Liver transplant recipients are more likely to tolerate withdrawal from immunosuppressant therapy if cessation is initiated well after transplantation, according to recent study results.
Researchers gradually discontinued immunosuppressive drug therapy during a 6- to 9-month period in 102 stable liver transplant recipients. All participants had undergone transplantation more than 3 years earlier and had no history of autoimmune liver disease.
Successful discontinuation of therapy while maintaining stable graft function and without any evidence of rejection for 12 months or longer was considered operational tolerance. Discontinuation tolerance was observed in 41 cases during a mean of 41.8 months, while 57 participants experienced rejection. Four patients withdrew from the study.
Rejection episodes among nontolerant participants were typically mild, occurred a mean of 6.44 months after the start of discontinuation (range 1.28 to 21.35 months) and dysfunction related to rejection resolved in 96.5% of cases after a mean of 5.6 months. No participants experienced chronic rejection, and no rejection episodes resulted in graft loss.
Transient allograft dysfunction occurred in 23 tolerant participants, with all episodes resolving spontaneously. None of these cases was attributable to rejection, and no tolerant patients developed rejection during follow-up.
The length of time between transplantation and discontinuation (OR=1.353; 95% CI, 1.166-1.570), patient age at transplantation (OR=1.073; 95% CI, 1.018-1.130) and male sex (OR=4.375; 95% CI, 1.315-14.412) were associated with tolerance via multivariate analysis. Using a predictive model, including time from transplantation, investigators calculated a successful withdrawal rate of 79% among those who began discontinuation more than 10.6 years after transplant.
“The proportion of adult liver recipients who can discontinue immunosuppressive drugs is higher than previously estimated, particularly in selected non-HCV and non-autoimmune patients in whom drug withdrawal is performed a long period of time after transplantation,” the researchers wrote. “Additional prospective studies are now needed to confirm the generalizability of this approach, to determine its safety and efficacy compared to maintenance immunosuppression and to refine and validate accurate biomarkers of tolerance.”
Disclosure: See the study for a full list of relevant disclosures.