New Insights in Recurrent HCV Infection after Liver Transplantation

Hsu, Shih-Hsien; Yeh, Ming-Lun; Wang, Shen-Nien

MMF and MPA. Mycophenolate mofetil (MMF) belongs to the class of antimetabolite immunosuppressive agents. Mycophenolic acid (MPA), the active metabolite of MMF, is a selective noncompetitive inhibitor of inosine monophosphate dehydrogenase (IMPDH). In addition to its potent immunosuppressive capacity, the in vitro assay has indicated that MPA has antiviral effect against HCV [45] . In HCV cell culture models, MPA could induce the expression of important antiviral interferon-stimulated genes, including interferon regulatory factor (IRF) 1, IRF 9, and interferoninduced transmembrane protein 3 (IFITM3) [46] . Among these proteins, data showed that IRF1 was directly involved in the anti-HCV activity of MPA. Moreover, MPA could have effects in synergy with IFN-on HCV replication in the same HCV experiments. In addition, when combined with IFN-, MPA augmented the transcription of multiple interferon-stimulated genes. With the molecular basis of how MPA works in synergy with IFN , proper prospective clinical studies are warranted to confirm their synergistic effects against HCV in vivo. On the other hand, although the safety and efficacy of MMF as an immunosuppressive medication in HCV patients undergoing LT have been demonstrated, the exact effects on HCV recurrence have not been clearly studied.