Возможности и недостатки современных неинвазивных методов диагностики метаболически ассоциированной жировой болезни печени

Метаболически-ассоциированная жировая болезнь печени представляет собой широко распространенное заболевание, частота которого увеличивается по всему миру и стала одной из ведущих причин терминальных стадий заболеваний печени и гепатоцеллюлярной карциномы с повышенной заболеваемостью и смертностью, связанными с печенью, и в целом. Новый термин, жировая болезнь печени, связанная с метаболической дисфункцией, имеет набор положительных диагностических критериев и, как было показано, имеет большую клиническую полезность. На данный момент не существует стандартизированных универсальных методов скрининга стеатоза печени, несмотря на то, что данное заболевание оказывает значительное воздействие на здоровье. Метаболически-ассоциированная жировая болезнь охватывает широкий спектр состояний, от простого стеатоза и стеатогепатита до фиброза и гепатоцеллюлярной карциномы. Она также сопровождается многочисленными внепеченочными проявлениями, такими как сердечно-сосудистые заболевания, злокачественные новообразования вне печени, а также когнитивные и респираторные изменения. Учитывая обширные целевые органы поражения и высокую распространенность заболевания, критически важно своевременно выявлять людей с высоким риском метаболической дисфункции. Биопсия печени до настоящего времени считалась эталонным методом оценки стадии стеатоза и фиброза печени. Учитывая ограничения биопсии для широкомасштабного скрининга, неинвазивные тесты для оценки стадии стеатоза и фиброза, включая алгоритмы на основе сыворотки и методы, основанные на ультразвуке и магнитно-резонансной томографии, будут играть все возрастающую роль в ведении пациентов с МАЖБП. В данной статье представлен обзор научных данных посвященных неинвазивным диагностическим возможностям используемых в клинической практике для выявления стеатоза печени.

метаболически ассоциированная жировая болезнь печени, неинвазивные методы диагностики, пожилой и старческий возраст, стеатоз печени

1. Younossi Z., Koenig A., Abdelatif D. et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016 Jul;64(1):73-84. doi: 10.1002/hep.28431.

2. Paik J., Golabi P., Younossi Y. et al. Changes in the Global Burden of Chronic Liver Diseases From 2012 to 2017: The Growing Impact of NAFLD. Hepatology. 2020;72(5):1605-1616. doi: 10.1002/hep.31173.

3. Eslam M., Sanyal A., George J.International Consensus Panel. MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology. 2020;158(7):1999-2014.e1. doi: 10.1053/j.gastro.2019.11.312.

4. Eslam M., Newsome P., Sarin S. et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol. 2020;73(1):202-209. doi: 10.1016/j.jhep.2020.03.039.

5. Younossi Z., Paik J., Stepanova M. et al. Clinical profiles and mortality rates are similar for metabolic dysfunction-associated steatotic liver disease and non-alcoholic fatty liver disease. J Hepatol. 2024. doi: 10.1016/j.jhep.2024.01.014.

6. Bassal T., Basheer M., Boulos M. et al. Nonalcoholic fatty liver disease - a concise review of noninvasive tests and biomarkers. Metabolites. 2022;12(11):1073. doi: 10.3390/metabo12111073.

7. Ramírez-Mejía M., Jiménez-Gutiérrez C., Eslam M. et al. Breaking new ground: MASLD vs. MAFLD - which holds the key for risk stratification? Hepatol Int. 2024;18(1):168-78. doi: 10.1007/s12072-023-10620-y.

8. Trukhan D.I. Nonalcoholic fatty liver disease: therapeutic and dietary recommendations at the stage of primary health care. Medical Council.2015;17: 78-84. (In Russ.)@@ Трухан Д.И. Неалкогольная жировая болезнь печени: лечебные и диетические рекомендации на этапе оказания первичной медико-санитарной помощи. Медицинский совет. 2015;17: 78-84.

9. Byrne C., Targher G. NAFLD: a multisystem disease. J Hepatol. 2015;62(1 Suppl):47-64. doi: 10.1016/j.jhep.2014.12.012.

10. Sumida Y., Nakajima A., Itoh Y. Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol. 2014;20:475-485. doi: 10.3748/wjg.v20.i2.475.

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 for the management of non-alcoholic fatty liver disease. J. Hepatol. 2016;64(6):1388-1402. doi: 10.1016/j.jhep.2015.11.004.

12. Maev I.V., Samsonov A.A., Lazebnik L.B. et al. A New NonInvasive Scale for Steatosis Developed Using Real- World Data From Russian Outpatients to Aid in the Diagnosis of Non- Alcoholic Fatty Liver Disease. Adv Ther. 2020;(37):4627-4640. doi: 10.1007/s12325-020-01493-w.

13. Bedogni G., Bellentani S., Miglioli L. et al. The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol. 2006;6(33). doi: 10.1186/1471-230X-6-33.

14. Gastaldelli A., Kozakova M., Højlund K. et al. Fatty liver is associated with insulin resistance, risk of coronary heart disease, and early atherosclerosis in a large European population. Hepatology. 2009;49(5):1537-1544. doi: 10.1002/hep.22845.

15. Iwasaki Y., Shiina K., Matsumoto C. et al. Correlation of the Fatty Liver Index with the Pathophysiological Abnormalities Associated with Cardiovascular Risk Markers in Japanese Men without any History of Cardiovascular Disease: Comparison with the Fibrosis-4 Score. J Atheroscler Thromb. 2021;28(5):524-534. doi: 10.5551/jat.56945.

16. Li X., Heiskanen J.S., Ma H. et al. Fatty liver index and left ventricular mass: prospective associations from two independent cohorts. J Hypertens. 2021;39(5):961-969. doi: 10.1097/HJH.0000000000002716.

17. Niu Z., Wu Q., Sun L. et al. Circulating Glycerolipids, Fatty Liver Index, and Incidence of Type 2 Diabetes: A Prospective Study Among Chinese. J Clin Endocrinol Metab. 2021;106(7):2010-2020. doi: 10.1210/clinem/dgab165.

18. Takahashi S., Tanaka M., Furuhashi M. et al. Fatty liver index is independently associated with deterioration of renal function during a 10-year period in healthy subjects. Sci Rep. 2021;11(1):8606. doi: 10.1038/s41598-021-88025-w.

19. Huang X. Xu M. Chen Y. et al. Validation of the Fatty Liver Index for Nonalcoholic Fatty Liver Disease in Middle-Aged and Elderly Chinese. Medicine (Baltimore). 2015;94(40): e1682. doi: 10.1097/MD.0000000000001682.

20. Han A. Lee H.Comparison of the Diagnostic Performance of Steatosis Indices for Discrimination of CT-Diagnosed Metabolic Dysfunction-Associated Fatty Liver Disease. Metabolites.2022.12:664. doi: 10.3390/metabo12070664.

21. Castellana M., Donghia R., Guerra V. et al. Performance of Fatty Liver Index in Identifying Non-Alcoholic Fatty Liver Disease in Population Studies. A Meta-Analysis. J Clin Med. 2021;10(9):1877. doi: 10.3390/jcm10091877.

22. Fedchuk L., Nascimbeni F., Pais R. et al. Performance and limitations of steatosis biomarkers in patients with nonalcoholic fatty liver disease. Aliment Pharmacol Ther. 2014;40(10):1209-1222. doi: 10.1111/apt.12963.

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

24. Kotronen A., Peltonen M., Hakkarainen A. et al. Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors. Gastroenterology. 2009;137(3):865-872. doi: 10.1053/j.gastro.2009.06.005.

25. Koot B., van der Baan-Slootweg O., Bohte A. et al. Accuracy of prediction scores and novel biomarkers for predicting nonalcoholic fatty liver disease in obese children. Obesity (Silver Spring). 2013;21(3):583-590. doi: 10.1002/oby.20173.

26. Poynard T., Ratziu V., Naveau S. et al. The diagnostic value of biomarkers (SteatoTest) for the prediction of liver steatosis.Comp Hepatol. 2005;4:10. doi: 10.1186/1476-5926-4-10.

27. Poynard T., Lassailly G., Diaz E. et al. Performance of biomarkers FibroTest, ActiTest, SteatoTest, and NashTest in patients with severe obesity: meta analysis of individual patient data. PLoS ONE. 2012;7(3): e30325. doi: 10.1371/journal.pone.0030325.

28. Kotronen A., Peltonen M., Hakkarainen A. et al. Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors. Gastroenterology. 2009;137(3):865-872. doi: 10.1053/j.gastro.2009.06.005.

29. Koneru K., Bhatt V., Kakrani A. et al. A study of non-alcoholic fatty liver disease-liver fat score in overweight and obese individuals. J Family Med Prim Care. 2022;11(8):4368-4374. doi: 10.4103/jfmpc.jfmpc_58_22.

30. Lee C., Li H., Tsoi M. et al. Association between the liver fat score (LFS) and cardiovascular diseases in the national health and nutrition examination survey 1999-2016. Ann Med. 2021;53(1):1065-1073. doi: 10.1080/07853890.2021.1943514.

31. Wang J., Xu C., Xun Y. et al. ZJU index: a novel model for predicting nonalcoholic fatty liver disease in a Chinese population. Sci Rep. 2015;5:16494. doi: 10.1038/srep16494.

32. Amato M., Giordano C., Galia M. et al. Visceral Adiposity Index: a reliable indicator of visceral fat function associated with cardiometabolic risk. Diabetes Care. 2010;33(4):920-922. doi: 10.2337/dc09-1825.

33. Ismaiel A., Jaaouani A., Leucuta D. et al. The Visceral Adiposity Index in Non-Alcoholic Fatty Liver Disease and Liver Fibrosis-Systematic Review and Meta-Analysis. Biomedicines. 2021;9(12):1890. doi: 10.3390/biomedicines9121890.

34. Yi X., Zhu S., Zhu L. Diagnostic accuracy of the visceral adiposity index in patients with metabolic-associated fatty liver disease: a meta-analysis. Lipids Health Dis. 2022;21:28. doi: 10.1186/s12944-022-01636-8.

35. Yip T., Ma A., Wong V. et al. Laboratory parameter-based machine learning model for excluding non-alcoholic fatty liver disease (NAFLD) in the general population. Aliment Pharmacol Ther. 2017;46(4):447-456. doi: 10.1111/apt.14172.

36. Saadeh S., Younossi Z.M., Remer E. et al. The Utility of Radiological Imaging in Nonalcoholic Fatty Liver disease. Gastroenterology. 2002;123:745-750. doi: 10.1053/gast.2002.35354.

37. Hernaez R., Lazo M., Bonekamp S. et al. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology. 2011;54(3):1082-1090. doi: 10.1002/hep.24452.

38. Chalasani N., Younossi Z., Lavine J. et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-357. doi: 10.1002/hep.29367.

39. De Lucia Rolfe E., Brage S., Sleigh A. et al. Validity of ultrasonography to assess hepatic steatosis compared to magnetic resonance spectroscopy as a criterion method in older adults. PLoS One. 2018;13(11): e0207923. doi: 10.1371/journal.pone.0207923.

40. Park S., Kim P., Kim K. et al. Macrovesicular hepatic steatosis in living liver donors: use of CT for quantitative and qualitative assessment. Radiology. 2006;239(1):105-112. doi: 10.1148/radiol.2391050361.

41. Pickhardt P.J., Graffy P.M., Reeder S. et al. Quantification of Liver Fat Content With Unenhanced MDCT: Phantom and Clinical Correlation With MRI Proton Density Fat Fraction. AJR Am J Roentgenol. 2018;211(3):151-157. doi: 10.2214/AJR.17.19391.

42. Springer F., Machann J., Claussen C. et al. Liver fat content determined by magnetic resonance imaging and spectroscopy. World J Gastroenterol. 2010;16(13):1560-1566. doi: 10.3748/wjg.v16.i13.1560.

43. Dulai P.S., Sirlin C.B., Loomba R. MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in NAFLD and NASH: Clinical trials to clinical practice. J Hepatol. 2016;65(5):1006-1016. doi: 10.1016/j.jhep.2016.06.005.

44. Tang A., Tan J., Sun M. et al. Nonalcoholic fatty liver disease: MR imaging of liver proton density fat fraction to assess hepatic steatosis. Radiology. 2013;267(2):422-431. doi: 10.1148/radiol.12120896.

45. Bassal T., Basheer M., Boulos M., Assy N. Nonalcoholic fatty liver disease - a concise review of noninvasive tests and biomarkers. Metabolites. 2022;12(11):1073. doi: 10.3390/metabo12111073.

46. Feldstein A., Wieckowska A., Lopez A. et al. Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study. Hepatology (Baltimore, Md.). 2009 Oct;50(4):1072-1078. doi: 10.1002/hep.23050.

47. Kwok R., Tse Y., Wong G. et al. Systematic review with meta-analysis: non-invasive assessment of non-alcoholic fatty liver disease-the role of transient elastography and plasma cytokeratin-18 fragments. Aliment Pharmacol Ther. 2014;39(3):254-69. doi: 10.1111/apt.12569.

48. Musso G., Gambino R., Cassader M., Pagano G. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med. 2011;43(8):617-49. doi: 10.3109/07853890.2010.518623.

49. Grigorescu M. Crisan D., Radu C. et al. A novel pathophysiological-based panel of biomarkers for the diagnosis of nonalcoholic steatohepatitis. J Physiol pharmacol. 2012;63(4):347-53. PMID: 23070083.

50. Qi S., Xu D., Li K. et al. Metabonomic screening of serum identifies pyroglutamate as a diagnostic biomarker of nonalcoholic steatohepatitis. Clin Chim Act. 2017; 473: 89-95. doi: 10.1016/j.cca.2017.08.022.

51. Poynard T., Ratziu V., Charlotte F. et al. Diagnostic value of biochemical markers (NashTest) for the prediction of non alcoholo steato hepatitis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol. 2006;6:34. doi: 10.1186/1471-230X-6-34.

52. Kleiner D., Brunt E., Van Natta M. et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313-1321. doi: 10.1002/hep.20701.

53. Zhou Y, Orešič M, Leivonen M. et al. Noninvasive Detection of Nonalcoholic Steatohepatitis Using Clinical Markers and Circulating Levels of Lipids and Metabolites. Clin Gastroenterol Hepatol. 2016;14(10):1463-1472.e6. doi: 10.1016/j.cgh.2016.05.046.