title: Natural YMDD-motif mutants affect clinical course of lamivudine in chronic hepatitis B.
abstract: OBJECTIVE
  To investigate the prevalence of nature tyrosine-methionine-aspartic acid-aspartic acid motif mutations in chronic hepatitis B (CHB) patients and to evaluate the efficacy of lamivudine.
  
  
  METHODS
  A total of 1268 CHB patients were recruited from the outpatient and inpatient departments of six centers. Tyrosine-methionine-aspartic acid-aspartic acid (YMDD) mutations were analyzed using the hepatitis B virus (HBV) drug resistance line probe assay. Forty voluntary patients were selected from those with positive or negative natural YMDD mutations to undergo treatment with lamivudine.
  
  
  RESULTS
  YMDD mutations were detected in 288 (22.71%) of the 1268 CHB patients. Multivariate analysis revealed that the patients' HBV DNA level (P=0.0282) and hepatitis B e antigen status (P=0.0133) were also associated with natural YMDD mutations. The rates of normalization of alanine aminotransferase levels and HBV DNA nondetection at 6, 24, 36, and 48 wk were compared between the patients with natural YMDD mutations and those without, and the differences were not significant. However, there was a significant difference in the cumulative emergence rates of virological breakthrough at 48 wk in the patients with natural YMDD mutations and those without (32.5% vs 12.5%, P=0.032).
  
  
  CONCLUSIONS
  Naturally occurring YMDD mutations are detectable in a large proportion of CHB patients; breakthrough hepatitis tended to occur in patients with natural YMDD mutations.
authors.affiliation: You-Wen Tan, Yun Ye, Guo-Hong Ge, Li Chen, Xue-Jun Yu, Li-Jun Yang, Department of Liver Diseases, the Third Hospital of Zhenjiang Affiliated to Jiangsu University, Zhenjiang 212000, Jiangsu Province, China.
authors.forename: You-Wen
authors.initials: YW
authors.lastname: Tan
authors.affiliation: You-Wen Tan, Yun Ye, Guo-Hong Ge, Li Chen, Xue-Jun Yu, Li-Jun Yang, Department of Liver Diseases, the Third Hospital of Zhenjiang Affiliated to Jiangsu University, Zhenjiang 212000, Jiangsu Province, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ye
authors.affiliation: You-Wen Tan, Yun Ye, Guo-Hong Ge, Li Chen, Xue-Jun Yu, Li-Jun Yang, Department of Liver Diseases, the Third Hospital of Zhenjiang Affiliated to Jiangsu University, Zhenjiang 212000, Jiangsu Province, China.
authors.forename: Guo-Hong
authors.initials: GH
authors.lastname: Ge
authors.affiliation: You-Wen Tan, Yun Ye, Guo-Hong Ge, Li Chen, Xue-Jun Yu, Li-Jun Yang, Department of Liver Diseases, the Third Hospital of Zhenjiang Affiliated to Jiangsu University, Zhenjiang 212000, Jiangsu Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: You-Wen Tan, Yun Ye, Guo-Hong Ge, Li Chen, Xue-Jun Yu, Li-Jun Yang, Department of Liver Diseases, the Third Hospital of Zhenjiang Affiliated to Jiangsu University, Zhenjiang 212000, Jiangsu Province, China.
authors.forename: Jian-He
authors.initials: JH
authors.lastname: Gan
authors.affiliation: You-Wen Tan, Yun Ye, Guo-Hong Ge, Li Chen, Xue-Jun Yu, Li-Jun Yang, Department of Liver Diseases, the Third Hospital of Zhenjiang Affiliated to Jiangsu University, Zhenjiang 212000, Jiangsu Province, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: You-Wen Tan, Yun Ye, Guo-Hong Ge, Li Chen, Xue-Jun Yu, Li-Jun Yang, Department of Liver Diseases, the Third Hospital of Zhenjiang Affiliated to Jiangsu University, Zhenjiang 212000, Jiangsu Province, China.
authors.forename: Zhi-Lin
authors.initials: ZL
authors.lastname: Niu
authors.affiliation: You-Wen Tan, Yun Ye, Guo-Hong Ge, Li Chen, Xue-Jun Yu, Li-Jun Yang, Department of Liver Diseases, the Third Hospital of Zhenjiang Affiliated to Jiangsu University, Zhenjiang 212000, Jiangsu Province, China.
authors.forename: Dong-Jun
authors.initials: DJ
authors.lastname: Zhang
authors.affiliation: You-Wen Tan, Yun Ye, Guo-Hong Ge, Li Chen, Xue-Jun Yu, Li-Jun Yang, Department of Liver Diseases, the Third Hospital of Zhenjiang Affiliated to Jiangsu University, Zhenjiang 212000, Jiangsu Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: You-Wen Tan, Yun Ye, Guo-Hong Ge, Li Chen, Xue-Jun Yu, Li-Jun Yang, Department of Liver Diseases, the Third Hospital of Zhenjiang Affiliated to Jiangsu University, Zhenjiang 212000, Jiangsu Province, China.
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Yu
authors.affiliation: You-Wen Tan, Yun Ye, Guo-Hong Ge, Li Chen, Xue-Jun Yu, Li-Jun Yang, Department of Liver Diseases, the Third Hospital of Zhenjiang Affiliated to Jiangsu University, Zhenjiang 212000, Jiangsu Province, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Yang
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D020816:Amino Acid Motifs / Q000235:genetics*; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002681:China; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D019259:Lamivudine; D000410:Alanine Transaminase
keywords: Chronic hepatitis B; Lamivudine; Mutation; Tyrosine-methionine-aspartic acid-aspartic acid; Virological breakthrough