title: [Viral breakthrough in HBeAg-negative chronic hepatitis B patients receiving lamivudine therapy].
abstract: OBJECTIVE
  Long-term efficacy and the rate of viral breakthrough in patients with HBeAg- negative chronic hepatitis B receiving lamivudine therapy is uncertain. This study was conducted to determine the rate of viral breakthrough according to the HBeAg status and the relation of viral breakthrough with YMDD mutants.
  
  
  METHODS
  Two hundred and five patients with HBeAg-positive and 49 patients with HBeAg-negative chronic hepatitis B, who had received lamivudine for at least 9 months, were included. The mean durations of the lamivudine treatment were 176 months and 155 months in HBeAg-positive and negative patients, respectively. Analysis of HBV genome for YMDD mutations was performed by restriction-fragment-length polymorphism assay and direct sequencing.
  
  
  RESULTS
  While the cumulative rates of viral breakthrough at 12th and 24th months of the lamivudine therapy were 0% and 7% in the HBeAg-negative group, they were 12% and 39% in the HBeAg-positive group. The cumulative rate of viral breakthrough in the HBeAg-negative group was significantly lower than in the HBeAg-positive group (p<0.01). In multivariate analysis, the only significant factor related to viral breakthrough was the HBeAg status (p<0.05). The YMDD mutants were detected in all patients with viral breakthrough irrespective of HBeAg status. However, in patients without viral breakthrough, the rate of YMDD mutants was significantly higher in the HBeAg-negative group than in the HBeAg-positive group (13.3% vs 5.1%; p<0.01).
  
  
  CONCLUSIONS
  Lamivudine is expected to be more persistently effective in HBeAg-negative chronic hepatitis B because of a lower viral breakthrough rate than in HBeAg-positive chronic hepatitis B in spite of the emergence of YMDD mutants.
authors.affiliation: Department of Internal Medicine, University of Korea College of Medicine, Seoul, Korea.
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Chang
authors.forename: Jeong Yoon
authors.initials: JY
authors.lastname: Yim
authors.forename: Nam Young
authors.initials: NY
authors.lastname: Cho
authors.forename: Chang Won
authors.initials: CW
authors.lastname: Choi
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Baek
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Ahn
authors.forename: Do Won
authors.initials: DW
authors.lastname: Choi
authors.forename: Yong Dae
authors.initials: YD
authors.lastname: Kwon
authors.forename: Sun Suk
authors.initials: SS
authors.lastname: Kim
authors.forename: Oh Sang
authors.initials: OS
authors.lastname: Kwon
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Jong Eun
authors.initials: JE
authors.lastname: Yeon
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Song
authors.forename: Kwan Soo
authors.initials: KS
authors.lastname: Byun
authors.forename: Chang Hong
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000328:Adult; D020816:Amino Acid Motifs / Q000235:genetics; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D019259:Lamivudine