Incidence and severity of acute allograft rejection in liver transplant recipients treated with alfa interferon.
Interferon alfa-2b (IFN-alpha) therapy has been shown to be effective in the treatment of viral hepatitis B (HBV) or viral hepatitis C (HCV) in patients who did not undergo transplantation. However, in allograft recipients, treatment with IFN-alpha often leads to allograft rejection. The aim of the present study was to determine if IFN-alpha therapy increases the incidence or severity of acute rejection in human liver allograft recipients. One hundred five orthotopic liver transplant (OLT) recipients with HBV (n = 32), HCV (n = 58), or Non A Non B Non C (n = 15) viral infections were treated with a 6-month course of IFN-alpha, 5 million U subcutaneously three times a week, which began 2 to 97 months after transplantation. The mean hepatitis activity index (HAI) at the beginning of the therapy was 10.1 +/- 3.0. The baseline immunosuppression was achieved by tacrolimus in 77 patients and by cyclosporine A (CyA) in 28 patients. Contemporaneous controls consisted of 132 OLT patients (100 who received tacrolimus and 32 who received CyA) who did not receive IFN-alpha. A retrospective analysis was performed on this group of patients. The incidence of rejection and the baseline immunosuppression were compared. All biopsies were reviewed without knowledge of clinical data and scored for HAI and for rejection activity index (RAI). The biochemical response to IFN-alpha was also examined. The mean baseline maintenance dose of prednisone was greater by 2 mg daily in patients who received IFN-alpha with tacrolimus compared with control patients who did not receive IFN-alpha with tacrolimus (IFN-alpha 5. 3 +/- 5.2 mg daily v controls 3.3 +/- 4.9 mg daily; P </= .05). Similarly, the mean maintenance dose of prednisone was greater by 2.5 mg daily in patients who received IFN-alpha compared with controls who received CyA-based immunosuppression (IFN-alpha 9.8 +/- 3.1 mg daily v controls 7.3 +/- 3.3 mg daily; P = .01). Acute rejection episodes were detected in 10.5% (n = 11) of IFN-alpha-treated patients compared with 8.8% of controls for the similar time period from OLT and period of exposure to risk of rejection. Mean RAI was 2.0 +/- 2.4 for the IFN-alpha-treated group and 2.1 +/- 1.7 for controls. Rejection episodes with IFN-alpha treatment were mild and responded to steroid therapy. In OLT recipients, the risk of acute rejection was not increased by the introduction of IFN-alpha. However, in this study, patients were exposed to greater levels of immunosuppression.
Jain
A
A
Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center and the Veterans Administration Medical Center, Pittsburgh, PA 15213, USA.
Demetris
A J
AJ
Manez
R
R
Tsamanadas
A C
AC
Van Thiel
D
D
Rakela
J
J
Starzl
T E
TE
Fung
J J
JJ
D001706:Biopsy; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood; D006084:Graft Rejection / Q000473:pathology; D006525:Hepatitis, Viral, Human / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D008111:Liver Function Tests; D016031:Liver Transplantation; D011241:Prednisone / Q000008:administration & dosage / Q000097:blood; D011994:Recombinant Proteins; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D016572:Cyclosporine; D011241:Prednisone; D016559:Tacrolimus