AUTOIMMUNE HEPATITIS AS A LATE COMPLICATION OF ORTHOTOPIC LIVER TRANSPLANTATION (OLT)

Abstract

21 De novo autoimmune hepatitis has been reported as a cause of late graft dysfunction in patients following OLT (Lancet 1998;351: 409-13). We report 5 cases of chronic hepatitis presenting with autoimmune features, representing an incidence of 2% of the population at risk. Patients: Patients included 2 boys and 3 girls; median age at OLT was 3.9 yrs. (range 5- 14 yrs); median age at presentation was 9 yrs. (range: 2-17 yrs.), and median interval following OLT was 4 yrs. (range: 15- 9 yrs). Indications for OLT were biliary atresia n=4 and sclerosing cholangitis n=1. All patients were receiving cyclosporine and either daily (n=1), every other day (n=2) steroids. Only one patients had a history of rejection, which had resolved. Patients presented with increased transaminases, and one had modestly elevated conjugated bilirubin. Only one had constitutional complaints (fatique and poor school performance). Acute viral hepatitis was excluded by serologies in all patients. ANA was elevatedin 4 patients (range 1:160 to 1:640), one of these also had a positive anti-smooth muscle antibody (1:80). The fifth patient had elevated serum gamma globulin. Liver kidney microsome antibody was negative in all. Liver biopsies of the 5 showed histological changes consistent with chronic autoimmune hepatitis (portal and periportal hepatitis with plasma cell infiltrate), all showed mild to moderately active lobular infiltrates and piecemeal necrosis. There were no histologic findings suggesting graft rejection, biliary obstruction or acute viral hepatitis. Treatment and Outcome: Patients were initially treated with prednisone (1 mg/kg/day). Four received azathioprine (1mg/kg/day). Cyclosporine dosage was reduced in 3 and the drug eliminated in 2. All patients responded to therapy with improvement (n=3) or normalization (n=2) of liver enzymes with the first three months of therapy. Follow-up liver biopsy was obtained in 3, all showing improvement. Four remain on azathioprine (same 4), four on prednisone (0.2 - 0.7 mg/kg/day). Conclusions: Auto-immune hepatitis occurs after liver transplantation, even in patients with no previous history of autoimmune liver disease. The risk appears to be greater in children after OLT than in the general pediatric population. Standard therapy for autoimmune hepatitis is effective. Altering primary immunosuppression may help to alter the immunologic imbalance which could be important in initiating the process.