Epidemiologic, Genetic, Pathogenic, Metabolic, Epigenetic Aspects Involved in NASH-HCC: Current Therapeutic Strategies

Simple Summary Hepatocellular carcinoma (HCC) is an aggressive human cancer and is caused as consequences of chronic liver diseases. Although HCC is more common in patients with cirrhosis, there is increasing evidence that this cancer may develop in the setting of noncirrhotic nonalcoholic steatohepatitis (NASH), even simple hepatic steatosis may progress to carcinogenesis development. NASH is associated with obesity, hyperlipidemia, insulin resistance, and type 2 diabetes (T2D), which are becoming emerging risk factors for the development of HCC, as well as for cardiovascular disease. In this review, we discuss the current molecular data supporting the link between HCC and NASH, with a focus on metabolic alterations, genetic and epigenetic drivers, including current therapeutic strategies for NASH and HCC prevention and treatment. Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the sixth most frequent cancer in the world, being the third cause of cancer-related deaths. Nonalcoholic steatohepatitis (NASH) is characterized by fatty infiltration, oxidative stress and necroinflammation of the liver, with or without fibrosis, which can progress to advanced liver fibrosis, cirrhosis and HCC. Obesity, metabolic syndrome, insulin resistance, and diabetes exacerbates the course of NASH, which elevate the risk of HCC. The growing prevalence of obesity are related with increasing incidence of NASH, which may play a growing role in HCC epidemiology worldwide. In addition, HCC initiation and progression is driven by reprogramming of metabolism, which indicates growing appreciation of metabolism in the pathogenesis of this disease. Although no specific preventive pharmacological treatments have recommended for NASH, dietary restriction and exercise are recommended. This review focuses on the molecular connections between HCC and NASH, including genetic and risk factors, highlighting the metabolic reprogramming and aberrant epigenetic alterations in the development of HCC in NASH. Current therapeutic aspects of NASH/HCC are also reviewed.

Automated summary

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, often caused by chronic liver diseases. Nonalcoholic steatohepatitis (NASH) is a risk factor for HCC and is associated with obesity, hyperlipidemia, insulin resistance, and type 2 diabetes. This review discusses the molecular connections between HCC and NASH, focusing on metabolic alterations and genetic and epigenetic drivers, as well as therapeutic strategies.