Abstract
Abstract
CYTOKERATIN-18 FRAGMENTS FOR PREDICTING STEATOHEPATITIS IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE
Babak O., Zhelezniakova N., Molodan V., Prosolenko K., Lapshyna K., Vizir M.
The aim of the study was to investigate metabolic parameters, cytokeratin 18 (CK-18) levels in blood plasma and the state of the liver parenchyma of patients with non-alcoholic fatty liver disease (NAFLD) in non-alcoholic steatohepatitis (NASH) stage. Materials and methods: Fasting serum CK-18 was measured in 30 NASH patients (mean age (49.3±3.6). The control group consisted of 20 practically healthy volunteers. The diagnosis of NADH was established on the basis of clinical, biochemical and instrumental data. In addition to basic laboratory tests and ultrasonographic examination, the Fibromax test (Biopredective, France) was performed. Results: In patients with NAFLD, the lipid profile showed a tendency to hyper- and dyslipidemia. The obtained data showed a significant increase in the parameters of enzymatic activity of the liver, the average level of aspartate aminotransferase (AST) exceeded the control group 2.5 times, the alanine aminotransferase (ALT) – 2.9 times, respectively (˂ 0.05). In NAFLD in NASH stage CK-18 levels in blood plasma were significantly increased, exceeded the results of the control group 3 and more times, and allowed to establish NASH in patients of the main group. Conclusions: Increased levels of CK-18 in NASH patients as well as its association with atherogenic dyslipidemia and increasing of liver enzymatic activity were revealed. The obtained data showed the possibility of using biomarker for non‑invasive diagnostics of NASH and represent the prospect of further research.
Key words: nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, noninvasive diagnosis, cytokeratin-18.
Резюме.
ФРАГМЕНТИ ЦИТОКЕРАТИНУ-18 ДЛЯ ПРОГНОЗУВАННЯ СТЕАТОГЕПАТИТУ У ПАЦІЄНТІВ З НЕАЛКОГОЛЬНОЮ ЖИРОВОЮ ХВОРОБОЮ ПЕЧІНКИ
Бабак О.Я., Железнякова Н.М., Молодан В.І., Просоленко К.О., Лапшина К.А., Візір М.О.
Мета дослідження: вивчити метаболічні показники, рівні цитокератину 18 (СК-18) у плазмі крові та стан паренхіми печінки у хворих на неалкогольну жирову хворобу печінки (НАЖХП) y стадії неалкогольного стеатогепатиту (НАСГ). Матеріали і методи: Обстежено 30 хворих з НАЖХП в стадії НАСГ, у віці від 30 до 60 років (середній вік (49.3 ± 3.6) років). Групу контролю склали 20 практично здорових добровольців. Діагноз НАЖХП був встановлений на підставі клініко-біохімічних та інструментальних даних. Всім пацієнтам, окрім основних лабораторних і ультрасонографічних досліджень, було проведено тест Fibromax (Biopredective, Франція). Визначення цитокератину-18 (СК-18) в плазмі крові проводилось імуноферментним методом з використанням наборів ELISA. Результати дослідження: У пацієнтів з НАЖХП ліпідний профіль показав тенденцію до гіпер- і дисліпідемії. Отримані дані свідчили про достовірне підвищення показників ферментативної активності печінки, середній рівень аспартатамінотрансферази (АСТ) перевищував показник контрольної групи у 2,5 рази, аланінамінотрансферази (АлАТ) - в 2,9 рази, відповідно (˂ 0,05). У хворих НАЖХП в стадії НАСГ рівні СК-18 в плазмі крові були достовірно підвищені, перевищували результати групи контрою в 3 та більше разів, і дозволяли встановити НАСГ у пацієнтів основної групи. Висновки: Виявлено підвищені рівні СК-18 у пацієнтів з НАСГ, а також його асоціація з атерогенною дисліпідемією і порушенням ферментативної активності печінки. Отримані дані свідчать про можливість використання біомаркеру для неінвазивної діагностики НАСГ і представляють перспективу подальших досліджень.
Ключові слова: неалкогольна жирова хвороба печінки, неалкогольний стеатогепатит, неінвазивна діагностика, цитокератин-18.
Резюме.
ФРАГМЕНТЫ ЦИТОКЕРАТИНА-18 ДЛЯ ПРОГНОЗИРОВАНИЯ СТЕАТОГЕПАТИТА У ПАЦИЕНТОВ С НЕАЛКОГОЛЬНОЙ ЖИРОВОЙ БОЛЕЗНЬЮ ПЕЧЕНИ
Бабак О.Я., Железнякова Н.М., Молодан В.И., Просоленко К.А., Лапшина Е.А., Визир М.А.
Цель исследования: изучить метаболические показатели, уровни цитокератина 18 (СК-18) в плазме крови и состояния паренхимы печени у больных неалкогольной жировой болезнью печени (НАЖБП) в стадии неалкогольного стеатогепатита (НАСГ). Материалы и методы: Обследовано 30 больных с НАЖБП в стадии НАСГ, в возрасте от 30 до 60 лет (средний возраст (49.3 ± 3.6) лет). Группу контроля составили 20 практически здоровых добровольцев. Диагноз НАЖБП был установлен на основании клинико-биохимических и инструментальных данных. Всем пациентам, помимо основных лабораторных и ультрасонографических исследований, был проведен тест Fibromax (Biopredective, Франция). Определение цитокератина-18 (СК-18) в плазме крови проводилось иммуноферментным методом с использованием наборов ELISA.
Результаты. У пациентов с НАЖБП липидный профиль показал тенденцию к гипер- и дислипидемии. Полученные данные свидетельствовали о достоверном повышении показателей ферментативной активности печени, средний уровень АсАТ (АСТ) превышал показатель контрольной группы в 2,5 раза, аланинаминотрансферазы (АЛТ) - в 2,9 раза, соответственно (˂ 0,05). У больных НАЖБП в стадии НАСГ уровни СК-18 в плазме крови были достоверно повышены, превышали результаты группы контроля в 3 и более раз, и позволяли установить НАСГ у пациентов основной группы. Выводы. Выявлены повышенные уровни СК-18 у пациентов с НАСГ, а также его ассоциация с атерогенной дислипидемией и нарушением ферментативной активности печени. Полученные данные свидетельствуют о возможности использования биомаркера для неинвазивной диагностики НАСГ и представляют перспективу дальнейших исследований.
Ключевые слова: неалкогольная жировая болезнь печени, неалкогольный стеатогепатит, неинвазивная диагностика, цитокератин-18.
References
Lonardo, A., Nascimbeni, F., Mantovani, A., & Targher, G. (2018). Hypertension, diabetes, atherosclerosis and NASH: cause or consequence?. Journal of hepatology, 68(2), 335-352.
Lokhov, P. G., Maslov, D. L., Balashova, E. E., Trifonova, O. P., Medvedeva, N. V., Torkhovskaya, T. I., ... & Shestakova, E. A. (2015). Mass spectrometry analysis of blood plasma lipidome as a method for diagnosing diseases, evaluating the effectiveness and optimizing drug therapy. Biomedical Chemistry, 61 (1), 7-18.
Chesnokova, L.V. (2015). Clinical and pathogenetic significance of non-alcoholic fatty liver disease in the formation of high cardiovascular risk in patients with metabolic syndrome. Possibilities of correction: Diss .
de Alwis, N. M. W., & Day, C. P. (2008). Non-alcoholic fatty liver disease: the mist gradually clears. Journal of hepatology, 48, S104-S112.
Ferraioli, G., Tinelli, C., Dal Bello, B., Zicchetti, M., Filice, G., Filice, C., & Liver Fibrosis Study Group. (2012). Accuracy of real‐time shear wave elastography for assessing liver fibrosis in chronic hepatitis C: a pilot study. Hepatology, 56(6), 2125-2133.
Araújo, A. R., Rosso, N., Bedogni, G., Tiribelli, C., & Bellentani, S. (2018). Global epidemiology of non‐alcoholic fatty liver disease/non‐alcoholic steatohepatitis: What we need in the future. Liver International, 38, 47-51.
Povsic, M., Wong, O. Y., Perry, R., & Bottomley, J. (2019). A Structured Literature Review of the Epidemiology and Disease Burden of Non-Alcoholic Steatohepatitis (NASH). Advances in therapy, 1-21.
Arab, J. P., Arrese, M., & Trauner, M. (2018). Recent insights into the pathogenesis of nonalcoholic fatty liver disease. Annual Review of Pathology: Mechanisms of Disease, 13, 321-350.
Darweesh, S. K., AbdElAziz, R. A., Abd-ElFatah, D. S., AbdElazim, N. A., Fathi, S. A., Attia, D., & AbdAllah, M. (2019). Serum cytokeratin-18 and its relation to liver fibrosis and steatosis diagnosed by FibroScan and controlled attenuation parameter in nonalcoholic fatty liver disease and hepatitis C virus patients. European journal of gastroenterology & hepatology, 31(5), 633-641.
Tada, T., Kumada, T., Toyoda, H., Saibara, T., Ono, M., & Kage, M. (2018). New scoring system combining the FIB-4 index and cytokeratin-18 fragments for predicting steatohepatitis and liver fibrosis in patients with nonalcoholic fatty liver disease. Biomarkers, 23(4), 328-334.
European Association for the Study of the Liver, & European Association for the Study of Diabetes (EASD. (2016). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Obesity facts, 9(2), 65-90.
Yousef, M. H., Al Juboori, A., Albarrak, A. A., Ibdah, J. A., & Tahan, V. (2017). Fatty liver without a large “belly”: Magnified review of non-alcoholic fatty liver disease in non-obese patients. World journal of gastrointestinal pathophysiology, 8(3), 100.
"Inter Collegas" is an open access journal: all articles are published in open access without an embargo period, under the terms of the CC BY-NC-SA (Creative Commons Attribution ‒ Noncommercial ‒ Share Alike) license; the content is available to all readers without registration from the moment of its publication. Electronic copies of the archive of journals are placed in the repositories of the KhNMU and V.I. Vernadsky National Library of Ukraine.
Copyright Agreement
1. This Agreement on the transfer of rights to use the work from the Co-authors to the publisher (hereinafter the Agreement) is concluded between all the Co-authors of the work, represented by the Corresponding Author, and Kharkiv National Medical University (hereinafter the University), represented by an authorized representative of the Editorial Board of scientific journals (hereinafter the Editorial Board).
2. This Agreement is an accession agreement within the meaning of clause 1 of Article 634 of the Civil Code of Ukraine: that is, a contract, "the terms of which are established by one of the parties in forms or other standard forms, which can be concluded only by joining the other party to the proposed contract as a whole. The other party cannot offer its terms of the contract." The party that established the terms of this contract is the University.
3. If there is more than one author, the authors choose the Corresponding Author, who communicates with the Editorial Board on his own behalf and on behalf of all Co-authors regarding the publication of a written work of a scientific nature (article or review, hereinafter referred to as the Work).
4. The contract begins from the moment of submission of the manuscript of the Work by the Corresponding Author to the Editorial Board, which confirms the following:
4.1. all Co-authors of the Work are familiar with and agree with its content, at all stages of reviewing and editing the manuscript and the existence of the published Work;
4.2. all Co-authors of the Work are familiar with and agree to the terms of this Agreement.
5. The published Work is in electronic form in public access on the websites of the University and any websites and electronic databases in which the Work is posted by the University and is available to readers under the terms of the "Creative Commons" license (Attribution NonCommercial Sharealike 4.0 International)" or more free licenses "Creative Commons 4.0".
6. The Corresponding Author transfers, and the University receives, the non-exclusive property right to use the Work by placing the latter on the University's websites for the entire term of copyright. The University participates in the creation of the final version of the Work by reviewing and editing the manuscript of the article or review provided to the Editorial Board by the Corresponding Author, translating the Work into any languages. For the participation of the University in the finalization of the Work, the Co-authors agree to pay the invoice issued to them by the University, if such payment is provided by the University. The size and procedure of such payment are not the subject of this contract.
7. The University has the right to reproduce the Work or its parts in electronic and printed forms, to make copies, permanent archival storage of the Work, distribution of the Work on the Internet, repositories, scientometric databases, commercial networks, including for monetary compensation from third parties.
8. The co-authors guarantee that the manuscript of the Work does not use works whose copyright belongs to third parties.
9. The authors of the Work guarantee that at the time of submission of the manuscript of the Work to the Editorial Board, the property rights to the Work belong only to them, neither in whole nor in part have they been transferred to anyone (not alienated), they are not the subject of a lien, litigation or claims by third parties.
10. The Work may not be posted on the University's website if it violates a person's right to the privacy of his personal and family life, harms public order and health.
11. The work may be withdrawn by the Editorial Board from the University websites, libraries and electronic databases where it was placed by the Editorial Board, in cases of detection of violations of the ethics of the authors and researchers, without any compensation for the losses of the Co-authors. At the time of submission of the manuscript to the Editorial Board and all stages of its editing and review, the manuscript must not have already been published or submitted to other editorial offices.
12. The right transferred under this Agreement extends to the territory of Ukraine and foreign countries.
13. The rights of Co-authors include the requirement to indicate their names on all copies of the Work or during any public use or public mention of the Work; the requirement to preserve the integrity of the Work; legal opposition to any distortion or other encroachment on the Work, which may harm the honor and reputation of the Co-authors.
14. Co-authors have the right to control their personal non-property rights by familiarizing themselves with the text (content) and form of the Work before its publication on the University's website, when transferring it to a printing company for reproduction or when using the Work in other ways.
15. The Co-authors, in addition to the property rights not transferred under this Agreement and taking into account the non-exclusive nature of the rights transferred under this Agreement, retain the property rights to finalize the Work and to use certain parts of the Work in other works created by the Co-authors.
16. The Co-authors are obliged to notify the Editorial Board of all errors in the Work, discovered by them independently after the publication of the Work, and to take all measures to eliminate such errors as soon as possible.
17. The University undertakes to indicate the names of the Co-authors on all copies of the Work during any public use of the Work. The list of Co-authors may be shortened according to the rules for the formation of bibliographic descriptions determined by the University or third parties.
18. The University undertakes not to violate the integrity of the Work, to agree with the Corresponding Author on all changes made to the Work during processing and editing.
19. In case of violation of their obligations under this Agreement, its parties bear the responsibility defined by this Agreement and the current legislation of Ukraine. All disputes under the Agreement are resolved through negotiations, and if the negotiations do not resolve the dispute – in the courts of the city of Kharkiv.
20. The parties are not responsible for the violation of their obligations under this Agreement, if it occurred through no fault of theirs. The party is considered innocent if it proves that it has taken all measures dependent on it for the proper fulfillment of the obligation.
21. The Co-authors are responsible for the truthfulness of the facts, quotes, references to legislative and regulatory acts, other official documentation, the scientific validity of the Work, all types of responsibility to third parties who have claimed their rights to the Work. The co-authors reimburse the University for all costs caused by claims of third parties for infringement of copyright and other rights to the Work, as well as additional material costs related to the elimination of identified defects.