Affiliation:
1. Division of Gastroenterology and Hepatology Miami VA Medical System Miami Florida USA
2. Division of Digestive Health and Liver Diseases University of Miami Miller School of Medicine Miami Florida USA
3. Department of Health Behavior and Policy Virginia Commonwealth University Richmond Virginia USA
4. Cambridge Liver Unit Cambridge University Hospital, NHS Foundation Trust Cambridge UK
5. Wellcome—MRC Cambridge Stem Cell Institute Cambridge UK
6. Division of Gastroenterology and Hepatology University of North Carolina Chapel Hill North Carolina USA
7. Herbert Wertheim Florida International University Miami Florida USA
8. Division of Gastroenterology and Hepatology University of Pennsylvania Philadelphia Pennsylvania USA
9. Section of Gastroenterology and Hepatology Corporal Michael J. Crescenz VA Medical Center Philadelphia Pennsylvania USA
10. Section of Digestive Diseases Yale School of Medicine New Haven Connecticut USA
11. Section of Gastroenterology VA Connecticut Healthcare System West Haven Connecticut USA
12. Department of Radiation Oncology Central Virginia Health System Richmond Virginia USA
Abstract
AbstractBackground and aimsStudies have demonstrated that reducing farnesoid X receptor activity with ursodeoxycholic acid (UDCA) downregulates angiotensin‐converting enzyme in human lung, intestinal and cholangiocytes organoids in vitro, in human lungs and livers perfused ex situ, reducing internalization of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) into the host cell. This offers a potential novel target against coronavirus disease 2019 (COVID‐19). The objective of our study was to compare the association between UDCA exposure and SARS‐CoV‐2 infection, as well as varying severities of COVID‐19, in a large national cohort of participants with cirrhosis.MethodsIn this retrospective cohort study among participants with cirrhosis in the Veterans Outcomes and Costs Associated with Liver cohort, we compared participants with exposure to UDCA, with a propensity score (PS) matched group of participants without UDCA exposure, matched for clinical characteristics, and vaccination status. The outcomes included SARS‐CoV‐2 infection, symptomatic, at least moderate, severe, or critical COVID‐19, and COVID‐19‐related death.ResultsWe compared 1607 participants with cirrhosis who were on UDCA, with 1607 PS‐matched controls. On multivariable logistic regression, UDCA exposure was associated with reduced odds of developing SARS‐CoV‐2 infection (adjusted odds ratio [aOR] 0.54, 95% confidence interval [CI] 0.41–0.71, p < 0.0001). Among patients who developed COVID‐19, UDCA use was associated with reduced disease severity, including symptomatic COVID‐19 (aOR 0.54, 95% CI 0.39–0.73, p < 0.0001), at least moderate COVID‐19 (aOR 0.51, 95% CI 0.32–0.81, p = 0.005), and severe or critical COVID‐19 (aOR 0.48, 95% CI 0.25–0.94, p = 0.03).ConclusionsIn participants with cirrhosis, UDCA exposure was associated with both a decrease in SARS‐CoV‐2 infection, and reduction in symptomatic, at least moderate, and severe/critical COVID‐19.