Early detection of hepatitis B drug resistance: implications for patient management

Despite the availability of safe and effective prophylactic vaccines, hepatitis B viral disease has remained a tenacious scourge, ranking ninth globally among all causes of mortality (up to 1 million deaths annually). Approximately 6% of the global population--more than 350 million people--have failed to resolve viral infection and become chronic carriers, eventually placing between 15 and 25% of such individuals at risk for end-stage liver disease. Until recently, the immunomodulator interferon-alpha and especially the nucleoside analog lamivudine (Epivir) have been the treatments of choice for chronic hepatitis B viral infection. However, the inexorable development of drug resistance to lamivudine has been a major clinical impediment to the long-term use of such treatment. Herein, the current and future diagnostic methods for early detection of emerging drug resistance to the hepatitis B virus is reviewed. Given the recent approval of adefovir dipivoxil (Hepsera) and the possibility that other nucleoside and nucleotide analogs could soon become part of the hepatitis B virus therapeutic arsenal, the clinical ramifications for co-ordinated use of diagnostic tests together with new antihepadenaviral agents for optimal patient management is also discussed.