title: Resistant mutants induced by adefovir dipivoxil in hepatitis B virus isolates.
abstract: OBJECTIVE
  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 (χ(2) = 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Su-Wen
authors.initials: SW
authors.lastname: Jiang
authors.affiliation: 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.
authors.forename: Li-Peng
authors.initials: LP
authors.lastname: Yao
authors.affiliation: 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.
authors.forename: Ai-Rong
authors.initials: AR
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Yao-Ren
authors.initials: YR
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Shi-Xiang
authors.initials: SX
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Xiong
authors.affiliation: 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.
authors.forename: Guo-Sheng
authors.initials: GS
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: Xiao-Yue
authors.initials: XY
authors.lastname: Liang
authors.affiliation: 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.
authors.forename: Shi-Xiong
authors.initials: SX
authors.lastname: Ding
authors.affiliation: 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.
authors.forename: Peng-Jian
authors.initials: PJ
authors.lastname: Weng
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000235:genetics; D003952:Diagnostic Imaging / Q000379:methods; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D000225:Adenine; C106812:adefovir dipivoxil
keywords: Adefovir dipivoxil; Drug-resistant mutant; Gene sequencing; Hepatitis B virus