Retrospective Cohort Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2018; 24(13): 1410-1418
Published online Apr 7, 2018. doi: 10.3748/wjg.v24.i13.1410
Potential triggering factors of acute liver failure as a first manifestation of autoimmune hepatitis-a single center experience of 52 adult patients
Matthias Buechter, Paul Manka, Falko Markus Heinemann, Monika Lindemann, Hideo Andreas Baba, Martin Schlattjan, Ali Canbay, Guido Gerken, Alisan Kahraman
Matthias Buechter, Paul Manka, Guido Gerken, Alisan Kahraman, Department of Gastroenterology and Hepatology, University Clinic of Essen, Essen 45147, Germany
Paul Manka, Division of Transplantation Immunology and Mucosal Biology, King’s College, London SE59RJ, United Kingdom
Falko Markus Heinemann, Monika Lindemann, Institute of Transfusion Medicine, University Clinic of Essen, Essen 45147, Germany
Hideo Andreas Baba, Martin Schlattjan, Institute of Pathology, University Clinic of Essen, Essen 45147, Germany
Ali Canbay, Department of Gastroenterology, Hepatology, and Infectious Diseases, Otto-von-Guericke University, Magdeburg 39120, Germany
Author contributions: Buechter M analyzed the data and wrote the manuscript; Manka P analyzed the data and performed the statistics; Heinemann FM and Lindemann M performed the HLA-typing; Baba HA and Schlattjan M evaluated the histological specimens; Canbay A and Gerken G treated the patients; Kahraman A treated the patients and designed the study.
Institutional review board statement: This study was reviewed and approved by the ethics committee of the University Clinic of Essen.
Informed consent statement: All patients gave their written informed consent prior to study inclusion.
Conflict-of-interest statement: All authors have nothing to declare.
Data sharing statement: No additional data are available.
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: Kahraman Alisan, MD, Associate Professor, Department of Gastroenterology and Hepatology, University Hospital of Essen, Hufelandstr 55, Essen 45122, Germany.
Telephone: +49-201-72384797 Fax: +49-201-7235655
Received: December 6, 2017
Peer-review started: December 6, 2017
First decision: January 18, 2018
Revised: February 21, 2018
Accepted: March 3, 2018
Article in press: March 3, 2018
Published online: April 7, 2018

To investigate potential triggering factors leading to acute liver failure (ALF) as the initial presentation of autoimmune hepatitis (AIH).


A total of 565 patients treated at our Department between 2005 and 2017 for histologically-proven AIH were retrospectively analyzed. However, 52 patients (9.2%) fulfilled the criteria for ALF defined by the “American Association for the Study of the Liver (AASLD)”. According to this definition, patients with “acute-on-chronic” or “acute-on-cirrhosis” liver failure were excluded. Following parameters with focus on potential triggering factors were evaluated: Patients’ demographics, causation of liver failure, laboratory data (liver enzymes, MELD-score, autoimmune markers, virus serology), liver histology, immunosuppressive regime, and finally, outcome of our patients.


The majority of patients with ALF were female (84.6%) and mean age was 43.6 ± 14.9 years. Interestingly, none of the patients with ALF was positive for anti-liver kidney microsomal antibody (LKM). We could identify potential triggering factors in 26/52 (50.0%) of previously healthy patients presenting ALF as their first manifestation of AIH. These were drug-induced ALF (57.7%), virus-induced ALF (30.8%), and preceding surgery in general anesthesia (11.5%), respectively. Unfortunately, 6 out of 52 patients (11.5%) did not survive ALF and 3 patients (5.7%) underwent liver transplantation (LT). Comparing data of survivors and patients with non-recovery following treatment, MELD-score (P < 0.001), age (P < 0.05), creatinine (P < 0.01), and finally, ALT-values (P < 0.05) reached statistical significance.


Drugs, viral infections, and previous surgery may trigger ALF as the initial presentation of AIH. Advanced age and high MELD-score were associated with lethal outcome.

Keywords: Acute liver failure, Autoimmune hepatitis, Drug-induced liver injury, Triggering factors, MELD-score

Core tip: Autoimmune hepatitis is considered to manifest as a chronic disease. In few cases, the clinician is challenged with patients revealing acute liver failure as their first manifestation of autoimmune hepatitis (AIH). The aim of our study was to investigate features of especially these patients with focus on potential triggering factors. We identified triggering factors in half of our patients (26 out of 52 patients with acute liver failure within a total cohort of 565 AIH patients). These were drugs, viral infections, and surgery. Advanced age and high MELD-score were associated with lethal outcome. Consequently, the clinician would be well-advised to document these underlying conditions.