自身免疫性肝炎和原发性胆汁性胆管炎患者血清胆汁酸成分变化及其对治疗应答的影响

Bile acid composition and their impact of response to immunosuppressant or UCDA therapy in patients with autoimmune hepatitis and primary biliary cholangitis

目的研究自身免疫性肝炎(AIH)和原发性胆汁性胆管炎(PBC)患者血清胆汁酸(BAs)成分变化及其对治疗应答的影响。方法2020年1月~2023年1月我院诊治的28例AIH患者和55例PBC患者,分别接受醋酸泼尼松或熊去氧胆酸胶囊治疗。采用液相色谱-质谱联用法(LC-MS/MS)检测血清BAs成分,包括游离胆酸(CA)、去氧胆酸(DCA)、鹅去氧胆酸(CDCA)、熊去氧胆酸(UDCA)和石胆酸(LCA),甘氨结合型BAs包括糖胆酸(GCA)、糖去氧胆酸(GDCA)、糖去氧胆酸(GCDCA)和糖去氧胆酸(GUDCA)和牛磺结合型BAs包括牛磺酸胆酸(TCA)、牛磺酸去氧胆酸(TDCA)、牛磺酸去氧胆酸(TCDCA)和牛磺酸石胆酸(TLCA)。结果在治疗6个月末,AIH患者获得应答20例(71.4%),PBC患者获得应答42例(76.4%);AIH应答组血清CA、CDCA、UDCA和LCA分别为(1.6±0.5)ng/ml、(2.6±0.4)ng/ml、(2.0±0.3)ng/ml和(0.7±0.4)ng/ml,均显著低于未应答组【分别为(2.4±0.7)ng/ml、(2.9±0.4)ng/ml、(2.4±1.0)ng/ml和(0.9±0.7)ng/ml,P<0.05】,血清GCA、GDCA、GCDCA和GUDCA水平分别为(1.3±0.5)ng/ml、(2.6±0.3)ng/ml、(2.9±0.3)ng/ml和(1.6±0.5)ng/ml,均显著低于未应答组【分别为(3.0±1.0)ng/ml、(3.2±0.6)ng/ml、(3.8±0.8)ng/ml和(2.6±1.2)ng/ml,P<0.05】,血清TCA、TDCA、TCDCA和TLCA水平分别为(0.5±0.1)ng/ml、(2.6±0.2)ng/ml、(2.5±0.3)ng/ml和(0.1±0.0)ng/ml,均显著低于未应答组【分别为(2.1±1.2)ng/ml、(3.3±0.6)ng/ml、(2.7±0.4)ng/ml和(0.4±0.1)ng/ml,P<0.05】;PBC应答组血清CA、CDCA、UDCA和LCA水平分别为(1.7±0.4)ng/ml、(2.7±0.4)ng/ml、(2.1±0.4)ng/ml和(0.8±0.4)ng/ml,均显著低于未应答组【分别为(2.3±0.9)ng/ml、(3.0±0.4)ng/ml、(2.5±0.7)ng/ml和(1.3±0.7)ng/ml,P<0.05】,血清GCA、GDCA、GCDCA和GUDCA水平分别为(1.4±0.7)ng/ml、(2.6±0.4)ng/ml、(3.0±0.5)ng/ml和(2.0±0.9)ng/ml,均显著低于未应答组【分别为(2.9±0.9)ng/ml、(3.2±0.5)ng/ml、(3.8±0.7)ng/ml和(3.0±1.1)ng/ml,P<0.05】,血清TCA、TDCA、TCDCA和TLCA水平分别为(0.5±0.2)ng/ml、(2.7±0.3)ng/ml、(2.5±0.4)ng/ml和(0.2±0.1)ng/ml,均显著低于未应答组【分别为(2.1±0.9)ng/ml、(3.2±0.5)ng/ml、(2.8±0.4)ng/ml和(0.5±0.2)ng/ml,P<0.05】。结论虽然PBC和AIH患者血清BAs水平有显著性差异,但血清Bas水平升高或在治疗过程中不下降者,可能影响对治疗的应答,其机制还有待于探讨。

Objective The aim of this study was to explore bile acid(BA)composition changes and their impact of response to immunosuppressant or ursodeoxycholic acid(UCDA)therapy in patients with autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC).Methods 28 patients with AIH and 55 patients with PBC were encountered in our hospital between January 2020 and January 2023,and they received prednisone or UDCA therapy.Serum free BAs,including cholic acid(CA),deoxycholic acid(DCA),chenodeoxycholic acid(CDCA),ursodeoxycholic acid(UDCA)and lithocholic acid(LCA),lycinebinding BAs(G-BAs),including glycocholic acid(GCA),glycodeoxycholic acid(GDCA),glycodeoxycholic acid(GCDCA)and glycodeoxycholic acid(GUDCA),and taurocholate-binding bile acid(T-BAs),including taurine cholic acid(TCA),taurine deoxycholic acid(TDCA),taurine deoxycholic acid(TCDCA)and taurine lithocholic acid(TLCA)levels were detected by liquid chromatography tandem mass spectrometry.Results By end of six month treatment,complete response to therapy in patients with AIH was found in 20 cases(71.4%)and in patients with PBC was found in 42 cases (76. 4%);serum CA, CDCA, UDCA and LCA levels in AIH responders were (1. 6±0. 5)ng/ ml, (2. 6±0. 4)ng/ ml, (2. 0± 0. 3)ng/ ml and (0. 7±0. 4)ng/ ml, all significantly lower than [(2. 4±0. 7)ng/ ml, (2. 9±0. 4)ng/ ml, (2. 4±1. 0)ng/ ml and (0. 9±0. 7)ng/ ml, respectively, P<0. 05], serum GCA, GDCA, GCDCA and GUDCA levels were (1. 3±0. 5)ng/ ml, (2. 6± 0. 3)ng/ ml, (2. 9±0. 3)ng/ ml and (1. 6±0. 5)ng/ ml, all significantly lower than [(3. 0±1. 0)ng/ ml, (3. 2±0. 6)ng/ ml, (3. 8±0. 8)ng/ ml and (2. 6±1. 2)ng/ ml, respectively, P<0. 05], and serum TCA, TDCA, TCDCA and TLCA levels were (0. 5± 0. 1)ng/ ml, (2. 6±0. 2)ng/ ml, (2. 5±0. 3)ng/ ml and (0. 1±0. 0)ng/ ml, all significantly lower than [(2. 1±1. 2)ng/ ml, (3. 3±0. 6)ng/ ml, (2. 7±0. 4)ng/ ml and (0. 4±0. 1)ng/ ml, respectively, P<0. 05] in non-responders;serum CA, CDCA, UDCA and LCA levels in PBC responders were(1. 7±0. 4)ng/ ml, (2. 7±0. 4)ng/ ml, (2. 1±0. 4)ng/ ml and (0. 8±0. 4)ng/ ml, all significantly lower than [(2. 3±0. 9)ng/ ml, (3. 0±0. 4)ng/ ml, (2. 5±0. 7)ng/ ml and (1. 3±0. 7)ng/ ml, respectively, P< 0. 05], serum GCA, GDCA, GCDCA and GUDCA levels were (1. 4±0. 7)ng/ ml, (2. 6±0. 4)ng/ ml, (3. 0±0. 5)ng/ ml and (2. 0±0. 9)ng/ ml, all significantly lower than [(2. 9±0. 9)ng/ ml, (3. 2±0. 5)ng/ ml, (3. 8±0. 7)ng/ ml and (3. 0±1. 1)ng/ ml, respectively, P<0. 05], and serum TCA, TDCA, TCDCA and TLCA levels were (0. 5±0. 2)ng/ ml, (2. 7±0. 3)ng/ ml, (2. 5± 0. 4)ng/ ml and (0. 2±0. 1)ng/ ml, all significantly lower than [(2. 1±0. 9)ng/ ml, (3. 2±0. 5)ng/ ml, (2. 8±0. 4)ng/ ml and (0. 5±0. 2)ng/ ml, respectively, P<0. 05] in non-responders. Conclusion There are significant differences in serum bile acid levels between patients with PBC and with AIH, and serum BAs changes might be involved in pathogenesis of autoimmune liver diseases, and have some influence on outcomes of the diseases.