Effects of genetic polymorphism on the development of hepatocellular carcinoma in patients with metabolic-associated fatty liver disease. Review

Abstract

Non‑alcoholic fatty liver disease (NAFLD) takes the first place among liver diseases in the countries with developed economies. In the year 2020, the group of experts proposed a new term, metabolic‑associated fatty liver disease, that allows to specify the diagnosis, to divide different NAFLD phenotypes and to optimize its treatment. The course of metabolic‑associated liver disease can range from mild forms (simple nonalcoholic steatosis, characterized by the accumulation of triglycerides in liver cells) up to an aggressive course with the development of cirrhosis and hepatocellular carcinoma (HCC). Aggressive course of the disease is observed in patients with type 2 diabetes mellitus, high body mass index, abdominal obesity and histologically confirmed steatohepatitis. Epidemiological and genetic studies have shown an association between the morphological stage of metabolic‑associated liver disease and hereditary factors. Progression to HCC is common in patients with severe steatohepatitis, although recent literature data showed a significant increase in the proportion of patients with F1/F2 fibrosis and НСС. This is due to the presence of metabolic syndrome and gene polymorphism. Three main genes can be singled out, the polymorphism of which is associated with the development of metabolic‑associated liver disease, insulin resistance, dyslipidemia, and fibrogenesis: PNPLA3, TM6SF2 and GCKR. Recently, an MBOAT7 gene polymorphism has been also identified, it peculiarly increases the risk of steatohepatitis development in patients who are alcohol abusers and/or have chronic viral hepatitis C. Detection of polymorphisms in these genes is useful for identifying groups at high risk for disease progression. Early diagnosis of HCC and risk stratification will allow to diagnose the disease at an early stage and optimize its treatment.