Autoimmune hepatitis as a late complication of liver transplantation

Background: The development of de novo autoimmune hepatitis as ii long-term complication after liver transplantation has been recently reported. The a uthors describe five liver allograft recipients who developed chronic hepat itis associated with autoimmune features. Methods: Five of 155 liver transplant recipients at risk (2.5%) developed t his particular form of graft dysfunction. The authors review the clinical r ecords, liver histology, therapy, and outcome of these five patients. Results: Patients included two boys and three girls. Median age at transpla ntation was 3.5 years (range, 0.5-14 years), median age at presentation was 9 years (range, 2-17 years), and median interval after transplantation was 5.1 years (range, 1.5-9 years). Indications for liver transplant included biliary atresia in four patients and primary sclerosing cholangitis in one patient. At the time of presentation, all patients were receiving cyclospor ine as their primary immunosuppressive agent. Only one patient had a histor y of rejection, which had resolved. All patients presented with increased t ransaminase levels, and one had a mildly elevated conjugated bilirubin leve l. Only one patient had constitutional complaints. Acute and chronic reject ion, viral hepatitis, vascular insufficiency, and biliary tract obstruction were excluded. Antinuclear antibody levels were elevated in four patients (titer range, 1:160-1:640), one of whom also had positive antismooth muscle antibody (titer 1:80) results. The fifth patient had an elevated serum tot al protein level. Histologic analysis of liver biopsy samples from the five patients showed findings consistent with chronic autoimmune hepatitis. All patients were treated with standard therapy for autoimmune hepatitis, whic h included daily steroids and azathioprine. Cyclosporine doses were reduced in three patients and eliminated in two. All patients responded with norma lization (n = 2) or improvement (n = 3) of liver transaminases within the f irst 3 months of therapy. Histologic analysis of the 3-month followup liver biopsy was normal (n = 2) or showed improvement in inflammation (n = 2). T wo patients developed acute allograft rejection within 6 to 12 months after discontinuation or reduction in cyclosporine. Conclusions: Autoimmune hepatitis occurs after liver transplantation in pat ients without a previous history of autoimmune hepatitis. The risk of devel oping autoimmune hepatitis appears to be greater in children after liver tr ansplantation than in the general pediatric population. Standard therapy fo r autoimmune hepatitis is effective.