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本研究旨在探索原发性胆汁性胆管炎(Primary biliary cholangitis, PBC)患者经熊去氧胆酸(Ursodeoxycholic acid, UDCA)治疗对新冠病毒感染及临床结局的影响。符合PBC诊断标准的患者入组，按照患者是否接受UDCA治疗分为两组：经UDCA治疗组和未经UDCA治疗组。收集患者PBC诊断相关资料、治疗信息等临床资料，观察新冠病毒感染患者感染率、发病及预后指标。共收集1137例自身免疫性肝病患者，筛选出569例PBC患者，其中56例患者在随访期间丢失，513例患者完成了随访，包括女性402例，男性111例，平均年龄58.17±11.03岁。UDCA治疗组和非UDCA治疗组分别406例、107例。UDCA治疗组中治疗PBC的激素使用率(11.08%)显著高于非UDCA治疗组(2.80%)(χ2=6.845, P=0.009)。总人群新冠病毒感染率为80.90%，感染者的年龄(57.08±10.84)显著低于未感染者(62.78±10.69)(t=4.691, P<0.001)，未感染者UDCA的使用率(87.76%)显著高于感染患者(77.11%)(χ2=5.444, P=0.020)，并且UDCA治疗者的新冠病毒感染率(80.79%)显著低于非UDCA治疗者(88.78%)(χ2=5.444, P=0.020)，单因素和多因素Logistic回归分析显示，年龄(OR=1.053,P<0.001,95%CI(1.029-1.077))和UDCA的使用率(OR=2.218,P=0.022,95%CI (1.115-4.059))与新冠病毒感染率较低有关。在新冠病毒感染患者中，UDCA治疗组中女性新冠病毒感染者的比例高于男性(82.81%vs. 17.19%, P<0.001),UDCA治疗组新冠病毒感染恢复时间显著长于非UDCA治疗组(9.63±6.80 vs. 7.46±3.58, P=0.003)。无论是否经UDCA治疗，所有新冠病毒感染患者均好转。PBC患者UDCA的使用与新冠病毒感染的低发生率相关，接受UDCA治疗的患者感染后的恢复时间更长。
Abstract：This study aims to explore the effect of ursodeoxycholic acid(UDCA) on severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection and clinical outcomes in patients with primary biliary cholangitis(PBC). Patients who met the diagnostic criteria of PBC were enrolled and divided into two groups according to whether they received UDCA treatment: the UDCA treatment group and the non-UDCA treatment group. Clinical data such as PBC diagnosis related data and treatment information were collected, and the infection rate, disease incidence and prognosis indicators of SARS-CoV-2 infected patients were observed.A total of 1137 patients with autoimmune liver disease were collected, and 569 patients with PBC were screened out. Among them, 56 patients were lost during follow-up, and 513 patients completed follow-up, including 402 females and 111 males, with a mean age of 58.17 ± 11.03 years. There were 406 patients in the UDCA treatment group and 107 in the non-UDCA treatment group. The hormone usage rate of PBC treatment in the UDCA treatment group(11.08%) was significantly higher than that in the non-UDCA treatment group(2.80%) (χ2=6.845, P=0.009). The overall SARS-CoV-2 infection rate was 80.90%. The age of infected patients(57.08 ± 10.84) was significantly lower than that of uninfected people(62.78 ± 10.69)(t=4.691, P<0.001). The use of UDCA was significantly higher in uninfected patients(87.76%) compared to infected patients(77.11%) (χ2=5.444, P=0.020). The SARS-CoV-2 infection rate was significantly lower in patients receiving UDCA(80.79%) compared to those not receiving UDCA(88.78%) (χ2=5.444, P=0.020).Univariate and multivariate logistic regression analyses showed that both age(OR=1.053, P<0.001, 95% CI [1.029-1.077]) and the use of UDCA(OR=2.218, P=0.022, 95% CI [1.115-4.059]) were associated with a lower SARS-CoV-2 infection rate. Among SARS-CoV-2 infected patients, the proportion of women in the UDCA treatment group was higher than men(82.81% vs 17.19%, P<0.001). The recovery time for SARSCoV-2 infection was significantly longer in the UDCA treatment group than in the non-UDCA treatment group(9.63 ± 6.80 vs 7.46 ± 3.58, P=0.003). Regardless of UDCA treatment, all patients with SARS-CoV-2infection showed improvement. The use of UDCA in PBC patients is associated with a lower incidence of SARS-CoV-2 infection, although patients receiving UDCA treatment had a longer recovery time after infection.
[1] Dyson JK, Hirschfield GM, Adams DH, et al. Novel therapeutic targets in primary biliary cirrhosis[J]. Nat Rev Gastroenterol Hepatol, 2015, 12(3):147-158.DOI:10. 1038/nrgastro. 2015. 12.
[2] European Association for the Study of the Liver. EASL clinical practice guidelines:the diagnosis and management of patients with primary biliary cholangitis[J]. J Hepatol, 2017, 67(1):145-172. DOI:10. 1016/j. jhep. 2017. 03. 022.
[3] Beuers U, Trauner M, Jansen P, et al. New paradigms in the treatment of hepatic cholestasis:from UDCA to FXR, PXR and beyond[J]. J Hepatol, 2015, 62(1Suppl):S25-37. DOI:10. 1016/j. jhep. 2015. 02. 023.
[4] Poupon R. Ursodeoxycholic acid and bile-acid mimetics as therapeutic agents for cholestatic liver diseases:an overview of their mechanisms of action[J]. Clin Res Hepatol Gastroenterol, 2012, 36 Suppl 1:S3-12. DOI:10. 1016/S2210-7401(12)70015-3.
[5] Lindor KD, Bowlus CL, Boyer J, et al. Primary biliary cholangitis:2018 practice guidance from the American Association for the Study of Liver Diseases[J].Hepatology, 2019, 69(1):394-419. DOI:10. 1002/hep. 30145.
[6] Parés A, Caballería L, Rodés J, et al. Long-term effects of ursodeoxycholic acid in primary biliary cirrhosis:results of a double-blind controlled multicentric trial. UDCA-Cooperative Group from the Spanish Association for the Study of the Liver[J]. J Hepatol, 2000, 32(4):561-566. DOI:10. 1016/s0168-8278(00)80216-0.
[7] Corpechot C, Abenavoli L, Rabahi N, et al.Biochemical response to ursodeoxycholic acid and longterm prognosis in primary biliary cirrhosis[J].Hepatology, 2008, 48(3):871-877. DOI:10. 1002/hep. 22428.
[8] Kuiper EM, Hansen BE, de Vries RA, et al. Improved prognosis of patients with primary biliary cirrhosis that have a biochemical response to ursodeoxycholic acid[J].Gastroenterology, 2009, 136(4):1281-1287. DOI:10. 1053/j. gastro. 2009. 01. 003.
[9] Zhang C, Shi L, Wang FS. Liver injury in COVID-19:management and challenges[J]. Lancet Gastroenterol Hepatol, 2020, 5(5):428-430. DOI:10. 1016/S2468-1253(20)30057-1.
[10]Banales JM, Huebert RC, Karlsen T, et al.Cholangiocyte pathobiology[J]. Nat Rev Gastroenterol Hepatol, 2019, 16(5):269-281. DOI:10. 1038/s41575-019-0125-y.
[11]Chai X, Hu L, Zhang Y, et al. Specific ACE2Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection. bioRxiv, 2020. DOI:10. 1101/2020. 02. 03. 931766.
[12]Brevini T, Maes M, Webb GJ, et al. FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2[J]. Nature, 2023, 615(7950):134-142. DOI:10. 1038/s41586-022-05594-0.
[13]Karlsen TH, Chung BK. Genetic risk and the development of autoimmune liver disease[J]. Dig Dis,2015, 33(Suppl 2):13-24. DOI:10. 1159/000440706.
[14]Efe C, Ozaslan E, Heurgué-Berlot A, et al. Sequential presentation of primary biliary cirrhosis and autoimmune hepatitis[J]. Eur J Gastroenterol Hepatol, 2014, 26(5):532-537. DOI:10. 1097/MEG. 0000000000000075.
[15]Lohse AW, zum Büschenfelde KH, Franz B, et al.Characterization of the overlap syndrome of primary biliary cirrhosis(PBC)and autoimmune hepatitis:evidence for it being a hepatitic form of PBC in genetically susceptible individuals[J]. Hepatology,1999, 29(4):1078-1084. DOI:10. 1002/hep. 510290409.
基本信息:
DOI：10.13242/j.cnki.bingduxuebao.004644
中图分类号:R575.7;R511
引用信息:
[1]曹卫华,王诗雨,张子昱等.经UDCA治疗原发性胆汁性胆管炎患者的新冠病毒感染临床特征研究[J].病毒学报,2025,41(01):16-22.DOI:10.13242/j.cnki.bingduxuebao.004644.
基金信息:
国家重点研发计划项目（项目号：2022YFC2603500,2022YFC2603505）,题目：高等级生物安全实验室个体防护装备关键技术研究与应用示范; 北京市医院管理局临床医学发展专项经费资助项目（项目号：XMLX 202127）,题目：干扰素治疗获得功能性治愈的慢性乙型肝炎患者持续应答及复发相关因素的研究; 北京市医院管理中心消化内科学科协同发展中心（项目号：XXZ0302）,题目：非酒精性脂肪肝组织学对终点时间的预测研究; 首都健康研发专项（项目号：2022-1-2172）,题目：慢性乙型肝炎经治低病毒血症患者的优化治疗及临床结局研究; 北京市卫健委高层次公共卫生技术人才建设项目（项目号：学科带头人-03-26）~~