Oral Ursodeoxycholic Acid Therapy & BA.5.2 Infection

Ursodeoxycholic acid (UDCA) was reported to reduce susceptibility to SARS-CoV-2 infection by downregulating farnesoid X receptor (FXR) -ACE2 signaling. However, we found a different story in real-world clinical studies. We attempted to verify whether UDCA can effectively prevent SARS-CoV-2 transmission or have positive therapeutic effects in a real-world clinical study. We performed a retrospective study, collected, and assessed clinical presentation and laboratory data on patients with liver diseases infected with SARS-CoV-2 Omicron sub-variant BA.5.2 who had been treated with or without UDCA. Treatment with UDCA did not prevent infection with the Omicron sub-variant BA.5.2, failed in reducing the duration of infection and hardly mitigated the severity of COVID-19. Meanwhile, the severity of liver diseases, especially TBil, ALP, γ-GT, liver cirrhosis and Child-Pugh classification, should be considered as risk factors for severe COVID-19 in chronic hepatic patients. In conclusion, UDCA failed to show inhibitory effects against SARS-CoV-2 infection in complex clinical settings. The regulatory mechanism of the novel UDCA-FXR-ACE2 pathway needs to be further investigated in real-world clinical studies.有研究报道，熊去氧胆酸（Ursodeoxycholic acid, UDCA）可通过下调法尼醇X受体（FXR）-血管紧张素转换酶2（ACE2）信号通路，降低新型冠状病毒（SARS-CoV-2）感染易感性。然而，本团队在真实世界临床研究中得到了截然不同的结果。本研究旨在验证UDCA能否在真实世界临床场景中有效阻断SARS-CoV-2传播，或发挥积极的治疗作用。本研究采用回顾性研究设计，收集并评估了感染SARS-CoV-2奥密克戎亚变体BA.5.2的肝病患者的临床表现与实验室检测数据，这些患者均接受或未接受UDCA治疗。研究结果显示，UDCA未能预防奥密克戎亚变体BA.5.2感染，亦未缩短感染持续时间，且几乎未缓解新型冠状病毒感染（COVID-19）的病情严重程度。同时，肝病严重程度——尤其是总胆红素（TBil）、碱性磷酸酶（ALP）、γ-谷氨酰转移酶（γ-GT）水平、肝硬化情况及Child-Pugh分级——应被视为慢性肝病患者发生重症COVID-19的危险因素。综上，在复杂的临床场景中，UDCA未表现出抗SARS-CoV-2感染的抑制作用。新型UDCA-FXR-ACE2通路的调控机制仍需在真实世界临床研究中进一步探索。