;22:394-406.
73. Maggiore G, Hsieh MH, Bellary A, et al. Chemoprevention of hepatocellular carcinoma using N-acetylgalactosamine-conjugated siRNAs. Dis Model Mech. 2025;18:dmm052370.
74. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol. 2025;82:315-74.
75. Ma Y, Wang J, Xiao W, Fan X. A review of MASLD-related hepatocellular carcinoma: progress in pathogenesis, early detection, and therapeutic interventions. Front Med. 2024;11:1410668.
76. Fujiwara N, Friedman SL, Goossens N, Hoshida Y. Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine. J Hepatol. 2018;68:526-49.
77. Marrero JA, Kulik LM, Sirlin CB, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68:723-50.
78. Della Corte C, Aghemo A, Colombo M. Individualized hepatocellular carcinoma risk: the challenges for designing successful chemoprevention strategies. World J Gastroenterol. 2013;19:1359-71.
