(138) Exploring the impact of ursodeoxycholic acid therapy on COVID-19 in a real-world setting

Publication Number: 474

Background: Very recently, Brevini et al. demonstrated that ursodeoxycholic acid (UDCA)-mediated ACE2 downregulation reduces susceptibility to SARS-CoV-2 infection in vitro, in vivo and in human biliary and pulmonary organoids perfused ex situ. They also observed an association between UDCA therapy and positive clinical outcomes following COVID-19 that still needs to be confirmed.

Objectives: To investigate the association between UDCA and hospitalization for COVID-19 in patients with primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC).

Methods: We designed a case-control study in the source population of adult patients followed at the APHP, Paris Hospitals Group, through their medical records in the APHP health data warehouse, with primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC). Liver transplant patients were excluded. Cases were patients hospitalized > 24h for COVID-19 as the main diagnosis between 01/03/2020 and 31/12/2020 (1st stay of the first hospitalization if multiple stays). Controls were patients from the same source population, not hospitalized for COVID-19 as the main diagnosis over the same period, secondarily matched on PBC/PSC, age, sex and index date (date of case admission). Exposure was defined by UDCA use prior to index date. The confounding factors, including age, severity of liver disease, autoimmune hepatitis, diabetes, cardiovascular disorders, obesity, alcoholism, chronic obstructive pulmonary disease, renal failure, chronic inflammation of gastrointestinal tract, and hospitalization prior to pandemics, were summarized in a risk score controlled for in the model.

Results: Among 1401 patients with PBC or PSC, 1330 (94.9%) used UDCA therapy. Out of the 7 cases and 1394 unmatched controls identified during the study period, 6 (85.7%) and 1324 (95.0%) were exposed to UDCA. The matching yielded to 6 cases and 52 matched controls. Comparison of exposure between cases (n=5, 83.3%) and matched controls (n=48, 92.3%), using a conditional logistic regression model estimated a crude and adjusted odds ratio (95% confidence interval) of 0.84 (0.07 – 9.86) and 2.67 (0.11 –63.93) respectively. Similar results were obtained from complete unmatched population adjusted for age, sex, PBC/PSC and above-mentioned confounding factors.

Conclusions: In this large real-world retrospective study, we could not establish any trend on the association between UDCA use and the occurrence of hospitalized COVID-19, a finding that does not support a protective effect of UDCA against SARS-CoV2 infection. However, the very high exposure to UDCA in this population and the very limited number of cases result in a lack of statistical power that prevents any definitive conclusion.