Successful rescue therapy with tenofovir in a patient with hepatic decompensation and adefovir resistant HBV mutant

After 2 years of therapy, a cirrhotic patient developed the rtN236T and rtA181T adefovir resistant mutations. He had been previously treated with lamivudine, developed lamivudine resistance and, despite good compliance, had an incomplete response to adefovir. Adefovir resistance resulted in viral breakthrough with hepatitis flare-up and liver decompensation. Tenofovir had an excellent antiviral effect allowing sustained control of viral replication and reversal of hepatic failure.In patients with cirrhosis, adefovir resistance can lead to severe hepatitis. Tenofovir appears to be an effective treatment of adefovir resistant mutants. Incomplete control of viral replication with adefovir requires monitoring for viral resistance and should prompt a change in antiviral treatment.In chronic hepatitis B, prolonged antiviral therapy with nucleoside analogues, such as lamivudine, is often necessary but may result in the emergence of escape mutants which can be detected in as many as 70% of patients, after 4 years of therapy [1]. Adefovir dipivoxil has potent antiviral activity on lamivudine-resistant hepatitis B virus (HBV) strains [2,3]; nonetheless, long term use of this nucleotide analogue is also associated with resistance in up to 18% of patients, after 4 years of therapy [4]. In the few cases published thus far, adefovir-resistant HBV displayed the rtN236T mutation and maintained susceptibility to lamivudine in vivo [5,6]. However, new adefovir-resistant mutations have been reported, such as the rtA181V mutation which is closely located to the rtL180M mutation conferring resistance to lamivudine [4]. It is uncertain whether those new adefovir escape mutants are susceptible to lamivudine [7] and thus drugs active on both adefovir and lamivudine-resistant HBV strains are needed.We report on the case of a patient with HBV-related cirrhosis and lamivudine-resistant HBV who developed adefovir resistance with viral breakthrough and liver failure. The patient had both an rtN