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Antiviral interventions for liver transplant patients with recurrent graft infection due to hepatitis C virus.

Abstract

BACKGROUND

Antiviral therapy for recurrent hepatitis C infection after liver transplantation is controversial due to unresolved balance between benefits and harms.

OBJECTIVES

To compare the therapeutic benefits and harms of different antiviral regimens in patients with hepatitis C re-infected grafts after liver transplantation.

SEARCH METHODS

We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 1, 2013), MEDLINE, EMBASE, and Science Citation Index Expanded to February 2013.

SELECTION CRITERIA

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.

DATA COLLECTION AND ANALYSIS

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.

MAIN RESULTS

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.

AUTHORS' CONCLUSIONS

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.

Authors+Show Affiliations

Department of Surgery, Royal Free Campus, UCL Medical School, Royal Free Hospital,, Rowland Hill Street, London, UK, NW3 2PF.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Review
Systematic Review

Language

eng

PubMed ID

24307460

Citation

Gurusamy, Kurinchi Selvan, et al. "Antiviral Interventions for Liver Transplant Patients With Recurrent Graft Infection Due to Hepatitis C Virus." The Cochrane Database of Systematic Reviews, 2013, p. CD006803.
Gurusamy KS, Tsochatzis E, Toon CD, et al. Antiviral interventions for liver transplant patients with recurrent graft infection due to hepatitis C virus. Cochrane Database Syst Rev. 2013.
Gurusamy, K. S., Tsochatzis, E., Toon, C. D., Xirouchakis, E., Burroughs, A. K., & Davidson, B. R. (2013). Antiviral interventions for liver transplant patients with recurrent graft infection due to hepatitis C virus. The Cochrane Database of Systematic Reviews, (12), CD006803. https://doi.org/10.1002/14651858.CD006803.pub4
Gurusamy KS, et al. Antiviral Interventions for Liver Transplant Patients With Recurrent Graft Infection Due to Hepatitis C Virus. Cochrane Database Syst Rev. 2013 Dec 4;(12)CD006803. PubMed PMID: 24307460.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antiviral interventions for liver transplant patients with recurrent graft infection due to hepatitis C virus. AU - Gurusamy,Kurinchi Selvan, AU - Tsochatzis,Emmanuel, AU - Toon,Clare D, AU - Xirouchakis,Elias, AU - Burroughs,Andrew K, AU - Davidson,Brian R, Y1 - 2013/12/04/ PY - 2013/12/6/entrez PY - 2013/12/7/pubmed PY - 2014/4/3/medline SP - CD006803 EP - CD006803 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 12 N2 - BACKGROUND: Antiviral therapy for recurrent hepatitis C infection after liver transplantation is controversial due to unresolved balance between benefits and harms. OBJECTIVES: To compare the therapeutic benefits and harms of different antiviral regimens in patients with hepatitis C re-infected grafts after liver transplantation. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 1, 2013), MEDLINE, EMBASE, and Science Citation Index Expanded to February 2013. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/24307460/Antiviral_interventions_for_liver_transplant_patients_with_recurrent_graft_infection_due_to_hepatitis_C_virus_ DB - PRIME DP - Unbound Medicine ER -