MASLD-Related HCC: Trends, Pathogenesis and Current Treatment Options
DOI:
https://doi.org/10.18063/apm.v10i2.896Keywords:
Hepatocellular carcinoma, Metabolic-dysfunction associated steatotic liver disease, etabolic dysfunctionassociated steatohepatitis, Metabolic syndrome, BiomarkersAbstract
Hepatocellular carcinoma (HCC) is a late-stage complication in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Recent epidemiological studies indicate that as the global burden of HCC continues to rise alarmingly, the proportion of MASLD-related HCC cases both in cirrhotic and non-cirrhotic populations has been steadily increasing. This review aims to provide an update on the HCC burden in individuals with MASLD, exploring its association with insulin resistance, metabolic inflammation, and gut-derived liver injury. Finally, we will outline risk-based HCC surveillance strategies and discuss the potential impact of novel targeted therapies for metabolic dysfunction-associated steatohepatitis (MASH) related fibrosis on HCC incidence.
References
Rumgay H, Arnold M, Ferlay J, et al., 2022, Global Burden of Primary Liver Cancer in 2020 and Predictions to 2040. J Hepatol, 77(6): 1598–1606.
Yang J, Benyam D, Kristin C, et al., 2020, GALAD Score for Hepatocellular Carcinoma Detection in Comparison with Liver Ultrasound and Proposal of GALADUS Score. Cancer, Epidemiology, Biomarkets & Prevention, 28(3): 531–538.
Tracey G, Rajani S, Hannes H, et al., 2021, Cancer Risk in Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study, 1–30.
Stine J, Wentworth B, Zimmet A, et al., 2018, Systematic Review with Meta-analysis: Risk of Hepatocellular Carcinoma in Non-Alcoholic Steatohepatitis Without Cirrhosis Compared to Other Liver Diseases. Aliment Pharmacol Ther, 48(7): 696–703.
Younossi Z, Stepanova M, Shabeeb R, et al., 2024, The Changing Epidemiology of Adult Liver Transplantation in the United States in 2013–2022: The Dominance of Metabolic Dysfunction-Associated Steatotic Liver Disease and Alcohol-Associated Liver Disease. Hepatol Commun, 8(1): e0352.
Haldar D, Kern B, Hodson J, et al., 2019, Outcomes of Liver Transplantation for Non-Alcoholic Steatohepatitis: A European Liver Transplant Registry Study. J Hepatol, 71(2): 313–322.
Xi L, Xi H, Xi Z, et al., 2024, Hepatocellular Carcinoma: Signaling Pathways, Targeted Therapy, and Immunotherapy. MedComm, 5(2): 474.
Fang D, Shi D, Lv L, et al., 2017, Bifidobacterium pseudocatenulatum LI09 and Bifidobacterium catenulatum LI10 Attenuate D-Galactosamine-Induced Liver Injury by Modifying the Gut Microbiota. Sci Rep, 7(1): 8770.
Wu W, Lv L, Shi D, et al., 2017, Protective Effect of Akkermansia muciniphila Against Immune-Mediated Liver Injury in a Mouse Model. Front Microbiol, 8: 1804.
Yang F, Huang X, Yi T, et al., 2007, Spontaneous Development of Liver Tumors in the Absence of the Bile Acid Receptor Farnesoid X Receptor. Cancer Res, 67(3): 863–867.
Liu Y, Patman G, Leathart J, et al., 2014, Carriage of the PNPLA3 rs738409 C >G Polymorphism Confers an Increased Risk of Non-Alcoholic Fatty Liver Disease Associated Hepatocellular Carcinoma. J Hepatol, 61(1): 75–81.
Liu Y, Reeves H, Burt A, et al., 2014, TM6SF2 rs58542926 Influences Hepatic Fibrosis Progression in Patients With Non-Alcoholic Fatty Liver Disease. Nat Commun, 5: 4309.
Tzartzeva K, Obi J, Rich N, et al., 2018, Surveillance Imaging and Alpha Fetoprotein for Early Detection of Hepatocellular Carcinoma in Patients With Cirrhosis: A Meta-analysis. Gastroenterology, 154(6): 1706–1718.e1.
Armandi A, Caviglia G, Abdulle A, et al., 2023, Prognostic Value of Simple Non-Invasive Tests for the Risk Stratification of Incident Hepatocellular Carcinoma in Cirrhotic Individuals With Non-Alcoholic Fatty Liver Disease. Cancers (Basel), 15(6): 1659.
Petta S, Sebastiani G, Viganò M, et al., 2021, Monitoring Occurrence of Liver-Related Events and Survival by Transient Elastography in Patients With Nonalcoholic Fatty Liver Disease and Compensated Advanced Chronic Liver Disease. Clin Gastroenterol Hepatol, 19(4): 806–815.e5.
Yang J, Addissie B, Mara K, et al., 2019, GALAD Score for Hepatocellular Carcinoma Detection in Comparison with Liver Ultrasound and Proposal of GALADUS Score. Cancer Epidemiol Biomarkers Prev, 28(3): 531–538.
Dang D, Park B, 2022, Circulating Tumor DNA: Current Challenges for Clinical Utility. J Clin Invest, 132(12): e154941.
Koutoukidis D, Koshiaris C, Henry J, et al., 2021, The Effect of the Magnitude of Weight Loss on Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis. Metabolism, 115: 154455.
Wang L, Berger N, Kaelber D, et al., 2024, Association of GLP-1 Receptor Agonists and Hepatocellular Carcinoma Incidence and Hepatic Decompensation in Patients With Type 2 Diabetes. Gastroenterology, 167(4): 689–703.
Harrison S, Bedossa P, Guy C, et al., 2024, A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH With Liver Fibrosis. N Engl J Med, 390(6): 497–509.
Francque S, Bedossa P, Ratziu V, et al., 2021, A Randomized, Controlled Trial of the Pan-PPAR Agonist Lanifibranor in NASH. N Engl J Med, 385(17): 1547–1558.
