title: The absence of chronic rejection in pediatric primary liver transplant patients who are maintained on tacrolimus-based immunosuppression: a long-term analysis.
abstract: BACKGROUND
  Although the outcome of liver transplantation has improved significantly during the past two decades, graft loss caused by chronic rejection after liver transplantation still occurs in 2% to 20% of recipients. The overall incidence of chronic rejection is also reported to be low in adult recipients, and risk factors have been identified. Chronic rejection is associated with the inability to maintain baseline immunosuppression. Additionally, the diagnoses of primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, hepatitis B virus, and hepatitis C virus, common indications for liver transplantation in adults, are associated with a higher incidence of chronic rejection. Fortunately, these diagnoses are rarely seen in children. Little is known about chronic rejection in long-term pediatric liver transplant survivors. The purpose of this longitudinal study was to examine the incidence of biopsy-proven chronic rejection in long-term survivors of primary pediatric liver transplantation under tacrolimus-based immunosuppression.
  
  
  METHODS
  From October 1989 to December 1992, 166 children (boys=95, girls=71; mean age=5.0+/-2.9 years) received a primary liver transplant. These patients were followed until March 2000 with a mean follow-up of 9+/-0.8 (range, 7.4-10.4) years. All liver biopsy specimens and explanted grafts were evaluated for evidence of chronic rejection using the International Banff Criteria.
  
  
  RESULTS
  The mortality rate during the follow-up period was 15% (n=25). Retransplantation was required in 11% (n=18) of recipients. Actuarial patient and graft survival rates at 10 years were 84.9% and 80.1%, respectively. There were 535 liver biopsy samples available for evaluation, including the 18 explanted allografts. Biopsy specimens of three other functioning allografts showed evidence of chronic rejection. Immunosuppression had been discontinued or drastically reduced in these recipients because of life-threatening infections, noncompliance, or both. On restoring baseline immunosuppression, all three children had normalized liver function and the allografts were maintained; the liver transplant patients who are alive currently have normal liver functions.
  
  
  CONCLUSIONS
  The findings of this study suggest that chronic rejection does not occur in pediatric liver transplant recipients receiving tacrolimus-based immunosuppression, provided baseline immunosuppression is maintained.
authors.affiliation: Thomas E. Starzl Transplantation Institute, Department of Surgery, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15213, USA.
authors.forename: Ashok
authors.initials: A
authors.lastname: Jain
authors.forename: George
authors.initials: G
authors.lastname: Mazariegos
authors.forename: Renu
authors.initials: R
authors.lastname: Pokharna
authors.forename: Maria
authors.initials: M
authors.lastname: Parizhskaya
authors.forename: Randeep
authors.initials: R
authors.lastname: Kashyap
authors.forename: Beverly
authors.initials: B
authors.lastname: Kosmach-Park
authors.forename: Amy
authors.initials: A
authors.lastname: Smith
authors.forename: John J
authors.initials: JJ
authors.lastname: Fung
authors.forename: Jorge
authors.initials: J
authors.lastname: Reyes
mesh_terms: D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006084:Graft Rejection / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D016031:Liver Transplantation; D008137:Longitudinal Studies; D008297:Male; D011241:Prednisone / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D011241:Prednisone; D016559:Tacrolimus