title: Clinical course of virologic breakthrough after emergence of YMDD mutations in HBeAg-positive chronic hepatitis B.
abstract: OBJECTIVE
  High rate of resistance to lamivudine is a major problem in treating chronic hepatitis B (CHB) patients. We investigated the course of virologic breakthrough (VB) after emergence of YMDD mutants in CHB patients receiving lamivudine.
  
  
  METHODS
  Ninety-three consecutive HBeAg-positive CHB patients treated with lamivudine (100 mg/day) who developed YMDD mutants and VB were enrolled. The clinical breakthrough (CB) was defined by elevation of alanine aminotransferase (ALT) >2 times the upper limit of normal.
  
  
  RESULTS
  The median age was 47 years, and genotype of hepatitis B virus (HBV) was all C. The median duration of lamivudine administration was 39 months, and median pre-lamivudine ALT and HBV DNA were 165 IU/l and 1.2 x 10(8) copies/ml. In all patients, CB concurred with VB or appeared some months following VB. When patients were divided into two groups according to time sequence of two breakthroughs - group 1 (VB followed by CB, n = 68) and group 2 (concurrent VB and CB, n = 25)--there was no difference in patient and virologic characteristics between the two groups. The median time from VB to CB was 8 months in group 1.
  
  
  CONCLUSIONS
  VB might eventually progress to CB in HBeAg-positive patients harboring YMDD mutants with high pretreatment ALT and HBV DNA.
authors.affiliation: BK 21 Project for Medical Science, Liver Cirrhosis Clinical Research Center, Yonsei Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Do Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Ahn
authors.forename: Hyun Woong
authors.initials: HW
authors.lastname: Lee
authors.forename: Jun Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Seung Up
authors.initials: SU
authors.lastname: Kim
authors.forename: Yong Han
authors.initials: YH
authors.lastname: Paik
authors.forename: Kwan Sik
authors.initials: KS
authors.lastname: Lee
authors.forename: Kwang-Hyub
authors.initials: KH
authors.lastname: Han
authors.forename: Chae Yoon
authors.initials: CY
authors.lastname: Chon
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D005260:Female; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000503:physiopathology / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D019259:Lamivudine; D000410:Alanine Transaminase