Ferreira AI, Costa Azevedo M, Macedo Silva V, Xavier S, Magalhães J, Cotter J. Not always autoimmune hepatitis: Hepatic steatosis is associated with autoantibodies positivity in patients with hepatocellular dysfunction. World J Hepatol 2026; 18(1): 114045 [DOI: 10.4254/wjh.v18.i1.114045]
Corresponding Author of This Article
Ana Isabel Ferreira, MD, Department of Gastroenterology, Unidade Local de Saúde do Alto Ave, R. dos Cutileiros 114, Creixomil, Guimaraes 4835-044, Portugal. ai.voferreira@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
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Retrospective Cohort Study
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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: http://creativecommons.org/licenses/by-nc/4.0/
Jan 27, 2026 (publication date) through Jan 27, 2026
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Publication Name
World Journal of Hepatology
ISSN
1948-5182
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Ferreira AI, Costa Azevedo M, Macedo Silva V, Xavier S, Magalhães J, Cotter J. Not always autoimmune hepatitis: Hepatic steatosis is associated with autoantibodies positivity in patients with hepatocellular dysfunction. World J Hepatol 2026; 18(1): 114045 [DOI: 10.4254/wjh.v18.i1.114045]
World J Hepatol. Jan 27, 2026; 18(1): 114045 Published online Jan 27, 2026. doi: 10.4254/wjh.v18.i1.114045
Not always autoimmune hepatitis: Hepatic steatosis is associated with autoantibodies positivity in patients with hepatocellular dysfunction
Ana Isabel Ferreira, Mariana Costa Azevedo, Vitor Macedo Silva, Sofia Xavier, Joana Magalhães, José Cotter
Ana Isabel Ferreira, Vitor Macedo Silva, Sofia Xavier, Joana Magalhães, José Cotter, Department of Gastroenterology, Unidade Local de Saúde do Alto Ave, Guimaraes 4835-044, Portugal
Ana Isabel Ferreira, Vitor Macedo Silva, Sofia Xavier, Joana Magalhães, José Cotter, Life and Health Sciences Research Institute, School of Medicine, University of Minho, Braga 4710-057, Portugal
Ana Isabel Ferreira, Vitor Macedo Silva, Sofia Xavier, Joana Magalhães, José Cotter, ICVS/3B’s, PT Government Associate Laboratory, Braga 4710-057, Portugal
Mariana Costa Azevedo, School of Medicine, University of Minho, Braga 4710-057, Portugal
Author contributions: Ferreira AI, Azevedo MC, Silva VM, Xavier S, Magalhães J, Cotter J contributed to the study conception and design; material preparation, data collection and analysis were performed by Ferreira AI; the first draft of the manuscript was written by Ferreira AI, and all authors commented on previous versions of the manuscript, read and approved the final manuscript.
Institutional review board statement: The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the Institutional Review Board (Ref: 116/2023).
Informed consent statement: The need for written informed consent was waived by the Ethics Review Board since this is a retrospective study.
Conflict-of-interest statement: All authors have no conflicts of interest to declare.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement- checklist of items.
Data sharing statement: The datasets generated and/or analyzed during the current study are not publicly available due to ethical concerns but are available from the corresponding author on reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ana Isabel Ferreira, MD, Department of Gastroenterology, Unidade Local de Saúde do Alto Ave, R. dos Cutileiros 114, Creixomil, Guimaraes 4835-044, Portugal. ai.voferreira@gmail.com
Received: September 11, 2025 Revised: October 9, 2025 Accepted: November 25, 2025 Published online: January 27, 2026 Processing time: 139 Days and 15.9 Hours
Abstract
BACKGROUND
Autoantibodies, including anti-nuclear antibodies (ANA), are typically present in autoimmune hepatitis (AIH), but may be detected in other liver conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD), even in the absence of an autoimmune disorder.
AIM
To identify predictive factors for the non-confirmation of AIH diagnosis in patients with liver dysfunction of unknown etiology and positive autoantibodies.
METHODS
A retrospective cohort study was conducted in a university-affiliated hospital, including consecutive adult patients with liver dysfunction of unknown etiology and positive autoantibodies typically present in hepatic autoimmune disorders, who underwent liver biopsy, between June 2016 and August 2023. Patients with other known liver diseases or contraindications to liver biopsy were excluded, as well as those who underwent liver biopsy and had a poor specimen quality.
RESULTS
A total of 81 patients were included, of whom 53.1% were diagnosed with AIH and 46.9% with MASLD. ANA had a high sensitivity (83.7%) in diagnosing AIH but the lowest specificity (18.4%). In patients with ANA positivity, male, diabetic and obese individuals were more likely to have a non-confirmed AIH (P = 0.022, P = 0.039 and P = 0.046, respectively). Higher controlled attenuation parameter (CAP) values in patients with ANA positivity were associated with non-confirmed AIH diagnosis (288 ± 56 vs 244 ± 60, P = 0.012). In multivariate analysis, male gender and higher CAP values were independent predictive factors for non-confirmed AIH diagnosis (P = 0.011 and P = 0.034, respectively).
CONCLUSION
AIH was not confirmed in 47% of patients with liver dysfunction and positive autoantibodies. Multivariate analysis identified male gender and elevated CAP values as independent predictive factors for a non-confirmed diagnosis of AIH in patients with liver dysfunction and ANA positivity. Further prospective and multicenter validation is required in order to corroborate our findings.
Core Tip: This retrospective study included 81 consecutive adult patients with liver dysfunction and positive autoantibodies undergoing liver biopsy. Autoimmune hepatitis was not confirmed in 47% of patients. In patients with anti-nuclear antibodies positivity, male gender and higher controlled attenuation parameter values emerged as independent predictive factors associated with non-confirmed diagnosis of autoimmune hepatitis. These findings generate a valuable hypothesis that may inform future updates to clinical decision algorithms, particularly considering the rising prevalence of metabolic dysfunction-associated steatotic liver disease.
