Treatment strategies for recurrent hepatitis C after liver transplantation

Chronic hepatitis C is a common indication for liver transplantation, accounting for 25% to 50% of all transplantation candidates in most transplant centers. Despite uncertainties regarding rates of disease progression after transplantation, a consensus is emerging that recurrent HCV infection results in liver failure in a significant although currently unmeasured proportion of patients, and that the period over which this progression occurs is shorter than in the immunocompetent population. As the disease process moves into its second decade after transplantation it can be anticipated that future morbidity and liver-related mortality will increase. Whether disease progression is accelerated by definable factors is not yet fully established, but HCV RNA levels before or soon after transplantation and aggressive immunosuppressive measures appear to influence the post-transplantation outcome. Strategies to prevent or to reduce the effect of HCV infection after liver transplantation are therefore essential. The ability to intervene in this disease is currently limited. The main obstacles are the difficulty in predicting the outcome in the individual patient and the lack of effective therapy. In contrast with hepatitis B, in which hepatitis B immune globulin has improved survival, there are no therapeutic strategies to prevent recurrent HCV infection. Neither IFN nor ribavirin, when administered as a single agent, results in sustained viral clearance. However, administration of both drugs in combination, either to prevent disease or to treat recurrence, appears promising. The inability of currently available antiviral therapy to eliminate HCV in the setting of liver transplantation suggests that indefinite treatment designed to suppress viral replication will be necessary. The feasibility of such an approach will depend on the development of drugs that reduce the histologic activity of hepatitis, improve graft and patient survival, and have side effect profiles that are acceptable to patients.