title: Antiviral prophylaxis for the prevention of chronic hepatitis C virus in patients undergoing liver transplantation.
abstract: 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.
  
  
  OBJECTIVE
  To compare the benefits and harms of different prophylactic antiviral therapies for patients undergoing liver transplantation for chronic HCV infection.
  
  
  METHODS
  We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 1, 2013), MEDLINE, EMBASE, and Science Citation Index Expanded to February 2013.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  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.
authors.affiliation: Department of Surgery, Royal Free Campus, UCL Medical School, Royal Free Hospital,, Rowland Hill Street, London, UK, NW3 2PF.
authors.forename: Kurinchi Selvan
authors.initials: KS
authors.lastname: Gurusamy
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Tsochatzis
authors.forename: Clare D
authors.initials: CD
authors.lastname: Toon
authors.forename: Brian R
authors.initials: BR
authors.lastname: Davidson
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Burroughs
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005838:Genotype; D006084:Graft Rejection / Q000453:epidemiology; D006085:Graft Survival; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control / Q000601:surgery*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D016031:Liver Transplantation; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use; D055502:Secondary Prevention
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b