Возможности применения индекса HSI для оценки степени стеатоза у пациентов с метаболически-ассоциированной болезнью печени: молекулярные механизмы, клиническая валидация и патофизиологические корреляции: ГАСТРОЭНТЕРОЛОГИЯ И ДИЕТОЛОГИЯ

Анатолий Ильич Хавкин; Азади  Газаль; Кирилл Михайлович  Николайчук; Ксения Алексеевна  Васильева; Евгения Владимировна  Крылова; Маргарита Михайловна  Гурова; Валерия Павловна  Новикова

doi:10.56871/

Comparative assessment of the HSI in patients with gastroenterological pathology and metabolic syndrome with overweight and obesity: molecular mechanisms, clinical validation, and pathophysiological correlations

GASTROENTEROLOGY AND DIETOLOGY

Anatoly I. Khavkin Scientific Research Clinical Institute of Childhood of the Ministry of Health of the Moscow Region; Belgorod State National Research University https://orcid.org/0000-0001-7308-7280
Azadi Gazal Novosibirsk National Research State University https://orcid.org/0009-0005-6181-3499
Kirill M. Nikolaychuk Novosibirsk National Research State University; Novosibirsk Institute of Organic Chemistry named after N.N. Vorozhtsov of the Siberian Branch of the Russian Academy of Sciences https://orcid.org/0000-0001-8364-6066
Ksenia A. Vasilyeva Novosibirsk National Research State University https://orcid.org/0000-0001-9643-8354
Evgenia V. Krylova Novosibirsk National Research State University; Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences; Center of New Medical Technologies LLC; S.LAB PHARM LLC (“Soloways”) https://orcid.org/0000-0002-9675-3044
Margarita M. Gurova Belgorod State National Research University; Saint Petersburg State Pediatric Medical University https://orcid.org/0000-0002-2666-4759
Valeria P. Novikova Saint Petersburg State Pediatric Medical University https://orcid.org/0000-0002-0992-1709

Keywords:

metabolic syndrome obesity metabolic-associated steatotic liver disease (MASLD) HSI index hepatic steatosis insulin resistance non-invasive diagnostics gut-liver axis метаболический синдром ожирение метаболически ассоциированная жировая болезнь печени (МАЖБП) индекс HSI стеатоз печени инсулинорезистентность неинвазивная диагностика ось «кишечник–печень»

Abstract

The article presents a comparative assessment of the Hepatic Steatosis Index (HSI) in patients with gastrointestinal pathology and metabolic syndrome. The molecular mechanisms linking the increase in body mass index to steatosis progression are analyzed, including insulin resistance, lipotoxicity, and dysfunction of the gut-liver axis. Special attention is paid to the validation of HSI as a non-invasive biomarker reflecting hepatocyte metabolic health. It is demonstrated that the index effectively stratifies risks and correlates with systemic inflammation markers, serving as an accessible and pathogenetically substantiated screening tool for metabolic-associated steatotic liver disease in clinical practice.

Author Biographies

Anatoly I. Khavkin, Scientific Research Clinical Institute of Childhood of the Ministry of Health of the Moscow Region; Belgorod State National Research University

Dr. Sci. (Med.), Professor, Head of the Moscow Regional Center of Pediatric Gastroenterology and Hepatology of the Research Clinical Institute of Childhood; Professor, Department of Pediatrics with a Course in Pediatric Surgical Diseases of the Medical Institute of the Belgorod National Research University

Azadi Gazal, Novosibirsk National Research State University

6th year student

Kirill M. Nikolaychuk, Novosibirsk National Research State University; Novosibirsk Institute of Organic Chemistry named after N.N. Vorozhtsov of the Siberian Branch of the Russian Academy of Sciences

Resident in Neurology at the Center for Postgraduate Medical Education, Institute of Medicine and Medical Technologies, Novosibirsk National Research State University; Junior Researcher at the Laboratory of Viral Protease Inhibitors, N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS

Ksenia A. Vasilyeva, Novosibirsk National Research State University

Resident in Dermatovenerology at the Center for Postgraduate Medical Education, Institute of Medicine and Medical Technologies

Evgenia V. Krylova, Novosibirsk National Research State University; Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences; Center of New Medical Technologies LLC; S.LAB PHARM LLC (“Soloways”)

Cand. Sci. (Med.), Gastroenterologist, Pediatrician, Researcher at the Institute of Chemical Biology and Fundamental Medicine; Associate Professor of the Department of Obstetrics and Gynecology, Medical Faculty, Novosibirsk National Research State University

Margarita M. Gurova, Belgorod State National Research University; Saint Petersburg State Pediatric Medical University

Dr. Sci. (Med.), Associate Professor of the Department of Pediatrics, Professor of the Department of Propaedeutics of Childhood Diseases, Leading Researcher of the Laboratory of Medical and Social Problems in Pediatrics, Research Center, Saint Petersburg State Pediatric Medical University; Professor of the Department of Pediatrics, Belgorod State National Research University

Valeria P. Novikova, Saint Petersburg State Pediatric Medical University

Dr. Sci. (Med.), Professor, Head of the Department of Propaedeutics of Childhood Diseases with a Course in General Child Care named after V.V. Yuryev

References

1. Rinella M.E. Examining the nomenclature change from NAFLD and NASH to MASLD and MASH. Gastroenterol Hepatol (N Y). 2023;19(11):697–699.

2. Sakurai Y., Kubota N., Yamauchi T. et al. Role of Insulin Resistance in MAFLD. Int J Mol Sci. 2021;22(8):4156. https://doi.org/10.3390/ijms22084156.

3. Zheng L., Zeng A., Liu L. et al. Metabolic syndrome: molecular mechanisms and therapeutic interventions. Mol Biomed. 2025;6(1):59. https://doi.org/10.1186/s43556-025-00303-5.

4. Wang C., Cai Z., Deng X. et al. Association of hepatic steatosis index and fatty liver index with carotid atherosclerosis in type 2 diabetes. Int J Med Sci. 2021;18(14):3280–3289. https://doi.org/10.7150/ijms.62010.

5. Lee J.H., Kim D., Kim H.J. et al. Hepatic steatosis index: A simple screening tool reflecting nonalcoholic fatty liver disease. Dig Liver Dis. 2010;42(7):503–508. https://doi.org/10.1016/j.dld.2009.08.002.

6. Rinella M.E., Sookoian S. From NAFLD to MASLD: updated naming and diagnosis criteria for fatty liver disease. J Lipid Res. 2024;65(1):100485. https://doi.org/10.1016/j.jlr.2023.100485.

7. Cusi K., Abdelmalek M.F., Apovian C.M. et al. Metabolic dysfunction-associated steatotic liver disease (MASLD) in people with diabetes: the need for screening and early intervention. A consensus report of the American Diabetes Association. Diabetes Care. 2025;48(7):1057–1082. https://doi.org/10.2337/dci24-0094.

8. Gaba R.C., Knuttinen M.G., Brodsky T.R. et al. Hepatic steatosis: correlations of body mass index, CT fat measurements, and liver density with biopsy results. Diagn Interv Radiol. 2012;18(3):282–287. https://doi.org/10.4261/1305-3825.DIR.4958-11.2.

9. Liu F., Chen S., Li X. et al. Obesity-induced hepatic steatosis is partly mediated by visceral fat accumulation in subjects with overweight/obesity: a cross-sectional study. Obes Facts. 2023;16(2):164–172. https://doi.org/10.1159/000527595.

10. Francisco V., Sanz M.J., Real J.T. et al. Adipokines in Non-alcoholic fatty liver disease: are we on the road toward new biomarkers and therapeutic targets? Biology (Basel). 2022;11(8):1237. https://doi.org/10.3390/biology11081237.

11. Heo Y.J., Choi S.E., Jeon J.Y. et al. Visfatin induces inflammation and insulin resistance via the NF-κB and STAT3 signaling pathways in hepatocytes. J Diabetes Res. 2019;2019:4021623. https://doi.org/10.1155/2019/4021623.

12. Botros M., Sikaris K.A. The de ritis ratio: the test of time. Clin Biochem Rev. 2013;34(3):117–130.

13. Kobayashi A., Suzuki Y., Sugai S. Specificity of transaminase activities in the prediction of drug-induced hepatotoxicity. J Toxicol Sci. 2020;45(9):515–537. https://doi.org/10.2131/jts.45.515.

14. Matsuzaka T., Shimano H. Molecular mechanisms involved in hepatic steatosis and insulin resistance. J Diabetes Investig. 2011;2(3):170–175. https://doi.org/10.1111/j.2040-1124.2011.00111.x.

15. Rabbani N., Thornalley P.J. Molecular mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD): functional analysis of glucose and fructose metabolism pathways. Clin Sci (Lond). 2025;139(21):CS20257727. https://doi.org/10.1042/CS20257727.

16. Han A.L., Lee H.K. Comparison of the diagnostic performance of steatosis indices for discrimination of CT-diagnosed metabolic dysfunction-associated fatty liver disease. Metabolites. 2022;12(7):664. https://doi.org/10.3390/metabo12070664.

17. Khani V., Momeni Moghaddam A., Hatami B. Comparison of hepatic steatosis index as noninvasive diagnostic tool and liver ultrasound for non-alcoholic steatosis in the adult population. Gastroenterol Hepatol Bed Bench. 2022;15(4):360–365. https://doi.org/10.22037/ghfbb.v15i4.2480.

18. Gong H., He Q., Zhu L. et al. Associations between systemic inflammation indicators and nonalcoholic fatty liver disease: evidence from a prospective study. Front Immunol. 2024;15:1389967. https://doi.org/10.3389/fimmu.2024.1389967.

19. Duan S., Tu Z., Duan L. et al. Differential effects of systemic immune inflammation indices on hepatic steatosis and hepatic fibrosis: evidence from NHANES 1999-2018. BMC Gastroenterol. 2024;24(1):463. https://doi.org/10.1186/s12876-024-03557-5.

20. Kawanaka M., Nishino K., Nakamura J. et al. Correlation between serum cytokeratin-18 and the progression or regression of non-alcoholic fatty liver disease. Ann Hepatol. 2015;14(6):837–844. https://doi.org/10.5604/16652681.1171767.

21. Cusi K., Chang Z., Harrison S. et al. Limited value of plasma cytokeratin-18 as a biomarker for NASH and fibrosis in patients with non-alcoholic fatty liver disease. J Hepatol. 2014;60(1):167–174. https://doi.org/10.1016/j.jhep.2013.07.042.

22. Silva M.B.B.E., Tustumi F., Dantas A.C.B. et al. Obesity and severe steatosis: the importance of biochemical exams and scores. Arq Bras Cir Dig. 2022;34(4):e1626. https://doi.org/10.1590/0102-672020210002e1626.

23. Sakurai Y., Kubota N., Yamauchi T. et al. Role of insulin resistance in MAFLD. Int J Mol Sci. 2021;22(8):4156. https://doi.org/10.3390/ijms22084156.

24. Postic C., Girard J. Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J Clin Invest. 2008;118(3):829–838. https://doi.org/10.1172/JCI34275.

25. Sanders F.W., Griffin J.L. De novo lipogenesis in the liver in health and disease: more than just a shunting yard for glucose. Biol Rev Camb Philos Soc. 2016;91(2):452–468. https://doi.org/10.1111/brv.12178.

26. Smith G.I., Shankaran M., Yoshino M. et al. Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease. J Clin Invest. 2020;130(3):1453–1460. https://doi.org/10.1172/JCI134165.

27. Ibrahim S.H., Kohli R., Gores G.J. Mechanisms of lipotoxicity in NAFLD and clinical implications. J Pediatr Gastroenterol Nutr. 2011;53(2):131–140. https://doi.org/10.1097/MPG.0b013e31822578db.

28. Marra F., Svegliati-Baroni G. Lipotoxicity and the gut-liver axis in NASH pathogenesis. J Hepatol. 2018;68(2):280–295. https://doi.org/10.1016/j.jhep.2017.11.014.

29. Wasilewska N., Lebensztejn D.M. Non-alcoholic fatty liver disease and lipotoxicity. Clin Exp Hepatol. 2021;7(1):1–6. https://doi.org/10.5114/ceh.2021.104441.

30. Parthasarathy G., Revelo X., Malhi H. Pathogenesis of Nonalcoholic steatohepatitis: an overview. Hepatol Commun. 2020;4(4):478–492. https://doi.org/10.1002/hep4.1479.

31. Petrescu M., Vlaicu S.I., Ciumărnean L. et al. Chronic Inflammation-A Link between Nonalcoholic Fatty Liver Disease (NAFLD) and Dysfunctional Adipose Tissue. Medicina (Kaunas). 2022;58(5):641. https://doi.org/10.3390/medicina58050641.

32. Neuman M.G., Cohen L.B., Nanau R.M. Biomarkers in nonalcoholic fatty liver disease. Can J Gastroenterol Hepatol. 2014;28(11):607–618. https://doi.org/10.1155/ 2014/757929.

33. Jasirwan C.O.M., Lesmana C.R.A., Hasan I. et al. The role of gut microbiota in non-alcoholic fatty liver disease: pathways of mechanisms. Biosci Microbiota Food Health. 2019;38(3):81–88. https://doi.org/10.12938/bmfh.18-032.

34. Pezzino S., Sofia M., Faletra G. et al. Gut-liver axis and non-alcoholic fatty liver disease: a vicious circle of dysfunctions orchestrated by the gut microbiome. Biology (Basel). 2022;11(11):1622. https://doi.org/10.3390/biology11111622.

35. Scarpellini E., Lupo M., Iegri C. et al. Intestinal permeability in non-alcoholic fatty liver disease: the gut-liver axis. Rev Recent Clin Trials. 2014;9(3):141–147. https://doi.org/10.2174/1574887109666141216104334.

36. Portincasa P., Bonfrate L., Khalil M. et al. Intestinal barrier and permeability in health, obesity and NAFLD. Biomedicines. 2021;10(1):83. https://doi.org/10.3390/biomedicines10010083.

37. Gudan A., Kozłowska-Petriczko K., Wunsch E. et al. Small intestinal bacterial overgrowth and non-alcoholic fatty liver disease: what do we know in 2023? Nutrients. 2023;15(6):1323. https://doi.org/10.3390/nu15061323.

38. Zisser A., Ipsen D.H., Tveden-Nyborg P. Hepatic stellate cell activation and inactivation in nash-fibrosis-roles as putative treatment targets? Biomedicines. 2021;9(4):365. https://doi.org/10.3390/biomedicines9040365.

39. Jiao T.Y., Ma Y.D., Guo X.Z. et al. Bile acid and receptors: biology and drug discovery for nonalcoholic fatty liver disease. Acta Pharmacol Sin. 2022;43(5):1103–1119. https://doi.org/10.1038/s41401-022-00880-z.

40. Portincasa P., Di Ciaula A., Bonfrate L. et al. Metabolic dysfunction-associated gallstone disease: expecting more from critical care manifestations. Intern Emerg Med. 2023;18(7):1897–1918. https://doi.org/10.1007/s11739-023-03355-z.

41. Chang Y., Noh Y.H., Suh B.S. et al. Bidirectional association between nonalcoholic fatty liver disease and gallstone disease: a cohort study. J Clin Med. 2018;7(11):458. https://doi.org/10.3390/jcm7110458.

42. Baeg M.K., Yoon S.K., Ko S.H. et al. Helicobacter pylori infection is not associated with nonalcoholic fatty liver disease. World J Gastroenterol. 2016;22(8):2592–2600. https://doi.org/10.3748/wjg.v22.i8.2592.

43. Chen X., Peng R., Peng D. et al. An update: is there a relationship between H. pylori infection and nonalcoholic fatty liver disease? Why is this subject of interest? Front Cell Infect Microbiol. 2023;13:1282956. https://doi.org/10.3389/fcimb.2023.1282956.

44. Ndrepepa G. De Ritis ratio and cardiovascular disease: evidence and underlying mechanisms. J Lab Precis Med. 2023;8:6. https://doi.org/10.21037/jlpm-22-68.

45. Xuan Y., Wu D., Zhang Q. et al. Elevated ALT/AST ratio as a marker for NAFLD risk and severity: insights from a cross-sectional analysis in the United States. Front Endocrinol (Lausanne). 2024;15:1457598. https://doi.org/10.3389/fendo.2024.1457598.

46. Zhang L., Ma X., Jiang Z. et al. Liver enzymes and metabolic syndrome: a large-scale case-control study. Oncotarget. 2015;6(29):26782–26788. https://doi.org/10.18632/oncotarget.5792.

47. Raya-Cano E., Molina-Luque R., Vaquero-Abellán M. et al. Metabolic syndrome and transaminases: systematic review and meta-analysis. Diabetol Metab Syndr. 2023;15(1):220. https://doi.org/10.1186/s13098-023-01200-z.

48. Feng S., Xie X., Li J. et al. Bile acids induce liver fibrosis through the NLRP3 inflammasome pathway and the mechanism of FXR inhibition of NLRP3 activation. Hepatol Int. 2024;18(3):1040–1052. https://doi.org/10.1007/s12072-023-10610-0.

49. Busquets-Cortés C., Bennasar-Veny M., López-González A.A. et al. Fatty liver index and progression to type 2 diabetes: a 5-year longitudinal study in Spanish workers with pre-diabetes. BMJ Open. 2021;11(8):e045498. https://doi.org/10.1136/bmjopen-2020-045498.

50. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis — 2021 update. J Hepatol. 2021;75(3):659–713. https://doi.org/10.1016/j.jhep.2021.05.025.

51. Ning Q., Zheng K., Yan J. et al. Triglyceride glucose index as a predictor for non-alcoholic fatty liver disease: insights from a longitudinal analysis in non-obese individuals. Frontiers in Medicine. 2024;11:1429413. https://doi.org/10.3389/fmed.2024.1429413.

52. Sun Y., Hu D., Yu M. et al. Diagnostic accuracy of non-invasive diagnostic tests for nonalcoholic fatty liver disease: a systematic review and network meta-analysis. Clin Epidemiol. 2025;17:53–71. https://doi.org/10.2147/CLEP.S501445.

53. Toyoda H., Atsukawa M. The best predictive model for post-SVR HCC: can it be universal? Hepatol Int. 2022;16(3):728–729. https://doi.org/10.1007/s12072-022-10336-5.

54. Баранов А.А., Волынец Г.В., Власов Н.Н., Горячева Л.Г., Гурова М.М., Грешнякова В.А. и др. Проект клинических рекомендаций по диагностике и лечению метаболически ассоциированной жировой болезни печени у детей (неалкогольной жировой болезни печени). Педиатрическая фармакология. 2025;22(2):147–163. https://doi.org/10.15690/pf.v22i2.2884. Baranov A.A., Volynets G.V., Vlasov N.N., Goryacheva L.G., Gurova M.M., Greshnyakova V.A. et al. Draft clinical guidelines for the diagnosis and treatment of metabolically associated fatty liver disease in children (non-alcoholic fatty liver disease). Pediatric pharmacology. 2025;22(2):147–163. (In Russ.). https://doi.org/10.15690/pf.v22i2.2884.

Comparative assessment of the HSI in patients with gastroenterological pathology and metabolic syndrome with overweight and obesity: molecular mechanisms, clinical validation, and pathophysiological correlations: GASTROENTEROLOGY AND DIETOLOGY. (2026). Children’s Medicine of the North-West, 14(2), 122-133. https://doi.org/10.56871/

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Comparative assessment of the HSI in patients with gastroenterological pathology and metabolic syndrome with overweight and obesity: molecular mechanisms, clinical validation, and pathophysiological correlations: GASTROENTEROLOGY AND DIETOLOGY. (2026). Children’s Medicine of the North-West, 14(2), 122-133. https://doi.org/10.56871/

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