高胆汁酸血症的常见病因及诊断

李茂萍; 罗开忠

doi:10.12449/JCH250528

高胆汁酸血症的常见病因及诊断

DOI: 10.12449/JCH250528

李茂萍,
罗开忠^, ,

中南大学湘雅二医院感染科，长沙 410011

基金项目:

湖南省自然科学基金 (2024JJ9150)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：李茂萍负责设计论文框架，起草论文；罗开忠负责论文修改，指导撰写文章并最后定稿。

详细信息

通信作者:
罗开忠， luo_kz@csu.edu.cn （ORCID： 0000-0001-5643-7103）

计量
- 文章访问数: 111
- HTML全文浏览量: 35
- PDF下载量: 20
- 被引次数: 0
出版历程
- 收稿日期: 2024-08-07
- 录用日期: 2024-09-30
- 出版日期: 2025-05-25

Common etiology and diagnosis of hyperbileacidemia

Maoping LI,
Kaizhong LUO^{,
,}

Department of Infectious Diseases，The Second Xiangya Hospital of Central South University，Changsha 410011，China

Research funding:

Natural Science Foundation of Hunan Province (2024JJ9150)

More Information

Corresponding author: LUO Kaizhong， luo_kz@csu.edu.cn （ORCID： 0000-0001-5643-7103）

摘要

摘要: 胆汁酸是胆汁的主要成分，是复杂的代谢调节剂和重要的信号分子，在脂肪代谢中发挥着关键作用。临床上高胆汁酸血症比较常见，但有时不易明确病因。本文综述了常见的引起高胆汁酸血症的疾病及其胆汁酸池组分的改变，以期为临床医生提供高胆汁酸血症的规范化诊断思路。
- 高胆汁酸血症 /
- 胆汁酸 /
- 诊断
Abstract: Bile acids （BAs） are the main components of bile and serve as complex metabolic regulators and important signaling molecules， and they play a crucial role in fat metabolism. Hyperbileacidemia （HBA） is relatively common in clinical practice， but sometimes it is difficult to clarify its etiology. This article reviews the common diseases that cause HBA and the changes in the composition of the bile acid pool， so as to provide clear insights for the diagnosis of HBA.
- Hyperbileacidemia /
- Bile Acids /
- Diagnosis

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参考文献(50)

[1]	WANG PW, DONG YW. Definition, etiology and classification of cholestasis[J]. J Intern Med Concepts Pract, 2022, 17( 1): 15- 23. DOI: 10.16138/j.1673-6087.2022.01.004. 汪佩文, 董育玮. 胆汁淤积的定义、病因及分类[J]. 内科理论与实践, 2022, 17( 1): 15- 23. DOI: 10.16138/j.1673-6087.2022.01.004.
[2]	ZHANG Y, LI JX, WANG YL. The role of bile acid metabolism and its receptors in the pathogenesis and progression of non-alcoholic fatty liver disease[J]. J Clin Hepatol, 2020, 36( 6): 1374- 1377. DOI: 10.3969/j.issn.1001-5256.2020.06.040. 张阳, 李军祥, 王允亮. 胆汁酸代谢及其受体在非酒精性脂肪性肝病发生发展中的作用[J]. 临床肝胆病杂志, 2020, 36( 6): 1374- 1377. DOI: 10.3969/j.issn.1001-5256.2020.06.040.
[3]	WINSTON JA, THERIOT CM. Diversification of host bile acids by members of the gut microbiota[J]. Gut Microbes, 2020, 11( 2): 158- 171. DOI: 10.1080/19490976.2019.1674124.
[4]	HAN CP, XU QF. Clinical application of serum total bile acid measurement in liver injury[J]. Med Innov China, 2013, 10( 22): 84- 85. DOI: 10.3969/j.issn.1674-4985.2013.22.040. 韩晨鹏, 徐清芳. 血清总胆汁酸测定在肝损伤中的临床应用[J]. 中国医学创新, 2013, 10( 22): 84- 85. DOI: 10.3969/j.issn.1674-4985.2013.22.040.
[5]	ZHANG JF, FU GS, WANG LH. Changes in serum bile acid levels in hepatitis patients and their clinical significance[J]. Chin J Clin Res, 1998, 11( 5): 371- 372. 张晶芬, 付广双, 王立红. 肝炎患者血清胆汁酸含量变化及临床意义[J]. 中国厂矿医学, 1998, 11( 5): 371- 372.
[6]	LYU JL. Association between changes in serum total bile acids, albumin, and cholinesterase levels and Child-Pugh classification in patients with hepatitis and cirrhosis[J]. Pract Clin J Integr Tradit Chin West Med, 2021, 21( 15): 113- 114. DOI: 10.13638/j.issn.1671-4040.2021.15.056. 吕金龙. 血清总胆汁酸、白蛋白、胆碱酯酶水平变化与肝炎肝硬化患者Child-Pugh分级的关联性[J]. 实用中西医结合临床, 2021, 21( 15): 113- 114. DOI: 10.13638/j.issn.1671-4040.2021.15.056.
[7]	LIU N, ZHOU YQ. The significance of bile acids in the progression and treatment of liver cirrhosis[J]. Chin Hepatol, 2022, 27( 3): 376- 379. DOI: 10.14000/j.cnki.issn.1008-1704.2022.03.021. 刘宁, 周莹群. 胆汁酸对肝硬化疾病进展及治疗的意义[J]. 肝脏, 2022, 27( 3): 376- 379. DOI: 10.14000/j.cnki.issn.1008-1704.2022.03.021.
[8]	NI YH, QIN DY, WANG L. Changes in serum levels of total bile acid, Golgi protein 73, and cancer antigen 19-9 in patients with cirrhosis and their clinical significance[J]. China J Gen Surg, 2024, 33( 2): 305- 310. DOI: 10.7659/j.issn.1005-6947.2024.02.019. 倪雅惠, 秦东媛, 王琳. 肝硬化患者血清总胆汁酸、高尔基体蛋白73及糖类抗原19-9的水平变化及其临床意义[J]. 中国普通外科杂志, 2024, 33( 2): 305- 310. DOI: 10.7659/j.issn.1005-6947.2024.02.019.
[9]	ZHU SS, LU X. Characteristics and research progress of serum bile acid profile in intrahepatic cholestasis[J]. Chin Hepatol, 2022, 27( 6): 715- 719. DOI: 10.14000/j.cnki.issn.1008-1704.2022.06.005. 朱时帅, 芦曦. 肝内胆汁淤积症血清胆汁酸谱的特征及研究进展[J]. 肝脏, 2022, 27( 6): 715- 719. DOI: 10.14000/j.cnki.issn.1008-1704.2022.06.005.
[10]	WU J, FAN Y, SHI G. Extrahepatic cholestatic jaundice[J]. J New Med, 2015, 25( 1): 5- 9. 吴杰, 范彦, 石干. 肝外胆汁淤积性黄疸[J]. 医学新知杂志, 2015, 25( 1): 5- 9.
[11]	LI X, ZHANG XL. Application of serum total bile acids in the diagnosis of hepatobiliary diseases[J]. Mod Med Health, 2006, 22( 15): 2372. DOI: 10.3969/j.issn.1009-5519.2006.15.105. 李雪, 张筱丽. 血清总胆汁酸在肝胆疾病诊断中的应用[J]. 现代医药卫生, 2006, 22( 15): 2372. DOI: 10.3969/j.issn.1009-5519.2006.15.105.
[12]	TROTTIER J, BIAŁEK A, CARON P, et al. Metabolomic profiling of 17 bile acids in serum from patients with primary biliary cirrhosis and primary sclerosing cholangitis: A pilot study[J]. Dig Liver Dis, 2012, 44( 4): 303- 310. DOI: 10.1016/j.dld.2011.10.025.
[13]	MONTE MJ, MARIN JJG, ANTELO A, et al. Bile acids: Chemistry, physiology, and pathophysiology[J]. World J Gastroenterol, 2009, 15( 7): 804- 816. DOI: 10.3748/wjg.15.804.
[14]	KRÄHENBÜHL S, FISCHER S, TALOS C, et al. Ursodeoxycholate protects oxidative mitochondrial metabolism from bile acid toxicity: Dose-response study in isolated rat liver mitochondria[J]. Hepatology, 1994, 20( 6): 1595- 1601. DOI: 10.1002/hep.1840200632.
[15]	PEREZ MJ, BRIZ O. Bile-acid-induced cell injury and protection[J]. World J Gastroenterol, 2009, 15( 14): 1677- 1689. DOI: 10.3748/wjg.15.1677.
[16]	SHARMA R, MAJER F, PETA VK, et al. Bile acid toxicity structure-activity relationships: Correlations between cell viability and lipophilicity in a panel of new and known bile acids using an oesophageal cell line(HET-1A)[J]. Bioorg Med Chem, 2010, 18( 18): 6886- 6895. DOI: 10.1016/j.bmc.2010.07.030.
[17]	HUANG HH, CHEN YY. Role of total bile acid determination in differential diagnosis of obstructive jaundice[J]. Med J Natl Defending Forces N China, 2006, 18( 2): 105- 107. DOI: 10.3969/j.issn.2095-140X.2006.02.012. 黄汇慧, 陈延演. 血清总胆汁酸测定在梗阻性黄疸鉴别诊断中的临床应用[J]. 华北国防医药, 2006, 18( 2): 105- 107. DOI: 10.3969/j.issn.2095-140X.2006.02.012.
[18]	JIAO N, BAKER SS, CHAPA-RODRIGUEZ A, et al. Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD[J]. Gut, 2018, 67( 10): 1881- 1891. DOI: 10.1136/gutjnl-2017-314307.
[19]	PURI P, DAITA K, JOYCE A, et al. The presence and severity of nonalcoholic steatohepatitis is associated with specific changes in circulating bile acids[J]. Hepatology, 2018, 67( 2): 534- 548. DOI: 10.1002/hep.29359.
[20]	DEVKOTA S, WANG YW, MUSCH MW, et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in IL-10^-/- mice[J]. Nature, 2012, 487: 104- 108. DOI: 10.1038/nature11225.
[21]	COPE K, RISBY T, DIEHL AM. Increased gastrointestinal ethanol production in obese mice: Implications for fatty liver disease pathogenesis[J]. Gastroenterology, 2000, 119( 5): 1340- 1347. DOI: 10.1053/gast.2000.19267.
[22]	DAPAS M, DUNAIF A. Deconstructing a syndrome: Genomic insights into PCOS causal mechanisms and classification[J]. Endocr Rev, 2022, 43( 6): 927- 965. DOI: 10.1210/endrev/bnac001.
[23]	MCILVRIDE S, DIXON PH, WILLIAMSON C. Bile acids and gestation[J]. Mol Aspects Med, 2017, 56: 90- 100. DOI: 10.1016/j.mam.2017.05.003.
[24]	LUO T, GUO XD, BAI XX. Research progress of asymptomatic hypercholanaemia of pregnancy[J]. J Int Obstet Gynecol, 2021, 48( 5): 499- 502, 534. DOI: 10.12280/gjfckx.20210365. 罗挺, 郭雪冬, 白晓霞. 妊娠期无症状高胆汁酸血症的研究进展[J]. 国际妇产科学杂志, 2021, 48( 5): 499- 502, 534. DOI: 10.12280/gjfckx.20210365.
[25]	ALEMI F, KWON E, POOLE DP, et al. The TGR5 receptor mediates bile acid-induced itch and analgesia[J]. J Clin Invest, 2013, 123( 4): 1513- 1530. DOI: 10.1172/JCI64551.
[26]	CHEN X, SHAO Y, XU B, et al. A clinical analysis of asymptomatic hypercholanaemia of pregnancy[J]. J Chongqing Med Univ, 2019, 44( 8): 1059- 1063. DOI: 10.13406/j.cnki.cyxb.002147. 陈霄, 邵勇, 胥飚, 等. 妊娠期无症状高胆汁酸血症的临床特点分析[J]. 重庆医科大学学报, 2019, 44( 8): 1059- 1063. DOI: 10.13406/j.cnki.cyxb.002147.
[27]	WANG RY. Combined serum bile acid concentrations in workers exposed to low doses of toluene and xylene[J]. J Prev Med Inf, 1991, 7( 2): 118- 119, 107. 王仁仪. 接触低剂量甲苯和二甲苯工人的结合血清胆汁酸浓度[J]. 预防医学情报杂志, 1991, 7( 2): 118- 119, 107.
[28]	LI NN, MENG XS, GUO WZ, et al. Effect of Ruangan chongji on CCl₄-induced hepatic fibrosis and intestinal flora in rats[J]. Liaoning J Tradit Chin Med, 2023, 50( 4): 191- 193, 228- 229. DOI: 10.13192/j.issn.1000-1719.2023.04.050. 李楠楠, 孟宪生, 郭文昭, 等. 软肝冲剂对四氯化碳诱导大鼠肝纤维化及肠道菌群的影响[J]. 辽宁中医杂志, 2023, 50( 4): 191- 193, 228- 229. DOI: 10.13192/j.issn.1000-1719.2023.04.050.
[29]	HUANG QZ, WANG CY. Clinical treatment and nursing of patients with liver damage caused by carbon tetrachloride poisoning[J]. Today Nurse(Specialist Edition), 2009, 16( 10): 48. 黄清珠, 王翠玉. 四氯乙烷中毒致肝损害患者的临床救治与护理[J]. 当代护士(专科版), 2009, 16( 10): 48.
[30]	LYU L, ZHANG GQ, JIN Y, et al. Clinical significance and research progress of changes in bile acid concentration in vivo[J]. J Clin Med Pract, 2013, 17( 9): 159- 161, 165. DOI: 10.7619/jcmp.201309063. 吕磊, 张国庆, 金彦, 等. 体内胆汁酸质量浓度变化的临床意义及研究进展[J]. 实用临床医药杂志, 2013, 17( 9): 159- 161, 165. DOI: 10.7619/jcmp.201309063.
[31]	HADY HM EL, METWALLY F, GENDY MF EL, et al. Serum bile acid as a screening tool in workers occupationally exposed to mixtures of organic solvents[J]. Toxicol Ind Health, 2014, 30( 7): 645- 652. DOI: 10.1177/0748233712462469.
[32]	NEGHAB M, QU SX, BAI CL, et al. Raised concentration of serum bile acids following occupational exposure to halogenated solvents, 1, 1, 2-trichloro-1, 2, 2-trifluoroethane and trichloroethylene[J]. Int Arch Occup Environ Health, 1997, 70( 3): 187- 194. DOI: 10.1007/s004200050205.
[33]	CHEN JD, WANG JD, TSAI SY, et al. Effects of occupational and nonoccupational factors on liver function tests in workers exposed to solvent mixtures[J]. Arch Environ Health, 1997, 52( 4): 270- 274. DOI: 10.1080/00039899709602197.
[34]	YANG S, LI HY, GU YY, et al. The association between total bile acid and bone mineral density among patients with type 2 diabetes[J]. Front Endocrinol(Lausanne), 2023, 14: 1153205. DOI: 10.3389/fendo.2023.1153205.
[35]	ZHAO X, LIU ZT, SUN FY, et al. Bile acid detection techniques and bile acid-related diseases[J]. Front Physiol, 2022, 13: 826740. DOI: 10.3389/fphys.2022.826740.
[36]	LIU JX, CHEN YX, LUO Q. The association of serum total bile acids with bone mineral density in Chinese adults aged 20-59: A retrospective cross-sectional study[J]. Front Endocrinol(Lausanne), 2022, 13: 817437. DOI: 10.3389/fendo.2022.817437.
[37]	HERRMANN M, RODRIGUEZ-BLANCO G, BALASSO M, et al. The role of bile acid metabolism in bone and muscle: From analytics to mechanisms[J]. Crit Rev Clin Lab Sci, 2024, 61( 6): 510- 528. DOI: 10.1080/10408363.2024.2323132.
[38]	ZHAO YX, SONG YW, ZHANG L, et al. Association between bile acid metabolism and bone mineral density in postmenopausal women[J]. Clinics(Sao Paulo), 2020, 75: e1486. DOI: 10.6061/clinics/2020/e1486.
[39]	SASAKI T, KUBOYAMA A, MITA M, et al. The exercise-inducible bile acid receptor Tgr5 improves skeletal muscle function in mice[J]. J Biol Chem, 2018, 293( 26): 10322- 10332. DOI: 10.1074/jbc.RA118.002733.
[40]	YOSHIDA T, DELAFONTAINE P. Mechanisms of IGF-1-mediated regulation of skeletal muscle hypertrophy and atrophy[J]. Cells, 2020, 9( 9): 1970. DOI: 10.3390/cells9091970.
[41]	OROZCO-AGUILAR J, TACCHI F, AGUIRRE F, et al. Ursodeoxycholic acid induces sarcopenia associated with decreased protein synthesis and autophagic flux[J]. Biol Res, 2023, 56( 1): 28. DOI: 10.1186/s40659-023-00431-8.
[42]	ARONSON SJ, BAKKER RS, SHI XX, et al. Liver-directed gene therapy results in long-term correction of progressive familial intrahepatic cholestasis type 3 in mice[J]. J Hepatol, 2019, 71( 1): 153- 162. DOI: 10.1016/j.jhep.2019.03.021.
[43]	GUO J, XIE SY, YANG LR, et al. Clinical characteristics of 2 cases of progressive familial intrahepatic cholestasis and literature review[J/CD]. Chin J Liver Dis Electron Version, 2024, 16( 1): 67- 72. DOI: 10.3969/j.issn.1674-7380.2024.01.012. 郭静, 谢双宇, 杨玲蓉, 等. 进行性家族性肝内胆汁淤积症2例临床特点分析及文献复习[J/CD]. 中国肝脏病杂志(电子版), 2024, 16( 1): 67- 72. DOI: 10.3969/j.issn.1674-7380.2024.01.012.
[44]	LI H, CHEN R, LIN GZ, et al. Molecular epidemiology of Na⁺-taurocholate cotransporting polypeptide deficiency in Guangdong Province, China: A pilot study by screening for four prevalent variants of the causative gene SLC10A1[J]. Front Genet, 2022, 13: 874379. DOI: 10.3389/fgene.2022.874379.
[45]	ZHAO H, YU XM, BAI XX. Research progress on sodium-taurocholate cotransporting polypeptide deficiency disease and its impact on mother and fetus[J]. J Int Obstet Gynecol, 2023, 50( 6): 684- 688. DOI: 10.12280/gjfckx.20230675. 赵欢, 余晓明, 白晓霞. 钠离子牛磺胆酸共转运多肽缺陷病及其对母胎影响的研究进展[J]. 国际妇产科学杂志, 2023, 50( 6): 684- 688. DOI: 10.12280/gjfckx.20230675.
[46]	IBRAHIM SH, KAMATH BM, LOOMES KM, et al. Cholestatic liver diseases of genetic etiology: Advances and controversies[J]. Hepatology, 2022, 75( 6): 1627- 1646. DOI: 10.1002/hep.32437.
[47]	KOHUT TJ, GILBERT MA, LOOMES KM. Alagille syndrome: A focused review on clinical features, genetics, and treatment[J]. Semin Liver Dis, 2021, 41( 4): 525- 537. DOI: 10.1055/s-0041-1730951.
[48]	WU LN, SUN LY, ZHU ZJ, et al. Clinical and histological characteristics of patients with Alagille syndrome[J]. Chin Hepatol, 2023, 28( 3): 351- 354, 363. DOI: 10.14000/j.cnki.issn.1008-1704.2023.03.018. 武丽娜, 孙丽莹, 朱志军, 等. Alagille综合征的临床及病理特征分析[J]. 肝脏, 2023, 28( 3): 351- 354, 363. DOI: 10.14000/j.cnki.issn.1008-1704.2023.03.018.
[49]	SIDDIQUI AH, ALSABE MR, TEHSEEN Z, et L. Dubin-Johnson syndrome: A case report[J]. Cureus, 2023, 15( 3): e36115. DOI: 10.7759/cureus.36115.
[50]	WANG YL, QIAO HJ, DONG YH, et al. Clinical characteristics analysis of 11 cases of Dubin-Johnson syndrome[J]. Henan Med Res, 2022, 31( 24): 4437- 4441. DOI: 10.3969/j.issn.1004-437X.2022.24.004. 王亚丽, 乔会菊, 董燕红, 等. 11例Dubin-Johnson综合征患者临床特征分析[J]. 河南医学研究, 2022, 31( 24): 4437- 4441. DOI: 10.3969/j.issn.1004-437X.2022.24.004.