Incidence, timing, and risk factors for acute and chronic rejection.

Rejection of the liver allograft may be classified as massive hemorrhagic necrosis or acute and chronic rejection. Massive hemorrhagic necrosis is now rarely seen; it occurs within the first few days after transplantation and is associated with transplantation across the blood-type groups. Early acute rejection (within 28 days of transplantation) is usually of little clinical significance and responds well to additional immunosuppression, whereas later rejection is associated with a greater risk for progression to graft loss. The incidence of early, acute rejection is dependent on the immunosuppressive regimen used and will vary between 20% and 70%. Patients who undergo transplantation for hepatitis B viral infection and alcohol-related liver disease have a lower incidence of rejection compared with those who undergo transplantation for cholestatic diseases, such as primary sclerosing cholangitis and primary biliary cirrhosis. Other factors that influence the incidence of acute rejection include age, race of recipient, and preservation injury. The incidence of chronic rejection is declining; most centers report current rates of 4% to 8%, whereas in earlier series, rates of 15% to 20% were observed. The reasons for this decline are unknown, but may relate to better immunosuppression. Chronic rejection usually presents within the first year posttransplantation. The greatest risk factor for chronic rejection is transplantation for chronic rejection; other factors include indication (especially primary sclerosing cholangitis, primary biliary cirrhosis, and autoimmune hepatitis); cytomegalovirus infection, and low levels of immune suppression.