Treatment of progressive hepatitis C recurrence after liver transplantation with combination interferon plus ribavirin

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation ( OLT) is common, although the majority of cases are mild. A subset of transp lant recipients develops progressive allograft injury, including cirrhosis and allograft failure. Minimal data are available on the safety and efficac y of antiviral treatment in this group of patients. The aim of this study i s to review our experience in the treatment of moderate to severe HCV recur rence with combination interferon-alpha 2b and ribavirin (IFN/RIB), Between October 1993 and October 1999, a total of 197 patients underwent OLT for H CV-related liver failure. This study describes 12 transplant recipients wit h moderate to severe recurrence treated with IFN/RIB, All patients met at l east 1 of the following inclusion criteria: (1) moderate to severe inflamma tion (grade III to TV) on allograft biopsy, (2) bridging fibrosis on allogr aft biopsy, or (3) severe cholestasis attributable solely to HCV recurrence . Two patients had undergone re-OLT for allograft cirrhosis secondary to HC V recurrence and now had evidence of progressive HCV in their second allogr afts. Appropriate dose reductions of both IFN and RIB, as well as initiatio n of granulocyte colony-stimulating factor (G-CSF), for marked leukopenia w ere recorded. IFN/RIB therapy was started GO to 647 days post-OLT, and dura tion of therapy ranged from 39 to 515 days. Seven patients were administere d G-CSF to successfully treat leukopenia. Six of the 12 patients (50%) beca me HCV RNA negative by polymerase chain reaction. One of these 6 patients ( no. 1) was HCV RNA negative at 6 months but chose to discontinue therapy be cause of intolerable side effects, experienced a relapse, and was HCV RNA p ositive at 12 months. Two of the remaining 5 patients were HCV RNA negative at 2 and 3 months off therapy. For the entire group, there was a statistic ally significant decrease in serum biochemical indices assessed at initiati on of therapy and 1, 3, and 6 months into therapy. Most patients required d ose reductions of both IFN and RIB. Five patients died; 3 patients died of liver-related complications that included severe intrahepatic biliary chole stasis, severe HCV recurrence, and chronic rejection with profound cholesta sis. In the subset of HCV-positive liver transplant recipients with moderat e to severe recurrence, combination IFN/RIB therapy resulted in complete vi rological response (serum RNA negative) in 6 of 12 patients (similar to 50% ). However, only 1 of 12 patients (8.3%) had sustained virological clearanc e after cessation of IFN/RIB therapy. Dose reductions of both IFN and RIB w ere required in most patients. The use of G-CSF (sometimes preemptively) al lowed correction of leukopenia and full-dose antiviral therapy. Multicenter trials using combination therapy to identify factors predictive of respons e are needed in the subset of patients with progressive allograft injury.