Outcome and Risk Factors of De Novo Autoimmune Hepatitis in Living-Donor Liver Transplantation

Abstract

BACKGROUND: Graft dysfunction mimicking autoimmune hepatitis (AIH) develops only rarely after liver transplantation for nonautoimmune liver disease. The long-term prognosis and risk factors of de novo AIH after living-donor liver transplantation (LDLT) are unknown. METHODS: We review our LDLT series to investigate the incidence and outcome of this form of graft dysfunction, focusing on follow-up histology. RESULTS: Of 633 patients who underwent LDLT at Kyoto University from 1990 to 2002, 13 (2.1%) developed graft dysfunction with interface hepatitis resembling AIH (2 males, 11 females). The median age at LDLT of these 13 patients was 10 years (8 months to 26 years). All received tacrolimus-based immunosuppression. The dysfunction presented at a median interval of 3.1 (0.7-9.5) years after LDLT. Nine had definite AIH, and four had probable AIH at the onset of hepatitis. Patients were followed after a median of 3.5 (0.1-8) years from the onset of de novo AIH. Of 11 patients who underwent follow-up histologic evaluation, 3 underwent retransplantation, and 8 continued to have similar findings on subsequent biopsies, with fluctuations in the amount of necroinflammatory activity and an increase in fibrosis despite treatment. In a multivariate analysis, acute rejection episodes and recipient age between 11 and 15 years at LDLT independently had predictive value for the development of de novo AIH. Human leukocyte antigen-A, B, and DR mismatches and sex mismatch did not influence the occurrence of de novo AIH. CONCLUSION: This series highlights the more severe histologic outcome of de novo AIH with longer follow-up despite immunosuppressive treatment. De novo AIH may arise from alloimmunologic injury, marked by clinically obvious episodes of acute rejection.