The natural history of liver disease caused by persistent infection with hepatitis B virus (HBV) can be quite variable. The wide range of liver injury suggests a great degree of variability in the interaction between the replicating virus and possible immune responses. At the current time, Interferon is the most extensively studied antiviral agent for chronic hepatitis B, but because of the substantial number of nonresponders, relapses and side events, it continues the search of alternative therapies. Many nucleoside analogues agents have been found to have antiviral activity in vitro or in vivo. The second generation nucleoside analogues with the most promising potential at present include Famciclovir. We report the case of a patient with HBV infection in whom a reactivation of his disease lead to hepatic failure, analysing the possible pathogenic mechanisms implied and calling attention upon the excellent results achieved with a combine regimen of Interferon and Famciclovir.