The 12 young liver transplant recipients in the Immune Tolerance Network’s WISP-R Study (Withdrawal of Immunosuppression in Pediatric Liver Transplant Recipients) show no immunological or histological signs of rejection four years after coming off all immunosuppressive medications. The data were published last week in Hepatology.
WISP-R is a multi-center, single arm pilot study that assessed immunosuppression withdrawal in stable pediatric liver transplant recipients with a parental living donor. Of the 20 participants that began withdrawal in WISP-R, 12 were able to successfully come off of immunosuppression and were considered operationally tolerant. Investigators followed these 12 participants for an additional four years to monitor safety as well as immunologic and histologic changes associated with being off immunosuppression (11 remained in the study at the five-year time point). While there are potential benefits to being off immune suppressing drugs, there are concerns that reduced or fully discontinued immunosuppression might contribute to allograft injury in the long term.
Liver biopsy specimens were collected at years three and five to identify evidence of graft rejection during the follow-up period. Biopsies at both time points showed no evidence of inflammation or fibrosis, and there were no instances of chronic rejection or graft loss. Despite the positive clinical and histologic findings, during the follow-up period 7 of the 12 participants developed donor-specific antibodies (DSAs). Development of DSAs is generally indicative of an inflammatory response and a precursor to fibrosis. The investigators hypothesize there may be immunological mechanisms unique to the liver that help thwart DSA-driven inflammation.
Overall, this study demonstrates long-term safety and stable graft histology in a small cohort of pediatric living-donor liver recipients who were able to come off immunosuppression. This is the first study to evaluate long-term outcomes of immunosuppression withdrawal in a pediatric liver transplant population. Eleven of the 12 tolerant WISP-R participants have continued into another four-year study extension and will be reported on separately. In addition, the similar but substantially larger study, “Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients (iWITH),” is assessing immunosuppression withdrawal in pediatric recipients of both living and deceased donor liver transplants.