[Viral breakthrough in HBeAg-negative chronic hepatitis B patients receiving lamivudine therapy].
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.
Chang
Yun Jung
YJ
Department of Internal Medicine, University of Korea College of Medicine, Seoul, Korea.
Yim
Jeong Yoon
JY
Cho
Nam Young
NY
Choi
Chang Won
CW
Baek
Soo Jung
SJ
Ahn
Soo Hyun
SH
Choi
Do Won
DW
Kwon
Yong Dae
YD
Kim
Sun Suk
SS
Kwon
Oh Sang
OS
Kim
Ju Hyun
JH
Yeon
Jong Eun
JE
Song
Jin Won
JW
Byun
Kwan Soo
KS
Lee
Chang Hong
CH
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
D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D019259:Lamivudine