Georgia Institute of Technology College of Sciences

Chronic HBV infection affects 350 million people and can lead to death through cirrhosis-induced liver failure or hepatocellular carcinoma. We present the rich dynamics of two recent models of HBV infection with logistic hepatocyte growth and a standard incidence function governing viral infection. One of these models also incorporates an explicit time delay in virus production. All model parameters can be estimated from biological data. We simulate a course of lamivudine therapy and find that the models give good agreement with clinical data. Previous models considering constant hepatocyte growth have permitted only two dynamical possibilities: convergence to a virus free or an endemic steady state. Our models admit periodic solutions. Minimum hepatocyte populations are very small in the periodic orbit, and such a state likely represents acute liver failure. Therefore, the often sudden onset of liver failure in chronic HBV patients can be explained as a switch in stability caused by the gradual evolution of parameters representing the disease state.