Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
E-institute of Shanghai Municipal Education Committee, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
J Proteome Res. 2021 May 7;20(5):2340-2351. doi: 10.1021/acs.jproteome.0c00852. Epub 2021 Mar 23.
A significant increase of bile acid (BA) levels has been recognized as a general metabolic phenotype of diverse liver diseases. Monitoring of BA profiles has been proposed for etiology differentiation on liver injury. Here, we quantitatively profiled serum BAs of healthy controls and 719 patients with chronic liver disease of five etiologies, hepatitis B virus (HBV), hepatitis C virus (HCV), nonalcoholic steatohepatitis (NASH), alcohol-induced liver disease (ALD), and primary biliary cirrhosis (PBC), and investigated the generality and specificity of different etiologies. The raw data have been deposited into MetaboLights (ID: MTBLS2459). We found that patients with HBV, HCV, and NASH appeared to be more similar, and ALD and PBC patients clustered together. BA profiles, consisting of a total concentration of the 21 quantified BAs [total BAs (TBAs)], 21 BA proportions, and 24 BA relevant variables, were highly different among the etiologies. Specifically, the total BAs was higher in ALD and PBC patients compared with the other three groups. The proportion of conjugated deoxycholates was the highest in HBV-infected patients. The ratio of 12α-hydroxylated (12α-OH) to non-12α-OH BAs was the highest in NASH patients. The proportion of taurine-conjugated BAs was the highest in ALD patients. For PBC patients, the proportion of ursodeoxycholate species was the highest, and the ratio of primary to secondary BAs was the lowest. Comparatively, the difference of BA profiles among cirrhosis patients was consistent but weaker than that of all patients. The correlations between BA profiles and clinical indices were also quite different in different pathological groups, both in all patients and in patients with cirrhosis. Overall, our findings suggested that BA compositions are distinct among patients with different etiologies of chronic liver disease, and some BA-relevant variables are of clinical potentials for liver injury type differentiation, although further validations on more etiologies and populations are needed.
胆汁酸（BA）水平的显著升高已被认为是多种肝脏疾病的一般代谢表型。BA 谱的监测已被提议用于肝损伤的病因学鉴别。在这里，我们对 5 种病因的慢性肝病患者（乙型肝炎病毒（HBV）、丙型肝炎病毒（HCV）、非酒精性脂肪性肝炎（NASH）、酒精性肝病（ALD）和原发性胆汁性胆管炎（PBC））的健康对照和 719 名患者的血清 BA 进行了定量分析，并研究了不同病因的普遍性和特异性。原始数据已存入代谢物数据库（ID：MTBLS2459）。我们发现 HBV、HCV 和 NASH 患者似乎更相似，而 ALD 和 PBC 患者聚集在一起。BA 谱由 21 种定量 BA 的总浓度[总 BA（TBAs）]、21 种 BA 比例和 24 种 BA 相关变量组成，在病因之间差异很大。具体来说，与其他三组相比，ALD 和 PBC 患者的总 BA 更高。HBV 感染患者的结合去氧胆酸比例最高。NASH 患者 12α-羟化（12α-OH）与非 12α-OH BA 的比值最高。ALD 患者中牛磺酸结合 BA 的比例最高。对于 PBC 患者，熊去氧胆酸种类的比例最高，初级和次级 BA 的比例最低。相比之下，肝硬化患者的 BA 谱差异虽然一致，但比所有患者的差异要弱。不同病理组患者的 BA 谱与临床指标的相关性也存在很大差异，无论是在所有患者还是在肝硬化患者中。总体而言，我们的研究结果表明，不同病因慢性肝病患者的 BA 成分存在明显差异，一些与 BA 相关的变量在肝损伤类型鉴别方面具有临床潜力，尽管还需要在更多病因和人群中进行进一步验证。
