Operational tolerance in clinical liver transplantation: emerging developments

There is still little understanding of the immune events that occur in transplant patients as they develop a relationship with their graft alloantigens. Though, there is an enormous interest and motivation in inducing specific unresponsiveness to organ allografts in order to allow minimization or complete withdrawal of immunosuppression in the recipient, given that life-long immunosuppressive treatment entails a high risk of infectious and metabolic complications, malignancies, and drug-specific toxicity. Clinical tolerance is defined as stable normal graft function in the total absence of a requirement for maintenance immunosuppression. Effective clinical tolerance has been reported more frequently in liver transplant recipients than after transplantation of other organs, as the liver is an immune-privileged organ for several mechanisms, most of which still remain unclear. According to the English medical literature, cautious, carefully supervised weaning of immunosuppressive drugs in controlled trials is not unreasonable, especially when monitored by protocol biopsies. The five centers in which the weaning has been attempted have reported a similar degree of success (1 out of 4 patients) and no harm to the patient over the short-term. Though, long-term follow-up has been lacking and, at present, there are no reliable immunological parameters that enable patients who can be withdrawn from immunosuppressants without the risk of rejection to be identified. To achieve that goal, appropriate collaboration and interaction between clinicians, immunologists and other basic scientists are desirable, as well as the creation of an international, maybe intercontinental, registry for tolerant patients.