Assessing the associations between immunosuppressant use and COVID-19 severity in patients with autoimmune hepatitis

doi:10.4254/wjh.v18.i2.114481

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Feb 27, 2026 (publication date) through Feb 12, 2026

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World Journal of Hepatology

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1948-5182

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

World J Hepatol. Feb 27, 2026; 18(2): 114481
Published online Feb 27, 2026. doi: 10.4254/wjh.v18.i2.114481

Assessing the associations between immunosuppressant use and COVID-19 severity in patients with autoimmune hepatitis

Krish Rai, Karla J Lindquist, John Kornak, Jin Ge

Krish Rai, Karla J Lindquist, John Kornak, Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143, United States

Jin Ge, Department of Medicine, University of California, San Francisco, CA 94143, United States

Author contributions: Rai K contributed to manuscript drafting; Rai K and Ge J contributed to data extraction and statistical analysis; Rai K, Lindquist KJ, Kornak J, and Ge J contributed to critical revision of the manuscript for important intellectual content, analysis and interpretation of data; Ge J contributed to study concept and design, study supervision.

Supported by National Institute of Diabetes and Digestive and Kidney Diseases, No. K23DK139455; and UCSF Liver Center Grant, No. 5P30DK026743-43.

Institutional review board statement: Submissions of data from individual centers to N3C are governed by a central institutional review board (IRB) protocol #IRB00249128 hosted at Johns Hopkins University School of Medicine via the SMART IRB40 master common reciprocal reliance agreement. This central IRB covers data contributions and transfers to N3C but does not cover research using N3C data. If elected, individual sites may choose to exercise their own local IRB agreements instead of utilizing the central IRB. As the National Institutes of Health (NIH) National Center for Advancing Translational Sciences (NCATS) is the steward of the repository, data received and hosted by NCATS on the N3C COVID data enclave, its maintenance, and its storage are covered under a central NIH IRB protocol to make EHR-derived data available for the clinical and research community to use for studying COVID-19. Our institution has an active data transfer agreement with N3C. This specific analysis of the N3C COVID data enclave was approved by N3C under data use agreements titled “[RP-E77B79] COVID-19 outcomes in vaccinated patients with liver diseases. The use of N3C data for this study was authorized by the IRB at the University of California, San Francisco under study, No. 21-35861.

Informed consent statement: Informed consent was waived for this study as this was a retrospective analysis of a de-identified electronic health record database.

Conflict-of-interest statement: Ge J reports grants from Merck and Co, other from Gilead Sciences, other from Madrigal Pharmaceuticals, other from Astellas Pharmaceuticals/Iota Biosciences, outside the submitted work.

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: Data utilized for this analysis is available from the National Clinical Cohort Collaborative (N3C) COVID enclave.

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: Jin Ge, MD, Assistant Professor, Department of Medicine, University of California, 513 Parnassus Avenue, S-357, San Francisco, CA 94143, United States. jin.ge@ucsf.edu

Received: September 22, 2025
Revised: October 13, 2025
Accepted: December 16, 2025
Published online: February 27, 2026
Processing time: 145 Days and 8.5 Hours

Abstract

BACKGROUND

Due to immunosuppression (IS) use, patients with autoimmune hepatitis (AIH) may be at high risk for poor coronavirus disease 2019 (COVID-19) outcomes.

AIM

To investigate the associations between IS type and COVID-19 severity in AIH patients using the National Clinical Cohort Collaborative (N3C) COVID enclave.

METHODS

We identified all AIH patients with COVID-19 in the N3C COVID enclave. We used adjusted logistic regressions to determine associations between IS type and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We used Cox models to determine associations between IS type and all-cause mortality in the subset of AIH patients infected with SARS-CoV-2.

RESULTS

Of 15187 AIH patients, 5106 (33%) had IS exposure, and 1604 (11%) tested positive for SARS-CoV-2 during the study period from March 2020 through March 2025. There was an association with prednisone [odds ratio (OR): 0.81, 95%CI: 0.65-0.99, P = 0.04] exposure and SARS-CoV-2 test positivity. For interactions between different IS combinations and SARS-CoV-2 test positivity in the overall cohort, budesonide and azathioprine (OR: 1.88, 95%CI: 1.02-3.44, P = 0.04) and prednisone and tacrolimus interactions (OR: 1.99, 95%CI: 1.14-3.53, P = 0.02) showed significant associations. Within the subgroup finding of patients with full model for end stage liver disease data, budesonide and azathioprine interaction (OR: 4.44, 95%CI: 1.29-16.72, P = 0.02) also had a significant association. In our adjusted Cox regressions and corresponding subgroup analysis, we found no specific IS type that was statistically significant in association with all-cause mortality.

CONCLUSION

Prednisone exposure was negatively associated, and statistically significant IS interactions were positively associated with testing positive for SARS-CoV-2. Further work involves determining the impact of vaccinations and advances in COVID-19 treatment on outcomes in this population.

Keywords: Autoimmune hepatitis; COVID-19; Immunosuppressants; Chronic liver disease; Model for end stage liver disease 3.0 score

Core Tip: The effect of immunosuppressive medications on coronavirus disease 2019 (COVID-19) outcomes, including for patients with autoimmune hepatitis (AIH), has been variable across research studies. To address these uncertainties, we utilized data from the National Clinical Cohort Collaborative COVID enclave, a national COVID-19 multi-center electronic health record database to determine the influence of immunosuppressive therapy on testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and clinical outcomes in AIH patients. In this study of 15187 patients with AIH, we found a negative association between prednisone use and SARS-CoV-2 infection, while interactions between prednisone and tacrolimus and budesonide and azathioprine had a positive association with SARS-CoV-2 infection.