An appraisal of tolerance in liver transplantation

Human liver allografts have a lower susceptibility to rejection than other organs. In addition, in some liver transplant recipients immunosuppressive drugs can be completely withdrawn, and these patients are considered as 'operationally' tolerant. Careful scrutiny of accumulated clinical experience indicates that elective immunosuppressive drug weaning is feasible in almost 20% of selected liver transplant recipients. This is associated with an incidence of 12% to 76% of acute cellular rejection, but these episodes are commonly mild and often resolve by return to baseline immunosuppression (IS), many times without the need to administer steroid boluses. Study of tolerance in liver transplantation (LT) has been hampered by confusion regarding the definitions of rejection and tolerance, and by the absence of prospective studies correlating results of immune monitoring assays and clinical outcome. Thus, we lack a clinically validated treatment-stopping rule capable of predicting the success of IS withdrawal and this procedure has to be performed on a 'trial and error' basis. The search for an accurate means to identify allograft tolerance among immunosuppressed recipients should become a priority in LT research. This information would provide a biological basis for guiding IS withdrawal protocols and for the implementation of tolerance-promoting strategies in LT.