title: Deep sequencing analysis of HBV genotype shift and correlation with antiviral efficiency during adefovir dipivoxil therapy.
abstract: BACKGROUND
  Viral genotype shift in chronic hepatitis B (CHB) patients during antiviral therapy has been reported, but the underlying mechanism remains elusive.
  
  
  METHODS
  38 CHB patients treated with ADV for one year were selected for studying genotype shift by both deep sequencing and Sanger sequencing method.
  
  
  RESULTS
  Sanger sequencing method found that 7.9% patients showed mixed genotype before ADV therapy. In contrast, all 38 patients showed mixed genotype before ADV treatment by deep sequencing. 95.5% mixed genotype rate was also obtained from additional 200 treatment-naïve CHB patients. Of the 13 patients with genotype shift, the fraction of the minor genotype in 5 patients (38%) increased gradually during the course of ADV treatment. Furthermore, responses to ADV and HBeAg seroconversion were associated with the high rate of genotype shift, suggesting drug and immune pressure may be key factors to induce genotype shift. Interestingly, patients with genotype C had a significantly higher rate of genotype shift than genotype B. In genotype shift group, ADV treatment induced a marked enhancement of genotype B ratio accompanied by a reduction of genotype C ratio, suggesting genotype C may be more sensitive to ADV than genotype B. Moreover, patients with dominant genotype C may have a better therapeutic effect. Finally, genotype shifts was correlated with clinical improvement in terms of ALT.
  
  
  CONCLUSIONS
  Our findings provided a rational explanation for genotype shift among ADV-treated CHB patients. The genotype and genotype shift might be associated with antiviral efficiency.
authors.affiliation: Department of Laboratory Medicine, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China; Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China; Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Shan
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Youlan
authors.initials: Y
authors.lastname: Shan
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Dazhi
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Aizhong
authors.initials: A
authors.lastname: Zen
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Xuyang
authors.initials: X
authors.lastname: Gong
authors.affiliation: Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Xiuyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Ailong
authors.initials: A
authors.lastname: Huang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D000225:Adenine; C106812:adefovir dipivoxil