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The possibilities of using ursodeoxycholic acid in the practice of a gastroenterologist and therapist
https://doi.org/10.33667/2078-5631-2024-26-28-32
Abstract
Relevance. Ursodeoxycholic acid (UDCA) is a natural hydrophilic bile acid, which initially found its use in the treatment of a number of liver diseases as a first–line therapy. UDCA reduces the secretion of cholesterol into bile and is actively used in the treatment and prevention of gallstone disease; UDCA also has the ability to stimulate hepatobiliary secretion, which is important for patients with primary biliary cholangitis and primary sclerosing cholangitis. More recent studies have shown the pleiotropy of the effects of UDCA, in terms of effects on pathophysiological processes in the liver and the entire hepatobiliary complex, for example, anti-inflammatory and antifibrotic effects, immunomodulatory and anticarcinogenic effects. Even more interesting and important were the complex mechanisms of the effect of UDCA on the development and progression of non-alcoholic fatty liver disease (NAFLD) and, further, on the pathogenetic relationships of NAFLD and cardio-vascular pathology. The article examines the possibilities of using UDCA in diseases of the gastrointestinal tract and, more broadly, the possibilities of the drug in influencing NAFLD and the development and progression of cardiovascular and metabolic diseases.
About the Authors
G. Yu. Knorring
Russian University of Medicine
Russian Federation
Russian Federation
Knorring German Yu. - PhD Med, associate professor at Dept of Therapy, Clinical Pharmacology and Emergency Medical Care
Moscow
Yu. V. Sedyakina
Russian University of Medicine
Russian Federation
Russian Federation
Sedyakina Yulia V. - PhD Med, associate professor at Dept of Therapy, Clinical Pharmacology and Emergency Medical Care
Moscow
S. S. Kurdzhieva
Russian University of Medicine
Russian Federation
Russian Federation
Kurdzhieva Svetlana S. - assistant at Dept of Therapy, Clinical Pharmacology and Emergency Medical Care
Moscow
References
1. Maevskayа M.V. Ursodeoxycholic acid: unique properties and clinical applications. Meditsinskiy Sovet. 2023 8): 96–105. (In Russ.). https://doi.org/10.21518/ms2023–136
2. Lonardo A., Sookoian S., Chonchol M. et al. Cardiovascular and systemic risk in no- nalcoholic fatty liver disease – atherosclerosis as a major player in the natural course of NAFLD. Curr Pharm Des. 2013; 19 (29): 5177–5192.
3. Adams LA, Anstee QM, Tilg H, Targher G. Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut. 2017; 66 (6): 1138–1153. https://doi.org/10.1136/gutjnl-2017-313884
4. Byrne C.D., Targher G. NAFLD: a multisystem disease. J. Hepatol. 2015; 62 (Suppl. 1): 47–64.
5. Volynets GV, Khavkin AI. Ursodeoxycholic acid and hepatic diseases. Lechaschi Vrach. 2020; (6): 62–68. (In Russ.). https://doi.org/10.26295/OS.2020.75.99.012
6. Russell DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem. 2003; 72: 137–174.
7. Alrefai WA, Gill RK. Bile acid transporters: structure, function, regulation and pathophysiological implications. Pharm Res. 2007 Oct; 24 (10): 1803–23.
8. Beuers U. Drug insight: Mechanisms and sites of action of ursodeoxycholic acid in cholestasis. Nat Clin Pract Gastroenterol Hepatol. 2006; 3 (6): 318–328. https://doi.org/10.1038/ncpgasthep0521
9. Ivashkin V.T., Mayev I.V., Baranskaya Y.K., Okhlobystin A.V., Shulpekova Yu.O., Trukhmanov A.S. et al. Gallstone disease diagnosis and treatment: guide- lines of the Russian gastroenterological association. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2016; 26 (3): 64–80. (In Russ.). https://doi.org/10.22416/1382-4376-2016-26-3-64-80
10. Güldütuna S., Zimmer G., Imhof M., Bhatti S., You T., Leuschner U. Molecular aspects of membrane stabilization by ursodeoxycholate. Gastroenterology. 1993; 104 (6): 1736–1744. https://doi.org/10.1016/0016-5085(93)90653-t
11. Heuman D.M., Bajaj R. S., Lin Q. Adsorption of mixtures of bile salt taurine conjugates to lecithin-cholesterol membranes: implications for bile salt toxicity and cytoprotection. J. Lipid Res. 1996; 37: 562–573.
12. Beuers U., Bilzer M., Chittattu A., Kullak-Ublick G. A., Keppler D., Paumgartner G., Dombrowski F. Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into canalicular membranes and stimulates organic anion secretion by protein kinase C-dependent mechanisms in cholestatic rat liver, Hepatology. 2001; 33 (5): 1206–1216. https://doi.org/10.1053/jhep.2001.24034
13. Rodrigues C.M., Fan G., Wong P.Y., Kren B. T., Steer C. J. Ursodeoxycholic acid may inhibit deoxycholic acid-induced apoptosis by modulating mitochondrial transmembrane potential and reactive oxygen species production. Mol Med. 1998; 4 (3): 165–178.
14. Bellentani S. Immunomodulating and anti-apoptotic action of ursodeoxycholic acid: where are we and where should we go? Eur. J. Gastroenterol Hepatol. 2005 Feb; 17 (2): 137–140. DOI: 10.1097/00042737-200502000-00001
15. Castro R.E., Solá S., Ma X., Ramalho R.M., Kren B. T., Steer C.J., Rodrigues C.M. A distinct microarray gene expression profile in primary rat hepatocytes incubated with ursodeoxycholic acid. J. Hepatol. 2005; 42: 897–906. https://doi.org/10.1016/j.jhep.2005.01.026
16. Solá S., Ma X., Castro R.E., Kren B.T., Steer C.J., Rodrigues C.M. Ursodeoxycholic acid modulates E2F-1 and p53 expression through a caspase-independent mechanism in transforming growth factor β1-induced apoptosis of rat hepatocytes. J. Biol. Chem. 2003; 278 (49): 48831–48838. https://doi.org/10.1074/jbc.M300468200
17. Yoshikawa M., Tsujii T., Matsumura K., Yamao J., Matsumura Y., Kubo R. et al. Immunomodulatory effects of ursodeoxycholic acid on immune responses. Hepatology. 1992; 16 (2): 358–364. https://doi.org/10.1002/hep.1840160213
18. Zhang H., Xu H., Zhang C., Qiulin Tang, Feng Bi. Ursodeoxycholic acid suppresses the malignant progression of colorectal cancer through TGR5-YAP axis. Cell Death Discov. 2021; 7 (1): 207. https://doi.org/10.1038/s41420-021-00589-8
19. Königshofer P., Brusilovskaya K., Petrenko O., Hofer B. S., Schwabl P., Trauner M., Reiberger T. Nuclear receptors in liver fibrosis. Biochim Biophys Acta Mol Basis Dis. 2021; 1867 (12): 166235. https://doi.org/10.1016/j.bbadis.2021.166235
20. Polyakova O.A., Ostroumova O.D., Kovaleva G.P., Pavleeva Е.Е. Comorbidity of non-alcoholic fatty liver disease and cardiovascular disease: focus on ademetionine and ursodeoxycholic acid. Medical alphabet. 2021; (29): 13–20. (In Russ.). https://doi.org/10.33667/2078-5631-2021-29-13-20
21. Pakhomova I.G., Knorring G. Yu. Non-alcoholic fatty liver disease and cardiovascular pathology: features of patient management on a clinical example. Experimental and Clinical Gastroenterology. 2022; 205 (9): 290–297. (In Russ.). https://doi.org/10.31146/1682–8658-ecg-205-9-290-297
22. Byrne C.D. Dorothy Hodgkin Lecture 2012: non-alcoholic fatty liver disease, insulin resistance and ectopic fat: a new problem in diabetes management. Diabet Med. 2012; 29 (9): 1098–1107. https://doi.org/10.1111/j.1464–5491.2012.03732.x
23. Ivashkin V.T., Drapkina O.M., Maev I.V. et al. The prevalence of non-alcoholic fatty liver disease in patients of outpatient practice in the Russian Federation: the results of the study DIREG 2. RZhGGK. 2015; 6: 31–41. (In Russ.).
24. Sayiner M., Koenig A., Henry L., Younossi Z.M. Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis in the United States and the Rest of the World. Clin Liver Dis. 2016; 20: 205–214.
25. Koenig A.B., Younossi Z.M., Koenig A.B. et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepathology. 2016; 64 (1): 73–84. https://doi.org/10.1002/hep.28431
26. Drapkina O.M., Smirin V.I., Ivashkin V.T. Pathogenesis, treatment and epidemiology of NAFLD – what’s new? Epidemiology of NAFLD in Russia. Russian Medical Journal. 2011; 28: 1–4. (In Russ.).
27. Diagnosis and treatment of non-alcoholic fatty liver disease / ed. acad. RAS, prof. V.T. Ivashkin. Russian Society for the Study of the Liver. M., 2015. 29 p. (In Russ.).
28. Korneeva O.N., Drapkina O.M., Bueverov A.O., Ivashkin V.T. Non-alcoholic fatty liver disease as a manifestation of metabolic syndrome. Clinical Perspectives in Gastroenterology and Hepatology. 2005; 4: 21–24. (In Russ.).
29. Maevskaya M.V., Kotovskaya Yu.V., Ivashkin V.T. еt al. The National Consensus statement on the management of adult patients with non-alcoholic fatty liver disease and main comorbidities. Terapevticheskii arkhiv. 2022; 94 (2): 216–253. (In Russ.). https://doi.org/10.26442/00403660.2022.02.201363
30. Eslam M., Newsome P.N., Sarin S.K., Anstee Q.M., Targher G., Romero-Gomez M. et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J. Hepatol. 2020; 73 (1): 202–9. https://doi.org/10.1016/j.jhep.2020.03.039
31. Caligiuri A., Gentilini A., Marra F. Molecular Pathogenesis of NASH. International Journal of Molecular Sciences. 2016; 17 (9): 1575. https://doi.org/10.3390/ijms17091575
32. Byrne C.D. Ectopic fat, insulin resistance and non-alcoholic fatty liver disease. Proc Nutr Soc. 2013; 72 (4): 412–419. https://doi.org/10.1017/S0029665113001249
33. Bhatia L.S. et al. Non-alcoholic fatty liver disease: a new and important cardiovascular risk factor? European Heart Journal. 2012; (33): 1190–1200. https://doi.org/10.1093/eurheartj/ehr453
34. Oni E.T. et al. A systematic review: burden and severity of subclinical cardiovascular disease among those with nonalcoholic fatty liver; should we care? Atherosclerosis. 2013; 230: 258–267.
35. Targher G., Day C.P., Bonora E. Risk of Cardiovascular Disease in Patients with Nonalcoholic Fatty Liver Disease. N Engl. J. Med. 2010. 363: 1341–1350. https://doi.org/10.1056/NEJMra0912063
36. Fracanzani A.L., Pisano G., Consonni D. et al. Epicardial Adipose Tissue (EAT) Thickness Is Associated with Cardiovascular and Liver Damage in Nonalcoholic Fatty Liver Disease//PLoS ONE. 2016; 11 (9): e0162473. https://doi.org/10.1371/journal.pone.0162473
37. Nandini M. Meyersohn Th., Mayrhofer K.E., Corey P.S. Douglas U.H., Maros F.S. еt al. Association of Hepatic Steatosis With Major Adverse Cardiovascular Events, Independent of Coronary Artery Disease. 2021 Jul; 19 (7): 1480–1488. e14. https://doi.org/10.1016/j.cgh.2020.07.030
38. Schaffer J.E. Lipotoxicity: Many Roads to Cell Dysfunction and Cell Death: Introduction to a Thematic Review Series. Journal of Lipid Research. 2016; 57 (8): 1327–1328. https://doi.org/10.1194/jlr.E069880
39. Drapkina O.M., Chaparkina S.O. Relationship between metabolic syndrome, aseptic inflammation and endothelial dysfunction. Rossijskie medicinskie vesti. 2007; 12 (3): 67–75. (In Russ.).
40. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L. et al. Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis. Gastroenterology. 2015; 149 (2): 367–78. https://doi.org/10.1053/j.gastro.2015.04.005
41. Wu P, Zhao J, Guo Y. et al. Ursodeoxycholic acid alleviates nonalcoholic fatty liver disease by inhibiting apoptosis and improving autophagy via activating AMPK. Biochem Biophys Res Commun. 2020 Aug 27; 529 (3): 834–838.
42. Dufour JF, Oneta CM, Gonvers JJ. et al. Swiss Association for the Study of the Liver. Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis. Clin Gastroenterol Hepatol. 2006; 4 (12): 1537–43. https://doi.org/10.1016/j.cgh.2006.09.025
43. Simental-Mendía LE, Simental-Mendía M, Sánchez-García A, et al. Impact of ursodeoxycholic acid on circulating lipid concentrations: a systematic review and meta-analysis of randomized placebo-controlled trials. Lipids Health Dis. 2019; 18 (1): 88. https://doi.org/10.1186/s12944-019-1041-4
44. Sánchez-García A, Sahebkar A, Simental-Mendía M, SimentalMendía LE. Effect of ursodeoxycholic acid on glycemic markers: A systematic review and meta-analysis of clinical trials. Pharmacol Res. 2018; 135: 144–9. https://doi.org/10.1016/j.phrs.2018.08.008
45. Higinio Mappala et al.The efficacy of ursodeoxycholic acid in the treatment of non-alcoholic steatohepatitis: A 15-year systematic review. Gut. 2019; 68 (Suppl 1): A1–A166.
46. Trauner M, Claudel T, Fickert P. et al. Bile acids as regulators of hepatic lipid and glucose metabolism. Dig Dis. 2010; 28 (1): 220–4.
47. Korneeva O.N., Drapkina O.M. Possibilities of using ursodeoxycholic acid and statins to reduce cardiovascular risk in patients with metabolic syndrome and non-alcoholic fatty liver disease. Russian medical news. 2011; 16 (3): 57–64. (In Russ.).
48. Akhmedov V.A. Metabolic effects of ursodeoxycholic acid in patients with non-alcoholic fatty liver disease. Lechaschi Vrach. 2024; 4 (27): 71–76. (In Russ.). https://doi.org/10.51793/OS.2024.27.4.010
49. Martsevich S. Yu., Kutishenko N.P., Drozdova L. Yu., Lerman O.V. et al. A. To study the effect of ursodeoxycholic acid on the efficacy and safety of statin therapy in patients with diseases of the liver, gallbladder and/or biliary tract. Rational pharmacotherapy in cardiology. 2014; 10 (2): 147–152. (In Russ.).
50. Lazebnik L.B., Golovanova E.V., Turkina S.V. et al. Non-alcoholic fatty liver disease in adults: clinic, diagnostics, treatment. Guidelines for therapists, third version. Experimental and Clinical Gastroenterology. 2021; 1 (1): 4–52. (In Russ.). https://doi.org/10.31146/1682–8658-ecg-185-1-4-52
51. Federal Guidelines on the use of medicines (formulary system). Issue XVI, edited by A.G. Chuchalin (editor-in-chief), V.V. Yasnetsov. M.: Echo, 2015: 1016. (In Russ.).
52. Non-alcoholic fatty liver disease. Clinical recommendations of the Ministry of Health of the Russian Federation, 2024. (In Russ.).
53. Hlynov I.B., Akimenko R.I., Gurikova I.A. et al. Biliary sludge: therapeutic experience in the real clinical practice. Lechaschi Vrach. 2019; 4: 80–83. (In Russ.).
54. Skvortsov VV, Eremenko AA, Vinogradova MV. Modern pharmacotherapy for cholestasis syndrome. Meditsinskiy Sovet. 2024; 18 (8): 60–64. (In Russ.). https://doi.org/10.21518/ms2024–106
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Knorring G.Yu., Sedyakina Yu.V., Kurdzhieva S.S. The possibilities of using ursodeoxycholic acid in the practice of a gastroenterologist and therapist. Medical alphabet. 2024;(26):28-32. (In Russ.) https://doi.org/10.33667/2078-5631-2024-26-28-32
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