Increased Mortality Risk in Autoimmune Hepatitis: A Nationwide Population-Based Cohort Study With Histopathology

Rajani Sharma, Elizabeth C Verna, Jonas Söderling, Bjorn Roelstraete, Hannes Hagström, Jonas F Ludvigsson, Rajani Sharma, Elizabeth C Verna, Jonas Söderling, Bjorn Roelstraete, Hannes Hagström, Jonas F Ludvigsson

Abstract

Background and aims: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that may lead to cirrhosis and liver failure, but data on overall mortality in AIH are conflicting.

Methods: This was a nationwide population-based cohort study in Sweden from 1969-2017 of 6,016 adults with AIH and 28,146 matched general population reference individuals. AIH was defined by a combination of a medical diagnosis of AIH plus a liver biopsy from any of Sweden's 28 pathology departments. Through Cox regression, we estimated hazard ratios (HRs) for overall and cause-specific death. Liver transplant was included in our main outcome of death.

Results: During follow-up, 3,185 individuals with AIH died (41.4/1000 person-years) compared with 10,477 reference individuals (21.9/1000 person-years). The 10-year cumulative incidence of death was 32.3% (95%CI = 31.1-33.6) for AIH individuals and 14.1% (95%CI = 13.7-14.5) for reference individuals. This corresponded to an adjusted HR of 2.29 (95%CI = 2.17-2.41), which remained elevated ≥20 years follow-up. AIH individuals with cirrhosis on biopsy had a high risk of death (HR = 4.55; 95%CI = 3.95-5.25), while mortality in patients with fibrosis, inflammation without fibrosis, or necrosis did not differ. Portal hypertension and overlap with cholestatic liver diseases were also associated with death. AIH was associated with an increased risk of death from cardiovascular disease (HR = 1.27; 95%CI = 1.15-1.40), liver disease (HR = 66.24; 95%CI = 48.19-91.03) and extrahepatic malignancy (HR = 1.69; 95%CI = 1.51-1.89). In a sibling comparison, AIH individuals remained at increased risk of death.

Conclusion: AIH is associated with a 2-fold increased risk of death. Risks were particularly high in individuals with cirrhosis, portal hypertension, and overlap with cholestatic liver disease.

Keywords: Autoimmune Liver Disease; Death; Epidemiology; Histopathology.

Conflict of interest statement

Conflicts of Interest

These authors disclose the following: Jonas F. Ludvigsson coordinates a study unrelated to the present study on behalf of the Swedish IBD Quality Register (SWIBREG), and the study has received funding from Janssen. Hannes Hagström has received institutional research funding from Intercept, AstraZeneca, and Gilead; and has served as a scientific board advisor for BMS and Gilead; none of these are deemed relevant for the current study. Elizabeth C. Verna has served on the advisory board for Gilead has received research support from Salix; This study did not receive any support from these organizations, and these organizations did not have a role in the design and conduct of the study. The remaining authors disclose no conflicts.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.
Figure 1.
Flowchart of individuals with AIH and their matched general population comparators. CHF, congestive heart failure; NAFLD, nonalcoholic fatty liver disease.
Figure 2.
Figure 2.
Kaplan-Meier failure curves of time to (A) transplant-free all-cause mortality, (B) transplant-free cause-specific mortality, and (C) transplant-free all-cause mortality by histopathology group.

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