Published online May 8, 2015. doi: 10.4254/wjh.v7.i7.968
Peer-review started: August 31, 2014
First decision: November 14, 2014
Revised: January 21, 2015
Accepted: January 30, 2015
Article in press: February 2, 2015
Published online: May 8, 2015
Oxidative stress is becoming recognized as a key factor in the progression of chronic liver disease (CLD) and hepatocarcinogenesis. The metabolically important liver is a major reservoir of mitochondria that serve as sources of reactive oxygen species, which are apparently responsible for the initiation of necroinflammation. As a result, CLD could be a major inducer of oxidative stress. Chronic hepatitis C is a powerful generator of oxidative stress, causing a high rate of hepatocarcinogenesis among patients with cirrhosis. Non-alcoholic steatohepatitis is also associated with oxidative stress although its hepatocarcinogenic potential is lower than that of chronic hepatitis C. Analyses of serum markers and histological findings have shown that hepatocellular carcinoma correlates with oxidative stress and experimental data indicate that oxidative stress increases the likelihood of developing hepatocarcinogenesis. However, the results of antioxidant therapy have not been favorable. Physiological oxidative stress is a necessary biological response, and thus adequate control of oxidative stress and a balance between oxidative and anti-oxidative responses is important. Several agents including metformin and L-carnitine can reportedly control mechanistic oxidative stress. This study reviews the importance of oxidative stress in hepatocarcinogenesis and of control strategies for the optimal survival of patients with CLD and hepatocellular carcinoma.
Core tip: Oxidative stress is a key biological response that correlates with the progression of chronic liver disease. However, oxidative stress is an essential survival mechanism and thus to erase it is an unsuitable approach to disease control. As hepatocarcinogenesis is closely associated with increased oxidative stress via viral proteins or chronic inflammation and lipids, controlling oxidative stress should be effective against progressive liver disease. Agents that can control oxidative stress might represent a more effective approach than reactive oxygen species-scavenging agents.