PERSISTENT CYTOMEGALOVIRUS IN LIVER ALLOGRAFTS WITH CHRONIC REJECTION

Cytomegalovirus (CMV) infection is one of the suggested risk factors f or chronic allograft rejection. Clinical and experimental studies have shown that CMV is somehow implicated in rejection mechanisms and in t he generation of graft arteriosclerosis, characteristic of chronic rej ection. In liver transplantation, there is also evidence of an associa tion between CMV and vanishing bile duct-syndrome (VBDS), which is cha racteristic of chronic liver allograft rejection. In this study, the r ole of posttransplant CMV infection and of acute rejection in the pati ents with irreversible, histologically confirmed chronic liver rejecti on with VBDS and vasculopathy was analyzed. Ten of 200 (5%) consecutiv e liver transplants were lost due to chronic rejection, from between 5 and 28 months from transplantation. In these 10 patients, acute rejec tions were frequent, and nine of ten patients had at least one episode of rejection early after transplantation. All patients (10 of 10) had a history of CMV infection usually following acute rejection. To inve stigate the role of CMV in chronic rejection, nine available removed g rafts were examined for the presence of the CMV genome by DNA-hybridiz ation in situ using a biotinylated CMV-DNA probe. Persistent CMV-DNA w as found in all of those available grafts with chronic rejection. CMV- DNA was strongly expressed in the remaining bile ducts and moderately expressed in the endothelial cells of the vascular structures, the CMV positivity of hepatocytes varied from graft to graft. Thus, persisten t CMV genome was found in those structures that are the major targets of the chronic rejection process in the liver. These findings support the previous suggestion of an association between CMV and chronic allo graft rejection.