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

{ 'indexed': {'date-parts': [[2023, 11, 3]], 'date-time': '2023-11-03T01:17:42Z', 'timestamp': 1698974262032}, 'reference-count': 35, 'publisher': 'Wiley', 'issue': '5', 'license': [ { 'start': { 'date-parts': [[2023, 4, 5]], 'date-time': '2023-04-05T00:00:00Z', 'timestamp': 1680652800000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'http://onlinelibrary.wiley.com/termsAndConditions#vor'}], 'content-domain': {'domain': ['pericles.pericles-gcp.literatumonline.com'], 'crossmark-restriction': True}, 'published-print': {'date-parts': [[2023, 5]]}, 'abstract': '<jats:title>Abstract</jats:title><jats:sec><jats:title>Background and ' 'aims</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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, ' '<jats:italic>p</jats:italic>\xa0&lt;\xa00.0001). 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, <jats:italic>p</jats:italic>\xa0&lt;\xa00.0001), at least moderate COVID‐19 ' '(aOR 0.51, 95% CI 0.32–0.81, <jats:italic>p</jats:italic>\xa0=\xa00.005), and severe or ' 'critical COVID‐19 (aOR 0.48, 95% CI 0.25–0.94, <jats:italic>p</jats:italic>\xa0=\xa0' '0.03).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>In ' '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.</jats:p></jats:sec>', 'DOI': '10.1111/joim.13630', 'type': 'journal-article', 'created': {'date-parts': [[2023, 4, 5]], 'date-time': '2023-04-05T16:54:11Z', 'timestamp': 1680713651000}, 'page': '636-647', 'update-policy': 'http://dx.doi.org/10.1002/crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 9, 'title': 'Ursodeoxycholic acid is associated with a reduction in SARS‐CoV‐2 infection and reduced severity ' 'of COVID‐19 in patients with cirrhosis', 'prefix': '10.1111', 'volume': '293', 'author': [ { 'given': 'Binu V.', 'family': 'John', 'sequence': 'first', 'affiliation': [ { 'name': 'Division of Gastroenterology and Hepatology Miami VA Medical ' 'System Miami Florida USA'}, { 'name': 'Division of Digestive Health and Liver Diseases University of ' 'Miami Miller School of Medicine Miami Florida USA'}]}, { 'given': 'Dustin', 'family': 'Bastaich', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Health Behavior and Policy Virginia Commonwealth ' 'University Richmond Virginia USA'}]}, { 'given': 'Gwilym', 'family': 'Webb', 'sequence': 'additional', 'affiliation': [ { 'name': 'Cambridge Liver Unit Cambridge University Hospital, NHS ' 'Foundation Trust Cambridge UK'}]}, { 'given': 'Teresa', 'family': 'Brevini', 'sequence': 'additional', 'affiliation': [{'name': 'Wellcome—MRC Cambridge Stem Cell Institute Cambridge UK'}]}, { 'given': 'Andrew', 'family': 'Moon', 'sequence': 'additional', 'affiliation': [ { 'name': 'Division of Gastroenterology and Hepatology University of North ' 'Carolina Chapel Hill North Carolina USA'}]}, { 'given': 'Raphaella D.', 'family': 'Ferreira', 'sequence': 'additional', 'affiliation': [ { 'name': 'Division of Gastroenterology and Hepatology Miami VA Medical ' 'System Miami Florida USA'}]}, { 'given': 'Allison M.', 'family': 'Chin', 'sequence': 'additional', 'affiliation': [ { 'name': 'Herbert Wertheim Florida International University Miami Florida ' 'USA'}]}, { 'given': 'David E.', 'family': 'Kaplan', 'sequence': 'additional', 'affiliation': [ { 'name': 'Division of Gastroenterology and Hepatology University of ' 'Pennsylvania Philadelphia Pennsylvania USA'}, { 'name': 'Section of Gastroenterology and Hepatology Corporal Michael J. ' 'Crescenz VA Medical Center Philadelphia Pennsylvania USA'}]}, { 'given': 'Tamar H.', 'family': 'Taddei', 'sequence': 'additional', 'affiliation': [ { 'name': 'Section of Digestive Diseases Yale School of Medicine New Haven ' 'Connecticut USA'}, { 'name': 'Section of Gastroenterology VA Connecticut Healthcare System ' 'West Haven Connecticut USA'}]}, { 'given': 'Marina', 'family': 'Serper', 'sequence': 'additional', 'affiliation': [ { 'name': 'Division of Gastroenterology and Hepatology University of ' 'Pennsylvania Philadelphia Pennsylvania USA'}]}, { 'given': 'Nadim', 'family': 'Mahmud', 'sequence': 'additional', 'affiliation': [ { 'name': 'Division of Gastroenterology and Hepatology University of ' 'Pennsylvania Philadelphia Pennsylvania USA'}]}, { 'given': 'Yangyang', 'family': 'Deng', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Health Behavior and Policy Virginia Commonwealth ' 'University Richmond Virginia USA'}]}, { 'given': 'Hann‐Hsiang', 'family': 'Chao', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Radiation Oncology Central Virginia Health System ' 'Richmond Virginia USA'}]}, { 'given': 'Fotios', 'family': 'Sampaziotis', 'sequence': 'additional', 'affiliation': [ {'name': 'Wellcome—MRC Cambridge Stem Cell Institute Cambridge UK'}, { 'name': 'Cambridge Liver Unit Cambridge University Hospital, NHS ' 'Foundation Trust Cambridge UK'}]}, { 'given': 'Bassam', 'family': 'Dahman', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Health Behavior and Policy Virginia Commonwealth ' 'University Richmond Virginia USA'}]}], 'member': '311', 'published-online': {'date-parts': [[2023, 4, 5]]}, 'reference': [ { 'key': 'e_1_2_11_2_1', 'volume-title': 'Coronavirus disease 2019 (COVID‐19) treatment guidelines', 'author': 'COVID‐19 Treatment Guidelines Panel'}, { 'key': 'e_1_2_11_3_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1053/j.gastro.2021.07.010'}, { 'key': 'e_1_2_11_4_1', 'volume-title': 'Centers for disease control and prevention COVID‐19 data tracker'}, {'key': 'e_1_2_11_5_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/hep.32337'}, { 'key': 'e_1_2_11_6_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jamainternmed.2021.4325'}, {'key': 'e_1_2_11_7_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.cgh.2022.05.038'}, {'key': 'e_1_2_11_8_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s10620-022-07644-z'}, {'key': 'e_1_2_11_9_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/gutjnl-2022-327799'}, { 'key': 'e_1_2_11_10_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s12072‐020‐10077‐3'}, { 'key': 'e_1_2_11_11_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1053/j.gastro.2022.09.008'}, { 'key': 'e_1_2_11_12_1', 'unstructured': 'Fact sheet for healthcare providers: emergency use authorization for ' 'PAXLOVIDTM.https://www.fda.gov/media/155050/download. Acccessed ' '11/30/22'}, { 'key': 'e_1_2_11_13_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41586-022-05053-w'}, { 'key': 'e_1_2_11_14_1', 'unstructured': "The COVID‐19 Treatment Guidelines Panel's Statement on Omicron " 'Subvariants.Pre‐exposure prophylaxis and therapeutic management of ' 'non‐hospitalized patients with ' 'COVID‐19.https://www.covid19treatmentguidelines.nih.gov/therapies/statement‐on‐omicron‐subvariants/Accessed ' '11/30/22'}, { 'key': 'e_1_2_11_15_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41586-022-05594-0'}, { 'key': 'e_1_2_11_16_1', 'unstructured': 'AchufusiTGO SafadiAO MahabadiN.Ursodeoxycholic acid. [Updated 2022 Jan ' '30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls ' 'Publishing; 2022 Jan. Available ' 'from:https://www.ncbi.nlm.nih.gov/books/NBK545303/'}, { 'key': 'e_1_2_11_17_1', 'doi-asserted-by': 'publisher', 'DOI': '10.14309/ajg.0000000000001280'}, {'key': 'e_1_2_11_18_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/hep.31776'}, { 'key': 'e_1_2_11_19_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1097/TP.0000000000003615'}, { 'key': 'e_1_2_11_20_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1053/j.gastro.2021.11.001'}, { 'key': 'e_1_2_11_21_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jhep.2022.07.036'}, {'key': 'e_1_2_11_22_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/hep.32619'}, { 'key': 'e_1_2_11_23_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S2666-7568(22)00009-5'}, { 'key': 'e_1_2_11_24_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s42399-020-00341-w'}, { 'key': 'e_1_2_11_25_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.pmed.1003379'}, { 'key': 'e_1_2_11_26_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jhep.2020.09.024'}, {'key': 'e_1_2_11_27_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.cgh.2020.09.027'}, {'key': 'e_1_2_11_28_1', 'doi-asserted-by': 'publisher', 'DOI': '10.15585/mmwr.mm7010e4'}, { 'key': 'e_1_2_11_29_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jiph.2020.07.014'}, {'key': 'e_1_2_11_30_1', 'doi-asserted-by': 'publisher', 'DOI': '10.18332/tid/119324'}, { 'key': 'e_1_2_11_31_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jiph.2020.07.014'}, { 'key': 'e_1_2_11_32_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1053/j.gastro.2013.09.019'}, {'key': 'e_1_2_11_33_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.cgh.2015.07.010'}, { 'key': 'e_1_2_11_34_1', 'unstructured': 'COVID data tracker‐variant ' 'proportions.https://covid.cdc.gov/covid‐data‐tracker/#variant‐proportions. ' 'Accessed 11/30/2022'}, { 'key': 'e_1_2_11_35_1', 'unstructured': 'Frequently asked questions about COVID‐19 ' 'vaccination.https://www.cdc.gov/coronavirus/2019‐ncov/vaccines/faq.html. ' 'Accessed 1/24/23'}, { 'key': 'e_1_2_11_36_1', 'doi-asserted-by': 'publisher', 'DOI': '10.1136/gutjnl-2021-325700'}], 'container-title': 'Journal of Internal Medicine', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://onlinelibrary.wiley.com/doi/pdf/10.1111/joim.13630', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 9, 5]], 'date-time': '2023-09-05T12:26:16Z', 'timestamp': 1693916776000}, 'score': 1, 'resource': {'primary': {'URL': 'https://onlinelibrary.wiley.com/doi/10.1111/joim.13630'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 4, 5]]}, 'references-count': 35, 'journal-issue': {'issue': '5', 'published-print': {'date-parts': [[2023, 5]]}}, 'alternative-id': ['10.1111/joim.13630'], 'URL': 'http://dx.doi.org/10.1111/joim.13630', 'relation': {}, 'ISSN': ['0954-6820', '1365-2796'], 'subject': ['Internal Medicine'], 'container-title-short': 'J Intern Med', 'published': {'date-parts': [[2023, 4, 5]]}, 'assertion': [ { 'value': '2023-04-05', 'order': 2, 'name': 'published', 'label': 'Published', 'group': {'name': 'publication_history', 'label': 'Publication History'}}]}