Outcomes of immunosuppression minimization and withdrawal early after liver transplantation

Abraham Shaked*, Michele R. DesMarais, Heather Kopetskie, Sandy Feng, Jeffrey D. Punch, Josh Levitsky, Jorge Reyes, Goran B. Klintmalm, Anthony J. Demetris, Bryna E. Burrell, Allison Priore, Nancy D. Bridges, Peter H. Sayre

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1397-1409
Number of pages13
JournalAmerican Journal of Transplantation
Volume19
Issue number5
DOIs
StatePublished - May 2019

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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