Evolving concepts in the diagnosis, pathogenesis, and treatment of chronichepatic allograft rejection

Chronic hepatic allograft rejection is characterized by the histological fi ndings of ductopenia and a decreased number of hepatic arteries in portal t racts in the presence of foam cell (obliterative) arteriopathy. Recent stud ies have extended the histological spectrum of chronic rejection to include the presence of biliary epithelial atrophy or pyknosis involving the major ity of small ducts present in the liver biopsy specimen. Overall, the incid ence of chronic rejection in adults appears to be decreasing and is current ly approximately 4%. However, the incidence of chronic rejection in pediatr ic liver transplant recipients has been more stable and ranges from 8% to 1 2% in most studies. Clinical risk factors associated with chronic rejection Include: underlying liver disease, HLA donor-recipient matching, positive lymphocytotoxic cross-match, cytomegalovirus infection, recipient age, dono r-recipient ethnic origin, male donor into female recipient, number of acut e rejection episodes, histological severity of acute rejection episodes, lo w cyclosporine trough levels, and retransplantation for chronic rejection. Chronic rejection, once diagnosed, frequently leads to graft failure; howev er, a number of reports indicated 20% to 30% of the patients with this diag nosis may respond to additional immunosuppressive therapy or even resolve s pontaneously receiving baseline immunosuppression. Newer immunosuppressive agents, such as tacrolimus and mycophenolate, may successfully reverse chro nic rejection, particularly when it is diagnosed in its early histological stages. Copyright (C) 1999 by the American Association for the Study of Liv er Diseases.