Safety and efficacy of peginterferon-α2a plus ribavirin treatment in renal transplant recipients with chronic hepatitis C

Background & Aims: Interferon (IFN)-based therapy in chronic hepatitis C virus (HCV)-infected renal transplant (RT) recipients has been associated with a high risk of acute allograft rejection (AAR) and poor efficacy. We assessed the safety and efficacy of PegIFN alpha-2a and ribavirin (RBV) combination therapy in HCV-infected RT recipients. Methods: Thirty-two adult RT recipients of >12-month duration, infected with HCV genotypes 1(62.5%) and 4 (37.5%), and significant fibrosis (Metavir >= F2) were recruited in an open-label trial with PegIFN alpha-2a 135-180 mu g/week, plus RBV 200-1200 mg/day for 48 weeks, based on the estimated glomerular filtration rate. Safety assessments were performed weekly for 4 weeks, 2-weekly for 8 weeks, and 6-weekly for 36 weeks. Study end points were sustained virologic response (SVR) or development of AAR. Allograft biopsies were performed for 20% increase in creatinine from pretreatment levels, or optionally at week 12 on surveillance protocol. Renal safety was compared with matched untreated historical controls (n = 31). Results: None of the treated patients showed AAR when biopsied for raised creatinine (12.5%) or during surveillance (37.5%), with incremental and sustained creatinine increases occurring in 6.3% of treated patients and 16.1% of untreated controls (p = 0.148), by week 72 assessment. Mean pretreatment and end-of-assessment creatinine in treated patients remained similar (106.8 +/- 32.0 vs. 113.4 +/- 62.8, respectively; p = 0.140), while levels increased significantly in the controls (106.6 +/- 35.6 vs. 142.5 +/- 93.0, respectively; p = 0.013). Rapid, early virologic response (EVR) and SVR occurred in 12.5%, 56.3%, and 37.5% of cases, respectively. SVR was similar in both genotypes (p = 1.000). PegIFN and RBV dose reductions were required in 34.4% and 78.1%, respectively; discontinuation was required in 12.5%. Binary logistic regression identified only EVR (OR, 20.4; 95% CI: 2.2-192.6; p = 0.008) as an independent predictor of SVR. Conclusions: PegIFN/RBV therapy is not associated with AAR in RT recipients at low risk for rejection but has modest efficacy in the treatment of HCV. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.