title: Antiviral efficacy of entecavir for hepatitis B virus rtA181V/T mutants.
abstract: The amino acid substitution at position 181 of the Hepatitis B virus (HBV) polymerase is a multi-drug resistance affecting both the L-nucleoside and acyclic phosphonate nucleotide groups. Data is limited on the efficacy of entecavir (ETV) rescuing chronic hepatitis B (CHB) patients with rtA181T/V mutation.
  
  
  
  Thirty-one patients with rtA181T/V mutation and 25 patients with rtA181T/V and rtN236T mutation were enrolled. Virological, serological and biochemical outcomes of ETV rescue therapy over 12 months in CHB patients with rtA181T/V mutation strains were investigated. All patients were treated with ETV 0.5 mg/day for 12 months and scheduled follow-up every 3 months. Patients' characteristics, laboratory tests results and clinical outcomes were collected and compared.
  
  
  
  After emergence of rtA181T/V mutant, serum HBV DNA levels increased over 4 log10 IU/mL, but the total bilirubin, alanine aminotransferase (ALT) levels raised moderately. No significant difference in baseline characteristics was observed between the rtA181T/V group and rtA181T/V + rtN236T group. After 12 months rescue therapy, total 85.7% (48/56) patients achieved HBV DNA undetectable. No significant difference in the mean reduction of serum HBV DNA and biochemical response was observed between both groups (3.59 ± 1.85 vs. 3.76 ± 2.15 log10 IU/ml; P = 0.756 and 90.3 vs. 80.0%; P = 0.272, respectively). The mean HBV DNA reduction, HBsAg and ALT levels were also similar between different rtA181T/sW172 mutations (P > 0.05). HBV DNA level is the only predictor of 12 months antiviral outcomes (odds ratio 6.723, P = 0.022).
  
  
  
  The results of the present study suggested that ETV is efficient in rescuing rtA181T/V mutation CHB patients. HBV DNA level could predict viral clearance at the 12thmonth.
authors.affiliation: Department of Liver Disease Center, Bayi Hospital Affiliated Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Liver Disease Center, Bayi Hospital Affiliated Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
authors.forename: Jiabao
authors.initials: J
authors.lastname: Geng
authors.affiliation: Department of Infection Disease Center, Henan Province People's Hospital, Zhengzhou, Henan Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Gastroenterology and Hepatology, Nanjing General Hospital of Nanjing Military Command, Nanjing, Jiangsu Province, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Liver Disease Center, Bayi Hospital Affiliated Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Liver Disease Center, Bayi Hospital Affiliated Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
authors.forename: Wenkai
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Liver Disease Center, Bayi Hospital Affiliated Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
authors.forename: Yuecheng
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Liver Disease Center, Bayi Hospital Affiliated Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Liver Disease Center, Bayi Hospital Affiliated Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China. maorongwang@yeah.net.
authors.forename: Maorong
authors.initials: M
authors.lastname: Wang
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D050505:Mutant Proteins / Q000235:genetics; D020125:Mutation, Missense; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D012189:Retrospective Studies; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D050505:Mutant Proteins; C413685:entecavir; D006147:Guanine; D012194:RNA-Directed DNA Polymerase
keywords: Chronic hepatitis B; Entecavir; Mutation; Nucleoside and nucleotide analogs (NAs)