Hepatocellular and Extrahepatic Cancer Risk in People with Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Much of the recognised health-care burden occurs in the minority of people with NAFLD who progress towards cirrhosis and require specialist follow-up, including risk stratification and hepatocellular carcinoma surveillance. NAFLD is projected to become the leading global cause of cirrhosis and hepatocellular carcinoma, but the frequency of non-cirrhotic hepatocellular carcinoma provides a challenge to existing surveillance strategies. Deaths from extrahepatic cancers far exceed those from hepatocellular carcinoma in NAFLD. Unlike hepatocellular carcinoma, the increased extrahepatic cancer risk in NAFLD is not dependent on liver fibrosis stage. Given that almost 30% of the world's adult population has NAFLD, extrahepatic cancer could represent a substantial health and economic issue. In this Review, we discuss current knowledge and controversies regarding hepatocellular carcinoma risk stratification and surveillance practices in people with NAFLD. We also assess the associations of extrahepatic cancers with NAFLD and their relevance both in the clinic and the wider community.