Pathophysiological basis for antioxidant therapy in chronic liver disease

Oxidative stress is a common pathogenetic mechanism contributing to initiation and progression of hepatic damage in a variety of liver disorders. Cell damage occurs when there is an excess of reactive species derived from oxygen and nitrogen, or a defect of antioxidant molecules. Experimental research on the delicately regulated molecular strategies whereby cells control the balance between oxidant and antioxidant molecules has progressed in recent years. On the basis of this evidence, antioxidants represent a logical therapeutic strategy for the treatment of chronic liver disease. Clinical studies with large numbers of patients have not yet been performed. However, results from several pilot trials support this concept and indicate that it may be worth performing multicentre studies, particularly combining antioxidants with anti-inflammatory and/or antiviral therapy. Oxidative stress plays a pathogenetic role in liver diseases such as alcoholic liver disease, chronic viral hepatitis, autoimmune liver diseases and non-alcoholic steatohepatitis. The use of antioxidants (e.g. S-adenosylmethionine [SAMe; ademetionine], tocopherol [vitamin E], polyenylphosphatidylcholine or silymarin) has already shown promising results in some of these pathologies.