Risk Factors for Hepatocellular Carcinoma in Patients With Non-Alcoholic Fatty Liver Disease

Abstract

Non-alcoholic fatty liver disease is growing in worldwide prevalence and thus, is expected to have a higher number of NAFLD-related hepatocellular carcinoma (HCC) in the following years. This review describes the risk factors associated with HCC in NAFLD-patients. The presence of liver cirrhosis is the preponderant one. Male gender, PNPLA3 variants, diabetes, and obesity also appear to predispose to the development of HCC, even in non-cirrhotic subjects. Thus far, intensive lifestyle modifications, including glycemic control, and obesity treatment, are effective therapies for NAFLD/ non-alcoholic steatohepatitis and, therefore, probably, also for HCC. Some drugs that aimed at decreasing inflammatory activity and fibrosis, as well as obesity, were studied. Other data have suggested the possibility of HCC chemoprevention. So far, however, there is no definitive evidence for the routine utilization of these drugs. We hope, in the future, to be able to profile patients at higher risk of NAFLD-HCC and outline strategies for early diagnosis and prevention.

Mitigating a Bioactivation Liability with an Azetidine-Based Inhibitor of Diacylglycerol Acyltransferase 2 (DGAT2) En Route to the Discovery of the Clinical Candidate Ervogastat

“…Nonalcoholic fatty liver disease (NAFLD) comprises a gamut of liver disorders, including nonalcoholic fatty liver, defined as steatosis, and the more advanced subgroup, nonalcoholic steatohepatitis (NASH). , Progression from nonalcoholic fatty liver to NASH increases the risk of cirrhosis and liver-related mortalities. − Altered lipid metabolism is thought to be a leading contributor to the pathogenesis of NAFLD, and elevated rates of de novo lipogenesis are a hallmark characteristic of NAFLD, which cause accumulation of hepatic triglycerides (TGs) . Since diacylglycerol acyltransferase 2 (DGAT2), expressed in adipose tissue and liver, catalyzes the esterification of fatty acids with diacylglycerol, resulting in the formation of TGs, inhibition of DGAT2 is expected to reduce steatosis by blocking TG synthesis.…”