Antiviral prophylactic intervention for chronic hepatitis C virus in patients undergoing liver transplantation
Abstract
Background
It is not clear whether prophylactic antiviral therapy is indicated in patients undergoing liver transplantation for chronic decompensated hepatitis C virus (HCV) infection.
Objectives
To compare the benefits and harms of different prophylactic anti‐viral therapies for patients undergoing liver transplantation for chronic HCV infection.
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 August 2010.
Selection criteria
Only randomised clinical trials irrespective of language, blinding, or publication status and comparing various prophylactic antiviral therapies (alone or in combination) in the prophylactic treatment of patients undergoing liver transplantation for chronic HCV infection.
Data collection and analysis
Two authors collected the data independently. We calculated the risk ratio (RR) or mean difference (MD) or hazard ratio (HR) with 95% confidence intervals (CI) using the fixed‐effect and the random‐effects models based on available case analysis.
Main results
A total of 477 liver transplant recipients undergoing liver transplantation for chronic HCV infection were randomised in eleven trials to various interventions and controls. The proportion of genotype I varied between 49% to 88% in the five 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 significant differences in the patient survival, graft rejection, re‐transplantation, or HCV recurrence between intervention and control groups in any of the comparisons that reported these outcomes. None of the trials reported liver decompensation, primary graft non‐function, intensive therapy unit stay, hospital stay, or quality of life. Life‐threatening adverse events were not reported in either group in any of the comparisons. Up to 91% of patients required reduction in dose and up to 36% of patients required cessation of treatment in the various comparisons because of adverse events or because of patient's choice to stop treatment.
Authors' conclusions
There is currently no evidence to recommend prophylactic antiviral treatment to prevent recurrence of HCV infection either in primary liver transplantation or re‐transplantation. Further randomised clinical trials with adequate trial methodology and adequate duration of follow‐up are necessary.
PICOs
Plain language summary
No evidence to support use of preventive antiviral drugs in patients undergoing liver transplantation for hepatitis C viral infection
It is not clear whether antiviral therapy is indicated in patients undergoing liver transplantation for chronic liver disease incompatible with long‐term survival resulting from hepatitis C virus (HCV) infection. We performed a Cochrane review of randomised clinical trials to assess the benefits and adverse events of the different antiviral treatments used for preventing the recurrence of chronic liver disease due to HCV infection. A total of 477 liver transplant recipients undergoing liver transplantation for chronic HCV infection were randomised in eleven trials to various interventions and controls. The proportion of genotype I (a subtype, which is more difficult to treat than other subtypes) varied between 49% to 88% in the five trials that reported the genotype. Only one or two trials were included under each comparison. All the trials were of high risk of systematic error bias. There was no statistically significant difference in the patient survival, liver graft survival (ie, requirement for retransplantation), or incidence of chronic liver disease due to HCV reinfection. None of the trials reported liver decompensation, primary graft non‐function (graft failure before the liver graft starts functioning), intensive therapy unit stay, hospital stay, or quality of life. Life‐threatening adverse events were not reported in either group in any of the comparisons. Up to 91% of patients required reduction in dose and up to 36% of patients required cessation of treatment in the various comparisons because of adverse events or because of patient's choice to stop treatment. Due to the limited number of patients and observed outcomes as well as due to the trials of systematic errors, it is not possible to advocate or refute prophylactic antivirals in patients undergoing liver transplantation. Further randomised clinical trials at low risk of random errors or systematic errors are necessary to assess the long‐term survival benefits for various treatment options in these patients.
