Background/Aims: Nucleoside analogues inhibit hepatitis B virus (HBV) replication. Entecavir, a new guanine nucleoside, has also been shown to reduce covalently closed circular DNA (cccDNA) to undetectable levels in woodchucks chronically infected with hepatitis virus. Mathematical description of changes in viral load during and after therapy may help to understand the several events that take place during nucleoside analogue treatment. Methods: Ten chronic hepatitis B patients were evaluated with a mathematical model during and after withdrawal of four doses of entecavir. Blood was drawn for HBV DNA measurement at frequent intervals. Non-linear modelling was used to fit individual patient data. Results: The median effectiveness in blocking viral production is 96% (n = 10, range 87-98%). The median half-life of viral turn-over was 16 h (range 12-29 h). The median half-life of infected hepatocytes was 257 h (= 10.7 days) (n = 9, range 112-762 h). Rebound of viral replication also followed a bi-phasic return to baseline levels. Conclusions: Decay and rebound of viral concentration during and after entecavir therapy, respectively, showed a biphasic pattern. Both can be described with a mathematical model. Data on levels of cccDNA in the liver in these patients could be helpful in supporting the parameters as calculated with the model.

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Journal of Hepatology
Department of Virology

Wolters, L., Hansen, B., Niesters, B., DeHertogh, D., & de Man, R. (2002). Viral dynamics during and after entecavir therapy in patients with chronic hepatitis B. Journal of Hepatology, 37(1), 137–144. doi:10.1016/S0168-8278(02)00115-0