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Clin. Mol. Hepatol., Published online: June 9, 2026 | https://doi.org/10.3350/cmh.2026.0283 Ursodeoxycholic Acid and Long COVID in Steatotic Liver Disease: A Nationwide Cohort Study

Kyungyeon Jung1, Gi-Ae Kim2, Jieun Woo1, Jin Youn3, Eun-Young Choi3,4, Sungho Bea3,5, Ahhyung Choi3, Ju Hwan Kim3, Heejoon Jang6,7, Dong Hyeon Lee6,7, Sae Kyung Joo6,7, Ju-Young Shin1,3, Won Kim6,7

1Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea
2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyung Hee University Hospital, College of Medicine, Kyung Hee University, Seoul, South Korea
3School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
4Centre for Pharmacoepidemiology, Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
5Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
6Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
7Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, South Korea

Kyungyeon Jung and Gi-Ae Kim contributed equally to this study as co-first authors.
Corresponding author: Ju-Young Shin, Won Kim

Abstract

Background/Aims
Ursodeoxycholic acid (UDCA) downregulates angiotensin-converting enzyme 2, the cellular entry receptor for SARS-CoV-2, and may reduce acute COVID-19 severity. However, it remains unknown whether UDCA prevents long COVID outcomes in patients with steatotic liver disease (SLD)—a population vulnerable to adverse outcomes. We investigated the association between pre-infection UDCA use and risk of long COVID outcomes in patients with SLD.

Methods
We conducted a nationwide retrospective cohort study using the Korean COVID-19 registry linked to National Health Insurance Service claims data (2019–2022). Patients with SLD (fatty liver index ≥30) who experienced COVID-19 were included. Exposure was defined as at least one UDCA prescription within the 90 days preceding infection. Outcomes of interest were 20 incident long COVID conditions across eight organ systems assessed ≥84 days post-infection. After propensity score (PS) fine stratification, hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox regression.

Results
Among 469,108 patients with SLD and COVID-19, 23,560 (5.0%) were UDCA users. After PS fine stratification weighting, UDCA use was not associated with reduced risk for most long COVID outcomes. A protective association was observed for atrial fibrillation (HR 0.51, 95% CI 0.30–0.88), whereas increased risks were found for type 2 diabetes mellitus (HR 1.24, 95% CI 1.09–1.42) and epilepsy (HR 1.69, 95% CI 1.09–2.61).

Conclusions
Pre-infection UDCA use was not associated with reduced risk for most long COVID outcomes in patients with SLD. The observed associations warrant cautious interpretation given potential residual confounding and surveillance bias.

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