Obesity, non-alcoholic fatty liver disease and hepatocellular carcinoma: current status and therapeutic targets

Obesity is a global epidemic and overwhelming evidence indicates that it is a risk factor for numerous cancers, including hepatocellular carcinoma (HCC), the third leading cause of cancer-related deaths worldwide. Obesity-associated hepatic tumorigenesis develops from nonalcoholic fatty liver disease (NAFLD), progressing to nonalcoholic steatohepatitis (NASH), cirrhosis and ultimately to HCC. The rising incidence of obesity is resulting in an increased prevalence of NAFLD and NASH, and subsequently HCC. Obesity represents an increasingly important underlying etiology of HCC, in particular as the other leading causes of HCC such as hepatitis infection, are declining due to effective treatments and vaccines. In this review, we provide a comprehensive overview of the molecular mechanisms and cellular signaling pathways involved in the pathogenesis of obesity-associated HCC. We summarize the preclinical experimental animal models available to study the features of NAFLD/NASH/HCC, and the non-invasive methods to diagnose NAFLD, NASH and early-stage HCC. Finally, since HCC is an aggressive tumor with a 5-year survival of less than 20%, we will also discuss novel therapeutic targets for obesity-associated HCC and ongoing clinical trials.

Automated summary

Obesity is a global epidemic and is strongly associated with an increased risk of hepatocellular carcinoma (HCC), the third leading cause of cancer deaths worldwide. The development of obesity-associated HCC starts from nonalcoholic fatty liver disease (NAFLD), progresses to nonalcoholic steatohepatitis (NASH), cirrhosis, and eventually to HCC. This review provides a comprehensive overview of the molecular mechanisms and cellular signaling pathways involved in the pathogenesis of obesity-associated HCC, as well as the available experimental models and diagnostic methods. The discussion also includes novel therapeutic targets and ongoing clinical trials for obesity-associated HCC.