Outcomes of immunosuppression minimization and withdrawal early after liver transplantation

Am J Transplant. 2019 May;19(5):1397-1409. doi: 10.1111/ajt.15205. Epub 2018 Dec 31.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Graft Rejection / diagnosis*
  • Graft Rejection / drug therapy
  • Graft Rejection / etiology
  • Graft Survival / immunology*
  • Humans
  • Immune Tolerance / immunology*
  • Immunosuppression / statistics & numerical data*
  • Immunosuppressive Agents / administration & dosage*
  • Liver Diseases / surgery*
  • Liver Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Severity of Illness Index
  • Treatment Outcome
  • Withholding Treatment

Substances

  • Immunosuppressive Agents