熊去氧胆酸与肝硬化患者的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染减少及新型冠状病毒肺炎（COVID-19）严重程度降低有关。
Ursodeoxycholic acid is associated with a reduction in SARS-CoV-2 infection and reduced severity of COVID-19 in patients with cirrhosis.
作者信息
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
机构信息
Division of Gastroenterology and Hepatology, Miami VA Medical System, Miami, Florida, USA.
Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida, USA.
出版信息
J Intern Med. 2023 May;293(5):636-647. doi: 10.1111/joim.13630. Epub 2023 Apr 5.
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 < 0.0001). 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, p < 0.0001), at least moderate COVID-19 (aOR 0.51, 95% CI 0.32-0.81, p = 0.005), and severe or critical COVID-19 (aOR 0.48, 95% CI 0.25-0.94, p = 0.03).
CONCLUSIONS
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.
背景与目的
研究表明，使用熊去氧胆酸（UDCA）降低法尼酯X受体活性，可在体外人肺、肠和胆管细胞类器官中，以及在离体灌注的人肺和肝脏中，下调血管紧张素转换酶，减少严重急性呼吸综合征冠状病毒2（SARS-CoV-2）进入宿主细胞。这为对抗2019冠状病毒病（COVID-19）提供了一个潜在的新靶点。我们研究的目的是在一个大型全国性肝硬化患者队列中，比较UDCA暴露与SARS-CoV-2感染以及COVID-19不同严重程度之间的关联。
方法
在退伍军人肝脏相关结局与成本队列中针对肝硬化患者开展的这项回顾性队列研究中，我们将暴露于UDCA的患者与倾向评分（PS）匹配的未暴露于UDCA的患者组进行比较，匹配因素包括临床特征和疫苗接种状态。结局包括SARS-CoV-2感染、有症状的、至少中度、重度或危重型COVID-19以及与COVID-19相关的死亡。
结果
我们将1607例接受UDCA治疗的肝硬化患者与1607例PS匹配的对照进行比较。在多变量逻辑回归分析中，UDCA暴露与SARS-CoV-2感染几率降低相关（调整后的优势比[aOR]为0.54，95%置信区间[CI]为0.41 - 0.71，p < 0.0001）。在发生COVID-19的患者中，使用UDCA与疾病严重程度降低相关，包括有症状的COVID-19（aOR为0.54，95% CI为0.39 - 0.73，p < 0.0001）、至少中度COVID-19（aOR为0.51，95% CI为0.32 - 0.81，p = 0.005）以及重度或危重型COVID-19（aOR为0.48，95% CI为0.25 - 0.94，p = 0.03）。
结论
在肝硬化患者中，UDCA暴露与SARS-CoV-2感染减少以及有症状的、至少中度和重度/危重型COVID-19减少相关。
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