Natural history of recurrent hepatitis C: Impact of immunosuppression

Chronic infection with the hepatitis C virus is at epidemic proportions and is currently the leading indication for liver transplantation. Despite advances in antiviral therapies, many patients remain infected at the time of transplant. In this circumstance, the allograft universally becomes infected. The recurrent viral infection can follow a more aggressive and accelerated course in the posttransplant setting with an early, rapid increase in graft fibrosis followed by a more linear increase after 3 years. Multiple factors are known to affect the rate of progression of recurrent chronic hepatitis C, including genetic, operative, donor, and recipient factors. Immunosuppression appears to also play a profound role in the progression of disease, but is understudied and not well understood. Bolus corticosteroids are associated with increased progression of fibrosis, increased graft loss and worse overall survival, thus their use needs to be balanced based on the competing goals of virologic control and prevention or treatment of cellular rejection. Induction steroids, on the other hand, do not appear to be detrimental if tapered slowly to prevent damage from immune reconstitution. There is no significant difference in the choice of calcineurin inhibitor used for maintenance therapy. The antimetabolites such as mycophenolate mofetil appear to be neutral or beneficial while certain T-cell depletion therapies are associated with severe recurrence of disease and are not recommended. The effect of the mTOR inhibitors is controversial and unclear, therefore these agents should be used with caution until further studies are available.