Ursodeoxycholic acid and severe COVID-19 outcomes in a cohort study using the OpenSAFELY platform

Abstract Background Biological evidence suggests ursodeoxycholic acid (UDCA)—a common treatment of cholestatic liver disease—may prevent severe COVID-19 outcomes. We aimed to compare the hazard of COVID-19 hospitalisation or death between UDCA users versus non-users in a population with primary bili...

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Main Authors: Ruth E. Costello, Karen M. J. Waller, Rachel Smith, George F. Mells, Angel Y. S. Wong, Anna Schultze, Viyaasan Mahalingasivam, Emily Herrett, Bang Zheng, Liang-Yu Lin, Brian MacKenna, Amir Mehrkar, Sebastian C. J. Bacon, Ben Goldacre, Laurie A. Tomlinson, John Tazare, Christopher T. Rentsch, the OpenSAFELY collaborative, the LH&W NCS (or CONVALESCENCE) Collaborative
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Communications Medicine
Online Access:https://doi.org/10.1038/s43856-024-00664-y
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author Ruth E. Costello
Karen M. J. Waller
Rachel Smith
George F. Mells
Angel Y. S. Wong
Anna Schultze
Viyaasan Mahalingasivam
Emily Herrett
Bang Zheng
Liang-Yu Lin
Brian MacKenna
Amir Mehrkar
Sebastian C. J. Bacon
Ben Goldacre
Laurie A. Tomlinson
John Tazare
Christopher T. Rentsch
the OpenSAFELY collaborative
the LH&W NCS (or CONVALESCENCE) Collaborative
author_facet Ruth E. Costello
Karen M. J. Waller
Rachel Smith
George F. Mells
Angel Y. S. Wong
Anna Schultze
Viyaasan Mahalingasivam
Emily Herrett
Bang Zheng
Liang-Yu Lin
Brian MacKenna
Amir Mehrkar
Sebastian C. J. Bacon
Ben Goldacre
Laurie A. Tomlinson
John Tazare
Christopher T. Rentsch
the OpenSAFELY collaborative
the LH&W NCS (or CONVALESCENCE) Collaborative
author_sort Ruth E. Costello
collection DOAJ
description Abstract Background Biological evidence suggests ursodeoxycholic acid (UDCA)—a common treatment of cholestatic liver disease—may prevent severe COVID-19 outcomes. We aimed to compare the hazard of COVID-19 hospitalisation or death between UDCA users versus non-users in a population with primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC). Methods With the approval of NHS England, we conducted a population-based cohort study using primary care records between 1 March 2020 and 31 December 2022, linked to death registration data and hospital records through the OpenSAFELY-TPP platform. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between time-varying UDCA exposure and COVID-19 related hospitalisation or death, stratified by geographical region and considering models unadjusted and fully adjusted for pre-specified confounders. Results We identify 11,305 eligible individuals, 640 were hospitalised or died with COVID-19 during follow-up, 400 (63%) events among UDCA users. After confounder adjustment, UDCA is associated with a 21% relative reduction in the hazard of COVID-19 hospitalisation or death (HR 0.79, 95% CI 0.67–0.93), consistent with an absolute risk reduction of 1.35% (95% CI 1.07%–1.69%). Conclusions We found evidence that UDCA is associated with a lower hazard of COVID-19 related hospitalisation and death, support calls for clinical trials investigating UDCA as a preventative measure for severe COVID-19 outcomes.
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spelling doaj-art-a62a24bd015247d1b69dcc670ee26d1b2024-11-24T12:41:02ZengNature PortfolioCommunications Medicine2730-664X2024-11-01411810.1038/s43856-024-00664-yUrsodeoxycholic acid and severe COVID-19 outcomes in a cohort study using the OpenSAFELY platformRuth E. Costello0Karen M. J. Waller1Rachel Smith2George F. Mells3Angel Y. S. Wong4Anna Schultze5Viyaasan Mahalingasivam6Emily Herrett7Bang Zheng8Liang-Yu Lin9Brian MacKenna10Amir Mehrkar11Sebastian C. J. Bacon12Ben Goldacre13Laurie A. Tomlinson14John Tazare15Christopher T. Rentsch16the OpenSAFELY collaborativethe LH&W NCS (or CONVALESCENCE) CollaborativeLondon School of Hygiene and Tropical MedicineCollaborative Centre for Organ Donation Evidence, Sydney School of Public Health, Faculty of Medicine and Health, University of SydneyCambridge Liver Unit, Cambridge University Hospitals NHS Foundation TrustCambridge Liver Unit, Cambridge University Hospitals NHS Foundation TrustLondon School of Hygiene and Tropical MedicineLondon School of Hygiene and Tropical MedicineLondon School of Hygiene and Tropical MedicineLondon School of Hygiene and Tropical MedicineLondon School of Hygiene and Tropical MedicineLondon School of Hygiene and Tropical MedicineBennett Institute for Applied Data Science, Nuffield Department of Primary Care Health Sciences, University of OxfordBennett Institute for Applied Data Science, Nuffield Department of Primary Care Health Sciences, University of OxfordBennett Institute for Applied Data Science, Nuffield Department of Primary Care Health Sciences, University of OxfordBennett Institute for Applied Data Science, Nuffield Department of Primary Care Health Sciences, University of OxfordLondon School of Hygiene and Tropical MedicineLondon School of Hygiene and Tropical MedicineLondon School of Hygiene and Tropical MedicineAbstract Background Biological evidence suggests ursodeoxycholic acid (UDCA)—a common treatment of cholestatic liver disease—may prevent severe COVID-19 outcomes. We aimed to compare the hazard of COVID-19 hospitalisation or death between UDCA users versus non-users in a population with primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC). Methods With the approval of NHS England, we conducted a population-based cohort study using primary care records between 1 March 2020 and 31 December 2022, linked to death registration data and hospital records through the OpenSAFELY-TPP platform. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between time-varying UDCA exposure and COVID-19 related hospitalisation or death, stratified by geographical region and considering models unadjusted and fully adjusted for pre-specified confounders. Results We identify 11,305 eligible individuals, 640 were hospitalised or died with COVID-19 during follow-up, 400 (63%) events among UDCA users. After confounder adjustment, UDCA is associated with a 21% relative reduction in the hazard of COVID-19 hospitalisation or death (HR 0.79, 95% CI 0.67–0.93), consistent with an absolute risk reduction of 1.35% (95% CI 1.07%–1.69%). Conclusions We found evidence that UDCA is associated with a lower hazard of COVID-19 related hospitalisation and death, support calls for clinical trials investigating UDCA as a preventative measure for severe COVID-19 outcomes.https://doi.org/10.1038/s43856-024-00664-y
spellingShingle Ruth E. Costello
Karen M. J. Waller
Rachel Smith
George F. Mells
Angel Y. S. Wong
Anna Schultze
Viyaasan Mahalingasivam
Emily Herrett
Bang Zheng
Liang-Yu Lin
Brian MacKenna
Amir Mehrkar
Sebastian C. J. Bacon
Ben Goldacre
Laurie A. Tomlinson
John Tazare
Christopher T. Rentsch
the OpenSAFELY collaborative
the LH&W NCS (or CONVALESCENCE) Collaborative
Ursodeoxycholic acid and severe COVID-19 outcomes in a cohort study using the OpenSAFELY platform
Communications Medicine
title Ursodeoxycholic acid and severe COVID-19 outcomes in a cohort study using the OpenSAFELY platform
title_full Ursodeoxycholic acid and severe COVID-19 outcomes in a cohort study using the OpenSAFELY platform
title_fullStr Ursodeoxycholic acid and severe COVID-19 outcomes in a cohort study using the OpenSAFELY platform
title_full_unstemmed Ursodeoxycholic acid and severe COVID-19 outcomes in a cohort study using the OpenSAFELY platform
title_short Ursodeoxycholic acid and severe COVID-19 outcomes in a cohort study using the OpenSAFELY platform
title_sort ursodeoxycholic acid and severe covid 19 outcomes in a cohort study using the opensafely platform
url https://doi.org/10.1038/s43856-024-00664-y
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