Metainflammation: new horizons for the administration of ursodeoxycholic acid
DOI: 10.32364/2587-6821-2025-9-9-8
M.A. Livzan, G.R. Bikbavova, O.V. Gaus, R.A. Karimov, D.A. Gavrilenko
Omsk State Medical University, Omsk, Russian Federation
Ursodeoxycholic acid (UDCA), a natural hydrophilic bile acid with established efficacy in the treatment of hepatobiliary pathology, currently represents a therapeutic agent whose clinical possibilities have been significantly reconsidered due to new data regarding its pleiotropic mechanisms of action. Contemporary research demonstrates UDCA's capacity to influence key pathogenetic links of metabolically-associated diseases through the modulation of nuclear receptors (FXR, TGR5), mitochondrial function, and the reduction of oxidative stress and systemic inflammation. Particular clinical interest lies in the use of UDCA for managing comorbid conditions unified by the phenomenon of metabolic inflammation (metainflammation): namely, non-alcoholic fatty liver disease, obesity, type 2 diabetes mellitus, hypertension, and neurodegenerative diseases. The effects of UDCA have been proven to result in the improvement of glycemic control, lipid profile, reduction in body weight, and lowering of cardiometabolic risk. Furthermore, UDCA exhibits neuroprotective potential by regulating oxidative phosphorylation and suppressing neuronal apoptosis, which opens up prospects for its application in neurology. Thus, UDCA exemplifies the successful expansion of a drug's clinical application, where a profound understanding of its molecular mechanisms of action unveils new opportunities for utilizing a long-established treatment to address critical challenges in modern medicine.
Keywords: non-alcoholic fatty liver disease, metainflammation, biliary sludge, ursodeoxycholic acid, Ursofalk.
For citation: Livzan M.A., Bikbavova G.R., Gaus O.V., Karimov R.A., Gavrilenko D.A. Metainflammation: new horizons for the administration of ursodeoxycholic acid. Russian Medical Inquiry. 2025;9(9):587–595 (in Russ.). DOI: 10.32364/2587-6821-2025-9-9-8
About the authors:
Maria A. Livzan — Corresponding Member of the Russian Academy of Sciences (RAS), Dr. Sc. (Med.), Professor, Rector, Head of the Department of Faculty Therapy and Gastroenterology, Omsk State Medical University; 12, Lenina str., Omsk, 644099, Russian Federation; ORCID iD 0000-0002-6581-7017
Galiya R. Bikbavova — C. Sc. (Med.), Associate Professor of the Department of Hospital Therapy and Endocrinology, Omsk State Medical University; 12, Lenina str., Omsk, 644099, Russian Federation; ORCID iD 0000-0001-9252-9152
Olga V. Gaus — Dr. Sc. (Med.), Associate Professor, Professor of the Department of Faculty Therapy and Gastroenterology, Omsk State Medical University; 12, Lenina str., Omsk, 644099, Russian Federation; ORCID iD 0000-0001-9370-4768
Ruslan A. Karimov — 5th-year student of the Faculty of Medicine, Omsk State Medical University; 12, Lenina str., Omsk, 644099, Russian Federation; ORCID iD 0009-0007-6955-2160
Darya A. Gavrilenko — Assistant Professor of the Department of Faculty Therapy and Gastroenterology, Omsk State Medical University; 12, Lenina str., Omsk, 644099, Russian Federation; ORCID iD 0000-0001-5245-7190
Contact information: Olga V. Gaus, e-mail: gaus_olga@bk.ru
Financial Disclosure: no authors have a financial or property interest in any material or method mentioned.
There is no conflict of interest.
Received 27.05.2025.
Revised 23.06.2025.
Accepted 16.07.2025.
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4. Lindor K.D., Bowlus C.L., Boyer J. et al. Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394–419. DOI: 10.1002/hep.30145
5. Bowlus C.L., Arrivé L., Bergquist A. et al. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma. Hepatology. 2023;77(2):659–702. DOI: 10.1002/hep.32771
6. Lindor K.D., Kowdley K.V., Harrison M.E.; American College of Gastroenterology. ACG Clinical Guideline: Primary Sclerosing Cholangitis. Am J Gastroenterol. 2015;110(5):646–660. DOI: 10.1038/ajg.2015.112
7. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on genetic cholestatic liver diseases. J Hepatol. 2024;81(2):303–325. DOI: 10.1016/j.jhep.2024.04.006
8. Yu X., Yang H., Qi H. Clinical Management Guidelines for Intrahepatic Cholestasis of Pregnancy. Matern Fetal Med. 2024;6(1):13–22. DOI: 10.1097/FM9.0000000000000207
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11. European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol. 2024;81(3):492–542. DOI: 10.1016/j.jhep.2024.04.031
12. Fujita N., Yasuda I., Endo I. et al. Evidence-based clinical practice guidelines for cholelithiasis 2021. J Gastroenterol. 2023;58(9):801–833. DOI: 10.1007/s00535-023-02014-6
13. Parés A., Caballería L., Rodés J. et al. Long-term effects of ursodeoxycholic acid in primary biliary cirrhosis: results of a double-blind controlled multicentric trial. UDCA-Cooperative Group from the Spanish Association for the Study of the Liver. J Hepatol. 2000;32(4):561–566. DOI: 10.1016/s0168-8278(00)80216-0
14. Mao Q., Lin B., Zhang W. et al. Understanding the role of ursodeoxycholic acid and gut microbiome in non-alcoholic fatty liver disease: current evidence and perspectives. Front Pharmacol. 2024;15:1371574. DOI: 10.3389/fphar.2024.1371574
15. Combes B., Carithers R.L. Jr, Maddrey W.C. et al. Biliary bile acids in primary biliary cirrhosis: effect of ursodeoxycholic acid. Hepatology. 1999;29(6):1649–1654. DOI: 10.1002/hep.510290618
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17. Hillaire S., Boucher E., Calmus Y. et al. Effects of bile acids and cholestasis on major histocompatibility complex class I in human and rat hepatocytes. Gastroenterology. 1994;107(3):781–788. DOI: 10.1016/0016-5085(94)90127-9
18. Pinto C., Ninfole E., Benedetti A. et al. Involvement of Autophagy in Ageing and Chronic Cholestatic Diseases. Cells. 2021;10(10):2772. DOI: 10.3390/cells10102772
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