Clinical course of virologic breakthrough after emergence of YMDD mutations in HBeAg-positive chronic hepatitis B.
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.
Kim
Do Young
DY
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.
Ahn
Sang Hoon
SH
Lee
Hyun Woong
HW
Park
Jun Yong
JY
Kim
Seung Up
SU
Paik
Yong Han
YH
Lee
Kwan Sik
KS
Han
Kwang-Hyub
KH
Chon
Chae Yoon
CY
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
D000998:Antiviral Agents; D004279:DNA, Viral; D019259:Lamivudine; D000410:Alanine Transaminase