Antiviral therapy for recurrent liver graft infection with hepatitis C virus
Abstract
Background
Antiviral therapy to treat recurrent hepatitis C infection after liver transplantation is controversial.
Objectives
To compare the therapeutic efficacy and side effects of different antiviral regimens in patients with hepatitis C re‐infected grafts after liver transplantation.
Search methods
We searched The Cochrane Hepato‐Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until September 2007.
Selection criteria
Only randomised clinical trials (irrespective of language, blinding, or publication status) comparing various antiviral therapies (alone or in combination) in the treatment of hepatitis C virus recurrence in liver transplantation were considered for the review.
Data collection and analysis
Two authors collected the data independently. We calculated the relative risk (RR) or weighted mean difference (WMD) with 95% confidence intervals (CI) using the fixed‐effect and the random‐effects models based on available case‐analysis.
Main results
A total of 389 liver transplant recipients with proven hepatitis C recurrence were randomised in eleven trials to various interventions and controls. The mean proportion of genotype I was 77.8% in the seven trials that reported the genotype. Only one or two trials were included under each comparison. All the trials were of high risk of bias. There was no difference in the mortality, graft rejection, or in re‐transplantation between intervention and control in any of the comparisons that reported these outcomes. None of the trials reported liver decompensation or quality of life. Life‐threatening adverse effects were not reported in either group in any of the comparisons. Up to 87.5% of patients required reduction in dose and up to 42.9% of patients required cessation of treatment in the various comparisons because of adverse effects or because of patient's choice to stop treatment.
Authors' conclusions
1. Considering the lack of clinical benefit and the frequent adverse effects, there is currently no evidence to recommend antiviral treatment for recurrent liver graft infection with HCV.
2. Further randomised clinical trials with adequate trial methodology and adequate duration of follow‐up are necessary.
Plain language summary
No evidence to support used of antiviral drugs in patients with recurrent hepatitis C infection after liver transplantation
Antiviral therapy to treat recurrent hepatitis C infection after liver transplantation is controversial. This systematic review of randomised clinical trials was performed to compare the benefits and side effects of different antiviral therapies in patients with hepatitis C re‐infected grafts after liver transplantation. A total of 389 liver transplant recipients with proven hepatitis C recurrence were randomised in 11 trials to various interventions and controls (including single drug regimen or multidrug regimen of interferon, ribavirin, and amantadine). Seven trials reported the proportion of patients belonging to genotype I (a subtype, which is more difficult to treat than other subtypes). More than three‐quarters of the patients belonged to genotype I in these seven trials. Only one or two trials were included under each comparison. All the trials were of high risk of bias (risk of systematic error due to inadequate methodological quality). There was no difference in the mortality, graft rejection, or in re‐transplantation between intervention and control in any of the comparisons that reported these outcomes. None of the trials reported liver decompensation or quality of life. Life threatening adverse effects were not reported in either group in any of the comparisons. Up to 87.5% of patients required reduction in dose and up to 42.9% of patients required cessation of treatment in the various comparisons because of adverse effects or because of patient's choice to stop treatment. Further high‐quality randomised clinical trials are necessary to assess the long‐term survival benefits for various treatment options, particularly combination pegylated interferon and ribavirin therapy with or without the use of granulocyte colony‐stimulating‐factor and synthetic erythropoietin, which are helpful in treating the adverse effects of the therapies without reducing the dosage.
