Telbivudine in the treatment of chronic hepatitis B

The treatment of chronic hepatitis B virus (HBV) infection has been revolutionized in the past decade by the increased availability of effective antiviral agents. Telbivudine is an L-nucleoside that is structurally related to lamivudine and has recently been approved for use in patients with chronic HBV infection. Telbivudine is highly selective for HBV DNA and inhibits viral DNA synthesis with no effect on human DNA or other viruses. This article reviews the pharmacology, pharmacokinetics, therapeutic efficacy and safety of telbivudine, and discusses its place in the current armamentarium against HBV. Relevant publications were identified from searches of Medline and PubMed between 2000 and 2008, using the search terms "hepatitis B/HBV," "telbivudine/LdT," "beta-L-thymidine," "pharmacokinetics," "safety," "adverse events," and "resistance." The reference lists of retrieved articles were searched for relevant studies. Phase 3 clinical studies demonstrate that telbivudine is superior to lamivudine over a 2-year period in hepatitis B e-antigen (HBeAg)-positive and HBeAg-negative patients. Telbivudine was associated with a statistically signficantly greater reduction in HBV DNA, greater proportion of alanine aminotransferase normalization, and greater histological response than lamivudine. Furthermore, telbivudine use resulted in fewer cases of treatment failure and less virological resistance than lamivudine. However, after 2 years of therapy, telbivudine resistance was appreciable (25%) and considerably higher than that seen with other new antivirals such as tenofovir and entecavir. Overall, telbivudine was found to be safe, although grade 3 or 4 adverse events, including elevations in creatine kinase, were more commonly found in patients receiving telbivudine than lamivudine. Telbivudine is not active against lamivudine-resistant HBV. Telbivudine is a new antiviral agent joining the armamentarium against HBV. It is superior to lamivudine in terms of therapeutic response and resistance profile. However, concerns about resistance with long-term use, along with inferior cost-effective analyses, have relegated telbivudine to a second-line agent in the management of chronic HBV infection.