Global trends in metabolic-associated hepatocellular carcinoma: genetic and socio-demographic drivers

Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023;77(4):1335–1347

Article  PubMed  PubMed Central  Google Scholar 

Miao L, Targher G, Byrne CD, Cao Y-Y, Zheng M-H. Current status and future trends of the global burden of MASLD. Trends Endocrinol Metab. 2024;35(8):697–707

Article  CAS  PubMed  Google Scholar 

Mak L-Y, Liu K, Chirapongsathorn S, Yew KC, Tamaki N, Rajaram RB, et al. Liver diseases and hepatocellular carcinoma in the Asia-Pacific region: burden, trends, challenges and future directions. Nat Rev Gastroenterol Hepatol. 2024;21(12):834–851

Article  PubMed  Google Scholar 

Rumgay H, Arnold M, Ferlay J, Lesi O, Cabasag CJ, Vignat J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol. 2022;77(6):1598–1606

Article  PubMed  PubMed Central  Google Scholar 

Sagnelli E, Macera M, Russo A, Coppola N, Sagnelli C. Epidemiological and etiological variations in hepatocellular carcinoma. Infection. 2020;48(1):7–17

Article  CAS  PubMed  Google Scholar 

Wang X, Zhang L, Dong B. Molecular mechanisms in MASLD/MASH-related HCC. Hepatology. 2025;82(5):1303–1324

Article  PubMed  Google Scholar 

Fu S, Groothuismink ZM, Balderramo D, Mattos AZ, Hoppe L, Carrera E, et al. Genetic risk score correlates with immune profile and risk of HCC and cirrhosis development in Hispanics with MASLD. JHEP Reports. 2025;7(10): 101508

Article  PubMed  PubMed Central  Google Scholar 

Murray CJ, Aravkin AY, Zheng P, Abbafati C, Abbas KM, Abbasi-Kangevari M, et al. Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1223–1249

Article  Google Scholar 

Toh MR, Wong EYT, Wong SH, Ng AWT, Loo LH, Chow PK, et al. Global epidemiology and genetics of hepatocellular carcinoma. Gastroenterology. 2023;164(5):766–782

Article  PubMed  Google Scholar 

Lazarus JV, Newsome PN, Francque SM, Kanwal F, Terrault NA, Rinella ME. Reply: A multi-society Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2024;79(3):E93–E94

Article  PubMed  Google Scholar 

Song SJ, Lai JC, Wong GL, Wong VW, Yip TC. Can we use old NAFLD data under the new MASLD definition? J Hepatol. 2024;80(2):e54–e56

Article  PubMed  Google Scholar 

Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40(12):1461–1465

Article  CAS  PubMed  PubMed Central  Google Scholar 

Letouzé E, Shinde J, Renault V, Couchy G, Blanc J-F, Tubacher E, et al. Mutational signatures reveal the dynamic interplay of risk factors and cellular processes during liver tumorigenesis. Nat Commun. 2017;8(1): 1315

Article  PubMed  PubMed Central  Google Scholar 

Vilar-Gomez E, Gawrieh S, Vuppalanchi R, Kettler C, Pike F, Samala N, et al. PNPLA3 rs738409, environmental factors and liver-related mortality in the US population. J Hepatol. 2025;82(4):571–581

Article  CAS  PubMed  Google Scholar 

Choi S, Kim BK, Yon DK, Lee SW, Lee HG, Chang HH, et al. Global burden of primary liver cancer and its association with underlying aetiologies, sociodemographic status, and sex differences from 1990–2019: a DALY-based analysis of the Global Burden of Disease 2019 study. Clin Mol Hepatol. 2023;29(2): 433

Article  PubMed  PubMed Central  Google Scholar 

Collaborators GBDCoD. Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403(10440):2100–2132

Article  Google Scholar 

Wu P, Wang Y, Cohen JC, Hobbs HH. Tissue-specific regulation of PNPLA3 promotes lipid remodeling in response to dietary and environmental challenges: tissue-specific PNPLA3 lipid remodeling. J Hepatol (2026)

Gellert‐Kristensen H, Nordestgaard BG, Tybjærg‐Hansen A, Stender S. High risk of fatty liver disease amplifies the alanine transaminase–lowering effect of a HSD17B13 variant. Hepatology. 2020;71(1):56–66

Article  PubMed  Google Scholar 

Wu N, Li J, Zhang J, Yuan F, Yu N, Zhang F, et al. Waist circumference mediates the association between rs1260326 in GCKR gene and the odds of lean NAFLD. Sci Rep. 2023;13(1):6488

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ma Y, Zuo S, Lo T, Phan D, Finley T, Mackay A, et al. Genetic variations in GCKR and PNPLA3 regulate metabolic balance across the liver. Diabetes. 2025;74(7):1300–1309

Article  CAS  PubMed  PubMed Central  Google Scholar 

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. https://doi.org/10.3350/cmh.2025.0043

Article  PubMed  PubMed Central  Google Scholar 

Ding J, Wang H. Multiple interactive factors in hepatocarcinogenesis. Cancer Lett. 2014;346(1):17–23

Article  CAS  PubMed  Google Scholar 

Yang F, Hilakivi-Clarke L, Shaha A, Wang Y, Wang X, Deng Y, et al. Metabolic reprogramming and its clinical implication for liver cancer. Hepatology. 2023;78(5):1602–1624

PubMed  PubMed Central  Google Scholar 

Yu J, Shen J, Sun TT, Zhang X, Wong N. Obesity, insulin resistance, NASH and hepatocellular carcinoma. Paper presented at: Seminars in cancer biology (2013)

Meex RC, Watt MJ. Hepatokines: linking nonalcoholic fatty liver disease and insulin resistance. Nat Rev Endocrinol. 2017;13(9):509–520

Article  CAS  PubMed  Google Scholar 

Huang DQ, Zhang Z, Dorajoo R, Khor CC, Pham YTH, Wang R, et al. PNPLA3 genotype and clinical factors impact hepatocellular carcinoma risk: findings from a prospective cohort study. Aliment Pharmacol Ther. 2026. https://doi.org/10.1111/apt.70532

Article  PubMed  Google Scholar 

Larter CZ, Yeh MM, Haigh WG, Van Rooyen DM, Brooling J, Heydet D, et al. Dietary modification dampens liver inflammation and fibrosis in obesity‐related fatty liver disease. Obesity Silver Spring. 2013;21(6):1189–1199

Article  CAS  PubMed  Google Scholar 

Lisa M, Jonathan M, Miranda L, Bhangdia K, Crist A, Penberthy L, et al. The Global, Regional and National burden of cancer, 1990–2023, with forecasts to 2050: a systematic analysis fort the global burden of disease study. THE LANCET. 2023;2025:1–22

Google Scholar 

Zhou M, Shen H. Forecasting the global burden of disease to 2050. Lancet. 2024;403(10440):1961–1963

Article  PubMed  Google Scholar 

Huang J, Lok V, Ngai CH, Chu C, Patel HK, Thoguluva Chandraseka V, et al. Disease burden, risk factors, and recent trends of liver cancer: a global country-level analysis. Liver Cancer. 2021;10(4):330–345

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mohamad B, Shah V, Onyshchenko M, Elshamy M, Aucejo F, Lopez R, et al. Characterization of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) patients without cirrhosis. Hep Intl. 2016;10(4):632–639

Article  Google Scholar 

Ertle J, Dechêne A, Sowa JP, Penndorf V, Herzer K, Kaiser G, et al. Non‐alcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis. Int J Cancer. 2011;128(10):2436–2443

Article  CAS  PubMed  Google Scholar 

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(4):775–782

Article  CAS  PubMed  Google Scholar 

Golabi P, Paik JM, AlQahtani S, Younossi Y, Tuncer G, Younossi ZM. Burden of non-alcoholic fatty liver disease in Asia, the Middle East and North Africa: data from Global Burden of Disease 2009-2019. J Hepatol. 2021;75(4):795–809

Article  CAS 

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