title: Clinical features of chronic hepatitis B patients with YMDD mutation after lamivudine therapy.
abstract: OBJECTIVE
  To study the clinical features of chronic hepatitis B (CHB) patients with tyrosine-methionine-aspartate-aspartate (YMDD) mutation after lamivudine therapy.
  
  
  METHODS
  This investigation was a retrospective study of 63 CHB patients with YMDD mutation during lamivudine therapy. Clinical data, including period and types of YMDD mutation; hepatitis B virus (HBV) DNA levels and alanine aminotransferase (ALT) levels before and after YMDD mutation were measured. YMDD mutation in the HBV DNA polymerase gene was determined using polymerase chain reaction (PCR) and direct sequencing. HBV DNA quantification was determined using real-time PCR. Relevant serum markers of HBV were measured. The follow-up period was 12 months after YMDD mutation.
  
  
  RESULTS
  YMDD mutation occurred 7-44 months (median, 21.5 months) after the start of lamivudine therapy. The majority of the cases (42/63, 66.6%) had YMDD mutants detected between 12 and 24 months. Four types of YMDD mutation were observed in this study, rtL180M/M204V mutation was the predominant type (26/63, 41.3%). A proportion of patients (16/63, 25.4%; 12/63, 19.1%) had higher HBV DNA levels and ALT levels (after mutation vs before mutation), respectively.
  
  
  CONCLUSIONS
  The majority of patients with YMDD mutants had similar or lower HBV DNA levels and ALT levels compared with baseline values. This subset of patients might have benefited from the continued lamivudine therapy. The patients with increased ALT and HBV DNA levels (breakthrough hepatitis) should benefit from the addition of a newer nucleotide analogue (e.g. adefovir).
authors.affiliation: Institute of Infectious Diseases, First Affiliated Hospital, School of Medcine, Zhejiang University, Hangzhou 310003, China. liukezhou@zju.edu.cn
authors.forename: Ke-zhou
authors.initials: KZ
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Hou
authors.forename: Edward
authors.initials: E
authors.lastname: Zumbika
authors.forename: Qin
authors.initials: Q
authors.lastname: Ni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D015684:Gene Products, pol / Q000097:blood* / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D015684:Gene Products, pol; C066027:P protein, Hepatitis B virus; D019259:Lamivudine