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Immunosuppression for liver transplantation in HCV-infected patients: Mechanism-based principles

Eghtesad, B and Fung, JJ and Demetris, AJ and Murase, N and Ness, R and Bass, DC and Gray, EA and Shakil, O and Flynn, B and Marcos, A and Starzl, TE (2005) Immunosuppression for liver transplantation in HCV-infected patients: Mechanism-based principles. Liver Transplantation, 11 (11). 1343 - 1352. ISSN 1527-6465

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Abstract

We retrospectively analyzed 42 hepatitis C virus (HCV)-infected patients who underwent cadaveric liver transplantation under two strategies of immunosuppression: (1) daily tacrolimus (TAC) throughout and an initial cycle of high-dose prednisone (PRED) with subsequent gradual steroid weaning, or (2) intraoperative antithymocyte globulin (ATG) and daily TAC that was later space weaned. After 36 ± 4 months, patient and graft survival in the first group was 18/19 (94.7%) with no examples of clinically serious HCV recurrence. In the second group, the three-year patient survival was 12/23 (52%), and graft survival was 9/23 (39%); accelerated recurrent hepatitis was the principal cause of the poor results. The data were interpreted in the context of a recently proposed immunologic paradigm that is equally applicable to transplantation and viral immunity. In the framework of this paradigm, the disparate hepatitis outcomes reflected different equilibria reached under the two immunosuppression regimens between the relative kinetics of viral distribution (systemically and in the liver) and the slowly recovering HCV-specific T-cell response. As a corollary, the aims of treatment of the HCV-infected liver recipients should be to predict, monitor, and equilibrate beneficial balances between virus distribution and the absence of an immunopathologic antiviral T-cell response. In this view, favorable equilibria were accomplished in the nonweaned group of patients but not in the weaned group. In conclusion, since the anti-HCV response is unleashed when immunosuppression is weaned, treatment protocols that minimize disease recurrence in HCV-infected allograft recipients must balance the desire to reduce immunosuppression or induce allotolerance with the need to prevent antiviral immunopathology. Copyright © 2005 by the American Association for the Study of Liver Diseases.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Eghtesad, B
Fung, JJ
Demetris, AJ
Murase, N
Ness, R
Bass, DC
Gray, EA
Shakil, O
Flynn, B
Marcos, A
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 November 2005
Date Type: Publication
Journal or Publication Title: Liver Transplantation
Volume: 11
Number: 11
Page Range: 1343 - 1352
DOI or Unique Handle: 10.1002/lt.20536
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 1527-6465
Other ID: uls-drl:31735062121227, Starzl CV No. 2214
Date Deposited: 08 Apr 2010 17:38
Last Modified: 13 Oct 2017 21:57
URI: http://d-scholarship.pitt.edu/id/eprint/5600

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