Review
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World J Virol. Dec 12, 2012; 1(6): 174-183
Published online Dec 12, 2012. doi: 10.5501/wjv.v1.i6.174
Antiviral treatment to prevent chronic hepatitis B or C-related hepatocellular carcinoma
Li-Ping Chen, Jun Zhao, Yan Du, Yi-Fang Han, Tong Su, Hong-Wei Zhang, Guang-Wen Cao
Li-Ping Chen, Yan Du, Yi-Fang Han, Tong Su, Hong-Wei Zhang, Guang-Wen Cao, Department of Epidemiology, the Second Military Medical University, Shanghai 200433, China
Jun Zhao, Department of Hepatobiliary Surgery, the Third Affiliated Hospital of the Second Military Medical University, Shanghai 200438, China
Author contributions: Chen LP and Zhao J collected the data from the published literature, drafted the first version and contributed equally to the work; Du Y, Han YF, Su T and Zhang HW critically read the draft; Cao GW presented the study conception, supervised data collection and drafted subsequent versions of this manuscript.
Supported by National Natural Scientific Foundation of China, No. 81025015 and 91129301
Correspondence to: Guang-Wen Cao, MD, PhD, Professor, Chairman, Department of Epidemiology, the Second Military Medical University, 800 Xiangyin Rd., Shanghai 200433, China. gcao@smmu.edu.cn
Telephone: +86-21-81871060 Fax: +86-21-81871060
Received: October 28, 2011
Revised: June 18, 2012
Accepted: November 7, 2012
Published online: December 12, 2012
Abstract

Antiviral treatment is the only option to prevent or defer the occurrence of hepatocellular carcinoma (HCC) in patients chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). The approved medication for the treatment of chronic HBV infection is interferon-α (IFNα) and nucleos(t)ide analogues (NAs), including lamivudine, adefovir dipivoxil, telbivudine, entecavir and tenofovir disoproxil fumarate. IFNα is the most suitable for young patients with less advanced liver diseases and those infected with HBV genotype A. IFNα treatment significantly decreases the overall incidence of HBV-related HCC in sustained responders. However, side effects may limit its long-term clinical application. Orally administered NAs are typically implemented for patients with more advanced liver diseases. NA treatment significantly reduces disease progression of cirrhosis and therefore HCC incidence, especially in HBV e antigen-positive patients. NA-resistance due to the mutations in HBV polymerase is a major limiting factor. Of the NA resistance-associated mutants, A181T mutant significantly increases the risk of HCC development during the subsequent course of NA therapy. It is important to initiate treatment with NAs that have a high genetic barrier to resistance, to counsel patients on medication adherence and to monitor virological breakthroughs. The recommended treatment for patients with chronic HCV infection is peg-IFN plus ribavirin that can decrease the occurrence of HCC in those who achieve a sustained virological response and have not yet progressed to cirrhosis. IFN-based treatment is reserved for patients with decompensated cirrhosis who are under evaluation of liver transplantation to reduce post-transplant recurrence of HCV. More effective therapeutic options such as direct acting antiviral agents will hopefully increase the response rate in difficult-to-treat patients with HCV genotype 1. However, the risk of HCC remains in cirrhotic patients (both chronic HBV and HCV infection) if treatment is initiated after cirrhosis is established. Future research should focus on investigating new agents, especially for those patients with hepatic decompensation or post-transplantation.

Keywords: Hepatitis B virus, Hepatitis C virus, Hepatocellular carcinoma, Antiviral therapy, Interferon, Nucleos(t)ide analogues, Virological response