title: Analysis of the prevalence of drug-resistant hepatitis B virus in patients with antiviral therapy failure in a Chinese tertiary referral liver centre (2010-2014).
abstract: To study the prevalence of drug-resistant HBV in patients with therapy failure in a Chinese tertiary referral liver centre.
  
  
  
  1223 HBV-infected patients who underwent genotypic resistance testing between 2010-2014 were studied.
  
  
  
  3TC genotypic resistance was the most common (46.5%), followed by LdT resistant (46.2%), ETV intermediate (37.9%), ADV resistant (11.4%), TDF intermediate (11.4%) and ETV resistant (1.7%). The 3TC resistance rate increased from 39.8% in 2010 to 56.6% in 2013, before decreasing to 49.5% in 2014, evidence of a lagging effect of l-nucleoside consumption. M204I, N236T and L180M+M204V+V173L/S202G were the most common substitutions for l-nucleoside (3TC and LdT), ADV and ETV genotypic resistant phenotypes, respectively. 3TC-exposed patients showed a high multiple genetic resistance rate (3TC-resistant+LdT-resistant+ETV intermediate; 58.8%). Resistance rates to 3TC, LdT and ETV in HCC patients were significantly higher than in cirrhosis and CHB patients. Resistance rates to different drugs showed no statistical difference between genotype B and C patients, whilst some amino acid substitution showed genotype bias, e.g. N236T incidence in genotype B was significantly higher than in genotype C (43.2% vs. 5.9%; P<0.0001), and genotype C isolates had a significantly higher A181V/T incidence than genotype B (54.9% vs. 19.3%; P<0.0001).
  
  
  
  3TC genotypic resistance was most common in this centre, whilst ETV had the lowest resistance rate. HBV genotypes had no impact on antiviral drug resistance, except for some drug resistance substitutions bias. Optional initial therapy and subsequent rescue treatment should be based on knowledge of nucleos(t)ide analogue resistance.
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases of Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Meng
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases of Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Shi
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases of Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xuyang
authors.initials: X
authors.lastname: Gong
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases of Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Deng
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases of Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Shan
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases of Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Youlan
authors.initials: Y
authors.lastname: Shan
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases of Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China. Electronic address: ahuang1964@163.com.
authors.forename: Ailong
authors.initials: A
authors.lastname: Huang
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases of Ministry of Education, Department of Infectious Diseases, Institute for Viral Hepatitis, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China. Electronic address: longquanxin@gmail.com.
authors.forename: Quanxin
authors.initials: Q
authors.lastname: Long
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002681:China / Q000453:epidemiology; D004279:DNA, Viral; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D005260:Female; D005355:Fibrosis / Q000821:virology; D016679:Genome, Viral; D005838:Genotype; D006515:Hepatitis B virus / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000453:epidemiology* / Q000821:virology; D006801:Humans; D008099:Liver / Q000821:virology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011795:Surveys and Questionnaires; D062606:Tertiary Care Centers; D017211:Treatment Failure
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral
keywords: China; Drug resistance; Hepatitis B virus; Long-term analysis; Nucleos(t)ide analogues