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Cell-Cept and/or ribavirin for HBV

More on immunosuppressants as antivirals :

Antiviral Research
Volume 73, Issue 3 , March 2007, Pages 192-196

http://tinyurl.com/yvazhr

Ribavirin and mycophenolic acid markedly potentiate the anti-hepatitis B virus activity of entecavir

Chunxiao Yinga, Richard Colonnob, Erik De Clercqa and Johan Neytsa, ,

aRega Institute for Medical Research, Faculty of Medicine, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium
bBristol-Myers Squibb Pharmaceutical Institute, Wallingford, CT, USA

Received 22 August 2006; revised 4 October 2006; accepted 5 October 2006. Available online 30 October 2006.

Abstract

MPA [the active metabolite of the immuno-suppressive agent CellCept] and ribavirin markedly potentiate the anti-HBV activity of the guanine-based nucleoside analogue entecavir (ETV) against both wild-type HBV and a lamivudine-resistant variant. Ribavirin (in its 5′-monophosphate form) and MPA are inhibitors of IMP-dehydrogenase and cause depletion of intracellular dGTP pools. The active triphosphorylated form of ETV may inhibit more efficiently the priming reaction, reverse transcription and DNA-dependent DNA polymerase activity of the HBV polymerase in the presence of reduced levels of dGTP. The potential for enhanced ETV activity is supported by the observation that exogenously added deoxyguanosine reversed the potentiating effect of ribavirin and MPA. Our observations may have important implications for those (liver) transplant recipients that receive MMF as part of their immunosuppressive regimen and who, because of a de novo or a persistent infection with HBV need antiviral therapy such as ETV. Further studies will need to be conducted to determine if combining ribavirin (a compound used for the treatment of HCV infections) with ETV could have an advantage for the treatment of HBV infections, in particular in patients co-infected with HCV.