Research Report
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 7, 2014; 20(45): 17100-17106
Published online Dec 7, 2014. doi: 10.3748/wjg.v20.i45.17100
Resistant mutants induced by adefovir dipivoxil in hepatitis B virus isolates
Su-Wen Jiang, Li-Peng Yao, Ai-Rong Hu, Yao-Ren Hu, Shi-Xiang Chen, Tao Xiong, Guo-Sheng Gao, Xiao-Yue Liang, Shi-Xiong Ding, Peng-Jian Weng
Su-Wen Jiang, Ai-Rong Hu, Yao-Ren Hu, Tao Xiong, Guo-Sheng Gao, Xiao-Yue Liang, Shi-Xiong Ding, Peng-Jian Weng, Institute of Liver Diseases, Ningbo No. 2 Hospital, Ningbo 315010, Zhejiang Province, China
Li-Peng Yao, Ai-Rong Hu, Department of Molecular Biology, School of Medicine, Ningbo University, Ningbo 315010, Zhejiang Province, China
Shi-Xiang Chen, Department of Infectious Diseases, No. 113 Hospital of the PLA, Ningbo 315010, Zhejiang Province, China
Author contributions: Jiang SW, Hu AR and Gao GS participated in research design; Gao GS and Ding SX tested the specimens; Weng PJ tested the specimens and collected the data; Jiang SW, Yao LP, Hu YR, Chen SX, Xiong T and Liang XY collected and analyzed the data; Gao GS analyzed the data and drafted the manuscript; Jiang SW and Hu AR drafted the manuscript.
Supported by BaoenWang Liver Fibrosis Research Fund of the Chinese Foundation for Hepatitis Prevention and Control, No. 20100009; Zhejiang Medicine and Health Sciences Research Fund, No. 2008B167 and No. 2014PYA018; Nanjing Military Area Command of the PLA Medical Technology Innovation, No. 11MA019; Ningbo Health Technology Project for Excellent Young and Middle-aged Talent, No. 2011-145; Ningbo Leader and Top Notch Person Training Project, No. 2012-131; and Zhejiang Medicine and Health Project for Excellent Young Talent, No. 2013-245
Correspondence to: Ai-Rong Hu, MD, Institute of Liver Diseases, Ningbo No. 2 Hospital, 41 Xibei Street, Haishu District, Ningbo 315010, Zhejiang Province, China. huairong6666@126.com
Telephone: +86-574-83870605 Fax: +86-574-83870626
Received: May 28, 2014
Revised: July 17, 2014
Accepted: August 13, 2014
Published online: December 7, 2014
Abstract

AIM: To investigate the loci of adefovir dipivoxil (ADV)-induced resistance in hepatitis B virus (HBV) isolates and optimize the management of ADV-treated patients.

METHODS: Between June 2008 and August 2010, a cross-sectional control study was conducted comprising 79 patients with chronic HBV infection-related liver disease who had been administered ADV monotherapy. Patients underwent liver imaging. Serum DNA extracts were analyzed for HBV DNA levels, genotypes, and serology markers, and deep sequencing of the HBV P gene was performed.

RESULTS: ADV-resistant patients were found either with a single mutated locus, or with coexisting mutated loci. The most prevalent mutations were rtA181T, rtV214A, and rtN236T. Twenty-six patients had more than two mutated loci. The mutants were distributed among the patients without any significant affinity for gender, age, end-stage of liver disease, complications of non-alcoholic fatty liver disease, or HBV DNA levels. Patients with the rtA181T mutant were primarily infected with genotype C and e-antigen negative HBV, while patients with the rtN236T mutant were primarily infected by genotype B HBV (χ2 = 6.004, 7.159; P = 0.023, 0.007). The duration of treatment with ADV was shorter in the single mutant group compared with the multi-mutant group (t = 2.426, P = 0.018).

CONCLUSION: Drug-resistant HBV mutants are complex and diverse. Patients should receive the standard and first-line antiviral treatment, strictly comply with medication dosage, and avoid short-term withdrawal.

Keywords: Hepatitis B virus, Adefovir dipivoxil, Drug-resistant mutant, Gene sequencing

Core tip: Currently, hepatitis B virus (HBV) resistance to adefovir dipivoxil (ADV) has become more prevalent. However, it is not known whether drug-resistant HBV mutants induced by ADV are related to the clinical features of patients. In this study, we analyzed the exhaustive resistant mutants induced by ADV. Of 79 patients, 26 (32.9%) had more than two loci of drug resistance in HBV mutants. Because drug-resistant HBV mutants induced by ADV are complicated and diverse, we conclude that testing for resistant mutants prior to antiviral treatment, administering standard and first-line antiviral treatment, and personalizing medication according to the clinical characteristics of patients is important to avoid subsequent noncompliance and the need for salvage treatment.