Posttransplant immune hepatitis in pediatric liver transplant recipients: incidence and maintenance therapy with azathioprine.

Details

Serval ID
serval:BIB_22C9E4B8F36F
Type
Article: article from journal or magazin.
Collection
Publications
Title
Posttransplant immune hepatitis in pediatric liver transplant recipients: incidence and maintenance therapy with azathioprine.
Journal
Transplantation
Author(s)
Andries S., Casamayou L., Sempoux C., Burlet M., Reding R., Bernard Otte J., Buts J.P., Sokal E.
ISSN
0041-1337 (Print)
ISSN-L
0041-1337
Publication state
Published
Issued date
2001
Peer-reviewed
Oui
Volume
72
Number
2
Pages
267-272
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
BACKGROUND: Cases of so-called autoimmune hepatitis (AH) have been reported after liver transplantation. Our aim was to evaluate the incidence in a series of 471 pediatric liver transplant recipients.
METHODS: Between 1984 and 1998, 471 children had orthotopic liver transplantation (OLT). Children are followed up on a regular basis, with full clinical, biochemical, and histologic evaluation at 6 months, 1, 2, 5, 7, and 10 years after OLT. Children with unexplained abnormal liver tests were screened for autoimmune markers (total gamma-globulins, smooth muscle antibodies [SMA], liver kidney microsome antibodies [LKM], antinuclear factor [ANA]). From January of 1998 until December of 1998, autoimmune markers were prospectively searched in all children admitted for regular posttransplant follow-up (n = 118).
RESULTS: Eleven of 471 children (2.35%) were found with autoimmune hepatitis, 9 retrospectively and 2 prospectively. None had previous autoimmune liver disease. Patients had a history of steroid-dependent hepatitis. Histology showed variable degree of portal and lobular inflammation, piecemeal necrosis, and bridging collapse. Mean (+/-SDS) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities at diagnosis were 173+/-145 and 196+/-157 IU/L, respectively (nl<32). Median gamma-globulin levels reached 1365 mg/dl versus 931 mg/dl in controls (P<0.05). Nine had ANA (titer 1/80 up to 1/10,000), 1 SMA (1/320), and 2 LKM1 antibodies (1/1280). Patients did not respond to increasing charge of cyclosporine (n=10) or tacrolimus (n=1). Eleven received steroids (prednisolone: 2 mg/kg per day, then tapered) and azathioprine (1.5 to 2.5 mg/kg per day). All patients normalized within 3 months (mean AST/ALT levels of 26+/-8 and 30+/-9 IU/L). Three had mild to moderate relapse with increase of ALT thereafter. Gamma-globulins decreased to 1190 mg/dl (ns). Amongst the 116 remaining prospectively evaluated patients, 85 had normal evaluation, despite low titers of autoantibodies in 15 (SMA< or =1/40, ANA 1/80). Thirty-one patients had graft dysfunction, related to well-explained posttransplant causes, among which 7 had similar low levels of autoantibodies.
CONCLUSIONS: A total of 2.35% of our transplant children present evidence of immune hepatitis after transplantation. Patients do not respond to increasing cyclosporine or tacrolimus levels and require steroid and azathioprine. In view of this specific treatment, systematic screening for "autoimmune" markers is advised in children with liver transplant.
Keywords
Adolescent, Alanine Transaminase/blood, Aspartate Aminotransferases/blood, Azathioprine/therapeutic use, Child, Child, Preschool, Cyclosporine/therapeutic use, Drug Therapy, Combination, Female, Hepatitis, Autoimmune/drug therapy, Hepatitis, Autoimmune/epidemiology, Humans, Immunosuppressive Agents/therapeutic use, Liver Function Tests, Liver Transplantation/immunology, Liver Transplantation/physiology, Male, Postoperative Complications/epidemiology, Prednisone/therapeutic use, Retrospective Studies, Tacrolimus/therapeutic use
Pubmed
Web of science
Create date
20/10/2016 16:31
Last modification date
20/08/2019 13:00
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