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Am J Transplant. 2018 Dec 1. doi: 10.1111/ajt.15205. [Epub ahead of print]

Outcomes of immunosuppression minimization and withdrawal early after liver transplantation.

Author information

1
University of Pennsylvania, Philadelphia, Pennsylvania.
2
Immune Tolerance Network, San Francisco, California.
3
Rho Federal Systems Division, Chapel Hill, North Carolina.
4
University of California San Francisco, San Francisco, California.
5
University of Michigan, Ann Arbor, Michigan.
6
Northwestern University, Chicago, Illinois.
7
University of Washington, Seattle, Washington.
8
Baylor University Medical Center, Dallas, Texas.
9
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
10
Immune Tolerance Network, Bethesda, Maryland.
11
National Institutes of Allergy and Infectious Diseases, Bethesda, Maryland.

Abstract

The Immune Tolerance Network ITN030ST A-WISH assessed immunosuppression withdrawal in liver transplant recipients with hepatitis C or nonimmune nonviral liver disease. Of 275 recipients enrolled before transplantation, 95 were randomly assigned 4:1 to withdrawal (n = 77) or maintenance (n = 18) 1- to 2-years posttransplant. Randomization eligibility criteria included stable immunosuppression monotherapy; adequate liver and kidney function; ≤Stage 2 Ishak fibrosis; and absence of rejection on biopsy. Immunosuppression withdrawal followed an 8-step reduction algorithm with ≥8 weeks per level. Fifty-two of 77 subjects (67.5%) reduced to ≤50% of baseline dose, and 10 of 77 (13.0%) discontinued all immunosuppression for ≥1 year. Acute rejection and/or abnormal liver tests were treated with increased immunosuppression; 5 of 32 rejection episodes required a methylprednisolone bolus. The composite end point (death or graft loss; grade 4 secondary malignancy or opportunistic infection; Ishak stage ≥3; or >25% decrease in glomerular filtration rate within 24 months of randomization) occurred in 12 of 66 (18%) and 4 of 13 (31%) subjects in the withdrawal and maintenance groups. Early immunosuppression minimization is feasible in selected liver recipients, while complete withdrawal is successful in only a small proportion. The composite end point comparison was inconclusive for noninferiority of the withdrawal to the maintenance group.

KEYWORDS:

clinical research/practice; clinical trial; immunosuppression/immune modulation; immunosuppressive regimens - minimization/withdrawal; infection and infectious agents - viral: hepatitis C; liver transplantation/hepatology; tolerance

PMID:
30506630
DOI:
10.1111/ajt.15205

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