Outcomes of immunosuppression minimization and withdrawal early after liver transplantation.
Göran Klintmalm M.D.
Shaked, A., M. R. DesMarais, H. Kopetskie, S. Feng, J. D. Punch, J. Levitsky, J. Reyes, G. B. Klintmalm, A. J. Demetris, B. E. Burrell, A. Priore, N. D. Bridges and P. H. Sayre (2018). “Outcomes of immunosuppression minimization and withdrawal early after liver transplantation.” Am J Transplant Dec 1. [Epub ahead of print].
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 post-transplant. 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 endpoint (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 endpoint comparison was inconclusive for non-inferiority of the withdrawal to the maintenance group.