Wang Xiaoning, Xie Guoxiang, Zhao Aihua, Zheng Xiaojiao, Huang Fengjie, Wang Yixing, Yao Chun, Jia Wei, Liu Ping
E-institute of Shanghai Municipal Education Committee, Shanghai University of Traditional Chinese Medicine , 1200 Cailun Road, Shanghai 201203, China.
Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital , 528 Zhangheng Road, Shanghai 201204, China.
J Proteome Res. 2016 Apr 1;15(4):1126-34. doi: 10.1021/acs.jproteome.5b00217. Epub 2016 Mar 22.
Recent metabonomic studies have identified an important role of bile acids in patients with liver cirrhosis. Serum bile acids, such as glycocholate (GCA), glycochenodeoxycholate (GCDCA), taurocholate (TCA), and taurochenodeoxycholate (TCDCA), increased significantly in liver cirrhosis patients. Our recently published urinary metabonomic study showed that glycocholate 3-glucuronide, taurohyocholate, TCA, glycolithocholate 3-sulfate, and glycoursodeoxycholate (GUDCA) were markedly increased in hepatitis B-induced cirrhotic patients (n = 63) compared with healthy controls (n = 31). The urinary levels of GUDCA were able to differentiate among three stages of cirrhotic patients with Child-Pugh (CP) score A, B, and C. In this study, we recruited two new cohorts of patients with hepatitis-B-induced cirrhosis and healthy control subjects and quantitatively profiled their serum bile acids using ultra-performance liquid chromatography triple quadrupole mass spectrometry. Serum bile acid profile and corresponding differential bile acids were characterized, in addition to the blood routine, liver, and renal function tests. The alterations of bile acids contributing to the intergroup variation between healthy controls and cirrhotic patients and among pathological stages of CP grade A, B and C were also investigated. Five bile acids, GCA, GCDCA, TCA, TCDCA, and GUDCA, were significantly altered among different stages of liver cirrhosis (n = 85), which was validated with an independent cohort of cirrhotic patients (n = 53). Our results show that dynamic alteration of serum bile acids is indicative of an exacerbated liver function, highlighting their potential as biomarkers for staging the liver cirrhosis and monitoring its progression.
最近的代谢组学研究已经确定了胆汁酸在肝硬化患者中的重要作用。肝硬化患者血清胆汁酸,如甘氨胆酸(GCA)、甘氨鹅脱氧胆酸(GCDCA)、牛磺胆酸(TCA)和牛磺鹅脱氧胆酸(TCDCA)显著升高。我们最近发表的尿液代谢组学研究表明,与健康对照者(n = 31)相比,乙型肝炎诱导的肝硬化患者(n = 63)中甘氨胆酸3-葡萄糖醛酸苷、牛磺猪去氧胆酸、TCA、甘氨石胆酸3-硫酸盐和甘氨熊去氧胆酸(GUDCA)显著升高。GUDCA的尿液水平能够区分Child-Pugh(CP)评分A、B和C的肝硬化患者的三个阶段。在本研究中,我们招募了两组新的乙型肝炎诱导的肝硬化患者和健康对照者,并使用超高效液相色谱三重四极杆质谱法定量分析了他们的血清胆汁酸。除了血常规、肝肾功能检查外,还对血清胆汁酸谱和相应的差异胆汁酸进行了表征。还研究了胆汁酸的变化对健康对照者与肝硬化患者之间以及CP A、B和C级病理阶段之间组间差异的影响。在肝硬化不同阶段(n = 85)中,五种胆汁酸GCA、GCDCA、TCA、TCDCA和GUDCA有显著变化,这在另一组独立的肝硬化患者(n = 53)中得到了验证。我们的结果表明,血清胆汁酸动态变化表明肝功能恶化,突出了它们作为肝硬化分期和监测其进展的生物标志物的潜力。