Specific
HBV Mutations Predict Loss of Sensitivity to Lamivudine (Epivir-HBV) Lamivudine
(3TC; Epivir-HBV) is an inexpensive and widely used therapy for chronic
hepatitis B virus (HBV) infection, but the development of drug resistance
-- especially when used as monotherapy -- limits its long-term efficacy. As
reported in the September 2007 Journal of Viral Hepatitis, Japanese researchers
aimed to identify the viral factors responsible for poor sensitivity to lamivudine.
They analyzed 49 lamivudine-treated chronic hepatitis B patients infected with
HBV genotype C. Results ·
Serum HBV
DNA reached a level below the limit of detection using a sensitive PCR assay in
31 patients (63.3%) within the first 24 weeks of lamivudine therapy (good responder
group).
·
Only 4 patients
(12.9%) in the good responder group experienced virological breakthrough.
·
Of the patients
who did not achieve undetectable HBV DNA within 24 weeks (poor responder group),
15 (83.3%) experienced virological breakthrough.
·
Multivariate
analysis revealed that failure to achieve an undetectable HBV viral load within
24 weeks of starting therapy was independently associated with occurrence of virological
breakthrough.
·
Sequence
analysis of the HBV genome revealed that point mutations in the precore region
(G1896A) and enhancer I (A1287G/C) were observed more frequently in the good responder
group than in the poor responder group (P = 0.002 and 0.019, respectively).
·
The number
of substitutions in the reverse transcriptase (RT) domain of the HBV polymerase
was significantly higher in the good responders compared with poor responders (P = 0.026). Conclusion In
conclusion, the authors wrote, “determining the sequence of preexisting HBV, especially
for enhancer I, the precore region, and the reverse transcriptase domain of the
polymerase region, may be useful in predicting sensitivity to lamivudine therapy.” 10/23/07 Reference
Fukai, KY Zhang, F Imazeki, and others. Association
between lamivudine sensitivity and the number of substitutions in the reverse
transcriptase region of the hepatitis B virus polymerase. Journal of Viral
Hepatitis 14(9): 661-666. September 2007.
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