Clinical course after stopping lamivudine in chronic hepatitis B patients with lamivudine-resistant mutants.
BACKGROUND
The efficacy of lamivudine therapy in chronic hepatitis B is well established. However, drug-resistant YMDD mutants emerge with extended therapy. This may result in the resurgence of viral replication, the return of hepatitis and histological deterioration.


OBJECTIVE
To study the safety of stopping lamivudine when the drug is no longer effective.


METHODS
In the 5-year Asian Lamivudine Study, 34 patients from a single centre were included in this study. They had harboured YMDD mutants for at least 2 years. Lamivudine was discontinued and they were followed up at regular intervals. Clinical symptoms, liver biochemistry and viral serology were monitored.


RESULTS
In a median follow-up of 20 months after stopping lamivudine (range, 7-39 months), 20 of the 34 patients (58.8%) had elevated alanine aminotransferase (ALT), 13 patients (38.2%) had elevated ALT one to five times the upper limit of normal and seven patients (20.6%) had an ALT flare (ALT more than five times the upper limit of normal with detectable hepatitis B virus DNA). There was no liver decompensation. ALT flare could be predicted by ALT over twice the upper limit of normal at the time of stopping lamivudine (P = 0.037).


CONCLUSIONS
It is relatively safe to stop lamivudine after YMDD mutants have emerged. ALT levels greater than or equal to twice the upper limit of normal at the time of stopping lamivudine have a higher risk for ALT flare.
Wong
V W-S
VW
Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong Department of Medicine, Hong Kong.
Chan
H L-Y
HL
Wong
M L
ML
Tam
J S-L
JS
Leung
N W-Y
NW
D000328:Adult; D024882:Drug Resistance, Viral; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*
D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine