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Weaning of immunosuppression in liver transplant recipients

Mazariegos, GV and Reyes, J and Marino, IR and Demetris, AJ and Flynn, B and Irish, W and McMichael, J and Fung, JJ and Starzl, TE (1997) Weaning of immunosuppression in liver transplant recipients. Transplantation, 63 (2). 243 - 249. ISSN 0041-1337

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Immunosuppression has been sporadically discontinued by noncompliant liver allograft recipients for whom an additional 4 1/2 years of follow-up is provided. These anecdotal observations prompted a previously reported prospective drug withdrawal program in 59 liver recipients. This prospective series has been increased to 95 patients whose weaning was begun between June 1992 and March 1996, 8.4±4.4 (SD) years after liver replacement. A further 4 1/2 years follow-up was obtained of the 5 self-weaned patients. The prospectively weaned recipients (93 livers; 2 liver/kidney) had undergone transplantation under immunosuppression based on azathioprine (AZA, through 1979), cyclosporine (CsA, 1980-1989), or tacrolimus (TAC, 1989-1994). In patients on CsA or TAC based cocktails, the adjunct drugs were weaned first in the early part of the trial. Since 1994, the T cell-directed drugs were weaned first. Three of the 5 original self-weaned recipients remain well after drug-free intervals of 14 to 17 years. A fourth patient died in a vehicular accident after 11 years off immunosuppression, and the fifth patient underwent retransplantation because of hepatitis C infection after 9 drug-free years; their allografts had no histopathologic evidence of rejection. Eighteen (19%) of the 95 patients in the prospective series have been drug free for from 10 months to 4.8 years. In the total group, 18 (19%) have had biopsy proved acute rejection; 7 (7%) had a presumed acute rejection without biopsy; 37 (39%) are still weaning; and 12 (13%, all well) were withdrawn from the protocol at reduced immunosuppression because of noncompliance (n=8), recurrent PBC (n=2), pregnancy (n=1), and renal failure necessitating kidney transplantation (n=1). No patients were formally diagnosed with chronic rejection, but 3 (3%) were placed back on preexisting immunosuppression or switched from cyclosporine (CsA) to tacrolimus (TAC) because of histopathologic evidence of duct injury. Two patients with normal liver function died during the trial, both from complications of prior chronic immunosuppression. No grafts suffered permanent functional impairment and only one patient developed temporary jaundice. Long surviving liver transplant recipients are systematically overimmunosuppressed. Consequently, drug weaning, whether incomplete or complete, is an important management strategy providing it is done slowly under careful physician surveillance. Complete weaning from CsA-based regimens has been difficult. Disease recurrence during drug withdrawal was documented in 2 of 13 patients with PBC and could be a risk with other autoimmune disorders.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Mazariegos, GV
Reyes, J
Marino, IR
Demetris, AJ
Flynn, B
Irish, W
McMichael, J
Fung, JJ
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: 27 January 1997
Date Type: Publication
Journal or Publication Title: Transplantation
Volume: 63
Number: 2
Page Range: 243 - 249
DOI or Unique Handle: 10.1097/00007890-199701270-00012
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0041-1337
Other ID: uls-drl:31735062133941, Starzl CV No. 1929
Date Deposited: 08 Apr 2010 17:32
Last Modified: 04 Feb 2019 15:58


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