Single-agent immunosuppression after liver transplantation: what is possible?

Orthotopic liver transplantation is a life saving and life enhancing procedure. The development of immunosuppressive drugs has contributed to the high rate of success in terms of both patient and graft survival. However, the considerable adverse effects of these therapies are affecting long-term outcomes of transplant recipients. Complications related to immunosuppression are responsible for the majority of deaths in patients surviving more than 1 year. Therefore, the search for an optimal immunosuppressive regimen has become of paramount importance. The liver has proved to be an 'immunologically privileged' organ, capable in several animal models to be accepted as an allograft without any intervention on the immune system of the recipient. In some human liver allografts acceptance of the new organ is recognised after withdrawal of immunosuppressants, but prior identification of such individuals is not yet possible, thus negating this management option. Graft-recipient interaction is peculiar in liver transplantation: acute cellular rejection does not always need to be treated, and if it is not severe, appears to be associated with a better survival of both patient and graft. In the last decade there has been an evolution of immunosuppressive protocols, driven by empirical observation and a deeper understanding of immunological events after transplant. However, most modifications have been made because of the necessity to reduce long-term drug related morbidity and mortality. Withdrawal of corticosteroids has proven to be safely achievable in most patients, with no deleterious effects on patient or graft survival but with a great benefit in terms of reduction of incidence of metabolic and cardiovascular complications. Long-term 'steroid-free' regimens are therefore now widely used. Patients with stable graft function can be easily maintained using a single drug usually after 6 or 12 months and usually with a calcineurin inhibitor. The more evolved step of using monotherapy ab initio has also proven to be effective in a few studies and needs to be explored further. In the future new strategies will be designed to help the development of tolerance of the allograft, selectively stimulating instead of suppressing the immune reaction of the recipient.