<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Therapy</journal-id><journal-title-group><journal-title xml:lang="en">Therapy</journal-title><trans-title-group xml:lang="ru"><trans-title>Терапия</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2412-4036</issn><issn publication-format="electronic">2713-1823</issn><publisher><publisher-name xml:lang="en">Bionika Media</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">717596</article-id><article-id pub-id-type="doi">10.18565/therapy.2026.5.80-91</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>ORIGINAL STUDIES</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Pleiotropic effects of hymecromone in the treatment of chronic liver and biliary tract diseases</article-title><trans-title-group xml:lang="ru"><trans-title>Плейотропные эффекты гимекромона в терапии хронических заболеваний печени и билиарного тракта</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6150-1808</contrib-id><name-alternatives><name xml:lang="en"><surname>Plotnikova</surname><given-names>Ekaterina Y.</given-names></name><name xml:lang="ru"><surname>Плотникова</surname><given-names>Екатерина Юрьевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Dr. Sci. (Medicine), professor, professor of the Department of postgraduate education and nursing, head of the clinical gastroenterology course</p></bio><bio xml:lang="ru"><p>д. м. н., профессор, профессор кафедры последипломного образования и сестринского дела, руководитель курса клинической гастроэнтерологии</p></bio><email>eka-pl@rambler.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3105-4645</contrib-id><name-alternatives><name xml:lang="en"><surname>Vologzhanina</surname><given-names>Lyudmila G.</given-names></name><name xml:lang="ru"><surname>Вологжанина</surname><given-names>Людмила Георгиевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD (Medicine), associate professor of the Department of faculty therapy No. 1</p></bio><bio xml:lang="ru"><p>к. м. н., доцент кафедры факультетской терапии № 1</p></bio><email>ludovica@mail.ru</email><xref ref-type="aff" rid="aff2"/><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Druzhinina</surname><given-names>Sofia R.</given-names></name><name xml:lang="ru"><surname>Дружинина</surname><given-names>Софья Романовна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, gastroenterologist</p></bio><bio xml:lang="ru"><p>врач-гастроэнтеролог</p></bio><email>eka-pl@rambler.ru</email><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2494-8694</contrib-id><contrib-id contrib-id-type="spin">8327-3979</contrib-id><name-alternatives><name xml:lang="en"><surname>Sinkov</surname><given-names>Maxim A.</given-names></name><name xml:lang="ru"><surname>Синьков</surname><given-names>Максим Алексеевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD (Medicine), cardiovascular surgeon</p></bio><bio xml:lang="ru"><p>к. м. н., сердечно-сосудистый хирург</p></bio><email>fox2you@mail.ru</email><xref ref-type="aff" rid="aff4"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7255-7794</contrib-id><name-alternatives><name xml:lang="en"><surname>Kotelevtsev</surname><given-names>Yuri V.</given-names></name><name xml:lang="ru"><surname>Котелевцев</surname><given-names>Юрий Васильевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Dr. Sci. (Biology), professor, Center for Biomedical Technologies</p></bio><bio xml:lang="ru"><p>д. б. н., профессор</p></bio><email>y.kotelevtsev@skoltech.ru</email><xref ref-type="aff" rid="aff5"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Kemerovo State Medical University</institution></aff><aff><institution xml:lang="ru">ФГБОУ ВО «Кемеровский государственный медицинский университет» Минздрава России</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Academician E.A. Wagner Perm State Medical University</institution></aff><aff><institution xml:lang="ru">ФГБОУ ВО «Пермский государственный медицинский университет имени академика Е.А. Вагнера» Минздрава России</institution></aff></aff-alternatives><aff-alternatives id="aff3"><aff><institution xml:lang="en">GASTROTSENTER LLC</institution></aff><aff><institution xml:lang="ru">ООО «ГАСТРОЦЕНТР»</institution></aff></aff-alternatives><aff-alternatives id="aff4"><aff><institution xml:lang="en">Research Institute for Complex Issues of Cardiovascular Diseases</institution></aff><aff><institution xml:lang="ru">ФГБНУ «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний»</institution></aff></aff-alternatives><aff-alternatives id="aff5"><aff><institution xml:lang="en">Center for Biomedical Technologies, Skolkovo Institute of Science and Technology (Skoltech)</institution></aff><aff><institution xml:lang="ru">Центр био- и медицинских технологий, Сколковский институт науки и технологий (Сколтех)</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2026-08-29" publication-format="electronic"><day>29</day><month>08</month><year>2026</year></pub-date><volume>12</volume><issue>5</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>80</fpage><lpage>91</lpage><history><date date-type="received" iso-8601-date="2026-08-28"><day>28</day><month>08</month><year>2026</year></date><date date-type="accepted" iso-8601-date="2026-08-28"><day>28</day><month>08</month><year>2026</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2026, “Bionika Media” LLC</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2026, ООО «Бионика Медиа»</copyright-statement><copyright-year>2026</copyright-year><copyright-holder xml:lang="en">“Bionika Media” LLC</copyright-holder><copyright-holder xml:lang="ru">ООО «Бионика Медиа»</copyright-holder><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://journals.eco-vector.com/2412-4036/about/editorialPolicies</ali:license_ref></license></permissions><self-uri xlink:href="https://journals.eco-vector.com/2412-4036/article/view/717596">https://journals.eco-vector.com/2412-4036/article/view/717596</self-uri><abstract xml:lang="en"><p>Liver fibrosis is a common end result of chronic hepatocyte damage. Clinical progress in the development of anti-fibrosis drugs is gaining momentum: various pharmaceutical products, including hymecromone (4-MU) are belonging to that group.</p> <p><bold>The aim:</bold> to evaluate the anti-inflammatory and antifibrotic efficacy of hymecromone in patients with combined biliary and hepatic pathology.</p> <p><bold>Material and methods.</bold> 55 patients (31 females and 24 males) aged 18–75 years with chronic hepatitis of various etiologies and liver fibrosis (F 1–4) associated with biliary pathology were involved in the study. Twenty of them completed the study. All participants were prescribed hymecromone 200 mg three times daily for 3 weeks, followed by a 1-week break; the course was repeated for 6 months. All patients also received ursodeoxycholic acid at a dose of 10 mg/kg body weight at night continuously for 6 months.</p> <p><bold>Results. </bold>All patients reported improved well-being, increased physical activity, and increased work capacity during the treatment period. They also experienced a statistically significant decrease in biochemical markers (p = 0.001–0.049) and positive statistically significant changes in fibroelastometry parameters (p &lt; 0.001) after 6 months of observation.</p> <p><bold>Conclusion. </bold>Our treatment regimen demonstrated significant antifibrotic efficacy (p = 0.001) and was accompanied by a statistically significant reduction in liver markers. It is necessary to continue the further studies on the use of hymecromone (4-MU) in chronic liver diseases.</p></abstract><trans-abstract xml:lang="ru"><p>Фиброз печени является распространенным конечным результатом хронического повреждения гепатоцитов. Клинический прогресс в разработке препаратов против фиброза печени набирает обороты: к ним относятся различные лекарственных средств, включая гимекромон (4-MU).</p> <p><bold>Цель </bold>– оценить противовоспалительную и антифибротическую эффективность гимекромона у пациентов с сочетанной патологией билиарного тракта и печени.</p> <p><bold>Материалы и методы. </bold>В исследовании приняли участие 55 пациентов (31 женщина и 24 мужчины) 18–75 лет с хроническими гепатитами различной этиологии и фиброзом печени (F 1–4) в сочетании с билиарной патологией. Исследование закончили 20 пациентов. Всем участникам назначался гимекромон по 200 мг 3 раза/сут. в течение 3 нед. с последующим перерывом в 1 нед., курс повторялся в течение 6 мес. Также все пациенты получали урсодезоксихолевую кислоту в дозе 10 мг/кг массы тела на ночь постоянно на протяжении 6 мес.</p> <p><bold>Результаты. </bold>Все пациенты на фоне проводившейся терапии отмечали улучшение самочувствия, повышение физической активности и работоспособности. Также у них отмечались статистически значимое снижение уровня биохимических маркеров (р = 0,001–0,049) и положительные статистически значимые изменения показателей фиброэластометрии (p &lt; 0,001) через 6 мес. наблюдения.</p> <p><bold>Заключение. </bold>Назначенная нами схема лечения продемонстрировала выраженную антифибротическую эффективность (р = 0,001), а также сопровождалась статистически значимым снижением печеночных маркеров. Необходимо продолжать исследования по применению гимекромона (4-MU) при хронических заболеваниях печени.</p></trans-abstract><kwd-group xml:lang="en"><kwd>chronic hepatitis</kwd><kwd>liver fibrosis</kwd><kwd>biliary tract pathology</kwd><kwd>cytolysis syndrome</kwd><kwd>hymecromone</kwd><kwd>pleiotropic effects of hymecromone</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>хронический гепатит</kwd><kwd>фиброз печени</kwd><kwd>патология билиарного тракта</kwd><kwd>синдром цитолиза</kwd><kwd>гимекромон</kwd><kwd>плейотропные эффекты гимекромона</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Lambrecht J, van Grunsven LA, Tacke F. Current and emerging pharmacotherapeutic interventions for the treatment of liver fibrosis. Expert Opin Pharmacother. 2020;21(13):1637–50. PMID: 32543284. https://doi.org/10.1080/14656566.2020.1774553</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Roehlen N, Crouchet E, Baumert TF. Liver fibrosis: mechanistic concepts and therapeutic perspectives. Cells. 2020;9(4):875. PMID: 32260126. PMCID: PMC7226751. https://doi.org/10.3390/cells9040875</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Zhao J, Qi YF, Yu YR. STAT3: A key regulator in liver fibrosis. Ann Hepatol. 2021;21:100224. PMID: 32702499. https://doi.org/10.1016/j.aohep.2020.06.010</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Chen S, Wu Z, Zhang J, Lin Y, Xie J, Yin D, Zhu Y. Research and application of medicines for treating liver fibrosis: Current status and prospects. Front Pharmacol. 2025;16:1582258. PMID: 40703362. PMCID: PMC12283635. https://doi.org/10.3389/fphar.2025.1582258</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Jeon S, Carr R. Alcohol effects on hepatic lipid metabolism. J Lipid Res. 2020;61(4):470–79. PMID: 32029510. PMCID: PMC7112138. https://doi.org/10.1194/jlr.R119000547</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Odenwald MA, Paul S. Viral hepatitis: Past, present, and future. World J Gastroenterol. 2022;28(14):1405–29. PMID: 35582678. PMCID: PMC9048475. https://doi.org/10.3748/wjg.v28.i14.1405</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Pouwels S, Sakran N, Graham Y, Leal A, Pintar T, Yang W et al. Non-alcoholic fatty liver disease (NAFLD): A review of pathophysiology, clinical management and effects of weight loss. BMC Endocr Disord. 2022;22(1):63. PMID: 35287643. PMCID: PMC8919523. https://doi.org/10.1186/s12902-022-00980-1</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Ahmed A, Wong RJ, Harrison SA. Nonalcoholic fatty liver disease review: Diagnosis, treatment, and outcomes. Clin Gastroenterol Hepatol. 2015;13(12):2062–70. PMID: 26226097. https://doi.org/10.1016/j.cgh.2015.07.029</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Bandmann O, Weiss KH, Kaler SG. Wilson’s disease and other neurological copper disorders. Lancet Neurol. 2015;14(1):103–13. PMID: 25496901. PMCID: PMC4336199. https://doi.org/10.1016/S1474-4422(14)70190-5</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Kane SF, Roberts C, Paulus R. Hereditary hemochromatosis: Rapid evidence review. Am Fam Physician. 2021;104(3):263–70. PMID: 34523883.</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Carbone M, Neuberger JM. Autoimmune liver disease, autoimmunity and liver transplantation. J Hepatol. 2014;60(1):210–23. PMID: 24084655. https://doi.org/10.1016/j.jhep.2013.09.020</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Sanyal AJ, Castera L, Wong VW. Noninvasive assessment of liver fibrosis in NAFLD. Clin Gastroenterol Hepatol. 2023;21(8):2026–39. PMID: 37062495. https://doi.org/10.1016/j.cgh.2023.03.042</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Kaplan DE, Teerlink CC, Schwantes-An TH, Norden-Krichmar TM, DuVall SL, Morgan TR et al. Clinical and genetic risk factors for progressive fibrosis in metabolic dysfunction-associated steatotic liver disease. Hepatol Commun. 2024;8(7):e0487. PMID: 38967582. PMCID: PMC11227360. https://doi.org/10.1097/HC9.0000000000000487</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Ericson E, Bergenholm L, Andreasson AC, Dix CI, Knochel J, Hansson SF et al. Hepatic patatin-like phospholipase domain-containing 3 levels are increased in I148M risk allele carriers and correlate with NAFLD in humans. Hepatol Commun. 2022;6(10):2689–701. PMID: 35833455. PMCID: PMC9512469. https://doi.org/10.1002/hep4.2032</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Liu J, Ginsberg HN, Reyes-Soffer G. Basic and translational evidence supporting the role of TM6SF2 in VLDL metabolism. Curr Opin Lipidol. 2024;35(3):157–61. PMID: 38465912. PMCID: PMC11168781. https://doi.org/10.1097/MOL.0000000000000930</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Fabbrini E, Rady B, Koshkina A, Jeon JY, Ayyar VS, Gargano C et al. Phase 1 trials of PNPLA3 siRNA in I148M homozygous patients with MAFLD. N Engl J Med. 2024;391(5):475–76. PMID: 39083780. https://doi.org/10.1056/NEJMc2402341</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Moran-Salvador E, Mann J. Epigenetics and liver fibrosis. Cell Mol Gastroenterol Hepatol. 2017;4(1):125–34. PMID: 28593184. PMCID: PMC5453904. https://doi.org/10.1016/j.jcmgh.2017.04.007</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Barchetta I, Zampieri M, Cimini FA, Dule S, Sentinelli F, Passarella G et al. Association between active DNA demethylation and liver fibrosis in individuals with metabolic-associated steatotic liver disease (MASLD). Int J Mol Sci. 2025;26(3):1271. PMID: 39941038. PMCID: PMC11818491. https://doi.org/10.3390/ijms26031271</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Akkız H, Gieseler RK, Canbay A. Liver fibrosis: From basic science towards clinical progress, focusing on the central role of hepatic stellate cells. Int J Mol Sci. 2024;25(14):7873. PMID: 39063116. PMCID: PMC11277292. https://doi.org/10.3390/ijms25147873</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Liu Y, Wen D, Ho C, Yu L, Zheng D, O’Reilly S et al. Epigenetics as a versatile regulator of fibrosis. J Transl Med. 2023;21(1):164. PMID: 36864460. PMCID: PMC9983257. https://doi.org/10.1186/s12967-023-04018-5</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Li H, Liu T, Yang Y, Cho WC, Flynn RJ, Harandi MF et al. Interplays of liver fibrosis-associated microRNAs: Molecular mechanisms and implications in diagnosis and therapy. Genes Dis. 2022;10(4):1457–69. PMID: 37397560. PMCID: PMC10311052. https://doi.org/10.1016/j.gendis.2022.08.013</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Rodimova S, Mikhailova L, Arabuli K, Kozlov D, Kozlova V, Kuzmin D et al. MicroRNA-200a as a therapeutic agent for acute and chronic liver pathologies and regeneration. Biomaterials. 2026;331:124125. PMID: 41855855. https://doi.org/10.1016/j.biomaterials.2026.124125</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Schwabe RF, Luedde T. Apoptosis and necroptosis in the liver: a matter of life and death. Nat Rev Gastroenterol Hepatol. 2018;15(12):738–52. PMID: 30250076. PMCID: PMC6490680. https://doi.org/10.1038/s41575-018-0065-y</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Woolbright BL, Jaeschke H. Role of the inflammasome in acetaminophen-induced liver injury and acute liver failure. J Hepatol. 2017;66(4):836–48. PMID: 27913221. PMCID: PMC5362341. https://doi.org/10.1016/j.jhep.2016.11.017</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Chen M, Zhong W, Xu W. Alcohol and the mechanisms of liver disease. J Gastroenterol Hepatol. 2023;38(8):1233–40. PMID: 37423758. https://doi.org/10.1111/jgh.16282</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Banerjee A, Farci P. Fibrosis and hepatocarcinogenesis: Role of gene-environment interactions in liver disease progression. Int J Mol Sci. 2024;25(16):8641. PMID: 39201329. PMCID: PMC11354981. https://doi.org/10.3390/ijms25168641</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Paradies G, Paradies V, Ruggiero FM, Petrosillo G. Oxidative stress, cardiolipin and mitochondrial dysfunction in nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20(39):14205–18. PMID: 25339807. PMCID: PMC4202349. https://doi.org/10.3748/wjg.v20.i39.14205</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Zheng H, Sechi LA, Navarese EP, Casu G, Vidili G. Metabolic dysfunction-associated steatotic liver disease and cardiovascular risk: A comprehensive review. Cardiovasc Diabetol. 2024;23(1):346. PMID: 39342178. PMCID: PMC11439309. https://doi.org/10.1186/s12933-024-02434-5</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Zhao YQ, Deng XW, Xu GQ, Lin J, Lu HZ, Chen J. Mechanical homeostasis imbalance in hepatic stellate cells activation and hepatic fibrosis. Front Mol Biosci. 2023;10:1183808. PMID: 37152902. PMCID: PMC10157180. https://doi.org/10.3389/fmolb.2023.1183808</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Yang AT, Kim YO, Yan XZ, Abe H, Aslam M, Park KS et al. Fibroblast activation protein activates macrophages and promotes parenchymal liver inflammation and fibrosis. Cell Mol Gastroenterol Hepatol. 2023;15(4):841–67. PMID: 36521660. PMCID: PMC9972574. https://doi.org/10.1016/j.jcmgh.2022.12.005</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Liu X, Liu D, Tan C, Feng W. Gut microbiome-based machine learning for diagnostic prediction of liver fibrosis and cirrhosis: A systematic review and meta-analysis. BMC Med Inform Decis Mak. 2023;23(1):294. PMID: 38115019. PMCID: PMC10731850. https://doi.org/10.1186/s12911-023-02402-1</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Fuchs CD, Simbrunner B, Baumgartner M, Campbell C, Reiberger T, Trauner M. Bile acid metabolism and signalling in liver disease. J Hepatol. 2025;82(1):134–53. PMID: 39349254. https://doi.org/10.1016/j.jhep.2024.09.032</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Tang YL, Zhu L, Tao Y, Lu W, Cheng H. Role of targeting TLR4 signaling axis in liver-related diseases. Pathol Res Pract. 2023;244:154410. PMID: 36917917. https://doi.org/10.1016/j.prp.2023.154410</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Wang XX, Xie C, Libby AE, Ranjit S, Levi J, Myakala K et al. The role of FXR and TGR5 in reversing and preventing progression of Western diet-induced hepatic steatosis, inflammation, and fibrosis in mice. J Biol Chem. 2022;298(11):102530. PMID: 36209823. PMCID: PMC9638804. https://doi.org/10.1016/j.jbc.2022.102530</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>Hizo GH, Rampelotto PH. The impact of probiotic Bifidobacterium on liver diseases and the microbiota. Life (Basel). 2024;14(2):239. PMID: 38398748. PMCID: PMC10890151. https://doi.org/10.3390/life14020239</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Gleeson J, Barry J, O’Reilly S. Use of liver imaging and biopsy in clinical practice. N Engl J Med. 2017;377(23):2296. PMID: 29215220. https://doi.org/10.1056/NEJMc1712445</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Wendum D, Lacombe K, Chevallier M, Callard P, Valet F, Miailhes P et al. Histological scoring of fibrosis and activity in HIV-chronic hepatitis B related liver disease: Performance of the METAVIR score assessed on virtual slides. J Clin Pathol. 2009;62(4):361–63. PMID: 19126564. https://doi.org/10.1136/jcp.2008.062349</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Scott DR, Levy MT. Liver transient elastography (Fibroscan): A place in the management algorithms of chronic viral hepatitis. Antivir Ther. 2010;15(1):1–11. PMID: 20167986. https://doi.org/10.3851/IMP1474</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Xu X, Jin J, Liu Y. Performance of FibroScan in grading steatosis and fibrosis in patients with nonalcoholic fatty liver disease: A meta-analysis. Arab J Gastroenterol. 2023;24(4):189–97. PMID: 37996351. https://doi.org/10.1016/j.ajg.2023.08.003</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>Liguori A, Esposto G, Ainora ME, Mignini I, Borriello R, Galasso L et al. Liver elastography for liver fibrosis stratification: A Comparison of three techniques in a biopsy-controlled MASLD Cohort. Biomedicines. 2025;13(1):138. PMID: 39857722. PMCID: PMC11762890. https://doi.org/10.3390/biomedicines13010138</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>Xiao H, Shi M, Xie Y, Chi X. Comparison of diagnostic accuracy of magnetic resonance elastography and Fibroscan for detecting liver fibrosis in chronic hepatitis B patients: A systematic review and meta-analysis. PLoS One. 2017;12(11):e0186660. PMID: 29107943. PMCID: PMC5673175. https://doi.org/10.1371/journal.pone.0186660</mixed-citation></ref><ref id="B42"><label>42.</label><mixed-citation>Castera L, Rinella ME, Tsochatzis EA. Noninvasive assessment of liver fibrosis. N Engl J Med. 2025;393(17):1715–29. PMID: 41160822. https://doi.org/10.1056/NEJMra2403308</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>Honda Y, Yoneda M, Kobayashi T, Iwaki M, Kawamura N, Nogami A et al. Meta-analysis of the diagnostic accuracy of serum type IV collagen 7S concentration for the staging of liver fibrosis in nonalcoholic fatty liver disease. Hepatol Res. 2023;53(3):219–27. PMID: 36378589. https://doi.org/10.1111/hepr.13857</mixed-citation></ref><ref id="B44"><label>44.</label><mixed-citation>Li W, Chi Y, Xiao X, Li J, Sun M, Sun S et al. Plasma FSTL-1 as a noninvasive diagnostic biomarker for patients with advanced liver fibrosis. Hepatology. 2025;82(3):669–82. PMID: 40833998. PMCID: PMC12356556. https://doi.org/10.1097/HEP.0000000000001167</mixed-citation></ref><ref id="B45"><label>45.</label><mixed-citation>Cerrito L, Galasso L, Iaccarino J, Pizzi A, Termite F, Esposto G et al. Present and future perspectives in the treatment of liver fibrosis. Pharmaceuticals (Basel). 2025;18(9):1321. PMID: 41011192. PMCID: PMC12472440. https://doi.org/10.3390/ph18091321</mixed-citation></ref><ref id="B46"><label>46.</label><mixed-citation>Qu J, Qin W, Dong M, Ma Z, Li S, Liu R et al. Liver fibrosis: Molecular pathogenesis and therapeutic interventions. MedComm. 2026;7(5):e70750. PMID: 42087905. PMCID: PMC13136092. https://doi.org/10.1002/mco2.70750</mixed-citation></ref><ref id="B47"><label>47.</label><mixed-citation>Wang X, Wang L, Geng L, Tanaka N, Ye B. Resmetirom ameliorates NASH-model mice by suppressing STAT3 and NF-κB signaling pathways in an RGS5-dependent manner. Int J Mol Sci. 2023;24(6):5843. PMID: 36982915. PMCID: PMC10058113. https://doi.org/10.3390/ijms24065843</mixed-citation></ref><ref id="B48"><label>48.</label><mixed-citation>Loomba R, Noureddin M, Kowdley KV, Kohli A, Sheikh A, Neff G et al.; for the ATLAS Investigators. Combination therapies including cilofexor and firsocostat for bridging fibrosis and cirrhosis attributable to NASH. Hepatology. 2021;73(2):625–43. PMID: 33169409. https://doi.org/10.1002/hep.31622</mixed-citation></ref><ref id="B49"><label>49.</label><mixed-citation>Gao YS, Qian MY, Wei QQ, Duan XB, Wang SL, Hu HY et al. WZ66, a novel acetyl-CoA carboxylase inhibitor, alleviates nonalcoholic steatohepatitis (NASH) in mice. Acta Pharmacol Sin. 2020;41(3):336–47. PMID: 31645659. PMCID: PMC7468331. https://doi.org/10.1038/s41401-019-0310-0</mixed-citation></ref><ref id="B50"><label>50.</label><mixed-citation>Newsome PN, Sanyal AJ, Engebretsen KA, Kliers I, Ostergaard L, Vanni D et al. Semaglutide 2.4 mg in participants with metabolic dysfunction-associated steatohepatitis: Baseline characteristics and design of the phase 3 ESSENCE trial. Aliment Pharmacol Ther. 2024;60(11–12):1525–33. PMID: 39412509. PMCID: PMC11599791. https://doi.org/10.1111/apt.18331</mixed-citation></ref><ref id="B51"><label>51.</label><mixed-citation>Desjardins EM, Wu J, Lavoie DCT, Ahmadi E, Townsend LK, Morrow MR et al. Combination of an ACLY inhibitor with a GLP-1R agonist exerts additive benefits on nonalcoholic steatohepatitis and hepatic fibrosis in mice. Cell Rep Med. 202;4(9):101193. PMID: 37729871. PMCID: PMC10518624. https://doi.org/10.1016/j.xcrm.2023.101193</mixed-citation></ref><ref id="B52"><label>52.</label><mixed-citation>Brown E, Heerspink HJL, Cuthbertson DJ, Wilding JPH. SGLT2 inhibitors and GLP-1 receptor agonists: Established and emerging indications. Lancet. 2021;398(10296):262–76. PMID: 34216571. https://doi.org/10.1016/S0140-6736(21)00536-5</mixed-citation></ref><ref id="B53"><label>53.</label><mixed-citation>Nguyen G, Park SY, Le CT, Park WS, Choi DH, Cho EH. Metformin ameliorates activation of hepatic stellate cells and hepatic fibrosis by succinate and GPR91 inhibition. Biochem Biophys Res Commun. 2018;495(4):2649–56. PMID: 29278707. https://doi.org/10.1016/j.bbrc.2017.12.143</mixed-citation></ref><ref id="B54"><label>54.</label><mixed-citation>Puengel T, Tacke F. Efruxifermin, an investigational treatment for fibrotic or cirrhotic nonalcoholic steatohepatitis (NASH). Expert Opin Investig Drugs. 2023;32(6):451–61. PMID: 37376813. https://doi.org/10.1080/13543784.2023.2230115</mixed-citation></ref><ref id="B55"><label>55.</label><mixed-citation>Loomba R, Sanyal AJ, Kowdley KV, Bhatt DL, Alkhouri N, Frias JP et al. Randomized, controlled trial of the FGF21 analogue pegozafermin in NASH. N Engl J Med. 2023;389(11):998–1008. PMID: 37356033. PMCID: PMC10718287. https://doi.org/10.1056/NEJMoa2304286</mixed-citation></ref><ref id="B56"><label>56.</label><mixed-citation>Ye HL, Zhang JW, Chen XZ, Wu PB, Chen L, Zhang G. Ursodeoxycholic acid alleviates experimental liver fibrosis involving inhibition of autophagy. Life Sci. 2020;242:117175. PMID: 31843528. https://doi.org/10.1016/j.lfs.2019.117175</mixed-citation></ref><ref id="B57"><label>57.</label><mixed-citation>Sanyal AJ, Ratziu V, Loomba R, Anstee QM, Kowdley KV, Rinella ME et al. Results from a new efficacy and safety analysis of the REGENERATE trial of obeticholic acid for treatment of pre-cirrhotic fibrosis due to non-alcoholic steatohepatitis. J Hepatol. 2023;79(5):1110–20. PMID: 37517454. https://doi.org/10.1016/j.jhep.2023.07.014</mixed-citation></ref><ref id="B58"><label>58.</label><mixed-citation>Loomba R, Bedossa P, Grimmer K, Kemble G, Bruno Martins E, McCulloch W et al. Denifanstat for the treatment of metabolic dysfunction-associated steatohepatitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Gastroenterol Hepatol. 2024;9(12):1090–100. PMID: 39396529. https://doi.org/10.1016/S2468-1253(24)00246-2</mixed-citation></ref><ref id="B59"><label>59.</label><mixed-citation>Okanoue T, Sakamoto M, Harada K, Inagaki M, Totsuka N, Hashimoto G, Kumada H. Efficacy and safety of apararenone (MT-3995) in patients with nonalcoholic steatohepatitis: A randomized controlled study. Hepatol Res. 2021;51(9):943–56. PMID: 34260795. https://doi.org/10.1111/hepr.13695</mixed-citation></ref><ref id="B60"><label>60.</label><mixed-citation>Fraser DA, Wang X, Lund J, Nikolic N, Iruarrizaga-Lejarreta M, Skjaeret T et al. A structurally engineered fatty acid, icosabutate, suppresses liver inflammation and fibrosis in NASH. J Hepatol. 2022;76(4):800–11. PMID: 34915054. https://doi.org/10.1016/j.jhep.2021.12.004</mixed-citation></ref><ref id="B61"><label>61.</label><mixed-citation>Scorletti E, Creasy KT, Vujkovic M, Vell M, Zandvakili I, Rader DJ et al. Dietary vitamin E intake is associated with a reduced risk of developing digestive diseases and nonalcoholic fatty liver disease. Am J Gastroenterol. 2022;117(6):927–30. PMID: 35288522. PMCID: PMC9177739. https://doi.org/10.14309/ajg.0000000000001726</mixed-citation></ref><ref id="B62"><label>62.</label><mixed-citation>Choi J, Nguyen VH, Przybyszewski E, Song J, Carroll A, Michta M et al. Statin use and risk of hepatocellular carcinoma and liver fibrosis in chronic liver disease. JAMA Intern Med. 2025;185(5):522–30. PMID: 40094696. PMCID: PMC11915111. https://doi.org/10.1001/jamainternmed.2025.0115</mixed-citation></ref><ref id="B63"><label>63.</label><mixed-citation>Navarro VJ, Belle SH, D’Amato M, Afdhal N, Brunt EM, Fried MW et al.; Silymarin in NASH and C Hepatitis (SyNCH) Study Group. Silymarin in non-cirrhotics with non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled trial. PLoS ONE 2019;14(10):e0223915. PMID: 31600349. PMCID: PMC6786547. https://doi.org/10.1371/journal.pone.0223915</mixed-citation></ref><ref id="B64"><label>64.</label><mixed-citation>Ramachandran G, Pottakkat B. Probiotics – a promising novel therapeutic approach in the management of chronic liver diseases. J Med Food. 2024;27(6):467–76. PMID: 38574254. https://doi.org/10.1089/jmf.2023.K.0129</mixed-citation></ref><ref id="B65"><label>65.</label><mixed-citation>Israelsen M, Madsen BS, Torp N, Johansen S, Hansen CD, Detlefsen S et al.; GALAXY; MicrobLiver Consortia. Rifaximin-α for liver fibrosis in patients with alcohol-related liver disease (GALA-RIF): A randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Gastroenterol Hepatol. 2023;8(6):523–32. PMID: 36893774. PMCID: PMC10172147. https://doi.org/10.1016/S2468-1253(23)00010-9</mixed-citation></ref><ref id="B66"><label>66.</label><mixed-citation>Ng SC, Xu Z, Mak JWY, Yang K, Liu Q, Zuo T et al. Microbiota engraftment after faecal microbiota transplantation in obese subjects with type 2 diabetes: A 24-week, double-blind, randomised controlled trial. Gut. 2022;71(4):716–23. PMID: 33785557. https://doi.org/10.1136/gutjnl-2020-323617</mixed-citation></ref><ref id="B67"><label>67.</label><mixed-citation>Tsitrina AA, Halimani N, Andreichenko IN, Sabirov M, Nesterchuk M, Dashenkova NO et al. 4-methylumbelliferone targets revealed by public data analysis and liver transcriptome sequencing. Int J Mol Sci. 2023;24(3):2129. PMID: 36768453. PMCID: PMC9917189. https://doi.org/10.3390/ijms24032129</mixed-citation></ref><ref id="B68"><label>68.</label><mixed-citation>Плотникова Е.Ю., Вологжанина Л.Г., Азанов А., Сухих А.С. Коморбидность заболеваний печени и билиарного тракта. Фарматека. 2025;32(1):76–86. [Plotnikova EYu, Vologzhanina LG, Azanov AZ, Sukhikh AS. Comorbidity of liver and biliary tract diseases. Farmateka. 2025;32(1):76–86 (In Russ.)]. EDN: SBEDSW. https://doi.org/10.18565/pharmateca.2025.1.76-86</mixed-citation></ref><ref id="B69"><label>69.</label><mixed-citation>Плотникова Е.Ю. Известный и неизвестный гимекромон. Consilium Medicum. 2024;26(5):324–330. [Plotnikova EYu. Known and unknown hymecromone. A review. Consilium Medicum. 2024;26(5):324–330 (In Russ.)]. EDN: OPOFNF. https://doi.org/10.26442/20751753.2024.5.202877</mixed-citation></ref><ref id="B70"><label>70.</label><mixed-citation>Охлобыстин А.В., Шульпекова Ю.О., Зольникова О.Ю., Ивашкин В.Т. Роль гимекромона в лечении дисфункции билиарного тракта: систематический обзор и метаанализ клинических исследований. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2026;36(2):46–58. [Okhlobystin AV, Shulpekova YuO, Zolnikova OYu, Ivashkin VT. The role of hymecromone in the treatment of biliary tract dysfunction: A systematic review and meta-analysis of clinical trials. Rossiyskiy zhurnal gastroenterologii, gepatologii, koloproktologii = Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2026;36(2):46–58 (In Russ.)]. EDN: NHKKDNю https://doi.org/10.22416/1382-4376-2026-1995-5633</mixed-citation></ref><ref id="B71"><label>71.</label><mixed-citation>Плотникова Е.Ю., Вологжанина Л.Г., Азанов А., Сухих А.С. Коморбидность заболеваний печени и билиарного тракта. Фарматека. 2025;32(1):76–86. [Plotnikova EYu, Vologzhanina LG, Azanov AZ, Sukhikh AS. Comorbidity of liver and biliary tract diseases. Farmateka. 2025;32(1):76–86 (In Russ.)]. EDN: SBEDSW. https://doi.org/10.18565/pharmateca.2025.1.76-86</mixed-citation></ref><ref id="B72"><label>72.</label><mixed-citation>Kim SM, Song GY, Shim A, Lee JH, Eom CB, Liu C et al. Hyaluronan synthase 2, a target of miR-200c, promotes carbon tetrachloride-induced acute and chronic liver inflammation via regulation of CCL3 and CCL4. Exp Mol Med. 2022;54(6):739–52. PMID: 35662287. PMCID: PMC9256637. https://doi.org/10.1038/s12276-022-00781-5</mixed-citation></ref><ref id="B73"><label>73.</label><mixed-citation>Andreichenko IN, Tsitrina AA, Fokin AV, Gabdulkhakova AI, Maltsev DI, Perelman GS et al. 4-methylumbelliferone prevents liver fibrosis by affecting hyaluronan deposition, FSTL1 expression and cell localization. Int J Mol Sci. 2019;20(24):6301. PMID: 31847129. PMCID: PMC6941058. https://doi.org/10.3390/ijms20246301</mixed-citation></ref><ref id="B74"><label>74.</label><mixed-citation>Kultti A, Pasonen-Seppänen S, Jauhiainen M, Rilla KJ, Karna R, Pyoria E et al. 4-Methylumbelliferone inhibits hyaluronan synthesis by depletion of cellular UDP-glucuronic acid and downregulation of hyaluronan synthase 2 and 3. Exp Cell Res. 2009;315(11):1914–23. PMID: 19285976. https://doi.org/10.1016/j.yexcr.2009.03.002</mixed-citation></ref><ref id="B75"><label>75.</label><mixed-citation>Rosser JI, Nagy N, Goel R, Kaber G, Demirdjian S, Saxena J et al. Oral hymecromone decreases hyaluronan in human study participants. J Clin Invest. 2022;132(9):e157983. PMID: 35499083. PMCID: PMC9057598. https://doi.org/10.1172/JCI157983</mixed-citation></ref><ref id="B76"><label>76.</label><mixed-citation>Nagy N, Gurevich I, Kuipers HF, Ruppert SM, Marshall PL, Xie BJ et al. 4-Methylumbelliferyl glucuronide contributes to hyaluronan synthesis inhibition. J Biol Chem. 2019;294(19):7864–77. PMID: 30914479. PMCID: PMC6514619. https://doi.org/10.1074/jbc.RA118.006166</mixed-citation></ref></ref-list></back></article>
