Occurrence of cytomegalovirus hepatitis in liver transplant patients

The differential diagnosis of liver dysfunction after orthotopic liver transplantation can be difficult. Cytomegalovirus (CMV) hepatitis is one possibility. This report reviews our experience with 17 cases of pathologically proven CMV hepatitis following liver transplantation and demonstrates the need for percutaneous liver biopsies to establish the diagnosis. There were seven pediatric patients (ages 2-11 years, five males, two females) and ten adult patients (ages 17-53 years, eight males, two females). The most common symptoms were prolonged fever (15 patients, with a mean duration of 22 +/- 5.5 days), elevation in total bilirubin (14 patients), and elevation in liver enzymes (15 patients); all symptoms were also found in rejection. Leukopenia and thrombocytopenia, reported to frequently occur with CMV infection, were found in only three and five patients, respectively. Twelve patients with the above symptoms underwent percutaneous biopsy on one or more occasions to differentiate CMV hepatitis from rejection. The diagnosis was made at retransplantation in five patients. CMV hepatitis followed treatment for acute rejection in 14 patients and occurred without additional immunosuppression in three patients. All patients were maintained on cyclosporine and prednisone. Acute rejection episodes were treated with a 5-day tapering dose of steroids (17 courses in 12 patients), OKT3 monoclonal antibody [Ortho (4 patients)] antithymocyte globulin [Upjohn (2 patients)], and azathioprine (1 patient). CMV was isolated from urine (nine patients), blood (nine patients), throat (seven patients), lungs (two patients), and other organs (two patients). CMV was cultured from the liver biopsy specimens in five of the seven attempts in pediatric patients. When the diagnosis was confirmed in the absence of rejection, immunosuppression was routinely lowered. When rejection occurred concomitantly with CMV hepatitis, therapy had to be individualized. Retrospectively, three patients treated for rejection were noted at retransplantation to have only CMV hepatitis, and all three patients died. A high index of suspicion and the judicious use of liver biopsies is essential in order to differentiate CMV hepatitis from other causes of posttransplant liver dysfunction.