Digestive Diseases and Sciences

, Volume 57, Issue 9, pp 2248–2266 | Cite as

Diagnosis, Pathogenesis, and Treatment of Autoimmune Hepatitis After Liver Transplantation

  • Albert J. Czaja


Autoimmune hepatitis can recur or appear de novo after liver transplantation, and it can result in hepatic fibrosis, graft loss, and re-transplantation. The goals of this review are to describe the prevalence, manifestations, putative pathogenic mechanisms, outcomes, and management of these occurrences. Autoimmune hepatitis recurs in 8–12 % of transplanted patients at 1 year and 36–68 % at 5 years. Recurrence may be asymptomatic and detected only by surveillance liver test abnormalities or protocol liver tissue examination. Autoantibodies that characterized the original disease, hypergammaglobulinemia, increased serum immunoglobulin G level, and histological findings of interface hepatitis, lymphoplasmacytic infiltration, perivenular hepatocyte necrosis, pseudo-rosetting, and acidophil bodies typify recurrence. Premature corticosteroid withdrawal and pre-transplant severity of the original disease are possible risk factors. De novo autoimmune hepatitis occurs in 1–7 % of patients 0.1–9 years after transplantation, especially in children. The appearance of autoantibodies may herald its emergence, and antibodies to glutathione-S-transferase T1 have been predictive of the disease. Recurrent disease may reflect recruitment of residual memory T lymphocytes and host-specific genetic predispositions, whereas de novo disease may reflect an allo-antigenic immune response and molecular mimicries that override self-tolerance. Treatment should be appropriate for autoimmune hepatitis and not based on anti-rejection drugs. Corticosteroid therapy alone or combined with azathioprine is the essential treatment. The substitution of mycophenolate mofetil for azathioprine and switch of the calcineurin inhibitor or its replacement with rapamycin have also been used for refractory disease. Re-transplantation has been necessary in 8–23 %.


Autoimmune hepatitis Post-transplantation Recurrence De novo 


Conflict of interest

This review did not receive financial support from a funding agency or institution, and Albert J. Czaja, MD has no conflict of interests to declare.


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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Division of Gastroenterology and HepatologyMayo Clinic College of MedicineRochesterUSA

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