Background: Prolonged nucleoside analogue therapy has been shown to reduce viral replication and normalize serum transaminases in the majority of chronic hepatitis B patients. However, from a theoretical point of view, monotherapy with lamivudine (a cytosine nucleoside analogue) will probably not result in eradication of hepatitis B virus. A prolonged course of lamivudine therapy would be needed to clear the virus from the liver. The occurrence of mutations, in combination with continuing low-grade viral replication in a number of patients, will prevent elimination of the virus from the liver. However, combination therapy with more than one nucleoside analogue could possibly overcome the disadvantages of monotherapy.
Patients and methods: In this study, we report on 12 patients who were evaluated by means of a mathematical model during lamivudine monotherapy and lamivudine-famciclovir and lamivudine-ganciclovir therapy.
Results: There was no difference in the parameters representing blocking of viral production (epsilon = 93%, 95% and 86%, respectively), turnover of free virus (half-life of 16 h, 10 h and 12 h, respectively) and turnover of infected hepatocytes (half-life of 9 days, 7 days and 4 days, respectively) between the lamivudine, lamivudine-famciclovir and lamivudine-ganciclovir treatment groups.
Conclusions: Although our study group is small, we do not think the drug combinations used offer a major advantage over lamivudine monotherapy. Different combinations of nucleoside analogues need to be studied in order to obtain a major breakthrough in this treatment strategy.