Oxidative stress in nonalcoholic fatty liver disease: a reappraisal of the role in supporting inflammatory mechanisms

Abstract

In the last decade, non-alcoholic fatty liver disease (NAFLD) and particularly its evolution to nonalcoholic steatohepatitis (NASH) have become a leading cause of chronic liver disease and cirrhosis as well as an important risk factor for hepatocellular carcinoma. Oxidative stress is a common feature of NAFLD/NASH and plays a key role in the complex of metabolic and cellular derangements that are involved in the development of liver steatosis, as well as in the transition to steatohepatitis. This review deals with the contribution of oxidative stress in promoting hepatic inflammation which represents a key factor in NAFLD evolution to liver fibrosis/cirrhosis. We discuss in detail recent data involving oxidative stress products as triggers for hepatic innate immunity and as a source of antigens implicated in sustaining lymphocyte-mediated adaptive immune responses. Attention is also paid to emerging evidence linking oxidative stress and extra-hepatic complications of NAFLD/NASH.