Chronic rejection of the liver: the role of immunosuppression.

ABSTRACT

Liver transplantation is now widely recognised as an effective treatment option for patients with advanced liver disease. Many units now achieve greater than 85% survival at 1 year, with the majority of patients having a high quality of life. The maintenance of a high quality of life requires careful clinical management to ensure that the continued maintenance of excellent liver graft function is not achieved at the expense of immunosuppressive drug complications or morbidity. Acute liver rejection will occur in between 30 to 45% of patients, although with modern immunosuppressive protocols, usually combining one of the calcineurin agents, either cyclosporin or tacrolimus, with both azathioprine and corticosteroids (prednisolone) ensures that relatively few grafts are lost from severe acute rejection. While the incidence and severity of acute rejection may be one factor in raising the risk of chronic rejection, it may not be the principal one in many patients. It is important to recognise that the frequency of rejection also varies with the primary underlying liver disease, with patients with hepatitis B or alcoholic liver disease having relatively low rejection rates, compared with patients with primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC), which range between 20 to 70%. Chronic rejection will account for some 5% of grafts lost in the first 3 to 5 years. Indeed, there is some evidence that the incidence of chronic rejection is actually declining over the past few years. While the reason for this apparent decline is uncertain, and it could relate to better immunosuppression management, or more likely to the growing recognition that chronic graft dysfunction may be due to recurrent liver disease, such as autoimmune hepatitis, PBC, PSC, or recurrent hepatitis C. The differentiation of recurrent primary liver disease from chronic rejection can prove to be very difficult in clinical practice. Thus, the clinician must carefully monitor liver and graft function, evaluate any biochemical changes, and try to reach a clear diagnosis before considering any modification of immunosuppressive schedules.