原发性胆汁性胆管炎合并脂质代谢异常的研究进展
DOI: 10.12449/JCH240125
利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:袁诗雨负责起草文章,对行文的思路和设计有关键贡献;杨焕焕、唐映梅参与了修改文章关键内容。
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摘要: 原发性胆汁性胆管炎(PBC)是一种以肝内中小胆管进行性、非化脓性炎症为特征的自身免疫性肝病。近期研究发现PBC患者中脂质代谢异常较为常见,76%的PBC患者常合并血脂异常,其作用及危害备受关注。脂质代谢紊乱在PBC发展中起重要作用,本文主要从脂质代谢紊乱在PBC中的表现及作用、诊断及治疗方面的研究进展展开综述,以期为PBC治疗提供新的思路。Abstract: Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by progressive and non-purulent inflammation of small- and medium-sized bile ducts in the liver. Recent studies have shown that abnormal lipid metabolism is relatively common in patients with PBC, and 76% of PBC patients have dyslipidemia. The effects and harms of dyslipidemia have attracted much attention. Lipid metabolism disorders play an important role in the progression of PBC. This article mainly reviews the research advances in the manifestation, role, diagnosis, and treatment of lipid metabolism disorders in PBC, so as to provide new ideas for the treatment of PBC.
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Key words:
- Primary Biliary Cholangitis /
- Lipid Metabolism Disorders /
- Inflammation
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[1] RESHETNYAK VI, MAEV IV. Features of lipid metabolism disorders in primary biliary cholangitis[J]. Biomedicines, 2022, 10( 12): 3046. DOI: 10.3390/biomedicines10123046. [2] ZENG N, DUAN WJ, CHEN S, et al. Epidemiology and clinical course of primary biliary cholangitis in the Asia-Pacific region: A systematic review and meta-analysis[J]. Hepatol Int, 2019, 13( 6): 788- 799. DOI: 10.1007/s12072-019-09984-x. [3] AHOUSSOUGBEMEY MELE A, MAHMOOD R, OGBUAGU H, et al. Hyperlipidemia in the setting of primary biliary cholangitis: A case report and review of management strategies[J]. Cureus, 2022, 14( 11): e31411. DOI: 10.7759/cureus.31411. [4] WAH-SUAREZ MI, DANFORD CJ, PATWARDHAN VR, et al. Hyperlipidaemia in primary biliary cholangitis: Treatment, safety and efficacy[J]. Frontline Gastroenterol, 2019, 10( 4): 401- 408. DOI: 10.1136/flgastro-2018-101124. [5] LOAEZA-DEL CASTILLO AM, GAYTÁN-SANTILLÁN A, LÓPEZ-TELLO A, et al. Patterns of serum lipids derangements and cardiovascular risk assessment in patients with primary biliary cholangitis[J]. Ann Hepatol, 2019, 18( 6): 879- 882. DOI: 10.1016/j.aohep.2019.07.006. [6] SEQUEIRA C, COELHO M, COSTA SANTOS I, et al. Severe Hypercholesterolemia mediated by lipoprotein X in an immunosuppressed patient: a case report[J]. GE Port J Gastroenterol, 2022, 30( 5): 398- 402. DOI: 10.1159/000526854. [7] FELLIN R, MANZATO E. Lipoprotein-X fifty years after its original discovery[J]. Nutr Metab Cardiovasc Dis, 2019, 29( 1): 4- 8. DOI: 10.1016/j.numecd.2018.09.006. [8] ZHANG Y, HU X, CHANG J, et al. The liver steatosis severity and lipid characteristics in primary biliary cholangitis[J]. BMC Gastroenterol, 2021, 21( 1): 395. DOI: 10.1186/s12876-021-01974-4. [9] KJELDSEN EW, NORDESTGAARD LT, FRIKKE-SCHMIDT R. HDL cholesterol and non-cardiovascular disease: A narrative review[J]. Int J Mol Sci, 2021, 22( 9): 4547. DOI: 10.3390/ijms22094547. [10] SARIN SK, KUMAR M, ESLAM M, et al. Liver diseases in the asia-pacific region: A lancet gastroenterology& hepatology commission[J]. Lancet Gastroenterol Hepatol, 2020, 5( 2): 167- 228. DOI: 10.1016/S2468-1253(19)30342-5. [11] LEMOINNE S, KEMGANG A, BELKACEM K BEN, et al. Fungi participate in the dysbiosis of gut microbiota in patients with primary sclerosing cholangitis[J]. Gut, 2020, 69( 1): 92- 102. DOI: 10.1136/gutjnl-2018-317791. [12] FELLIN R, MANZATO E. Lipoprotein-X fifty years after its original discovery[J]. Nutr Metab Cardiovasc Dis, 2019, 29( 1): 4- 8. DOI: 10.1016/j.numecd.2018.09.006. [13] NEMES K, ABERG F, GYLLING H, et al. Cholesterol metabolism in cholestatic liver disease and liver transplantation: From molecular mechanisms to clinical implications[J]. World J Hepatol, 2016, 8( 22): 924- 932. DOI: 10.4254/wjh.v8.i22.924. [14] HARRIS J, CAO S, HILE G, et al. Diffuse xanthomas in a patient with primary biliary cholangitis and lipoprotein X[J]. JAAD Case Rep, 2020, 7: 30- 32. DOI: 10.1016/j.jdcr.2020.10.029. [15] PAN XY, ZHANG ZM, LIU CQ, et al. Circulating levels of DDIT4 and mTOR, and contributions of BMI, inflammation and insulin sensitivity in hyperlipidemia[J]. Exp Ther Med, 2022, 24( 5): 666. DOI: 10.3892/etm.2022.11602. [16] MAHDAVI-ROSHAN M, SHOAIBINOBARIAN N, NOORMOHAMMADI M, et al. Inflammatory markers and atherogenic coefficient: Early markers of metabolic syndrome[J]. Int J Endocrinol Metab, 2022, 20( 4): e127445. DOI: 10.5812/ijem-127445. [17] SUN W, LI PC, CAI JP, et al. Lipid metabolism: Immune regulation and therapeutic prospectives in systemic lupus erythematosus[J]. Front Immunol, 2022, 13: 860586. DOI: 10.3389/fimmu.2022.860586. [18] SALAHUDDIN T, NATARAJAN B, PLAYFORD MP, et al. Cholesterol efflux capacity in humans with psoriasis is inversely related to non-calcified burden of coronary atherosclerosis[J]. Eur Heart J, 2015, 36( 39): 2662- 2665. DOI: 10.1093/eurheartj/ehv339. [19] WIDENMAIER SB, SNYDER NA, NGUYEN TB, et al. NRF1 is an ER membrane sensor that is central to cholesterol homeostasis[J]. Cell, 2017, 171( 5): 1094- 1109. e 15. DOI: 10.1016/j.cell.2017.10.003. [20] TALL AR, WESTERTERP M. Inflammasomes, neutrophil extracellular traps, and cholesterol[J]. J Lipid Res, 2019, 60( 4): 721- 727. DOI: 10.1194/jlr.S091280. [21] GILL PK, DRON JS, HEGELE RA. Genetics of hypertriglyceridemia and atherosclerosis[J]. Curr Opin Cardiol, 2021, 36( 3): 264- 271. DOI: 10.1097/HCO.0000000000000839. [22] ZHANG BH, YIN F, QIAO YN, et al. Triglyceride and triglyceride-rich lipoproteins in atherosclerosis[J]. Front Mol Biosci, 2022, 9: 909151. DOI: 10.3389/fmolb.2022.909151. [23] DEN HARTIGH LJ, ALTMAN R, NORMAN JE, et al. Postprandial VLDL lipolysis products increase monocyte adhesion and lipid droplet formation via activation of ERK2 and NFκB[J]. Am J Physiol Heart Circ Physiol, 2014, 306( 1): H109- H120. DOI: 10.1152/ajpheart.00137.2013. [24] LEE SH, KIM N, KIM M, et al. Single-cell transcriptomics reveal cellular diversity of aortic valve and the immunomodulation by PPARγ during hyperlipidemia[J]. Nat Commun, 2022, 13( 1): 5461. DOI: 10.1038/s41467-022-33202-2. [25] MANNE V, KOWDLEY KV. Obeticholic acid in primary biliary cholangitis: Where we stand[J]. Curr Opin Gastroenterol, 2019, 35( 3): 191- 196. DOI: 10.1097/MOG.0000000000000525. [26] LAZARIDIS KN, GORES GJ, LINDOR KD. Ursodeoxycholic acid‘mechanisms of action and clinical use in hepatobiliary disorders’[J]. J Hepatol, 2001, 35( 1): 134- 146. DOI: 10.1016/s0168-8278(01)00092-7. [27] NADINSKAIA M, MAEVSKAYA M, IVASHKIN V, et al. Ursodeoxycholic acid as a means of preventing atherosclerosis, steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease[J]. World J Gastroenterol, 2021, 27( 10): 959- 975. DOI: 10.3748/wjg.v27.i10.959. [28] MOUILLOT T, BEYLOT M, DRAI J, et al. Effect of bile acid supplementation on endogenous lipid synthesis in patients with short bowel syndrome: A pilot study[J]. Clin Nutr, 2020, 39( 3): 928- 934. DOI: 10.1016/j.clnu.2019.03.037. [29] HIRSCHFIELD GM, CHAZOUILLÈRES O, CORTEZ-PINTO H, et al. A consensus integrated care pathway for patients with primary biliary cholangitis: A guideline-based approach to clinical care of patients[J]. Expert Rev Gastroenterol Hepatol, 2021, 15( 8): 929- 939. DOI: 10.1080/17474124.2021.1945919. [30] PELLICCIARI R, FIORUCCI S, CAMAIONI E, et al. 6alpha-ethyl-chenodeoxycholic acid(6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity[J]. J Med Chem, 2002, 45( 17): 3569- 3572. DOI: 10.1021/jm025529g. [31] ROY PP, MAHTAB MA, RAHIM MA, et al. Treatment of nonalcoholic steatohepatitis by obeticholic acid: Current status[J]. Euroasian J Hepatogastroenterol, 2022, 12( Suppl 1): S46- S50. DOI: 10.5005/jp-journals-10018-1360. [32] NEVENS F, ANDREONE P, MAZZELLA G, et al. A placebo-controlled trial of obeticholic acid in primary biliary cholangitis[J]. N Engl J Med, 2016, 375( 7): 631- 643. DOI: 10.1056/NEJMoa1509840. [33] SAMUR S, KLEBANOFF M, BANKEN R, et al. Long-term clinical impact and cost-effectiveness of obeticholic acid for the treatment of primary biliary cholangitis[J]. Hepatology, 2017, 65( 3): 920- 928. DOI: 10.1002/hep.28932. [34] KURIHARA T, AKIMOTO M, ABE K, et al. Experimental use of pravastatin in patients with primary biliary cirrhosis associated with hypercholesterolemia[J]. Clin Ther, 1993, 15( 5): 890- 898. [35] GU Y, YANG XQ, LIANG H, et al. Comprehensive evaluation of effects and safety of statin on the progression of liver cirrhosis: A systematic review and meta-analysis[J]. BMC Gastroenterol, 2019, 19( 1): 231. DOI: 10.1186/s12876-019-1147-1. [36] SPELIOTES EK, BALAKRISHNAN M, FRIEDMAN LS, et al. Treatment of dyslipidemia in common liver diseases[J]. Clin Gastroenterol Hepatol, 2018, 16( 8): 1189- 1196. DOI: 10.1016/j.cgh.2018.04.023. [37] YAMAGUCHI M, ASANO T, ARISAKA T, et al. Effects of pemafibrate on primary biliary cholangitis with dyslipidemia[J]. Hepatol Res, 2022, 52( 6): 522- 531. DOI: 10.1111/hepr.13747. [38] DING DW, GUO GY, LIU YS, et al. Efficacy and safety of fenofibrate addition therapy in patients with cirrhotic primary biliary cholangitis with incomplete response to ursodeoxycholic acid[J]. Hepatol Commun, 2022, 6( 12): 3487- 3495. DOI: 10.1002/hep4.2103. [39] SHAPIRO MD, TAVORI H, FAZIO S. PCSK9: From basic science discoveries to clinical trials[J]. Circ Res, 2018, 122( 10): 1420- 1438. DOI: 10.1161/CIRCRESAHA.118.311227. [40] NISSEN SE, STROES E, DENT-ACOSTA RE, et al. Efficacy and tolerability of evolocumab vs ezetimibe in patients with muscle-related statin intolerance: The GAUSS-3 randomized clinical trial[J]. JAMA, 2016, 315( 15): 1580- 1590. DOI: 10.1001/jama.2016.3608. [41] HUR KY, MOON MK, PARK JS, et al. 2021 clinical practice guidelines for diabetes mellitus of the Korean diabetes association[J]. Diabetes Metab J, 2021, 45( 4): 461- 481. DOI: 10.4093/dmj.2021.0156. [42] GRUNDY SM, STONE NJ, BAILEY AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: A report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines[J]. Circulation. 2019, 139( 25): e1082- e1143. DOI: 10.1161/CIR.0000000000000625. [43] MACH F, BAIGENT C, CATAPANO AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk[J]. Eur Heart J, 2020, 41( 1): 111- 188. DOI: 10.1093/eurheartj/ehz455. [44] TUMMALA R, GUPTA M, DEVANABANDA AR, et al. Bempedoic acid and its role in contemporary management of hyperlipidemia in atherosclerosis[J]. Ann Med, 2022, 54( 1): 1287- 1296. DOI: 10.1080/07853890.2022.2059559. [45] AGHA AM, JONES PH, BALLANTYNE CM, et al. Greater than expected reduction in low-density lipoprotein-cholesterol(LDL-C) with bempedoic acid in a patient with heterozygous familial hypercholesterolemia(HeFH)[J]. J Clin Lipidol, 2021, 15( 5): 649- 652. DOI: 10.1016/j.jacl.2021.07.002.
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