Background/aims: Viral decline during lamivudine therapy in chronic hepatitis B patients is bi-phasic. We studied the influence of lamivudine dose and baseline characteristics on parameters obtained from a mathematical model.
Methods: Chronic hepatitis B patients were randomized to receive 150 mg (group 1; n=11) or 600 mg (group 2; n=10) lamivudine daily for 4 weeks. Hepatitis B virus DNA was measured frequently with the Digene Hybrid Capture II test and the Roche PCR assay.
Results: The description of viral decline in our closely monitored patients by means of the mixed-effects approach with both the bi-phasic model and a piecewise linear regression model resulted in a good fit. Baseline alanine aminotransferase (ALT) was significantly related to the slope of the second phase of viral decline. Previous lamivudine-treated patients showed a significant slower first phase than patients naive to lamivudine treatment.
Conclusions: The initial observed difference in viral decline between 150 and 600 mg of lamivudine disappeared when baseline ALT was taken into account. This strengthens the hypothesis that the level of intrinsic activity is related to the turnover of infected hepatocytes. Moreover, reintroduction of lamivudine in previously lamivudine-treated patients should be considered carefully.