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REVIEW

Pathogenesis of NAFLD-Related Hepatocellular Carcinoma: An Up-to-Date Review

ORCID Icon, , &
Pages 347-356 | Received 04 Dec 2022, Accepted 11 Feb 2023, Published online: 01 Mar 2023

References

  • Golabi P, Rhea L, Henry L, Younossi ZM. Hepatocellular carcinoma and non-alcoholic fatty liver disease. Hepatol Int. 2019;13(6):688–694. doi:10.1007/s12072-019-09995-8
  • Sung H, Ferlay J. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–249. doi:10.3322/caac.21660
  • Ioannou GN. Epidemiology and risk-stratification of NAFLD-associated HCC. J Hepatol. 2021;75(6):1476–1484. doi:10.1016/j.jhep.2021.08.012
  • Ramai D, Facciorusso A, Vigandt E, et al. Progressive Liver Fibrosis in Non-Alcoholic Fatty Liver Disease. Cells. 2021;10(12):3401. doi:10.3390/cells10123401
  • Bertot LC, Adams LA. Trends in hepatocellular carcinoma due to non-alcoholic fatty liver disease. Expert Rev Gastroenterol Hepatol. 2019;13(2):179–187. doi:10.1080/17474124.2019.1549989
  • Alexander M, Loomis AK, van der Lei J, et al. Risks and clinical predictors of cirrhosis and hepatocellular carcinoma diagnoses in adults with diagnosed NAFLD: real-world study of 18 million patients in four European cohorts. BMC Med. 2019;17(1):95. doi:10.1186/s12916-019-1321-x
  • van der Poorten D, Milner KL, Hui J, et al. Visceral fat: a key mediator of steatohepatitis in metabolic liver disease. Hepatology. 2008;48(2):449–457. doi:10.1002/hep.22350
  • Kanwal F, Kramer JR, Mapakshi S, et al. Risk of Hepatocellular Cancer in Patients With Non-Alcoholic Fatty Liver Disease. Gastroenterology. 2018;155(6):1828–1837.e2. doi:10.1053/j.gastro.2018.08.024
  • Vilar-Gomez E, Calzadilla-Bertot L, Wai-Sun Wong V, et al. Fibrosis Severity as a Determinant of Cause-Specific Mortality in Patients With Advanced Nonalcoholic Fatty Liver Disease: a Multi-National Cohort Study. Gastroenterology. 2018;155(2):443–457.e17. doi:10.1053/j.gastro.2018.04.034
  • Lebovitz HE. Insulin resistance: definition and consequences. Exp Clin Endocrinol Diabetes. 2001;109(Suppl 2):S135–148. doi:10.1055/s-2001-18576
  • Yu J, Shen J, Sun TT, Zhang X, Wong N. Obesity, insulin resistance, NASH and hepatocellular carcinoma. Semin Cancer Biol. 2013;23(6Pt B):483–491. doi:10.1016/j.semcancer.2013.07.003
  • Bae SDW, George J, Qiao L. From MAFLD to hepatocellular carcinoma and everything in between. Chin Med J. 2022;135(5):547–556. doi:10.1097/CM9.0000000000002089
  • Zoller H, Tilg H. Nonalcoholic fatty liver disease and hepatocellular carcinoma. Metabolism. 2016;65(8):1151–1160. doi:10.1016/j.metabol.2016.01.010
  • Samuel VT, Shulman GI. Mechanisms for insulin resistance: common threads and missing links. Cell. 2012;148(5):852–871. doi:10.1016/j.cell.2012.02.017
  • Arturi F, Succurro E, Procopio C, et al. Nonalcoholic fatty liver disease is associated with low circulating levels of insulin-like growth factor-I. J Clin Endocrinol Metab. 2011;96(10):E1640–1644. doi:10.1210/jc.2011-1227
  • Ohtani N, Hara E. Gut‐liver axis‐mediated mechanism of liver cancer: a special focus on the role of gut microbiota. Cancer Sci. 2021;112(11):4433–4443. doi:10.1111/cas.15142
  • Chrysavgis L, Giannakodimos I, Diamantopoulou P, Cholongitas E. Non-alcoholic fatty liver disease and hepatocellular carcinoma: clinical challenges of an intriguing link. World J Gastroenterol. 2022;28(3):310–331. doi:10.3748/wjg.v28.i3.310
  • Zhang Y, Su SS, Zhao S, et al. RIP1 autophosphorylation is promoted by mitochondrial ROS and is essential for RIP3 recruitment into necrosome. Nat Commun. 2017;8(1):14329. doi:10.1038/ncomms14329
  • Ma C, Kesarwala AH, Eggert T, et al. NAFLD causes selective CD4(+) T lymphocyte loss and promotes hepatocarcinogenesis. Nature. 2016;531(7593):253–257. doi:10.1038/nature16969
  • Grgurevic I, Bozin T, Mikus M, Kukla M, O’Beirne J. Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease: from Epidemiology to Diagnostic Approach. Cancers. 2021;13(22):5844. doi:10.3390/cancers13225844
  • 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(4):223–238. doi:10.1038/s41575-020-00381-6
  • Caricilli AM, Saad MJA. The role of gut microbiota on insulin resistance. Nutrients. 2013;5(3):829–851. doi:10.3390/nu5030829
  • Rajesh Y, Sarkar D. Association of Adipose Tissue and Adipokines with Development of Obesity-Induced Liver Cancer. Int J Mol Sci. 2021;22(4):2163. doi:10.3390/ijms22042163
  • Sun Q, Jiang N, Sun R. Leptin signaling molecular actions and drug target in hepatocellular carcinoma. DDDT. 2014;14(8):2295–2302. doi:10.2147/DDDT.S69004
  • Anstee QM, Reeves HL, Kotsiliti E, Govaere O, Heikenwalder M. From NASH to HCC: current concepts and future challenges. Nat Rev Gastroenterol Hepatol. 2019;16(7):411–428. doi:10.1038/s41575-019-0145-7
  • Zhou A, Tang L, Zeng S, Lei Y, Yang S, Tang B. Gut microbiota: a new piece in understanding hepatocarcinogenesis. Cancer Lett. 2020;474:15–22. doi:10.1016/j.canlet.2020.01.002
  • Tripathi A, Debelius J, Brenner DA, et al. The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol. 2018;15(7):397–411. doi:10.1038/s41575-018-0011-z
  • Baffy G. Potential mechanisms linking gut microbiota and portal hypertension. Liver Int. 2019;39(4):598–609. doi:10.1111/liv.13986
  • Behary J, Amorim N, Jiang XT, et al. Gut microbiota impact on the peripheral immune response in non-alcoholic fatty liver disease related hepatocellular carcinoma. Nat Commun. 2021;12(1):187. doi:10.1038/s41467-020-20422-7
  • Oh TG, Kim SM, Caussy C, et al. A Universal Gut-Microbiome-Derived Signature Predicts Cirrhosis. Cell Metab. 2020;32(5):878–888.e6. doi:10.1016/j.cmet.2020.06.005
  • Chu H, Williams B, Schnabl B. Gut microbiota, fatty liver disease, and hepatocellular carcinoma. Liver Res. 2018;2(1):43–51. doi:10.1016/j.livres.2017.11.005
  • Ma K, Saha PK, Chan L, Moore DD. Farnesoid X receptor is essential for normal glucose homeostasis. J Clin Invest. 2006;116(4):1102–1109. doi:10.1172/JCI25604
  • Mouzaki M, Loomba R. Insights into the evolving role of the gut microbiome in nonalcoholic fatty liver disease: rationale and prospects for therapeutic intervention. Therap Adv Gastroenterol. 2019;12:1756284819858470. doi:10.1177/1756284819858470
  • Zhu L, Baker SS, Gill C, et al. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology. 2013;57(2):601–609. doi:10.1002/hep.26093
  • Rabinowitz JD, White E. Autophagy and metabolism. Science. 2010;330(6009):1344–1348. doi:10.1126/science.1193497
  • Allaire M, Rautou PE, Codogno P, Lotersztajn S. Autophagy in liver diseases: time for translation? J Hepatol. 2019;70(5):985–998. doi:10.1016/j.jhep.2019.01.026
  • Udoh UAS, Rajan PK, Nakafuku Y, Finley R, Sanabria JR. Cell Autophagy in NASH and NASH-Related Hepatocellular Carcinoma. Int J Mol Sci. 2022;23(14):7734. doi:10.3390/ijms23147734
  • Dash S, Chava S, Chandra PK, Aydin Y, Balart LA, Wu T. Autophagy in hepatocellular carcinomas: from pathophysiology to therapeutic response. Hepat Med. 2016;8:9–20. doi:10.2147/HMER.S63700
  • Inokuchi-Shimizu S, Park EJ. TAK1-mediated autophagy and fatty acid oxidation prevent hepatosteatosis and tumorigenesis. J Clin Invest. 2014;124:8. doi:10.1172/JCI74068
  • Zhang W, Hou J, Wang X, et al. PTPRO-mediated autophagy prevents hepatosteatosis and tumorigenesis. Oncotarget. 2015;6(11):9420–9433. doi:10.18632/oncotarget.3353
  • Bartolini D, Dallaglio K, Torquato P, Piroddi M, Galli F. Nrf2-p62 autophagy pathway and its response to oxidative stress in hepatocellular carcinoma. Transl Res. 2018;193:54–71. doi:10.1016/j.trsl.2017.11.007
  • Mizushima N, Levine B. Autophagy in Human Diseases. N Engl J Med. 2020;383(16):1564–1576. doi:10.1056/NEJMra2022774
  • Yu S, Wang J, Zheng H, et al. Pathogenesis from Inflammation to Cancer in NASH-Derived HCC. J Hepatocell Carcinoma. 2022;9:855–867. doi:10.2147/JHC.S377768
  • Cai J, Zhang XJ, Li H. The Role of Innate Immune Cells in Nonalcoholic Steatohepatitis. Hepatology. 2019;70(3):1026–1037. doi:10.1002/hep.30506
  • Ramadori P, Kam S, Heikenwalder M. T cells: friends and foes in NASH pathogenesis and hepatocarcinogenesis. Hepatology. 2022;75(4):1038–1049. doi:10.1002/hep.32336
  • Méndez-Sánchez N, Córdova-Gallardo J, Barranco-Fragoso B, Eslam M. Hepatic Dendritic Cells in the Development and Progression of Metabolic Steatohepatitis. Front Immunol. 2021;12:641240. doi:10.3389/fimmu.2021.641240
  • Wolf MJ, Adili A, Piotrowitz K, et al. Metabolic activation of intrahepatic CD8+ T cells and NKT cells causes nonalcoholic steatohepatitis and liver cancer via cross-talk with hepatocytes. Cancer Cell. 2014;26(4):549–564. doi:10.1016/j.ccell.2014.09.003
  • Della Corte CM, Viscardi G, Papaccio F, et al. Implication of the Hedgehog pathway in hepatocellular carcinoma. WJG. 2017;23(24):4330–4340. doi:10.3748/wjg.v23.i24.4330
  • Sutti S, Albano E. Adaptive immunity: an emerging player in the progression of NAFLD. Nat Rev Gastroenterol Hepatol. 2020;17(2):81–92. doi:10.1038/s41575-019-0210-2
  • Barrow F, Khan S, Wang H, Revelo XS. The Emerging Role of B Cells in the Pathogenesis of NAFLD. Hepatology. 2021;74(4):2277–2286. doi:10.1002/hep.31889
  • Shalapour S, Lin XJ, Bastian IN, et al. Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity. Nature. 2017;551(7680):340–345. doi:10.1038/nature24302
  • Zhang S, Gang X, Yang S, et al. The Alterations in and the Role of the Th17/Treg Balance in Metabolic Diseases. Front Immunol. 2021;12:678355. doi:10.3389/fimmu.2021.678355
  • He B, Wu L, Xie W, et al. The imbalance of Th17/Treg cells is involved in the progression of nonalcoholic fatty liver disease in mice. BMC Immunol. 2017;18(1):33. doi:10.1186/s12865-017-0215-y
  • Loria P, Carulli L, Bertolotti M, Lonardo A. Endocrine and liver interaction: the role of endocrine pathways in NASH. Nat Rev Gastroenterol Hepatol. 2009;6(4):236–247. doi:10.1038/nrgastro.2009.33
  • Paschou SA, Polyzos SA, Anagnostis P, et al. Nonalcoholic fatty liver disease in women with polycystic ovary syndrome. Endocrine. 2020;67(1):1–8. doi:10.1007/s12020-019-02085-7
  • Rufinatscha K, Ress C, Folie S, et al. Metabolic effects of reduced growth hormone action in fatty liver disease. Hepatol Int. 2018;12(5):474–481. doi:10.1007/s12072-018-9893-7
  • Sun H, Yang W, Tian Y, et al. An inflammatory-CCRK circuitry drives mTORC1-dependent metabolic and immunosuppressive reprogramming in obesity-associated hepatocellular carcinoma. Nat Commun. 2018;9(1):5214. doi:10.1038/s41467-018-07402-8
  • Raza S, Rajak S, Upadhyay A, Tewari A, Sinha RA. Current treatment paradigms and emerging therapies for NAFLD/NASH. Front Biosci. 2021;26:206–237. doi:10.2741/4892
  • Pfister D, Núñez NG, Pinyol R, et al. NASH limits anti-tumour surveillance in immunotherapy-treated HCC. Nature. 2021;592(7854):450–456. doi:10.1038/s41586-021-03362-0