Журнал канцерогенеза и мутагенеза

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Current Genetic Advances in NAFLD/NASH: Related Hepatocellular Carcinoma Along with Characteristic Clinical Manifestation

Kazumi Fujioka

Non-Alcoholic Fatty Liver Disease (NAFLD) is the common liver disease worldwide because of the increasing rates in parallel to obesity and Type 2 Diabetes Mellitus (T2DM). Mechanically, lipid accumulation and insulin resistance serve as the first hit, second hit is considered as inflammation and fibrosis in NAFLD. NAFLD is attributed to liverrelated morbidity and mortality, there is also growing evidence that NAFLD is a multisystem disease and is associated with hepatic (hepatocellular carcinoma: HCC) and extrahepatic (Cardiovascular Disease: CVD, Coronary Artery Disease: CAD, and Chronic Kidney Disease: CKD) diseases. The author previously suggested that an association between chronic liver disease (NAFLD/NASH and chronic hepatitis C virus infection: HCV infection) and systemic atherosclerosis may be present due to the presence of the inflammation as a common pathway. In this article, the current genetic advances of NAFLD/NASH-related HCC including PNPLA3, TM6SF2, GCKR, MBOAT7, HSD17B13, and the combined effect of these variants along with characteristic clinical manifestation have been reviewed. NAFLDs clinically predispose to occur non-cirrhotic NAFLD-HCC. The study of polygenic risk scores may be attributed to the stratification of the risk of the NAFLD/NASH-related HCC in the near feature. On the basis of the characteristic clinical and genetic evidences, the author suggests that the risk stratification of the medium/high risk in NAFLD-related HCC, especially non-cirrhotic HCC may contribute to the prevention, prediction, and surveillance.