(140) Use of Ursodeoxycholic Acid and the Risk of Long COVID in Patients with Steatotic Liver Disease

Background: The biological mechanism of ursodeoxycholic acid (UDCA) downregulating angiotensin-converting enzyme, a key receptor for COVID-19, suggested that UDCA possibly reduced the risk of COVID-19 infection. A recent study has also indicated that UDCA improved COVID-19 severity in patients with liver disease, including COVID-19 related hospitalization and death. However, evidence on the association between UDCA and the risk of long-term effects of COVID-19 in patients with SLD is limited.

Objectives: To assess the risk of long COVID associated with the use of UDCA in patients with SLD following infection with COVID-19.

Methods: A retrospective cohort study was conducted using the Korean nationwide COVID-19 registry linked to NHIS claims data (2019-2022). The study cohort included patients with SLD who were infected with COVID-19 between January 2020 and December 2022. Exposure was defined as ≥1 prescription of UDCA within 90 days prior to COVID-19 infection. Outcomes were 31 long COVID with chronic conditions (e.g., cardiovascular, pulmonary, mental, gastrointestinal, endocrinal, dermatological, etc.), and the risks of outcomes were assessed in UDCA users compared to non-users. Based on the WHO definition of long COVID, the index date was defined as 84 days after COVID-19 infection, and followed until the earliest occurrence of outcome, COVID-19 reinfection, vaccination, death, or study end. Propensity score (PS) fine stratification was used to adjust for potential confounders, and hazard ratios (HR) and 95% confidence intervals (CI) for long COVID were estimated using the Cox proportional hazards model.

Results: Among 469,108 patients with SLD infected with COVID-19 users [age, mean (SD) = 51.5 (13.4); 73.4% male, 97.1% vaccinated], we identified 23,560 UDCA users and 445,548 non-users. After PS fine stratification for each long COVID outcome, the severity of SLD was well balanced and follow-up ranged from 134.3 to 141.6 days. The use of UDCA was not associated with most of long COVID outcomes, including hypertension (HR: 0.93, 95% CI: 0.63-1.37), asthma (1.03, 0.75-1.42), migraine (0.95, 0.67-1.35), gastroesophageal reflux disease (1.08; 0. 95-1.23), and atopic dermatitis (1.11, 0.78-1.57). However, there were exceptions to the findings, with an increased risk observed for anxiety (1.33; 1.05-1.69) and type 2 diabetes (1.32; 1.13-1.55).

Conclusions: In this nationwide cohort study, most of long COVID outcomes with chronic conditions were not significantly associated with the use of UDCA in patients with SLD, with the exception of increased risk of type 2 diabetes and anxiety. While the use of UDCA was expected to be protective for the long-term effects of COVID based on biological mechanisms, there was no association observed in our study using real-world data.