Therapy with Peginterferon Alfa Does Not Increase the Risk of Acute Rejection Post Liver Transplantation

Treatment of hepatitis C virus (HCV) with interferon after orthotopic liver transplantation (OLT) theoretically may precipitate acute cellular rejection (ACR), as is seen with kidney transplantation.

In practice, however, standard interferon has not been found to increase the incidence of ACR post OLT. Currently, there is little data regarding pegylated interferons and ACR risk.

Since January 2001, at the Mt Sinai Medical Center, patients with histological evidence of HCV recurrence post OLT have been treated with either pegylated interferon alfa-2a or 2b, in combination with ribavirin (PEG-riba), utilizing a standardized protocol.

Data was collected retrospectively. Episodes of biopsy proven ACR prior to PEG-riba therapy were classified as early (< 6 months post OLT) and late (> 6 months post OLT). Statistical significance was determined via Fisher's exact test.

Results

Fifty-two patients were treated with pegylated interferon Α2a or 2b and ribavirin (25 and 27 respectively) for a mean of 8.9 months (range 1-30). Forty patients (77%) were taking tacrolimus and 12 cyclosporin A titrated to standard trough levels.

Prior to PEG-riba therapy, there were 15 episodes of ACR in 15 patients in the early phase post OLT occurring over a total of 280 months (0.053 ACR/month) and 18 episodes in 14 patients during the late phase over a total of 1418 months (0.013 ACR/month), (p=0.0001).

Following institution of PEG-riba there were 6 episodes of ACR in 6 patients after a total of 464 months on treatment (0.012 ACR/month).

As expected, the ACR rate was significantly lower during the PEG-riba period compared to the early post OLT period (p=0.0025) with no difference demonstrated between the PEG-riba period and the late post OLT period (p=1.0).

In the 6 patients who developed an ACR episode on PEG-riba, 3 (50%) had therapy started in the early phase post OLT, 2 had a prior history of ACR, 2 subsequently developed features of chronic rejection and all were taking tacrolimus.

During immunosuppressive augmentation, PEG-riba therapy was continued in 5/6 patients, but none had a virological response.

Conclusions

·  PEG-riba therapy does not increase the risk of ACR post OLT. In this study, patients who developed ACR while on PEG-riba had a prior ACR episode or started therapy within 6 months of OLT;

·  ACR occurring during therapy may be a negative prognostic factor for virological response; and

·  Following an episode of ACR it appears safe to continue PEG-riba therapy as recurrence of ACR is low.

05-17-04

Reference
N Elhajj and others. The Risk of Acute Rejection in Patients Treated with Pegylated Interferon and Ribavirin for Recurrent Hepatitis C Post Liver Transplantation. Abstract S1176. Digestive Disease Week 2004. May 15-20. New Orleans, LA.