Weaning of immunosuppression in long-term liver transplant recipients.
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Journal: 1995/March - Transplantation
ISSN: 0041-1337
PUBMED: 7839442
Abstract:
Seventy-two long-surviving liver transplant recipients were evaluated prospectively, including a baseline allograft biopsy for weaning off of immunosuppression. Thirteen were removed from candidacy because of chronic rejection (n = 4), hepatitis (n = 2), patient anxiety (n = 5), or lack of cooperation by the local physician (n = 2). The other 59, aged 12-68 years, had stepwise drug weaning with weekly or biweekly monitoring of liver function tests. Their original diagnoses were PBC (n = 9), HCC (n = 1), Wilson's disease (n = 4), hepatitides (n = 15), Laennec's cirrhosis (n = 1), biliary atresia (n = 16), cystic fibrosis (n = 1), hemochromatosis (n = 1), hepatic trauma (n = 1), alpha-1-antitrypsin deficiency (n = 9), and secondary biliary cirrhosis (n = 1). Most of the patients had complications of long-term immunosuppression, of which the most significant were renal dysfunction (n = 8), squamous cell carcinoma (n = 2) or verruca vulgaris of skin (n = 9), osteoporosis and/or arthritis (n = 12), obesity (n = 3), hypertension (n = 11), and opportunistic infections (n = 2). When azathioprine was a third drug, it was stopped first. Otherwise, weaning began with prednisone, using the results of corticotropin stimulation testing as a guide. If adrenal insufficiency was diagnosed, patients reduced to < 5 mg/day prednisone were considered off of steroids. The baseline agents (azathioprine, cyclosporine, or FK506) were then gradually reduced in monthly decrements. Complete weaning was accomplished in 16 patients (27.1%) with 3-19 months drug-free follow-up, is progressing in 28 (47.4%), and failed in 15 (25.4%) without graft losses or demonstrable loss of graft function from the rejections. This and our previous experience with self-weaned and other patients off of immunosuppression indicate that a significant percentage of appropriately selected long-surviving liver recipients can unknowingly achieve drug-free graft acceptance. Such attempts should not be contemplated until 5-10 years posttransplantation and then only with careful case selection, close monitoring, and prompt reinstitution of immunosuppression when necessary.
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Transplantation 59(2): 212-217
PMID: 7839442

WEANING OF IMMUNOSUPPRESSION IN LONG-TERM LIVER TRANSPLANT RECIPIENTS<sup><a href="#FN1" rid="FN1" class=" fn">1</a></sup><sup>,</sup><sup><a href="#FN2" rid="FN2" class=" fn">2</a></sup>

The Transplantation Institute, University of Pittsburgh Medical Center, and the Veterans Administration Medical Center, Pittsburgh, Pennsylvania
Address requests for reprints to Hector C. Ramos, M.D., Division of Transplantation, University of New Mexico Health Sciences Center, 2211 Lomas Blvd, NE, Albuquerque, NM 87131
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Abstract

Seventy-two long-surviving liver transplant recipients were evaluated prospectively, including a baseline allograft biopsy for weaning off of immunosuppression. Thirteen were removed from candidacy because of chronic rejection (n=4), hepatitis (n=2), patient anxiety (n=5), or lack of cooperation by the local physician (n=2). The other 59, aged 12–68 years, had stepwise drug weaning with weekly or biweekly monitoring of liver function tests. Their original diagnoses were PBC (n=9), HCC (n=1), Wilson’s disease (n=4), hepatitides (n=15), Laennec’s cirrhosis (n=1), biliary atresia (n=16), cystic fibrosis (n=1), hemochromatosis (n=1), hepatic trauma (n=1), alpha-1-antitrypsin deficiency (n=9), and secondary biliary cirrhosis (n=1). Most of the patients had complications of long-term immunosuppression, of which the most significant were renal dysfunction (n=8), squamous cell carcinoma (n=2) or verruca vulgaris of skin (n=9), osteoporosis and/or arthritis (n=12), obesity (n=3), hypertension (n=11), and opportunistic infections (n=2). When azathioprine was a third drug, it was stopped first. Otherwise, weaning began with prednisone, using the results of corticotropin stimulation testing as a guide. If adrenal insufficiency was diagnosed, patients reduced to <5 mg/day prednisone were considered off of steroids. The baseline agents (azathioprine, cyclosporine, or FK506) were then gradually reduced in monthly decrements. Complete weaning was accomplished in 16 patients (27.1%) with 3–19 months drug-free follow-up, is progressing in 28 (47.4%), and failed in 15 (25.4%) without graft losses or demonstrable loss of graft function from the rejections. This and our previous experience with self-weaned and other patients off of immunosuppression indicate that a significant percentage of appropriately selected long-surviving liver recipients can unknowingly achieve drug-free graft acceptance. Such attempts should not be contemplated until 5–10 years posttransplantation and then only with careful case selection, close monitoring, and prompt reinstitution of immunosuppression when necessary.

Abstract

Lifetime immunosuppression has been a presumed necessity after clinical whole-organ transplantation. However, we have suggested elsewhere that liver allograft acceptance without a need for maintenance immunosuppression may have been accidentally achieved more often than realized (1). The recently proposed concept that donor leukocyte migration and long-term microchimerism is the basis of allograft acceptance (2) would account for the slow evolution of the self-sustaining drug-free tolerance that has been most frequently seen in, but not confined to, liver recipients (3).

The possibility of drug weaning had previously been demonstrated by 6 noncompliant liver recipients who were found in April 1992 to have successfully discontinued all medications from 5 to 13 years previously (1), and by 5 more with EBV-associated B cell lymphomas whose drugs had been stopped 6 months to 8 years posttransplantation with subsequent drug-free survival for 0.5 to 2.8 years (4). The present prospective weaning study did not include these 11 earlier recipients, all of whom continue to be well with 1½ to 2½ more years of follow-up.

We describe here a prospective trial of drug weaning of 59 more long-surviving liver recipients, all of whom had complications of chronic immunosuppression. All patients reported with complete drug discontinuance have been observed subsequently for 6.5 to 22.5 months.

Footnotes

Presented at the 20th Annual Meeting of the American Society of Transplant Surgeons, May 18–20, 1994, Chicago, IL.

Supported by Research Grants from the Veterans Administration and by Project Grant DK 29961 from the National Institutes of Health, Bethesda, MD.

Footnotes

REFERENCES

REFERENCES

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