Biomarkers of Operational Tolerance After Liver Transplantation: Are We There Yet?

Over the past 15 years, many studies have attempted to describe the immunophenotypic traits of patients reaching spontaneous operational tolerance (SOT) after liver transplantation (LT) [reviewed in (1)]. The majority of them have been cross-sectional retrospective studies, limited by small sample sizes and by the difficulty of adequately adjusting for clinical confounders, in particular the effect of pharmacological immunosuppression. Over the same period of time, three prospective multi-center trials of immunosuppression discontinuation that included sequential protocolized liver biopsies have revealed that not all recipients who maintain stable allograft function in the absence of immunosuppression can be considered as having reached SOT (2-5).