Telbivudine for the treatment of chronic hepatitis B

The hepatitis B virus (HBV) has a complex natural history and causes a wide spectrum of disease. Choices of therapy depend on a number of factors predictive of treatment response, clinical circumstances and stage of disease, and the likelihood and consequences of resistance to treatment. Telbivudine (beta-L-2'deoxythymidine) is a thymidine analogue that belongs to a new class of beta-L-configuration nucleoside analogues with specific activity against hepadnavirus. Phase III studies of telbivudine versus lamivudine in hepatitis B e antigen (HBeAg) and anti-HBe have been completed. In HBeAg-positive patients, HBV DNA was not detectable by polymerase chain reaction (PCR) assay in 56% of the HBeAg-positive patients receiving telbivudine after two years of treatment. In HBeAg-negative patients, at two years, HBV DNA was undetectable by PCR in 82% of HBeAg-negative patients (versus 52% of lamivudine recipients). Patients who were PCR-negative after 24 weeks were less likely to develop resistance. HBeAg seroconversion rates were also greatest in patients whose HBV DNA was undetectable at 24 weeks. These results are promising and could be used to devise a strategy to utilize combination therapy or to adjust therapy if an inadequate early viral response is observed. However, resistance is a potential shortcoming of the use of single agents for the treatment of HBV.