From Non-Alcoholic Steatohepatitis (NASH) to Hepatocellular Carcinoma (HCC): Epidemiology, Incidence, Predictions, Risk Factors, and Prevention

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2023 Nov 25

PMID 38001718

Authors

Benedetta Maria Motta

Mario Masarone

Pietro Torre

Marcello Persico

Affiliations

Soon will be listed here.

Abstract

Non-alcoholic fatty liver disease (NAFLD) affects up to a quarter of the adult population in many developed and developing countries. This spectrum of liver disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. The incidence of NASH is projected to increase by up to 56% over the next 10 years. There is growing epidemiological evidence that NAFLD has become the fastest-growing cause of hepatocellular carcinoma (HCC) in industrialized countries. The annual incidence of HCC varies between patients with NASH cirrhosis and patients with noncirrhotic NAFLD. In this review, NAFLD/NASH-associated HCC will be described, including its epidemiology, risk factors promoting hepatocarcinogenesis, and management of HCC in patients with obesity and associated metabolic comorbidities, including preventive strategies and therapeutic approaches to address this growing problem.

Citing Articles

A novel telomere-associated genes signature for the prediction of prognosis and treatment responsiveness of hepatocellular carcinoma.

Kang K, Nie H, Kuang W, Li X, Zhou Y Biol Proced Online. 2025; 27(1):8.

PMID: 40016654 PMC: 11866598. DOI: 10.1186/s12575-025-00271-8.

Gut Microbiome Modulation in Hepatocellular Carcinoma: Preventive Role in NAFLD/NASH Progression and Potential Applications in Immunotherapy-Based Strategies.

Monti E, Vianello C, Leoni I, Galvani G, Lippolis A, DAmico F Cells. 2025; 14(2).

PMID: 39851512 PMC: 11764391. DOI: 10.3390/cells14020084.

Statins decrease the risk of hepatocellular carcinoma in metabolic dysfunction-associated steatotic liver disease: A systematic review and meta-analysis.

Tarar Z, Farooq U, Inayat F, Basida S, Ibrahim F, Gandhi M World J Exp Med. 2024; 14(4):98543.

PMID: 39713070 PMC: 11551700. DOI: 10.5493/wjem.v14.i4.98543.

Predictive role of neutrophil percentage-to-albumin ratio, neutrophil-to-lymphocyte ratio, and systemic immune-inflammation index for mortality in patients with MASLD.

Dong K, Zheng Y, Wang Y, Guo Q Sci Rep. 2024; 14(1):30403.

PMID: 39638820 PMC: 11621551. DOI: 10.1038/s41598-024-80801-8.

Salidroside may target PPARα to exert preventive and therapeutic activities on NASH.

Chu X, Liu S, Qu B, Xin Y, Lu L Front Pharmacol. 2024; 15:1433076.

PMID: 39415834 PMC: 11479876. DOI: 10.3389/fphar.2024.1433076.

References

Li J, Zou B, Yeo Y, Feng Y, Xie X, Lee D . Prevalence, incidence, and outcome of non-alcoholic fatty liver disease in Asia, 1999-2019: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2019; 4(5):389-398. DOI: 10.1016/S2468-1253(19)30039-1. View

Hagstrom H, Tynelius P, Rasmussen F . High BMI in late adolescence predicts future severe liver disease and hepatocellular carcinoma: a national, population-based cohort study in 1.2 million men. Gut. 2017; 67(8):1536-1542. DOI: 10.1136/gutjnl-2016-313622. View

Baumeister S, Schlesinger S, Aleksandrova K, Jochem C, Jenab M, Gunter M . Association between physical activity and risk of hepatobiliary cancers: A multinational cohort study. J Hepatol. 2018; 70(5):885-892. DOI: 10.1016/j.jhep.2018.12.014. View

Sookoian S, Pirola C . Non-alcoholic fatty liver disease is strongly associated with carotid atherosclerosis: a systematic review. J Hepatol. 2008; 49(4):600-7. DOI: 10.1016/j.jhep.2008.06.012. View

Schuppan D, Afdhal N . Liver cirrhosis. Lancet. 2008; 371(9615):838-51. PMC: 2271178. DOI: 10.1016/S0140-6736(08)60383-9. View

Zhou H, Toshiyoshi M, Zhao W, Zhao Y, Zhao Y . Statins on nonalcoholic fatty liver disease: A systematic review and meta-analysis of 14 RCTs. Medicine (Baltimore). 2023; 102(26):e33981. PMC: 10313296. DOI: 10.1097/MD.0000000000033981. View

Liang G, Li Y, Lin Y, Yang X, Yang J, Hu S . Nicotinamide N-methyltransferase and liver diseases. Genes Dis. 2023; 10(5):1883-1893. PMC: 10363563. DOI: 10.1016/j.gendis.2022.03.019. View

Ferslew B, Xie G, Johnston C, Su M, Stewart P, Jia W . Altered Bile Acid Metabolome in Patients with Nonalcoholic Steatohepatitis. Dig Dis Sci. 2015; 60(11):3318-28. PMC: 4864493. DOI: 10.1007/s10620-015-3776-8. View

Frias J, Davies M, Rosenstock J, Perez Manghi F, Lando L, Bergman B . Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021; 385(6):503-515. DOI: 10.1056/NEJMoa2107519. View

10.

Mantovani A, Dalbeni A . Treatments for NAFLD: State of Art. Int J Mol Sci. 2021; 22(5). PMC: 7956331. DOI: 10.3390/ijms22052350. View

11.

Younossi Z, Golabi P, Paik J, 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. PMC: 10026948. DOI: 10.1097/HEP.0000000000000004. View

12.

Orci L, Sanduzzi-Zamparelli M, Caballol B, Sapena V, Colucci N, Torres F . Incidence of Hepatocellular Carcinoma in Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review, Meta-analysis, and Meta-regression. Clin Gastroenterol Hepatol. 2021; 20(2):283-292.e10. DOI: 10.1016/j.cgh.2021.05.002. View

13.

van Haren M, Zhang Y, Thijssen V, Buijs N, Gao Y, Mateuszuk L . Macrocyclic peptides as allosteric inhibitors of nicotinamide -methyltransferase (NNMT). RSC Chem Biol. 2021; 2(5):1546-1555. PMC: 8496086. DOI: 10.1039/d1cb00134e. View

14.

Williams C, Stengel J, Asike M, Torres D, Shaw J, Contreras M . Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology. 2010; 140(1):124-31. DOI: 10.1053/j.gastro.2010.09.038. View

15.

Gao Y, van Haren M, Buijs N, Innocenti P, Zhang Y, Sartini D . Potent Inhibition of Nicotinamide -Methyltransferase by Alkene-Linked Bisubstrate Mimics Bearing Electron Deficient Aromatics. J Med Chem. 2021; 64(17):12938-12963. PMC: 8436214. DOI: 10.1021/acs.jmedchem.1c01094. View

16.

Lefebvre E, Moyle G, Reshef R, Richman L, Thompson M, Hong F . Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis. PLoS One. 2016; 11(6):e0158156. PMC: 4922569. DOI: 10.1371/journal.pone.0158156. View

17.

Abdel-Rahman O, Helbling D, Schob O, Eltobgy M, Mohamed H, Schmidt J . Cigarette smoking as a risk factor for the development of and mortality from hepatocellular carcinoma: An updated systematic review of 81 epidemiological studies. J Evid Based Med. 2017; 10(4):245-254. DOI: 10.1111/jebm.12270. View

18.

Cariello M, Piccinin E, Moschetta A . Transcriptional Regulation of Metabolic Pathways via Lipid-Sensing Nuclear Receptors PPARs, FXR, and LXR in NASH. Cell Mol Gastroenterol Hepatol. 2021; 11(5):1519-1539. PMC: 8042405. DOI: 10.1016/j.jcmgh.2021.01.012. View

19.

Pacana T, Sanyal A . Vitamin E and nonalcoholic fatty liver disease. Curr Opin Clin Nutr Metab Care. 2012; 15(6):641-8. PMC: 4984672. DOI: 10.1097/MCO.0b013e328357f747. View

20.

El Hadi H, Vettor R, Rossato M . Vitamin E as a Treatment for Nonalcoholic Fatty Liver Disease: Reality or Myth?. Antioxidants (Basel). 2018; 7(1). PMC: 5789322. DOI: 10.3390/antiox7010012. View