Hepatitis B Virus Drug Resistance and Combination Therapy

Despite the development of new nucleoside analogs, antiviral therapy of chronic hepatitis B remains a major clinical challenge. Indeed, because of both viral genome persistence and hepatitis B virus genome heterogeneity, these antivirals may select for drug-resistant mutants. The development of drug resistance is associated with liver disease progression. The progress made in virologic assays also allows a better monitoring of antiviral therapy, which enables an early treatment adaptation based on the knowledge of cross resistance between antivirals before clinical deterioration. The management of antiviral drug resistance relies on the addition of a second drug having a complementary cross-resistance profile. This has evolved towards earlier intervention at the time of virologic breakthrough, and currently it is even recommended to adapt antiviral treatment in case of incomplete viral load suppression during the first year of therapy. The concept of de novo combination therapy to significantly prevent the delay of the occurrence of hepatitis B virus drug resistance is discussed and awaits confirmation by clinical trials. (Hepatology Rev. 2007;4:34-47) Corresponding author Fabien Zoulim, [email protected]