Document Detail


Randomized controlled trial of total immunosuppression withdrawal in liver transplant recipients: role of ursodeoxycholic acid.
MedLine Citation:
PMID:  17589339     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Total immunosuppression withdrawal (TIW) without causing rejection has been reported in stable liver recipients. The role of ursodeoxycholic acid (UDCA) and patient characteristics that predict the success of this tolerance are unclear. There are two goals, to determine: 1) whether TIW is frequently associated with rejection; and 2) whether UDCA decreases the risk of liver disease (both rejection and recurrence) after TIW. METHODS: Twenty-six liver recipients who had been free of rejection while on immunosuppressive agents for a minimum of 2 years were randomized to receive either (15 mg/kg) of UDCA (n=14) or identical placebo (n=12) followed by sequential withdrawal of their immunosuppressive regimen over several months. Endpoints were defined as biochemical and histological evidence of rejection, graft dysfunction without rejection, recurrence of pretransplant disease, or 6 months without immunosuppression and no rejection or dysfunction on repeat liver biopsy. RESULTS: Rejection occurred in 6 of 14 (43%) of the UDCA group and 9 of 12 (75%) of those receiving placebo (P=0.09). Degree of rejection was mild, moderate, and severe in 73%, 20%, and 7% of patients respectively. All responded to rescue therapy and none developed chronic rejection. Nine of the remaining 11 patients (eight of the UDCA recipients and three of controls) who did not develop rejection developed graft dysfunction which responded to reintroduction of immunosuppressive agents in each case. Disease recurrence was most common in patients with underlying immune-mediated disorders of the liver. One year after withdrawal only two patients were free of immunosuppression, 80% were able to discontinue prednisone therapy (steroid free), and 50% were able to reduce their dose of cyclosporine. Age, underlying cause of liver disease, and regimen of immunosuppression were favorable predictors. CONCLUSIONS: The results of this study suggest that TIW: 1) is frequently associated with subsequent rejection, 2) increases the risk of underlying disease recurrence, and 3) is not facilitated by UDCA use and responds properly to the reintroduction of immunosuppressive therapy.
Authors:
Nimer Assy; Paul C Adams; Paul Myers; Verra Simon; Gerry Y Minuk; William Wall; Cameron N Ghent
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Transplantation     Volume:  83     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-06-25     Completed Date:  2007-08-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1571-6     Citation Subset:  IM    
Affiliation:
Section of Hepatology, University of Manitoba, Winnipeg, Manitoba. Canada, and Liver Unit, Sieff Hospital, Safed, Israel. anny.n@ziv.health.gov.il
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Cholagogues and Choleretics / therapeutic use*
Cyclosporine / therapeutic use
Drug Administration Schedule
Female
Follow-Up Studies
Graft Rejection / drug therapy,  epidemiology
Humans
Immunosuppressive Agents / administration & dosage,  therapeutic use*
Liver Diseases / surgery
Liver Transplantation / immunology*
Male
Middle Aged
Patient Compliance
Placebos
Prednisone / therapeutic use
Safety
Ursodeoxycholic Acid / therapeutic use*
Chemical
Reg. No./Substance:
0/Cholagogues and Choleretics; 0/Immunosuppressive Agents; 0/Placebos; 128-13-2/Ursodeoxycholic Acid; 53-03-2/Prednisone; 59865-13-3/Cyclosporine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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