Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 14, 2016; 22(10): 2906-2914
Published online Mar 14, 2016. doi: 10.3748/wjg.v22.i10.2906
De novo autoimmune hepatitis in liver transplant: State-of-the-art review
Ranka Vukotic, Giovanni Vitale, Antonia D’Errico-Grigioni, Luigi Muratori, Pietro Andreone
Ranka Vukotic, Giovanni Vitale, Luigi Muratori, Pietro Andreone, Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Policlinico Sant’Orsola-Malpighi, 40138 Bologna, Italy
Antonia D’Errico-Grigioni, Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, “F. Addarii” Institute of Oncology and Transplantation Pathology, Policlinico Sant’Orsola-Malpighi, 40138 Bologna, Italy
Author contributions: Vukotic R performed the search and review of the literature data and drafted the manuscript; Vitale G contributed to the search and review of the literature and revised the draft; D’Errico-Grigioni A provided histological specimens images, their interpretation and description; Muratori L contributed to the expert review of the literature data and critically analyzed the manuscript for its scientific content; Andreone P contributed to the review and interpretation of the literature, revised the draft for its intellectual and scientific content and is the guarantor of this review article; all authors approved the final version of the manuscript.
Conflict-of-interest statement: The Authors have no conflicts of interest to declare with concerns to this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Pietro Andreone, MD, Professor of Internal Medicine, Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Policlinico Sant’Orsola-Malpighi, Via Massarenti, 9, 40138 Bologna, Italy.
Telephone: +39-51-2143618 Fax: +39-51-345806
Received: September 23, 2015
Peer-review started: September 26, 2015
First decision: October 14, 2015
Revised: November 6, 2015
Accepted: December 30, 2015
Article in press: December 30, 2015
Published online: March 14, 2016

In the two past decades, a number of communications, case-control studies, and retrospective reports have appeared in the literature with concerns about the development of a complex set of clinical, laboratory and histological characteristics of a liver graft dysfunction that is compatible with autoimmune hepatitis. The de novo prefix was added to distinguish this entity from a pre-transplant primary autoimmune hepatitis, but the globally accepted criteria for the diagnosis of autoimmune hepatitis have been adopted in the diagnostic algorithm. Indeed, de novo autoimmune hepatitis is characterized by the typical liver necro-inflammation that is rich in plasma cells, the presence of interface hepatitis and the consequent laboratory findings of elevations in liver enzymes, increases in serum gamma globulin and the appearance of non-organ specific auto-antibodies. Still, the overall features of de novo autoimmune hepatitis appear not to be attributable to a univocal patho-physiological pathway because they can develop in the patients who have undergone liver transplantation due to different etiologies. Specifically, in subjects with hepatitis C virus recurrence, an interferon-containing antiviral treatment has been indicated as a potential inception of immune system derangement. Herein, we attempt to review the currently available knowledge about de novo liver autoimmunity and its clinical management.

Keywords: De novo autoimmune hepatitis, Plasma-cell hepatitis, Liver transplant, Hepatitis C virus recurrence, Antiviral therapy, Autoimmunity, Differential diagnosis

Core tip: A post-transplant pathological entity that is characterized by liver enzyme peaks, circulating auto- and alloantibodies and histological findings of interface hepatitis and plasma-cell infiltrates has been described and is considered to be a diagnostic challenge. Although the optimization of the immunosuppressive regimen should be an efficacious tool for both its prevention and treatment, rescue onsets can occur with scenarios that threaten the graft and the patient’s life. Hepatitis C recurrence is not the only pathogenic context of its occurrence in liver transplants, thus the clinical interest in this condition remains high.