Immunosuppression withdrawal possible for young liver transplant patients
MedWire News: Results from a small exploratory study suggest that complete withdrawal of immunosuppression is possible for pediatric recipients of parental living-donor liver transplants.
"Although life-saving, liver transplantation burdens children with lifelong immunosuppression and substantial potential for morbidity and mortality," say Sandy Feng (University of California, San Francisco, USA) and colleagues.
They add that while "withdrawal of immunosuppression therapy in liver allograft recipients can precipitate rejection, most episodes are reversible without long-term consequences, rendering this patient population appropriate for drug minimization, discontinuation, or both."
To test the feasibility of immunosuppression withdrawal in these patients, Feng and team recruited 20 (11 boys) stable pediatric recipients of parental living-donor liver transplants. The children were aged a median of 6.9 months at transplantation and 8.6 years at study enrollment.
Children who had transplants due to viral hepatitis or autoimmune disease were excluded from the study, as were those who had experienced chronic rejection or significant fibrosis.
The patients gradually reduced their immunosuppression therapy over a minimum period of 36 weeks and were followed-up for a median period of 32.9 months in total.
Overall, 12 of the 20 patients met the primary endpoint and had normal liver function after a median of 35.7 months without immunosuppression therapy. Biopsies taken at baseline and study completion showed no significant structural changes.
Of the other patients, one did not meet the primary endpoint due to violation of the exclusion criteria, two had acute rejection, and five indeterminate rejection. The seven patients with symptoms of rejection were given immunosuppression therapy and successfully regained baseline allograft function.
Factors associated with successful withdrawal from immunosuppression included having a longer period between transplantation and withdrawal. Those who met the primary endpoint had 100.6 months on average prior to withdrawal, compared with 73.0 months for those who did not.
Reduced portal inflammation (42.9 vs 91.7%) and lower total C4d scores (6.1 vs 12.5) on screening liver biopsy also predicted an increased chance of successful withdrawal from immunosuppression.
"These outcomes demonstrate that immunosuppression withdrawal in this clinical trial setting appears to be feasible for both tolerant and nontolerant patients," write the authors in JAMA.
"Our surprising finding that an unexpectedly high proportion of a well-defined pediatric cohort are operationally tolerant with stable allograft function and histology sets the agenda for larger studies with longer follow-up to define the frequency, assess the durability, and derive a predictive profile of operational tolerance for pediatric liver transplant recipients."
By Helen Albert