应用奥贝胆酸和贝特类药物治疗对熊去氧胆酸治疗不完全应答的原发性胆汁性胆管炎患者临床研究*

doi:10.3969/j.issn.1672-5069.2023.02.019

摘要/Abstract

摘要： 目的探讨应用奥贝胆酸(OCA)和贝特类药物治疗对熊去氧胆酸(UDCA)治疗不完全应答的原发性胆汁性胆管炎(PBC)患者的临床疗效。方法 2019年1月～2020年12月我院收治的PBC患者41例,被随机分为观察组21例和对照组20例。所有患者在继续UDCA维持治疗的基础上,给予对照组OCA治疗,给予观察组OCA联合非诺贝特治疗,两组均治疗观察24 w。采用放射免疫法检测血清IV型胶原(IV-C)、透明质酸(HA)、III型前胶原(P Ⅲ P)和层粘连蛋白(LN)水平,采用免疫比浊法检测血清免疫球蛋白G(IgG)、IgA和IgM,采用ELISA法检测血清白细胞介素-2(IL-2)、IL-6、IL-10和肿瘤坏死因子-α(TNF-α)。结果在治疗24 w末,观察组血清ALT、TBIL、GGT和ALP水平分别为(29.1±5.3)U/L、(24.8±4.1)μmol/L、(86.4±15.7)U/L和(100.6±26.3)U/L,均显著低于对照组【分别为(42.8±7.6)U/L、(30.2±6.5)μmol/L、(121.7±18.6)U/L和(131.8±33.7)U/L,P＜0.05】;血清IV-C、HA和P Ⅲ P水平分别为(125.1±19.5)μg/L、(118.5±28.9)μg/L和(136.8±31.5)μg/L,均显著低于对照组【分别为(149.3±30.1)μg/L、 (165.3±40.2)μg/L和 (167.9±42.8)μg/L,P＜0.05】;血清IgG、IgA和IgM水平分别为(11.7±1.6)g/L、(2.9±0.5)g/L和(2.2±0.3)g/L,均显著低于对照组【分别为(15.9±2.2)g/L、(3.6±0.7)g/L和(3.0±0.8)g/L,P＜0.05】;血清IL-2水平为(84.6±18.4)pg/ml,显著高于对照组【(63.2±12.9)pg/ml,P＜0.05】,而血清IL-6和TNF-α水平分别为(3.3±1.4)pg/ml和(5.1±1.9)pg/ml,显著低于对照组【分别为(6.6±1.8)pg/ml和 (7.4±2.3)pg/ml,P＜0.05】。结论应用OCA和贝特类药物治疗对UDCA治疗不完全应答的PBC患者可以有效改善肝功能,缓解肝纤维化程度,可能与抑制了免疫球蛋白分泌,调节了血清细胞因子水平有关。

关键词: 原发性胆汁性胆管炎, 奥贝胆酸, 非诺贝特, 熊去氧胆酸, 治疗

Abstract: Objective The aim of this study was to explore the clinical efficacy of obeticholic acid (OCA) and fibrates rescue therapy in patients with primary biliary cholangitis (PBC) who didn’t response to ursodeoxycholic acid (UDCA) treatment. Methods 41 PBC patients without complete response to UDCA therapy were encountered in our hospital between January 2019 and December 2020, and were randomly divided into control (n=20) and observation group (n=21), receiving OCA or OCA and fenofibrate combination at base of UDCA maintaining treatment in both group for 24 weeks. Serum type IV collagen (IV-C), hyaluronic acid (HA), type III procollagen (PIIIP) and laminin (LN) were detected by radioimmunoassay, serum immunoglobulins (IgG, IgA and IgM) were detected by immunoturbidimetry, and serum interleukin-2 (IL-2), IL-6, IL-10 and tumor necrosis factor-α (TNF-α) were detected by ELISA. Results At the end of 24 week treatment, serum ALT, bilirubin, GGT and ALP levels in the observation group were (29.1±5.3)U/L, (24.8±4.1)μmol/L, (86.4±15.7)U/L and (100.6±26.3)U/L, all significantly lower than [(42.8±7.6)U/L, (30.2±6.5)μmol/L, (121.7±18.6)U/L and (131.8±33.7)U/L, respectively, P＜0.05] in the control; serum IV-C, HA and P Ⅲ P levels were (125.1±19.5)μg/L, (118.5±28.9)μg/L and (136.8±31.5)μg/L, all significantly lower than [(149.3±30.1)μg/L, (165.3±40.2)μg/L and (167.9±42.8)μg/L, respectively, P＜0.05] in the control; serum IgG, IgA and IgM levels were (11.7±1.6)g/L, (2.9±0.5)g/L and (2.2±0.3)g/L, all significantly lower than [(15.9±2.2)g/L, (3.6±0.7)g/L and (3.0±0.8)g/L, respectively, P＜0.05] in the control group; serum IL-2 level was (84.6±18.4)pg/ml, significantly higher than [(63.2±12.9)pg/ml, P＜0.05], while serum IL-6 and TNF-α levels were (3.3±1.4)pg/ml and (5.1±1.9)pg/ml, both significantly lower than [(6.6±1.8)pg/ml and (7.4±2.3)pg/ml, P＜0.05] in the control. Conclusion The rescue treatment of OCA and fibrate combination in dealing with PBC patients without complete response to UDCA therapy could improve liver function tests and alleviate liver fibrosis, which might be related to inhibition of immunoglobulins secretion and regulation of serum cytokine metabolism.

Key words: Primary biliary cholangitis, Obeticholic acid, Fenofibrate, Ursodeoxycholic acid, Therapy

李艳芬, 张晓文, 王艳茹, 齐慧芳, 支姗. 应用奥贝胆酸和贝特类药物治疗对熊去氧胆酸治疗不完全应答的原发性胆汁性胆管炎患者临床研究^*[J]. 实用肝脏病杂志, 2023, 26(2): 226-229.

Li Yanfen, Zhang Xiaowen, Wang Yanru, et al.. Rescuing therapy of obeticholic acid and fibrates in patients with primary biliary cholangitis without complete response to ursodeoxycholic acid treatment[J]. Journal of Practical Hepatology, 2023, 26(2): 226-229.

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应用奥贝胆酸和贝特类药物治疗对熊去氧胆酸治疗不完全应答的原发性胆汁性胆管炎患者临床研究^*

Rescuing therapy of obeticholic acid and fibrates in patients with primary biliary cholangitis without complete response to ursodeoxycholic acid treatment

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