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Antiviral prophylaxis for the prevention of chronic hepatitis C virus in patients undergoing liver transplantation

  1. Kurinchi Selvan Gurusamy1,*,
  2. Emmanuel Tsochatzis2,
  3. Clare D Toon3,
  4. Brian R Davidson1,
  5. Andrew K Burroughs4

Editorial Group: Cochrane Hepato-Biliary Group

Published Online: 2 DEC 2013

Assessed as up-to-date: 14 FEB 2013

DOI: 10.1002/14651858.CD006573.pub3


How to Cite

Gurusamy KS, Tsochatzis E, Toon CD, Davidson BR, Burroughs AK. Antiviral prophylaxis for the prevention of chronic hepatitis C virus in patients undergoing liver transplantation. Cochrane Database of Systematic Reviews 2013, Issue 12. Art. No.: CD006573. DOI: 10.1002/14651858.CD006573.pub3.

Author Information

  1. 1

    Royal Free Campus, UCL Medical School, Department of Surgery, London, UK

  2. 2

    Royal Free Hampstead NHS Foundation Trust and UCL Institute of Liver and Digestive Health, Sheila Sherlock Liver Centre, London, UK

  3. 3

    West Sussex County Council, Public Health, Chichester, West Sussex, UK

  4. 4

    Royal Free Hampstead NHS Foundation Trust, Sheila Sherlock Liver Centre, London, UK

*Kurinchi Selvan Gurusamy, Department of Surgery, Royal Free Campus, UCL Medical School, Royal Free Hospital,, Rowland Hill Street, London, NW3 2PF, UK. kurinchi2k@hotmail.com.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 2 DEC 2013

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary

Background

It is not clear whether prophylactic antiviral therapy is indicated to improve patient and graft survival in patients undergoing liver transplantation for chronic decompensated hepatitis C virus (HCV) infection.

Objectives

To compare the benefits and harms of different prophylactic antiviral therapies for patients undergoing liver transplantation for chronic HCV infection.

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

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 501 liver transplant recipients undergoing liver transplantation for chronic HCV infection were randomised in 12 trials to various experimental interventions and control interventions. The proportion of genotype I varied between 49% and 100% 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. Ten trials including 441 liver transplant recipients provided data for this review.

There were no significant differences in the 90-day mortality (1 trial; 81 participants; 5/35 (adjusted proportion: 14.2%) in interferon group versus 5/46 (10.9%) in control group; RR 1.31; 95% CI 0.41 to 4.19); mortality at maximal follow-up (2 trials; 105 participants; 7/47 (adjusted proportion: 14.8%) in interferon group versus 10/58 (17.2%) in control group; RR 0.86; 95% CI 0.36 to 2.08); long-term mortality (1 trial; 81 participants; HR 0.45; 95% CI 0.13 to 1.56); mortality at maximal follow-up (1 trial; 54 participants; 1/26 (3.9%) in pegylated interferon group versus 2/28 (7.1%) in control group; RR 0.54; 95% CI 0.05 to 5.59); 90-day mortality (1 trial; 115 participants; 5/55 (9.1%) in pegylated interferon plus ribavirin group versus 3/60 (5.0%) in control group; RR 1.82; 95% 0.46 to 7.25); 90-day mortality (3 trials; 53 participants; 3/37 (adjusted proportion: 4.3%) in HCV antibody group versus 1/16 (6.3%) in placebo group; RR 0.69; 95% CI 0.15 to 3.11); or 90-day mortality (2 trials; 31 participants; 2/14 (adjusted proportion: 16.2%) in HCV antibody high-dose group versus 1/17 (5.9%) in HCV antibody low-dose group; RR 2.75; 95% CI; 0.30 to 25.35). There were no significant differences in the retransplantation at maximal follow-up (2 trials; 105 participants; 2/47 (adjusted proportion: 4.0%) in interferon group versus 2/58 (3.4%) in control group; RR 1.17; 95% CI 0.22 to 6.2); 90-day retransplantation (1 trial; 18 participants; 1/12 (8.3%) in HCV antibody group versus 0/6 (0%) in control group; RR 1.71; 95% CI 0.09 to 32.93); or 90-day retransplantation (1 trial; 12 participants; 1/6 (17.7%) in HCV antibody high-dose group versus 0/6 (0%) in HCV antibody low-dose group; RR 3.00; 95% CI 0.15 to 61.74). There were no significant differences in serious adverse events, graft rejection, worsening of fibrosis, or HCV recurrence between intervention and control groups in any of the comparisons that reported these outcomes. None of the trials reported quality of life, liver decompensation, intensive therapy unit stay, or hospital stay. Life-threatening adverse events were not reported in either group in any of the comparisons.

Authors' conclusions

There is currently no evidence to recommend prophylactic antiviral treatment to prevent recurrence of HCV infection either in primary liver transplantation or retransplantation. Further randomised clinical trials with adequate trial methodology and adequate duration of follow-up are necessary.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary

Antiviral therapy to prevent the recurrence of chronic hepatitis C infection in patients undergoing liver transplantation

Background
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 virus infection). Sometimes, the liver damage can be so severe that the liver is not able to carry out the normal functions, which results in liver failure. Liver transplantation is effective in treating 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 prevent the recurrence of chronic hepatitis C infection in these patients is to give drug treatment before the donor liver graft is affected by chronic hepatitis C infection. The effectiveness of these preventive treatments is not known. The review authors performed a detailed review of the medical literature to February 2013 to determine the benefits and harms of different preventive antiviral treatments for patients undergoing liver transplantation for chronic hepatitis C virus infection. The review authors sought evidence from randomised clinical trials only. When conducted properly, such trials provide the best evidence. Two review authors independently identified the trials and obtained the information from the trials to minimise error.

Study characteristics
Ten trials including 441 liver transplant recipients provided data for this review. The patients were randomised to receive different treatments or no treatment in these 10 trials. We found two other trials, but data were not provided.

Key results
There were no significant differences in the proportion of patients who died or required retransplantation within 90 days or at maximal follow-up between the different treatment groups for any of the comparisons. There were no significant differences in serious complications, graft rejection, microscopic features of liver damage, or evidence of chronic hepatitis C recurrence between the different treatment groups or no treatment in any of the comparisons that reported these outcomes. None of the trials reported quality of life, liver failure, intensive therapy unit stay, or hospital stay. Life-threatening adverse events were not reported in any of the comparisons. There is currently no evidence to recommend preventive antiviral treatment to prevent recurrence of chronic HCV infection either in primary liver transplantation or retransplantation.

Quality of evidence
All the trials were at high risk of systematic errors (ie, there was potential to arrive at wrong conclusions because of the way the trial was conducted) and random errors (there was potential to arrive at the wrong conclusions because of the play of chance). Overall, the quality of evidence was very low.

Future research
Further randomised clinical trials with low risk of random errors and systematic errors are necessary to assess the long-term survival benefits for various treatment options in these patients. Such trials should include patient-oriented outcomes such as mortality, graft failure, graft rejections, and quality of life.