Immunological mechanisms of liver allograft rejection

摘要

Hepatic allograft rejection results from the transplant recipient's immune response to graft antigens. In the absence of immunosuppression the transplanted organ suffers progressive immune-mediated injury. Despite the fact that non-immunological mechanisms are also involved in the process of graft damage, the ability of the immune system to discriminate between self and non-self antigens through a variety of interrelated mechanisms is essential for the process of transplant organ rejection. As the liver is a vital organ, host survival is contingent upon controlling the response to donor alloantigens, a task currently achievable only by maintaining lifelong immunosuppressive treatment. This status of extended organ engraftment under conventional immunosuppression is characterized as a state of partial tolerance. According to the protocol of immunosuppressive therapy used, 30-70% of hepatic allograft recipients experience at least one episode of acute rejection. About half of these episodes require specific antirejection treatment In the early period of rejection only minor abnormalities in liver function tests, including mild elevations in bilirubin plasma concentration, gamma-glutamyl-transpeptidase (GGTP), alkaline phosphatase and aminotransferases, occur. Clinical signs of fever, malaise and right-upper abdominal pain are present in only the most severe cases An elevation in eosinophil granulocytes in peripheral blood cell count is found in over 80% of recipients with an acute rejection. The incidence of chronic rejection decreases to 2-5% of hepatic allografts over time. Both acute and chronic rejection could be serious clinical events leading eventually to graft failure. Although graft loss due to acute rejection is quite rare in the era of modem immunosuppression, chronic rejection remains as one of the most important causes of late graft loss after liver transplantation.