Interferon-Based Combination Anti-Viral Therapy for Hepatitis C Virus After Liver Transplantation: A Review and Quantitative Analysis

Abstract

Recurrence of hepatitis C virus (HCV) infection after liver transplantation (LT) is universal.However, the efficacy, tolerability and safety of combination interferon and ribavirin (IFN-RIB) or peginterferon and ribavirin (PEG-RIB) anti-viral therapies post-LT are uncertain. We performed a comprehensive search of major medical databases and conference proceedings (1996-2005). The main outcome measure was sustained virological response (SVR, undetectable HCV RNA) at 6 months. Summary estimates were calculated using random-effects models. Twenty-seven IFN-RIB and 21 PEG-RIB studies were included. IFN-RIB was associated with a pooled SVR rate of 24% (95% CI, 20-27%), while PEG-RIB was associated with an SVR rate of 27% (23-31%). Pooled discontinuation rates were 24% (21-27%) with IFN-RIB and 26% (20-32%) with PEG-RIB. The pooled rate of acute graft rejection was 2% (1-3%) with IFN-RIB and 5% (3-7%) with PEG-RIB. IFN-RIB and PEG-RIB therapies in HCV infection post-LT were associated with similar but overall low SVR and were poorly tolerated. The rate of acute rejection was small. The therapeutic advantage of PEG-RIB therapy observed in non-transplant chronic HCV infection appears to be attenuated post-LT. Clinical trials are needed to evaluate reasons for this posttransplant therapeutic disadvantage and to find strategies to ameliorate them.

Hepatitis C treatment before and after liver transplant

“…In uncontrolled studies the combined use of pegylated interferon and ribavirin proved to be the best strategy, with responses between 30% and 45% [2,[36][37][38].…”

Managing hepatitis C in liver transplant patients with recurrent infection

“…[93][94][95][96]100,101,104,105 A meta-analysis from over 40 treatment trials estimated that SVR rates of combination therapy were 24% and 27%. 147 A recent systematic review of predominantly therapeutic intervention studies by Berenguer et al confirmed that 30.2% of patients treated with PEG-IFN plus ribavirin will attain SVR. 131 Dose reductions and discontinuation of treatment were common in these studies: 73% and 27.6%, respectively.…”

Donor-Derived Infectious Complications and Disease Transmission

“…Combination therapy for HCV after liver transplantation is currently recommended, and the most widely used is pegylated-interferon (Peg-IFN) plus ribavirin. Treatment of HCV with Peg-IFN plus ribavirin after liver transplantation is generally only successful in achieving SVR in 20-45% of recipients and is associated with high rates (30-50%) of discontinuation due to intolerability (Ponziani et al, 2011;Wang et al, 2006). The inability to reach target RBV doses due to the high prevalence of renal insufficiency in recipients is a major limiting factor in achieving an acceptable SVR rate (Chalasani et al, 2005;Gane et al, 1998).…”