title: A pilot study of immunosuppressive monotherapy in liver transplantation: tacrolimus versus microemulsified cyclosporin.
abstract: BACKGROUND
  Many reports of successful early withdrawal of regular maintenance steroids in transplant recipients have appeared in recent years. The question now arises whether, in the current age of powerful nonsteroidal immunosuppressants such as Neoral and Tacrolimus, routine administration of steroids posttransplant is necessary at all. This single center pilot study reports on the feasibility, safety, and efficacy of single agent immunosuppression "ab initio" with either Neoral or Tacrolimus, and no routine or maintenance steroids.
  
  
  METHODS
  A total of 64 adult patients receiving first liver grafts for a variety of indications were randomized to receive either Neoral 5 mg/kg BDS or Tacrolimus 0.05 mg/kg BDS orally. Liver biopsies were performed on postoperative days 5 and 10, and whenever else clinically indicated. Rejection episodes were treated with 1.0 g of Methylprednisolone daily for 3 consecutive days. A further episode of rejection after two courses of Methylprednisolone was considered to be monotherapy failure, and consequently other immunosuppressive agents, usually Prednisolone 1 mg/kg/day, was started on a regular basis, tapering slowly.
  
  
  RESULTS
  Actuarial 1 year survival was 85% for Tacrolimus patients, and 78% for Neoral patients (P = NS), with 80% for Tacrolimus and 73.5% for Neoral at 30 months. Graft survival at 1 and 2.5 years was 73 and 62% for Tacrolimus and Neoral, respectively (P = NS). Two-thirds of patients in both groups showed biopsy evidence of acute cellular rejection. Rejection severity measured by a histological scoring system was similar for both patient groups. Additional longterm immunosuppressive therapy was necessary in 36% of patients receiving Neoral, compared with 13% of Tacrolimus patients (P = NS). No graft was lost on account of acute or chronic rejection. Short-term pulse steroid therapy to treat acute rejection was necessary for 60% of Tacrolimus patients and 40% of Neoral patients.
  
  
  CONCLUSIONS
  Tacrolimus or Neoral monotherapy after liver transplantation provides adequate immunosuppression for 87% of Tacrolimus patients and 64% of Neoral patients. In this study, 33% of patients in both groups showed no evidence of acute rejection, either clinically, biochemically or histologically, and were not exposed to steroids at any time. Evaluation of the long-term morbidity related to the side effects of the immunosuppressants given as monotherapy, for example, renal impairment and posttransplant lymphoproliferative disorder, and the effect on recurrent viral hepatitis in the graft, would be suitable areas for further study.
authors.affiliation: Liver Transplant Unit, Royal Free Hospital, London, UK.
authors.forename: K
authors.initials: K
authors.lastname: Rolles
authors.forename: B R
authors.initials: BR
authors.lastname: Davidson
authors.forename: A K
authors.initials: AK
authors.lastname: Burroughs
mesh_terms: D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use*; D004655:Emulsions; D005260:Female; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012086:Reoperation; D012720:Severity of Illness Index; D016019:Survival Analysis; D016559:Tacrolimus / Q000097:blood / Q000627:therapeutic use*
chemical_list: D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus