Genetic factors in NAFLD: Disease progression and hepatocellular carcinoma
Session type: Oral
Hepatocellular carcinoma (HCC) incidence is rising in the UK and globally. Due to rising worldwide obesity, non-alcoholic fatty liver disease (NAFLD) is an increasingly frequent underlying aetiology. NAFLD encompasses a spectrum that spans simple steatosis, through steatohepatitis (NASH) to fibrosis and ultimately cirrhosis and HCC. NAFLD is considered a complex disease trait that occurs when environmental exposures act upon a susceptible polygenic background composed of multiple independent modifiers. Genome-wide association studies and candidate-gene studies have informed our understanding of factors contributing to the well-recognised inter-individual variation in disease progression and outcomes in NAFLD. This presentation will discuss the role of genetic modifiers across the full spectrum from steatosis to HCC; in particular, functional coding variants in modifier genes including PNPLA3 and TM6SF2, as well as recent intriguing data suggesting an epigenetic contribution to disease pathogenesis. Future areas of genetic research, and the potential for these advances to influence clinical management will be discussed.