@article{b2210f7e1ffb4d2c84f2502f65061e1a,
title = "Outcomes of immunosuppression minimization and withdrawal early after liver transplantation",
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",
author = "Abraham Shaked and DesMarais, {Michele R.} and Heather Kopetskie and Sandy Feng and Punch, {Jeffrey D.} and Josh Levitsky and Jorge Reyes and Klintmalm, {Goran B.} and Demetris, {Anthony J.} and Burrell, {Bryna E.} and Allison Priore and Bridges, {Nancy D.} and Sayre, {Peter H.}",
note = "Funding Information: We thank Ms. Debra McCorristan and Ms. Mary Shaw (University of Pennsylvania), Ms. Sharon Blaschka (University of California San Francisco), Ms. Laura Coleman and Dr. Sorelly Gil (Northwestern University), Ms. Sharon G. Bruer and Ms. Jonnie B. Edwards (Baylor University Medical Center), Ms. Ana Valeria Martin and Ms. Kelly Yim (University of Washington), and Ms. Jen Mawby and Ms. Elizabeth Sandusky (University of Michigan) for contribu‐ tions to the execution of the study. David Ikl{\'e} and Kristen Mason (Rho) for their contribution to the study analysis and Travis Mason (Rho) for data management during the trial. This research was per‐ formed as a project of the Immune Tolerance Network, an interna‐ tional clinical research consortium headquartered at the Benaroya Research Institute, and RhoFed, Chapel Hill, NC, and supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Numbers UM1AI109565 (ITN) and UM2AI117870 (Rho). The content is solely the responsi‐ bility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: We thank Ms. Debra McCorristan and Ms. Mary Shaw (University of Pennsylvania), Ms. Sharon Blaschka (University of California San Francisco), Ms. Laura Coleman and Dr. Sorelly Gil (Northwestern University), Ms. Sharon G. Bruer and Ms. Jonnie B. Edwards (Baylor University Medical Center), Ms. Ana Valeria Martin and Ms. Kelly Yim (University of Washington), and Ms. Jen Mawby and Ms. Elizabeth Sandusky (University of Michigan) for contributions to the execution of the study. David Ikl? and Kristen Mason (Rho) for their contribution to the study analysis and Travis Mason (Rho) for data management during the trial. This research was performed as a project of the Immune Tolerance Network, an international clinical research consortium headquartered at the Benaroya Research Institute, and RhoFed, Chapel Hill, NC, and supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Numbers UM1AI109565 (ITN) and UM2AI117870 (Rho). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2018 The American Society of Transplantation and the American Society of Transplant Surgeons",
year = "2019",
month = may,
doi = "10.1111/ajt.15205",
language = "English (US)",
volume = "19",
pages = "1397--1409",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley-Blackwell",
number = "5",
}
