Kyungyeon Jung, Gi-Ae Kim, Jieun Woo, Jin Youn, Eun-Young Choi, Sungho Bea, Ahhyung Choi, Ju Hwan Kim, Heejoon Jang, Dong Hyeon Lee, Sae Kyung Joo, Ju-Young Shin, Won Kim
Clin Mol Hepatol 2026;32(3):1364-1378. Published online June 9, 2026
Background/Aims Ursodeoxycholic acid (UDCA) downregulates angiotensin-converting enzyme 2, the cellular entry receptor for SARS-CoV-2, and may reduce acute coronavirus disease 2019 (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.
Reply to correspondence on “Long-term gastrointestinal and hepatobiliary outcomes of COVID-19: A multinational population-based cohort study from South Korea, Japan, and the UK” Yang-Hyun Baek Clinical and Molecular Hepatology.2025; 31(1): e123. CrossRef
Kwanjoo Lee, Jaeyu Park, Jinseok Lee, Myeongcheol Lee, Hyeon Jin Kim, Yejun Son, Sang Youl Rhee, Lee Smith, Masoud Rahmati, Jiseung Kang, Hayeon Lee, Yeonjung Ha, Dong Keon Yon
Clin Mol Hepatol 2024;30(4):943-958. Published online August 29, 2024
Background/Aims Considering emerging evidence on long COVID, comprehensive analyses of the post-acute complications of SARS-CoV-2 infection in the gastrointestinal and hepatobiliary systems are needed. We aimed to investigate the impact of COVID-19 on the long-term risk of gastrointestinal and hepatobiliary diseases and other digestive abnormalities.
Methods We used three large-scale population-based cohorts: the Korean cohort (discovery cohort), the Japanese cohort (validation cohort-A), and the UK Biobank (validation cohort-B). A total of 10,027,506 Korean, 12,218,680 Japanese, and 468,617 UK patients aged ≥20 years who had SARS-CoV-2 infection between 2020 and 2021 were matched to non-infected controls. Seventeen gastrointestinal and eight hepatobiliary outcomes as well as nine other digestive abnormalities following SARS-CoV-2 infection were identified and compared with controls.
Results The discovery cohort revealed heightened risks of gastrointestinal diseases (HR 1.15; 95% CI 1.08–1.22), hepatobiliary diseases (HR 1.30; 95% CI 1.09–1.55), and other digestive abnormalities (HR 1.05; 95% CI 1.01–1.10) beyond the first 30 days of infection, after exposure-driven propensity score-matching. The risk was pronounced according to the COVID-19 severity. The SARS-CoV-2 vaccination was found to lower the risk of gastrointestinal diseases but did not affect hepatobiliary diseases and other digestive disorders. The results derived from validation cohorts were consistent. The risk profile was most pronounced during the initial 3 months; however, it persisted for >6 months in validation cohorts, but not in the discovery cohort.
Conclusions The incidence of gastrointestinal disease, hepatobiliary disease, and other digestive abnormalities increased in patients with SARS-CoV-2 infection during the post-acute phase.
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