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 language | English (US) |
|---|---|
| Pages (from-to) | 1397-1409 |
| Number of pages | 13 |
| Journal | American Journal of Transplantation |
| Volume | 19 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 1 2019 |
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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)
Cite this
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Outcomes of immunosuppression minimization and withdrawal early after liver transplantation. / Shaked, Abraham; DesMarais, Michele R.; Kopetskie, Heather; Feng, Sandy; Punch, Jeffrey D.; Levitsky, Josh; Reyes, Jorge; Klintmalm, Goran B.; Demetris, Anthony J.; Burrell, Bryna E.; Priore, Allison; Bridges, Nancy D.; Sayre, Peter H.
In: American Journal of Transplantation, Vol. 19, No. 5, 01.05.2019, p. 1397-1409.Research output: Contribution to journal › Article
TY - JOUR
T1 - Outcomes of immunosuppression minimization and withdrawal early after liver transplantation
AU - Shaked, Abraham
AU - DesMarais, Michele R.
AU - Kopetskie, Heather
AU - Feng, Sandy
AU - Punch, Jeffrey D.
AU - Levitsky, Josh
AU - Reyes, Jorge
AU - Klintmalm, Goran B.
AU - Demetris, Anthony J.
AU - Burrell, Bryna E.
AU - Priore, Allison
AU - Bridges, Nancy D.
AU - Sayre, Peter H.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
AB - 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.
KW - clinical research/practice
KW - clinical trial
KW - immunosuppression/immune modulation
KW - immunosuppressive regimens - minimization/withdrawal
KW - infection and infectious agents - viral: hepatitis C
KW - liver transplantation/hepatology
KW - tolerance
UR - http://www.scopus.com/inward/record.url?scp=85059264647&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85059264647&partnerID=8YFLogxK
U2 - 10.1111/ajt.15205
DO - 10.1111/ajt.15205
M3 - Article
C2 - 30506630
AN - SCOPUS:85059264647
VL - 19
SP - 1397
EP - 1409
JO - American Journal of Transplantation
JF - American Journal of Transplantation
SN - 1600-6135
IS - 5
ER -