Operational tolerance after liver transplantation☆

The achievement of an immunosuppression (IS)-free state after transplantation represents the ultimate goal of any immunosuppressive regimen. While clinical operational tolerance (COT) remains the exception after other types of solid organ transplantation, several cases of COT have been described after liver transplantation (LT). Overall, the experience gained so far worldwide demonstrates that COT can be achieved safely in one quarter of selected individuals, irrespective of the immunological background of donor and recipient, patient age, indication for LT, study endpoint, length of the weaning period and of pre/post-weaning follow-up, presence or not of chimerism. However, most transplant physicians still believe that the achievement of COT is still out of reach for the majority of LT recipients because of the potential risk for transplant survival, the non-randomized nature of most of the studies reported so far, and the selective nature of the patients enrolled in such studies, making them non-representative of the whole population of LT recipients. Despite these concerns, the present article demonstrates that this attitude is potentially no longer justified, given the growing evidence that a permanent and stable IS-free state can be achieved in a proportion of individuals who have received a LT for non-immune mediated liver diseases.

Abbreviations: COT, clinical operational tolerance, SOT, solid organ transplantation, IS, immunosuppression, LT, liver transplantation, GVHD, graft-versus-host disease, UDCA, ursodeoxycholic acid, MSC, mesenchymal stem cells, DBMC, donor bone marrow cells

Keywords: Liver transplantation, Immunosuppression, Clinical operational tolerance