The liver is an important organ of the body and has various functions including generation of energy from food; production of material necessary for congealing, processing, and excretion of drugs and waste products in blood; and filtering out the harmful bacteria that enter the body through the gut. Hepatitis C virus can cause damage to the liver usually in an insidious manner (chronic hepatitis C infection). Sometimes, the liver damage can be so severe that the liver is not able to carry out the normal functions, resulting in liver failure. Liver transplantation is an effective treatment for the treatment of liver failure due to chronic hepatitis C infection. However, liver transplantation does not eradicate the virus and the virus can affect the donor liver graft. One of the proposed strategies to treat the recurrence of chronic hepatitis C virus infection in these patients is using antiviral treatments. The effectiveness of these treatments is not known. We performed a detailed review of the medical literature (to February 2013) to determine the benefits and harms of different antiviral treatments for patients with recurrent hepatitis C infection after undergoing liver transplantation for chronic hepatitis C virus infection. We sought evidence from randomised clinical trials only. When conducted properly, such trials provide the best evidence. Two authors independently identified the trials and obtained the information from the trials to minimise error.
Eleven trials including 501 liver transplant recipients provided data for this review. The patients were randomised to receive different treatments including no treatment in these 11 trials. Long-term follow-up was not available in these trials.
There were no significant differences in the proportion of patients who died, required retransplantation, developed graft rejection that required treatment, or increased liver damage (as evaluated using a microscope) between the groups in any of the comparisons in which these outcomes were reported. Quality of life and liver decompensation were not reported in any of the trials. There was a significantly higher proportion of participants who developed serious complications in the ribavirin plus peg interferon combination therapy compared with peg interferon monotherapy. There was no significant difference in the proportion of participants who developed serious complications or in the number of serious adverse events between the intervention and control groups in the other comparisons that reported serious complications. There is currently no evidence to recommend antiviral treatment for patients with recurrence of chronic hepatitis C virus infection either in primary liver transplantation or retransplantation.
Quality of evidence
All the trials had high risk of systematic errors (that is, bias where was a potential to arrive at wrong conclusions because of the way the trials were conducted overestimating benefits and underestimating harms) and random errors (there was a potential to arrive at the wrong conclusions because of the play of chance). The overall quality of evidence was very low.
Further randomised clinical trials at low risk of random errors or systematic errors are necessary to assess the long-term survival and other benefits of various treatment options in these patients.
Considering the lack of clinical benefit, there is currently no evidence to recommend or refute antiviral treatment for recurrent liver graft infection with hepatitis C virus. Further randomised clinical trials with low risk of bias and low risk of random errors with adequate duration of follow-up are necessary.
Antiviral therapy for recurrent hepatitis C infection after liver transplantation is controversial due to unresolved balance between benefits and harms.
To compare the therapeutic benefits and harms of different antiviral regimens in patients with hepatitis C re-infected grafts after liver transplantation.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 1, 2013), MEDLINE, EMBASE, and Science Citation Index Expanded to February 2013.
We considered 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 for the review.
Two authors collected the data independently. We calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) using the fixed-effect and the random-effects models based on available case-analysis. In the presence of only trials for a dichotomous outcome, we performed the Fisher's exact test.
Overall, 17 trials with 736 patients met the inclusion criteria for this review. All trials had high risk of bias. Five hundred and one patients randomised in 11 trials provided information for various comparisons in this systematic review after excluding post-randomisation drop-outs and patients from trials that did not report any of the outcomes of interest for this review. The comparisons for which outcomes were available included pegylated (peg) interferon versus control; peg interferon plus ribavirin versus control; ribavirin plus peg interferon versus peg interferon; peg interferon (1.5 μg/kg/week) plus ribavirin versus peg interferon (0.5 μg/kg/week) plus ribavirin; amantadine plus peg interferon plus ribavirin versus peg interferon plus ribavirin; interferon versus control; interferon plus ribavirin versus control; ribavirin versus interferon; and ribavirin versus placebo. Long-term follow-up was not available in these trials. There were no significant differences in mortality, retransplantation, graft rejections requiring retransplantation or medical treatment, or fibrosis worsening between the groups in any of the comparisons in which these outcomes were reported. Quality of life and liver decompensation were not reported in any of the trials. There was a significantly higher proportion of participants who developed serious adverse events in the ribavirin plus peg interferon combination therapy group than in the peg interferon monotherapy group (1 trial; 56 participants; 17/28 (60.7%) in the intervention group versus 5/28 (17.9%) in the control group; RR 3.40; 95% CI 1.46 to 7.94). There was no significant difference in proportion of participants who developed serious adverse events or in the number of serious adverse events between the intervention and control groups in the other comparisons that reported serious adverse events.