New Antiviral Treatment for Chronic Hepatitis B

Abstract

Prolong treatment maintaining a low viraemic state may reduce the risk of longterm complications of chronic hepatitis B. Lamivudine has profound anti-viral effect with three to four logarithmic reduction of hepatitis B virus (HBV) DNA level after 1 year. Its long-term use is, however, associated with the emergence of drug resistant virus (YMDD mutations). High pretreatment alanine aminotransferase (ALT) levels and HBV DNA levels are associated with earlier HBV DNA breakthroughs due to YMDD mutations. In addition, HBV DNA levels over 10’ copies/ml at 6 months of lamivudine therapy are also associated with the chance of YMDD mutations. There are now several new nucleoside analogues currently being studied by phase II/ III clinical trials. (3-L-2’-deoxythymidine (LdT) and 13L-2’-deoxycytidine (val-LdC) are unsubstituted (3-L-2’deoxynucleosides with highly potent, selective and specific anti-HBV activity. In a phase I/ II dose escalation trial of LdT, there was a dose proportional response in the reduction of HBV DNA levels. Maximal reduction of 3.4-3.8 logs was achieved in the dose of 400-800 mg daily. In an ongoing phase IIb clinical trial, LdT with doses of 400 and 600 mg daily caused significantly higher greater HBV DNA reduction compared to lamivudine 100 mg daily monotherapy (-6.1 logs vs. -4.7 logs respectively, p=0.05). LdT is also very safe and without significant side effects. Trials using combination therapy combining immunomodulators and nucleoside analogues or combining different nucleoside analogues are currently being conducted.