Ursodeoxycholic acid is associated with a reduction in SARS‐CoV‐2 infection and reduced severity of COVID‐19 in patients with cirrhosis

• Published in: Journal of internal medicine 2023-05, Vol.293 (5), p.636-647
• Main Authors: John, Binu V., Bastaich, Dustin, Webb, Gwilym, Brevini, Teresa, Moon, Andrew, Ferreira, Raphaella D., Chin, Allison M., Kaplan, David E., Taddei, Tamar H., Serper, Marina, Mahmud, Nadim, Deng, Yangyang, Chao, Hann‐Hsiang, Sampaziotis, Fotios, Dahman, Bassam
• Format: Article
• Language: English
• Subjects: Angiotensin; Cirrhosis; Coronaviruses; COVID-19; COVID-19 - complications; Exposure; farnesoid X receptor; Humans; Infections; Internalization; Liver cirrhosis; Liver Cirrhosis - complications; Liver Cirrhosis - drug therapy; Liver Cirrhosis, Biliary; Lungs; Multivariable control; Organoids; primary biliary cholangitis; Reduction; Respiratory diseases; Retrospective Studies; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Statistical analysis; UDCA; Ursodeoxycholic acid; Ursodeoxycholic Acid - therapeutic use; Vaccination; Viral diseases
• ISSN: 0954-6820; 1365-2796
• DOI: 10.1111/joim.13630

Background and aims Studies 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. Methods In 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. Results We 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