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World J Gastroenterol. May 21, 2014; 20(19): 5708-5720
Published online May 21, 2014. doi: 10.3748/wjg.v20.i19.5708
Molecular diagnosis and treatment of drug-resistant hepatitis B virus
Jeong Han Kim, Yong Kwang Park, Eun-Sook Park, Kyun-Hwan Kim
Jeong Han Kim, Digestive Disease Center, Department of Internal Medicine, School of Medicine, Konkuk University, Seoul 143-729, South Korea
Yong Kwang Park, Eun-Sook Park, Kyun-Hwan Kim, Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul 143-729, South Korea
Yong Kwang Park, Eun-Sook Park, Kyun-Hwan Kim, Institute of Functional Genomics, Konkuk University, Seoul 143-729, South Korea
Author contributions: All authors contributed to this work.
Supported by Konkuk University
Correspondence to: Kyun-Hwan Kim, Associate Professor, Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Gwangjin-gu, Seoul 143-729, South Korea. khkim10@kku.ac.kr
Telephone: +82-2-20307833 Fax: +82-2-20496192
Received: October 27, 2013
Revised: January 29, 2014
Accepted: March 19, 2014
Published online: May 21, 2014
Processing time: 203 Days and 11.6 Hours
Abstract

Oral antiviral agents have been developed in the last two decades for the treatment of chronic hepatitis B (CHB). However, antiviral resistance remains an important challenge for long-term CHB therapy. All of the clinically available oral antiviral agents are nucleoside or nucleotide analogues that target the activity of viral reverse transcriptase (RT), and all are reported to have resistant mutations. Since the hepatitis B virus (HBV) RT, like other viral polymerases, lacks proofreading activity, the emergence of drug-resistance occurs readily under selective pressure from the administration of antiviral agents. The molecular diagnosis of drug-resistant HBV is based on sequence variations, and current diagnostic methods include sequencing, restriction fragment polymorphism analysis, and hybridization. Here, we will discuss the currently available molecular diagnosis tools, in vitro phenotypic assays for validation of drug-resistant HBV, and treatment options for drug-resistant HBV.

Keywords: Hepatitis B virus; Drug-resistance; Molecular diagnosis; Antiviral treatment; Chronic hepatitis B

Core tip: Although several antiviral agents have been developed in the last two decades for the treatment of chronic hepatitis B (CHB), antiviral resistance remains an important challenge for long-term CHB therapy. In this review, we discussed the currently available molecular diagnosis tools, in vitro phenotypic assays for validation of drug-resistant hepatitis B virus (HBV), and treatment options for drug-resistant HBV.