Hepatitis C virus and oxidative stress: a dangerous liaison

Chronic hepatitis C infection persists in more than 170 million people worldwide and is one of the major causes of hepatic failure and liver transplantation. Recent studies have demonstrated that hepatitis C virus (HCV)-derived proteins have the capacity to generate substantial oxidative stress within the hepatocyte. Subsequently, oxidative stress has been identified as a significant mechanistic pathway culminating in the development of hepatic cirrhosis, liver failure and liver cancer. In vitro HCV-induced oxidative stress has been demonstrated to activate cellular signaling pathways involved in both inflammatory and fibrogenic responses. In addition, oxidative stress has also been shown to play a role in HCV replication. Preliminary data from small clinical trials have implicated oxidative stress as a risk factor for liver fibrosis and increased HCV viral load. Although conclusive evidence from large-scale clinical trials is lacking, it is possible that antioxidant co-therapies may improve hepatic inflammation, retard fibrosis progression and improve the ability to achieve a sustained viral response with standard antiviral therapy.