Antiviral Therapy of HCV-Related Liver Disease in Renal Transplant

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Antiviral Therapy of HCV-Related Liver Disease in Renal Transplant

Summary and Introduction

Summary


Background: The efficacy and safety of interferon-based therapy in renal transplant recipients with hepatitis C remains unclear, although a number of small clinical trials have been published addressing this issue.
Aim: To evaluate efficacy and safety of antiviral therapy with interferon (interferon alone or interferon plus ribavirin) in renal transplant patients with hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical trials.
Methods: The primary outcomes were sustained virological response (as a measure of efficacy) and/or drop-out rate (as a measure of tolerability). We used the random-effects model of DerSimonian and Laird, with heterogeneity and sensitivity analysis.
Results: We identified 12 clinical trials (102 unique patients); there was one controlled study. The summary estimate for sustained virological response and drop-out rate was 18.0% (95% CI 7.0–29.0%) and 35.0% (95% CI 20–50%), respectively. The most frequent side-effect requiring interruption of treatment was graft dysfunction (n = 28; 71.7%). Meta-regression analysis showed an inverse and significant association between reference year and drop-out logit rate (P = 0.012); an inverse link between sustained virological response logit rate and frequency of hepatitis C virus genotype 1 (P = 0.067) and cirrhosis (P = 0.08) was found, even if no statistical significance was reached. No publication bias was observed.
Conclusions: Interferon-based therapy of hepatitis C has poor tolerance and safety after renal transplant. The optimal treatment of hepatitis C after renal transplant requires additional agents or alternative therapeutic approaches.

Introduction


The reported prevalence of hepatitis C virus (HCV) infection ranges from 5% to 15% in renal transplant (RT) recipients in the developed world; the frequency of HCV is much higher among RT patients in less-developed countries. The adverse consequences on long-term graft and patient survival related to the presence of HCV infection after kidney or kidney–pancreas transplantation have already been established.

Interferon (IFN)-based therapy is the mainstay for HCV-related liver disease. The literature about treatment of acute or chronic hepatitis C with IFN in the RT recipient population consists predominantly of case reports and small clinical trials. Data on alternative therapeutic options, such as combination therapy (IFN plus ribavirin), and ribavirin or amantadine monotherapy are even more preliminary in nature. Although some authors have shown a beneficial effect, no review summarized the size and consistency of IFN's effect on hepatitis C in the RT population. The optimal regimen for IFN-based therapy after RT in patients with hepatitis C remains poorly established.

The primary goal of our study was to synthesize the available evidence on the tolerability and efficacy of IFN-based therapy of hepatitis C after RT by performing a systematic review of the literature with a meta-analysis of clinical trials.

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