nogrЭкспериментальная и клиническая гастроэнтерологияExperimental and Clinical Gastroenterology1682-8658«Global Media Technologies»10.31146/1682-8658-ecg-199-3-50-56nogr-1942Research ArticleКЛИНИЧЕСКАЯ ГАСТРОЭНТЕРОЛОГИЯCLINICAL GASTROENTEROLOGYВозможности растворимых селектинов в предикции тяжелого фиброза при неалкогольной жировой болезни печениThe possibilities of soluble selectins in the prediction of severe fi brosis in nonalcoholic fatty liver diseasehttps://orcid.org/0000-0001-6392-8461КоройП. В.KoroyP. V.

Корой Павел Владимирович - доктор медицинских наук, профессор, профессор кафедры госпитальной терапии. Scopus Author ID: 56288630200.

355017, Ставрополь, ул. Мира, д. 310

Pavel V. Koroy - MD, PhD, Professor, Professor of Department of Hospital Therapy; Scopus Author ID: 56288630200.

355017, Stavropol, Mira str., 310

paule75@yandex.ruКравченкоЮ. А.KravchenkoYu. A.

Кравченко Юлия Александровна - соискатель кафедры госпитальной терапии.

355017, Ставрополь, ул. Мира, д. 310

Yuliya A. Kravchenko - candidate of Department of Hospital Therapy.

355017, Stavropol, Mira str., 310

https://orcid.org/0000-0002-5727-1640ЯгодаА. В.YagodaA. V.

Ягода Александр Валентинович - доктор медицинских наук, профессор, заслуженный деятель науки РФ, заведующий кафедрой госпитальной терапии. Scopus Author ID: 7007153293, ResearcherID: B-5336–2017.

355017, Ставрополь, ул. Мира, д. 310

Alexander V. Yagoda - MD, PhD, Professor, Honored Worker of Science of Russian Federation, Head of Department of Hospital Therapy; Scopus Author ID: 7007153293, ResearcherID: B-5336–2017.

355017, Stavropol, Mira str., 310

ФГБОУ ВО Ставропольский государственный медицинский университет Министерства здравоохранения Российской ФедерацииРоссияA.V. Yagoda Stavropol State Medical UniversityRussian Federation202204102022035056Copyright © Корой П.В., Кравченко Ю.А., Ягода А.В., 20222022Корой П.В., Кравченко Ю.А., Ягода А.В.Koroy P.V., Kravchenko Y.A., Yagoda A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.nogr.org/jour/article/view/1942

Цель работы — изучение взаимосвязи селектинов с печеночным фиброзом при неалкогольной жировой болезни печени (НАЖБП).

Материал и методы

Материал и методы. Содержание Е-, Р- и L-селектинов в крови было изучено у 40 пациентов с гистологически подтвержденной НАЖБП (42,5% женщин, 57,5% мужчин) в возрасте от 19 до 65 лет (средний возраст — 40,93±1,95 лет). Выраженный стеатоз печени встречался у 47,5% больных, неалкогольный стеатогепатит выявлен в 57,5% случаев, тяжелый фиброз печени наблюдался у 22,5% обследованных. Контрольную группу составили 60 практически здоровых людей.

Результаты

Результаты. При НАЖБП наблюдалось увеличение плазменных уровней всех селектинов. Количество Е-селектина в крови возрастало с усилением гистологических признаков печеночного стеатоза. У больных неалкогольным стеатогепатитом концентрация Е- и Р-селектинов в крови была выше, чем в случаях его отсутствия. Максимальное содержание Е- и Р- селектинов в крови отмечалось при тяжелом фиброзе печени. Выявлена корреляция растворимых Е- и Р-селектинов с индексом фиброза. Риск тяжелого фиброза при НАЖБП увеличивался в 27 раз при значениях Е-селектина выше 89 нг/ мл и в 33 раза в случаях величин Р-селектина более 166 нг/мл. Точность вышеуказанных показателей Е- и Р-селектинов в предикции тяжелого фиброза при НАЖБП составила 80,0 и 82,5% соответственно. Вероятность тяжелого фиброза печени при НАЖБП была связана с наличием инсулинорезистентности и повышенного содержания Р-селектина в крови.

Заключение

Заключение. Определение профиля растворимых селектинов при НАЖБП позволяет оценивать выраженность фиброза печени и стратифицировать больных на группы с различной его выраженностью.

The aim of the work was to study the relationship of selectins with hepatic fi brosis in nonalcoholic fatty liver disease (NAFLD).

Material and methods

Material and methods. In 40 patients with histologically confi rmed NAFLD (42.5% of women, 57.5% of men) aged 19 to 65 years (mean age — 40.93±1.95 years), the levels of E-, P- and L-selectins in the blood was studied. Severe liver steatosis was present in 47.5% of patients, nonalcoholic steatohepatitis was observed in 57.5% of cases, and severe liver fi brosis was detected in 22.5% of patients. The control group consisted of 60 practically healthy people.

Results

Results. The increase of plasma levels of all selectins was observed in NAFLD. The blood levels of E-selectin elevated with increasing of histological signs of hepatic steatosis. The concentration of E- and P-selectins in the blood was higher in patients with nonalcoholic steatohepatitis than in cases of its absence. The maximum values of E- and P-selectins in the blood were present in severe liver fi brosis. Correlation of soluble E- and P-selectins with fi brosis index was determined. The risk of severe fi brosis in NAFLD increased 27-fold with E-selectin values above 89 ng/ml and 33-fold in cases of P-selectin values greater than 166 ng/ml. The accuracy of the above levels of E- and P-selectins in predicting severe fi brosis in NAFLD was 80.0 and 82.5%, respectively. The probability of severe liver fi brosis in NAFLD was related with the presence of insulin resistance and increased levels of P-selectin in the blood.

Conclusion

Conclusion. Determination of the profi le of soluble selectins in NAFLD allows us to state the severity of liver fi brosis and stratify patients into groups with its diff erent severity.

неалкогольная жировая болезнь печенифиброз печениселектиныnonalcoholic fatty liver diseasenonalcoholic steatohepatitisliver fi brosisselectinsReferencesЛазебник Л. Б., Голованова Е. В., Туркина С. В. и др. Неалкогольная жировая болезнь печени у взрослых: клиника, диагностика, лечение. Рекомендации для терапевтов, третья версия. Экспериментальная и клиническая гастроэнтерология. 2021; 185(1): 4–52. doi: 10.31146/1682–8658-ecg-185–1–4–52Lazebnik 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; 185(1): 4–52. (In Russ.) doi: 10.31146/1682–8658-ecg-185–1–4–52Berardo C., Pasqua L. G. Di, Cagna M. et al. Nonalcoholic fatty liver disease and non-alcoholic steatohepatitis: current issues and future perspectives in preclinical and clinical research. Int. J. Mol. Sci. 2020; 21(24): 9646. doi: 10.3390/ijms21249646Berardo C., Pasqua L. G. Di, Cagna M. et al. Nonalcoholic fatty liver disease and non-alcoholic steatohepatitis: current issues and future perspectives in preclinical and clinical research. Int. J. Mol. Sci. 2020; 21(24): 9646. doi: 10.3390/ijms21249646Perumpail B. J., Khan M. A., Yoo E. R., et al. Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World J. Gastroenterol. 2017; 23(47): 8263–8276. doi: 10.3748/wjg.v23.i47.8263Perumpail B. J., Khan M. A., Yoo E. R., et al. Clinical epidemiology and disease burden of nonalcoholic fatty liver disease. World J. Gastroenterol. 2017; 23(47): 8263–8276. doi: 10.3748/wjg.v23.i47.8263Estes C., Anstee Q. M., Arias-L oste M. T. et al. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016–2030. J. Hepatol. 2018; 69: 896–904. doi: 10.1016/j.jhep.2018.05.036Estes C., Anstee Q. M., Arias-L oste M. T. et al. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016–2030. J. Hepatol. 2018; 69: 896–904. doi: 10.1016/j.jhep.2018.05.036Weston C. J., Shepherd E. L., Claridge L. C., et al. Vascular adhesion protein-1 promotes liver infl ammation and drives hepatic fi brosis. J. Clin. Invest. 2015; 125: 501–520. doi: 10.1172/JCI73722Weston C. J., Shepherd E. L., Claridge L. C., et al. Vascular adhesion protein-1 promotes liver infl ammation and drives hepatic fi brosis. J. Clin. Invest. 2015; 125: 501–520. doi: 10.1172/JCI73722Hammoutene A., Rautou P. E. Role of liver sinusoidal endothelial cells in non-alcoholic fatty liver disease. J. Hepatol. 2019; 70(6): 1278–1291. doi: 10.1016/j.jhep.2019.02.012Hammoutene A., Rautou P. E. Role of liver sinusoidal endothelial cells in non-alcoholic fatty liver disease. J. Hepatol. 2019; 70(6): 1278–1291. doi: 10.1016/j.jhep.2019.02.012Miyao M., Kotani H., Ishida T., et al. Pivotal role of liver sinusoidal endothelial cells in NAFLD/NASH progression. Lab. Invest. 2015; 95: 1130–1144. doi: 10.1038/labinvest.2015.95Miyao M., Kotani H., Ishida T., et al. Pivotal role of liver sinusoidal endothelial cells in NAFLD/NASH progression. Lab. Invest. 2015; 95: 1130–1144. doi: 10.1038/labinvest.2015.95Гилязова Г. И., Мухорамова И. С., Руденко Ю. А. и др. Роль молекул адгезии в иммунном ответе. Вестник молодого ученого. 2012; 2: 21–27.Gilyazova G. I., Mukhoramova I. S., Rudenko Yu. A., et al. Role of adhesion molecules in immune response. Journal of Young Scientist. 2012; 2: 21–27. (In Russ.)Комшилова К. А. Абдоминальное ожирение и неалкогольная жировая болезнь печени: клинико- лабораторные и морфологические сопоставления: автореф. дис. … канд. мед. наук. Москва, 2015: 26 с.Komshilova K. A. Abdominal obesity and non-alcoholic fattyliver disease: clinical, laboratory and morphological comparisons: dissertation thesis of the candidate of medical sciences. Moscow, 2015. 26 P. (In Russ.)Bilgir F., Bilgir O., Calan M., Calan O., Yuksel A. The Levels of Soluble Intercellular Adhesion Molecule, Vascular Adhesion Molecule and Se-S electin Levels in Patients with Non-A lcoholic Fatty Liver Disease. J Autacoids Horm. 2015;5:108. doi: 10.4172/2161–0479.1000108Bilgir F., Bilgir O., Calan M., Calan O., Yuksel A. The Levels of Soluble Intercellular Adhesion Molecule, Vascular Adhesion Molecule and Se-S electin Levels in Patients with Non-A lcoholic Fatty Liver Disease. J Autacoids Horm. 2015;5:108. doi: 10.4172/2161–0479.1000108Drescher H. K., Schippers A., Rosenhain S., et al. L-Selectin/ CD62L is a key driver of non-alcoholic steatohepatitis in mice and men. Cells. 2020; 9: 1106. doi: 10.3390/cells9051106Drescher H. K., Schippers A., Rosenhain S., et al. L-Selectin/ CD62L is a key driver of non-alcoholic steatohepatitis in mice and men. Cells. 2020; 9: 1106. doi: 10.3390/cells9051106Simons N., Bijnen M., Wouters K. A. M. Th e endothelial function biomarker soluble E-selectin is associated with nonalcoholic fatty liver disease. Liver Int. 2020; 40(5): 1079– 1088. doi: 10.1111/liv.14384Simons N., Bijnen M., Wouters K. A. M. Th e endothelial function biomarker soluble E-selectin is associated with nonalcoholic fatty liver disease. Liver Int. 2020; 40(5): 1079– 1088. doi: 10.1111/liv.14384Ustyol A., Ustyol E. A., Gurdol F., Kokali F. P-selectin, endocan, and some adhesion molecules in obese children and adolescents with non-alcoholic fatty liver disease. Scand. J. Clin. Lab. Invest. 2017; 77(3): 205–203. doi: 10.1080/00365513.2017.1292363Ustyol A., Ustyol E. A., Gurdol F., Kokali F. P-selectin, endocan, and some adhesion molecules in obese children and adolescents with non-alcoholic fatty liver disease. Scand. J. Clin. Lab. Invest. 2017; 77(3): 205–203. doi: 10.1080/00365513.2017.1292363Hammoutene A., Biquard L., Lasselin J. A defect in endothelial autophagy occurs in patients with non-alcoholic steatohepatitis and promotes infl ammation and fi brosis. J. Hepatol. 2020; 72(3): 528–538. doi: 10.1016/j.jhep.2019.10.028Hammoutene A., Biquard L., Lasselin J. A defect in endothelial autophagy occurs in patients with non-alcoholic steatohepatitis and promotes infl ammation and fi brosis. J. Hepatol. 2020; 72(3): 528–538. doi: 10.1016/j.jhep.2019.10.028Kus E., Kaczara P., Czyzynska- Cichon I. LSEC fenestrae are preserved despite pro-infl ammatory phenotype of liver sinusoidal endothelial cells in mice on high fat diet. Front. Physiol. 2019; 10: 6. doi: 10.3389/fphys.2019.00006Kus E., Kaczara P., Czyzynska- Cichon I. LSEC fenestrae are preserved despite pro-infl ammatory phenotype of liver sinusoidal endothelial cells in mice on high fat diet. Front. Physiol. 2019; 10: 6. doi: 10.3389/fphys.2019.00006Сляднев С. А., Корой П. В. Потенциал адгезинов в диагностике неалкогольной жировой болезни печени. Медицинский вестник Северного Кавказа. 2017; 12(1): 98–99. doi: 10.14300/mnnc.2017.12028Slyadnev S. А., Koroy P. V. Potential of adhesins in diagnostics of nonalcoholic fatty liver disease. Medical news of North Caucasus. 2017; 12(1): 98–99. (In Russ.) doi: 10.14300/mnnc.2017.12028Ягода А. В., Корой П. В., Сляднев С. А. Положительная корр ел яция уровня молекул суперсемейства иммуноглобулинов ICAM-1, VCAM-1, PECAM-1 с показателями индекса фиброза при неалкогольной жировой болезни печени. Экспериментальная и кли ни ческая гастроэнтерология. 2017; 138(2): 45–51.Yagoda A.V., Koroy P. V., Slyadnev S. A. Positive correlation of the level of molecules of superfamily immunoglobulins ICAM-1, VCAM-1 and PECAM-1 with the index of fi brosis in nonalcoholic fatty liver disease. Experimental and Clinical Gastroenterology. 2017;(2):45–51. (In Russ.)VanSaun M. N., Mendonsa A. M., Gorden D. L. Hepatocellular proliferation correlates with infl ammatory cell and cytokine changes in a murine model of nonalchoholic fatty liver disease. PLoS One. 2013; 8(9): e73054. doi: 10.1371/journal.pone.0073054VanSaun M. N., Mendonsa A. M., Gorden D. L. Hepatocellular proliferation correlates with infl ammatory cell and cytokine changes in a murine model of nonalchoholic fatty liver disease. PLoS One. 2013; 8(9): e73054. doi: 10.1371/journal.pone.0073054Pasarín M., Abraldes J. G., Liguori E., et al. Intrahepatic vascular changes in non-alcoholic fatty liver disease: potential role of insulin- resistance and endothelial dysfunction. World J. Gastroenterol. 2017; 23(37): 6777–6787. doi: 10.3748/wjg.v23.i37.6777Pasarín M., Abraldes J. G., Liguori E., et al. Intrahepatic vascular changes in non-alcoholic fatty liver disease: potential role of insulin- resistance and endothelial dysfunction. World J. Gastroenterol. 2017; 23(37): 6777–6787. doi: 10.3748/wjg.v23.i37.6777Marrone G., Shah V. H., Gracia- Sancho J. Sinusoidal communication in liver fi brosis and regeneration. J. Hepatol. 2016; 65: 608–617. doi: 10.1016/j.jhep.2016.04.018Marrone G., Shah V. H., Gracia- Sancho J. Sinusoidal communication in liver fi brosis and regeneration. J. Hepatol. 2016; 65: 608–617. doi: 10.1016/j.jhep.2016.04.018Almeda-V aldes P., Aguilar Olivos N. E., Barranco-F ragoso B., et al. Th e role of dendritic cells in fi brosis progression in nonalcoholic fatty liver disease. Biomed. Res. Int. 2015; 2015: 768071. doi: 10.1155/2015/768071Almeda-V aldes P., Aguilar Olivos N. E., Barranco-F ragoso B., et al. Th e role of dendritic cells in fi brosis progression in nonalcoholic fatty liver disease. Biomed. Res. Int. 2015; 2015: 768071. doi: 10.1155/2015/768071Parrinello C. M., Rudolph B. J., Lazo M., et al. Asso ci ations of insulin resistance and glycemia with liver enzymes in hispanic/latino youths: results from the Hispanic Community Children’s Health Study/Study of Latino Youth (SOL Youth). J. Clin. Gastroenterol. 2019; 53(2): e46-e53. doi: 10.1097/MCG.0000000000000946Parrinello C. M., Rudolph B. J., Lazo M., et al. Asso ci ations of insulin resistance and glycemia with liver enzymes in hispanic/latino youths: results from the Hispanic Community Children’s Health Study/Study of Latino Youth (SOL Youth). J. Clin. Gastroenterol. 2019; 53(2): e46-e53. doi: 10.1097/MCG.0000000000000946Vilaseca M., García- Calderó H., Lafoz E., et al. Th e anticoagulant rivaroxaban lowers portal hypertension in cirrhotic rats mainly by deactivating hepatic stellate cells. Hepatology. 2017; 65: 2031–2044. doi: 10.1002/hep.29084Vilaseca M., García- Calderó H., Lafoz E., et al. Th e anticoagulant rivaroxaban lowers portal hypertension in cirrhotic rats mainly by deactivating hepatic stellate cells. Hepatology. 2017; 65: 2031–2044. doi: 10.1002/hep.29084Kopec A. K., Joshi N., Towery K. L., et al. Th rombin inhibition with dabigatran protects against high-fat diet-induced fatty liver disease in mice. J. Pharmacol. Exp. Th er. 2014; 351: 288–297. doi: 10.1124/jpet.114.218545Kopec A. K., Joshi N., Towery K. L., et al. Th rombin inhibition with dabigatran protects against high-fat diet-induced fatty liver disease in mice. J. Pharmacol. Exp. Th er. 2014; 351: 288–297. doi: 10.1124/jpet.114.218545Virović-J ukić L., Stojsavljević-S hapeski S., Forgač J., et al. Non-alcoholic fatty liver disease – a procoagulant condition? Croat. Med. J. 2021; 62: 25–33. doi: 10.3325/cmj.2021.62.25Virović-J ukić L., Stojsavljević-S hapeski S., Forgač J., et al. Non-alcoholic fatty liver disease – a procoagulant condition? Croat. Med. J. 2021; 62: 25–33. doi: 10.3325/cmj.2021.62.25Taipale T., Seppälä I., Raitoharju E., et al. Fatty liver is associated with blood pathways of infl ammatory response, immune system activation and prothrombotic state in Young Finns Study. Scientifi c Reports. 2018; 8: 10358. doi: 10.1038/s41598–018–28563-yTaipale T., Seppälä I., Raitoharju E., et al. Fatty liver is associated with blood pathways of infl ammatory response, immune system activation and prothrombotic state in Young Finns Study. Scientifi c Reports. 2018; 8: 10358. doi: 10.1038/s41598–018–28563-yMadan S. A., John F., Pitchumoni C. S. Nonalcoholic fatty liver disease and mean platelet volume: a systemic review and meta-analysis. J. Clin. Gastroenterol. 2016; 50: 69–74. doi: 10.1097/MCG.0000000000000340Madan S. A., John F., Pitchumoni C. S. Nonalcoholic fatty liver disease and mean platelet volume: a systemic review and meta-analysis. J. Clin. Gastroenterol. 2016; 50: 69–74. doi: 10.1097/MCG.0000000000000340Potze W., Siddiqui M. S., Sanyal A. J. Vascular disease in patients with nonalcoholic fatty liver disease. Semin. Th romb. Hemost. 2015; 41: 488–493. doi: 10.1055/s-0035–1550433Potze W., Siddiqui M. S., Sanyal A. J. Vascular disease in patients with nonalcoholic fatty liver disease. Semin. Th romb. Hemost. 2015; 41: 488–493. doi: 10.1055/s-0035–1550433Lefere S., Van de Velde F., Devisscher L., et al. Serum vascular cell adhesion molecule-1 predicts signifi cant liver fi brosis in non-alcoholic fatty liver disease. Int. J. Obes. (Lond.). 2017; 41(8): 1207–1213. doi: 10.1038/ijo.2017.102Lefere S., Van de Velde F., Devisscher L., et al. Serum vascular cell adhesion molecule-1 predicts signifi cant liver fi brosis in non-alcoholic fatty liver disease. Int. J. Obes. (Lond.). 2017; 41(8): 1207–1213. doi: 10.1038/ijo.2017.102Ajmera V., Perito E. R., Bass N. M., et al. Novel plasma biomarkers associated with liver disease severity in adults with nonalcoholic fatty liver disease. Hepatology. 2017; 65(1): 65–77. doi: 10.1002/hep.28776Ajmera V., Perito E. R., Bass N. M., et al. Novel plasma biomarkers associated with liver disease severity in adults with nonalcoholic fatty liver disease. Hepatology. 2017; 65(1): 65–77. doi: 10.1002/hep.28776

The authors declare that there are no conflicts of interest present.