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World J Hepatol. May 8, 2015; 7(7): 968-979
Published online May 8, 2015. doi: 10.4254/wjh.v7.i7.968
Control of oxidative stress in hepatocellular carcinoma: Helpful or harmful?
Akinobu Takaki, Kazuhide Yamamoto
Akinobu Takaki, Kazuhide Yamamoto, Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama 700-8558, Japan
Author contributions: Takaki A designed and wrote this article; Yamamoto K contributed equally to this work by providing reviews and guidance.
Conflict-of-interest: The authors declare no conflicts of interest regarding this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Akinobu Takaki, MD, Associate Professor, Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Telephone: +81-86-2357219 Fax: +81-86-2255991
Received: August 28, 2014
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.

Keywords: Liver cancer, Liver cirrhosis, Hepatitis B, Hepatitis C, Non-alcoholic steatohepatitis, Reactive oxygen species

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.