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

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). 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. 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%). 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. Costello et al. assess the impact of ursodeoxycholic acid (UDCA) treatment on COVID-19-related outcomes among people with chronic primary biliary cirrhosis and primary sclerosing cholangitis. Using a population-based cohort, they show that treatment with UDCA was associated with a reduced risk of COVID-19-related hospitalisation or death. Ursodeoxycholic acid is a drug used to treat liver disease. It has been proposed that it may prevent severe COVID-19 outcomes, however previous studies of this have had inconsistent results. We used electronic health records from people in the UK and identified people with two liver diseases: primary biliary cholangitis and primary sclerosing cholangitis. We looked at differences in hospitalisation and death between people taking UDCA and people who were not taking it. We found UDCA reduced the risk of severe COVID-19 outcomes by one-fifth. This suggests UDCA may help prevent serious COVID-19. Further clinical studies of UCDA should be undertaken, particularly in other groups with high risk or hospitalisation and death from COVID.