title: Antibody induction versus corticosteroid induction for liver transplant recipients.
abstract: BACKGROUND
  Liver transplantation is an established treatment option for end-stage liver failure. To date, no consensus has been reached on the use of immunosuppressive T-cell specific antibody induction compared with corticosteroid induction of immunosuppression after liver transplantation.
  
  
  OBJECTIVE
  To assess the benefits and harms of T-cell specific antibody induction versus corticosteroid induction for prevention of acute rejection in liver transplant recipients.
  
  
  METHODS
  We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 30 September 2013 together with reference checking, citation searching, contact with trial authors and pharmaceutical companies to identify additional trials.
  
  
  METHODS
  We included all randomised clinical trials assessing immunosuppression with T-cell specific antibody induction versus corticosteroid induction in liver transplant recipients. Our inclusion criteria stated that participants within each included trial should have received the same maintenance immunosuppressive therapy.
  
  
  METHODS
  We used RevMan for statistical analysis of dichotomous data with risk ratio (RR) and of continuous data with mean difference (MD), both with 95% confidence intervals (CIs). We assessed risk of systematic errors (bias) using bias risk domains with definitions. We used trial sequential analysis to control for random errors (play of chance).
  
  
  RESULTS
  We included 10 randomised trials with a total of 1589 liver transplant recipients, which studied the use of T-cell specific antibody induction versus corticosteroid induction. All trials were with high risk of bias. We compared any kind of T-cell specific antibody induction versus corticosteroid induction in 10 trials with 1589 participants, including interleukin-2 receptor antagonist induction versus corticosteroid induction in nine trials with 1470 participants, and polyclonal T-cell specific antibody induction versus corticosteroid induction in one trial with 119 participants.Our analyses showed no significant differences regarding mortality (RR 1.01, 95% CI 0.72 to 1.43), graft loss (RR 1.12, 95% CI 0.82 to 1.53) and acute rejection (RR 0.84, 95% CI 0.70 to 1.00), infection (RR 0.96, 95% CI 0.85 to 1.09), hepatitis C virus recurrence (RR 0.89, 95% CI 0.79 to 1.00), malignancy (RR 0.59, 95% CI 0.13 to 2.73), and post-transplantation lymphoproliferative disorder (RR 1.00, 95% CI 0.07 to 15.38) when any kind of T-cell specific antibody induction was compared with corticosteroid induction (all low-quality evidence). Cytomegalovirus infection was less frequent in patients receiving any kind of T-cell specific antibody induction compared with corticosteroid induction (RR 0.50, 95% CI 0.33 to 0.75; low-quality evidence). This was also observed when interleukin-2 receptor antagonist induction was compared with corticosteroid induction (RR 0.55, 95% CI 0.37 to 0.83; low-quality evidence), and when polyclonal T-cell specific antibody induction was compared with corticosteroid induction (RR 0.21, 95% CI 0.06 to 0.70; low-quality evidence). However, when trial sequential analysis regarding cytomegalovirus infection was applied, the required information size was not reached. Furthermore, diabetes mellitus occurred less frequently when T-cell specific antibody induction was compared with corticosteroid induction (RR 0.45, 95% CI 0.34 to 0.60; low-quality evidence), when interleukin-2 receptor antagonist induction was compared with corticosteroid induction (RR 0.45, 95% CI 0.35 to 0.61; low-quality evidence), and when polyclonal T-cell specific antibody induction was compared with corticosteroid induction (RR 0.12, 95% CI 0.02 to 0.95; low-quality evidence). When trial sequential analysis was applied, the trial sequential monitoring boundary for benefit was crossed. We found no subgroup differences for type of interleukin-2 receptor antagonist (basiliximab versus daclizumab). Four trials reported on adverse events. However, no differences between trial groups were noted. Limited data were available for meta-analysis on drug-specific adverse events such as haematological adverse events for antithymocyte globulin. No data were available on quality of life.
  
  
  CONCLUSIONS
  Because of the low quality of the evidence, the effects of T-cell antibody induction remain uncertain. T-cell specific antibody induction seems to reduce diabetes mellitus and may reduce cytomegalovirus infection when compared with corticosteroid induction. No other clear benefits or harms were associated with the use of T-cell specific antibody induction compared with corticosteroid induction. For some analyses, the number of trials investigating the use of T-cell specific antibody induction after liver transplantation is small, and the numbers of participants and outcomes in these randomised trials are limited. Furthermore, the included trials are heterogeneous in nature and have applied different types of T-cell specific antibody induction therapy. All trials were at high risk of bias. Hence, additional randomised clinical trials are needed to assess the benefits and harms of T-cell specific antibody induction compared with corticosteroid induction for liver transplant recipients. Such trials ought to be conducted with low risks of systematic error and of random error.
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, Copenhagen, Denmark, DK-2100.
authors.forename: Luit
authors.initials: L
authors.lastname: Penninga
authors.forename: André
authors.initials: A
authors.lastname: Wettergren
authors.forename: Colin H
authors.initials: CH
authors.lastname: Wilson
authors.forename: An-Wen
authors.initials: AW
authors.lastname: Chan
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Steinbrüchel
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
mesh_terms: D000208:Acute Disease; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000918:Antibody Specificity / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects / Q000379:methods*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D060828:Induction Chemotherapy / Q000379:methods; D016031:Liver Transplantation; D016032:Randomized Controlled Trials as Topic; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2