**1. Introduction**

94 Liver Transplantation – Basic Issues

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induce allograft tolerance with combined donor-specific transfusion and anti-

Organ transplantation is the act of transferring organs from donors to recipients. Thus, the malfunction of an organ system can be corrected with the transplantation of an organ; organs that have successfully been transplanted include the kidney, liver, heart, lung, and pancreas. Over the past 50 years, the medical community has witnessed great advances in the care of liver transplant recipients, including new immunosuppression modalities, therapies for chronic rejection, and improved operative and preservation techniques. However, the immune system remains the most formidable barrier for clinicians to perform transplantations as a routine form of medical treatment[1].

The immune system has developed elaborate and effective mechanisms to combat foreign agents, including antigens derived transplantation; thus, in transplant recipients, transplantation elicits a complex series of immunological processes. Rejection results when a pathologic and intense inflammatory response develops, or when repair and remodeling of tissues fails. Knowledge of these mechanisms is important to understand the clinical features of rejection, which enables early diagnosis and the delivery of appropriate treatments[1]. These mechanisms are generally categorized as inflammation, immunity, tissue repair, and structural reinforcement of damaged tissues. Comprehension of these mechanisms is also critical for the development of novel drugs, treatments, and strategies to minimize rejection and inhibit the effects of the immune system on transplanted organs, helping to extend the survival and functionality of transplanted organs[2].

The introduction of routine pretransplant screening of graft recipients for anti-donor antibodies has made hyperacute rejection rare. However, no accepted therapeutic strategy to treat chronic rejection is currently recognized. The control of acute rejection has been the primary aim of immunosuppression, thereby allowing tissue repair to progress[3].

The use of combination immunosuppressive therapy has evolved over time. With all the successes of immunosuppressive therapies comes the obligation to tailor treatments to meet the individual patient's characteristics and to balance the risks and benefits of these medications.

Transplantation tolerance could eliminate many of the adverse events associated with immunosuppressive agents. Safe and reliable strategies for the induction of full tolerance have not yet been developed. However, methods to induce states of "partial tolerance" have been discovered, where lower-than-conventional amounts of ongoing pharmacologic immunosuppression are needed[3, 4]. Although the induction of immunologic tolerance has been achieved and studied in numerous laboratory animal models, immune tolerance remains an elusive goal of transplantation immunology and clinical organ transplantation.
