Improvement of liver fibrosis verification using new minimally invasive markers in patients with chronic diffuse liver diseases

Yu.M. Stepanov; V.I. Didenko; I.A. Klenina; O.M. Tatarchuk; O.P.  Petishko

doi:10.26641/2307-0404.2022.4.271181

Авторы

Yu.M. Stepanov SI “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Slobozhanskyi av. 96, Dnipro, 49074, Ukraine https://orcid.org/0000-0002-6721-2468
V.I. Didenko SI “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Slobozhanskyi av. 96, Dnipro, 49074, Ukraine https://orcid.org/0000-0001-8953-396X
I.A. Klenina SI “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Slobozhanskyi av. 96, Dnipro, 49074, Ukraine https://orcid.org/0000-0002-5878-179X
O.M. Tatarchuk SI “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Slobozhanskyi av. 96, Dnipro, 49074, Ukraine https://orcid.org/0000-0002-0672-972X
O.P. Petishko SI “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Slobozhanskyi av. 96, Dnipro, 49074, Ukraine https://orcid.org/0000-0002-4559-4055

DOI:

https://doi.org/10.26641/2307-0404.2022.4.271181

Ключевые слова:

non-alcoholic fatty liver disease, chronic hepatitis associated with virus C, alcoholic liver disease, toxic drug-induced hepatitis, cytokines, biochemical markers of fibrosis

Аннотация

The aim of our research was to obtain new minimally invasive serum markers of fibrotic changes of liver in patients with chronic diffuse liver diseases of different etiology and compare them with traditional markers. 364 patients aged 30 to 66 years were examined: 221 women (60.7%) and 143 men (39.3%). Depending on the etiological factors, all patients were divided into 4 groups: group I consisted of 108 patients with non-alcoholic fatty liver disease (NAFLD), group II – 143 patients with chronic hepatitis associated with virus C (CHC), group III – 56 patients with alcoholic liver disease (ALD), group IV – 57 patients with toxic drug-induced hepatitis (TH). The control group consisted of 30 practically healthy people. Using correlation and ROC-analyzes, we obtained minimally invasive diagnostics markers that show the risk of developing liver fibrosis. For patients with NAFLD these were the levels of HOMA-IR, TNFα/IL-10 and α1-acid glycopeptide content, which are better in quality of the diagnostic model than the traditional Forns index, APRI, FIB-4, AAR. For patients with CHC, these were the protein-bound hydroxyproline (HP_p/b) /HP_f ratio, phospholipids content, and IL-6, CD4+ levels, which are better diagnostic models than the traditional Forns index, APRI, FIB-4, AAR. The following markers were obtained for patients with ALD – TNFα levels, HP_p/band glycosaminoglycans content, which are better diagnostic models than the traditional Forns index, APRI, FIB-4, AAR. For patients with TH, these were medium molecular weight peptides content, IL-6/IL-10 ratio and CD4+/CD8+, which are better diagnostic models than the traditional Forns index, APRI, FIB-4, AAR. Thus, new minimally invasive markers of fibrosis in patients with chronic diffuse liver diseases have been obtained.

Библиографические ссылки

Younossi ZM, Stepanova M, Younossi Y, Go-labi P, Mishra A, Rafiq N, et al. Epidemiology of chronic liver diseases in the USA in the past three decades. Gut. 2020;69(3):564-8.

doi: https://doi.org/10.1136/gutjnl-2019-318813

Petta S, Ting J, Saragoni S, Degli Esposti L, Shreay S, Petroni ML, et al. Healthcare resource utilization and costs of nonalcoholic steatohepatitis patients with advanced liver disease in Italy. Nutrition, metabolism, and cardiovascular diseases. 2020;30(6):1014-22. doi: https://doi.org/10.1016/j.numecd.2020.02.016

Durazzo M, Ponzo E, Bonetto S, Fagoonee S, Pellicano R. Liver diseases in the elderly. Minerva medica. 2019;110(1):35-51.

doi: https://doi.org/10.23736/S0026-4806.18.05858-5

Asrani SK, Devarbhavi H, Eaton J, Kamath PS. Burden of liver diseases in the world. J. Hepatol. 2019;70:151-71.

doi: https://doi.org/10.1016/j.jhep.2018.09.014

Pimpin L, Cortez-Pinto H, Negro F, Corbould E, Lazarus JV, Webber L, et al. Burden of liver disease in Europe: Epidemiology and analysis of risk factors to identify prevention policies. Journal of hepatology. 2018;69(3):718-35. doi: https://doi.org/10.1016/j.jhep.2018.05.011

Park SH, Plank LD, Suk KT, Park YE, Lee J, Choi JH, et al. Trends in the prevalence of chronic liver disease in the Korean adult population, 1998-2017. Clinical and molecular hepatology. 2020;26(2):209-15. doi: https://doi.org/10.3350/cmh.2019.0065

Asrani SK, Devarbhavi H, Eaton J, Kamath PS. Burden of liver diseases in the world. Journal of hepatology. 2019;70(1):151-71. doi: https://doi.org/10.1016/j.jhep.2018.09.014

Paik JM, Golabi P, Younossi Y, Mishra A, Younossi ZM. Changes in the Global Burden of Chronic Liver Diseases From 2012 to 2017: The Growing Impact of NAFLD. Hepatology (Baltimore, Md.). 2020;72(5):1605-16. doi: https://doi.org/10.1002/hep.31173

Roehlen N, Crouchet E, Baumert TF. Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives. Cells. 2020;9(4):875. doi: https://doi.org/10.3390/cells9040875

Stepanov Y, Didenko V, Konenko I, Tatarchuk O, Petishko O. [The characteristics of immune status and carbohydrate metabolism at different stages of liver fibrosis in patients with hepatitis C virus-related chronic hepatitis]. Gastroenterology. 2021;54(1):18-23. Ukrainian. doi: https://doi.org/10.22141/2308-2097.54.1.2020.199137.

Niederreiter L, Til H. Cytokines and fatty liver diseases. Liver Research. 2018;2(1):14-20. doi: https://doi.org/10.1016/j.livres.2018.03.003

Caballería L, Pera G, Arteaga I, Rodríguez L, Alumà A, Morillas RM, et al. High prevalence of liver fibrosis among European adults with unknown liver disease: a population-based study. Clin Gastroenterol Hepatol. 2018;16(7):1138-45. doi: https://doi.org/10.1016/j.cgh.2017.12.048

Stepanov YM, Didenko VI, Konenko IS, Yahmur VB, Petishko OP. [Method for diagnosing hepatic steatosis in patients with non-alcoholic fatty liver disease]. Patent 136479 Ukraina: A61B8/00, A61B8/12. №u201900966, 30.01.2019. 27.08.2019. Ukrainian.

[Unified clinical protocol of primary, secondary (specialized) medical care for alcoholic hepatitis. Order of the Ministry of Health of Ukraine dated November 6, 2014 No. 826]. (2014). Ukrainian.

Danan G, Teschke R. RUCAM in Drug and Herb Induced Liver Injury: The Update. International Journal of Molecular Sciences. 2015;17(1):14. doi: https://doi.org/10.3390/ijms17010014

Zayadeen AR, Hijazeen S, Smadi M, Fayyad L, Halasa M, AlQusous S. et al. Comparing shear wave elastography with liver biopsy in the assessment of liver fibrosis at King Hussein Medical Center. Egypt Liver Journal. 2022;12(24). doi: https://doi.org/10.1186/s43066-022-00186-z

Stepanov YuM, Didenko VI, Konenko IS, Klenina IA, Yagmur VB, Petishko OP. [Role of biochemical and hemodynamic indicators in assessing the progression of liver fibrosis of various origins]. Suchasna gastro-enterolohiia. 2019:5:5-13. Ukrainian. doi: https:// doi.org/10.30978/MG-2019-5-5

Strakhova OP, Androsov OI. [Statistical methods of processing the results of medical and biological re-search: educational and methodological manual]. Ryzhova OA, editor. Lviv: Vydavets Marchenko T.V.; 2021. Ukrainian.

Zviahintseva TD, Chernobai AI. [Metabolically associated fatty liver disease: focus on metabolic disorders and their correction]. Zdorovia Ukrainy. 2021;4(62). Ukrainian.

Zhang D, Huang J, Luo D, Feng X; Liu Y, Liu Y. Glycosylation change of alpha1-acid glycoprotein as a serum biomarker for hepatocellular carcinoma and cirrhosis. Biomark Med. 2017;11(15):423-30. doi: https://doi.org/10.2217/bmm-2016-0284

Tanabe K, Kitagawa K, Kojima N, Iijima S. Multifucosylated alpha-1-acid glycoprotein as a novel marker for hepatocellular carcinoma. J Proteome Res. 2016;15(9):2935-44. doi: https://doi.org/10.1002/hep.21242

Hastings KL, Green MD, Gao B, Ganey PE, Roth RA, Burleson GR. Beyond metabolism: role of the immune system in hepatic toxicity. Int J Toxicol. 2020;39(2):151-64. doi: https://doi.org/10.1177/109158181989839914

Tatarchuk OM, Didenko VI, Melanich SL, Kudryavtseva VYe. [Immunological reactivity in patients with chronic diffuse liver diseases]. Hastroenterolohiia. 2018;52(4):222-6. Ukrainian. doi: https://doi.org/10.22141/2308-2097.52.4.2018.154142