<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" 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" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">medsovet</journal-id><journal-title-group><journal-title xml:lang="ru">Медицинский Совет</journal-title><trans-title-group xml:lang="en"><trans-title>Meditsinskiy sovet = Medical Council</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2079-701X</issn><issn pub-type="epub">2658-5790</issn><publisher><publisher-name>REMEDIUM GROUP Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.21518/2079-701X-2019-21-160-165</article-id><article-id custom-type="elpub" pub-id-type="custom">medsovet-5489</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ГАСТРОЭНТЕРОЛОГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>GASTROENTEROLOGY</subject></subj-group></article-categories><title-group><article-title>Опыт применения урсодезоксихолевой кислоты для растворения желчных камней</article-title><trans-title-group xml:lang="en"><trans-title>Experience of using ursodeoxycholic acid to dissolve gallstones</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9980-2294</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Цуканов</surname><given-names>В. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Tsukanov</surname><given-names>V. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Цуканов Владислав Владимирович, д.м.н., профессор, заведующий клиническим отделением патологии пищеварительной системы взрослых и детей</p><p>660022, Россия, Красноярск, ул. Партизана Железняка, д. 3Г</p></bio><bio xml:lang="en"><p>Vladislav V. Tsukanov, Dr. of Sci. (Med.), Professor, Head of Clinical Department of Digestive Pathology in Adults and Children</p><p>3G, Partizana Zheleznyaka St., Krasnoyarsk, 660022, Russia</p></bio><email xlink:type="simple">gastro@impn.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1954-6639</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Онучина</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Onuchina</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Онучина Елена Владимировна, д.м.н., профессор кафедры терапии и кардиологии</p><p>664079, Россия, Иркутск, микрорайон Юбилейный, д. 10</p></bio><bio xml:lang="en"><p>Elena V. Onuchina, Dr. of Sci. (Med.), Professor, Chair for Therapy and Cardiology</p><p>10, Yubileynyy Microdistrict, Irkutsk, 664079, Russia</p></bio><email xlink:type="simple">alek-a@mail.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6481-3196</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Васютин</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Vasyutin</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Васютин Александр Викторович, к.м.н., старший научный сотрудник клинического отделения патологии пищеварительной системы взрослых и детей</p><p>660022, Россия, Красноярск, ул. Партизана Железняка, д. 3Г</p></bio><bio xml:lang="en"><p>Aleksandr V. Vasyutin, Cand. of Sci. (Med.), Senior Resercher, Clinical Department of Digestive Pathology in Adults and Children</p><p>3G, Partizana Zheleznyaka St., Krasnoyarsk, 660022, Russia</p></bio><email xlink:type="simple">alexander@kraslan.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7518-1895</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Тонких</surname><given-names>Ю. Л.</given-names></name><name name-style="western" xml:lang="en"><surname>Tonkikh</surname><given-names>Yu. L.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Тонких Юлия Леонгардовна, к.м.н., ведущий научный сотрудник клинического отделения патологии пищеварительной системы взрослых и детей</p><p>660022, Россия, Красноярск, ул. Партизана Железняка, д. 3Г</p></bio><bio xml:lang="en"><p>Yuliya L. Tonkikh, Cand. of Sci. (Med.), Lead Resercher, Clinical Department of Digestive Pathology in Adults and Children</p><p>3G, Partizana Zheleznyaka St., Krasnoyarsk, 660022, Russia</p></bio><email xlink:type="simple">tjulia@bk.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Красноярский научный центр Сибирского отделения Российской академии наук, Научно-исследовательский институт медицинских проблем Севера</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Federal Research Center «Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences»</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Иркутская государственная медицинская академия последипломного образования – филиал Российской медицинской академии непрерывного профессионального образования</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Irkutsk State Medical Academy of Postgraduate Education - a branch of the Russian Medical Academy of Continuing Professional Education</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2019</year></pub-date><pub-date pub-type="epub"><day>26</day><month>01</month><year>2020</year></pub-date><volume>0</volume><issue>21</issue><fpage>160</fpage><lpage>165</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Цуканов В.В., Онучина Е.В., Васютин А.В., Тонких Ю.Л., 2020</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="ru">Цуканов В.В., Онучина Е.В., Васютин А.В., Тонких Ю.Л.</copyright-holder><copyright-holder xml:lang="en">Tsukanov V.V., Onuchina E.V., Vasyutin A.V., Tonkikh Y.L.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.med-sovet.pro/jour/article/view/5489">https://www.med-sovet.pro/jour/article/view/5489</self-uri><abstract><sec><title>Цель исследования</title><p>Цель исследования. С целью изучения эффективности растворения камней в желчном пузыре препаратом Урсосан выполнено 5-летнее проспективное исследование.</p></sec><sec><title>Материал и методы</title><p>Материал и методы. Пациенты, имевшие одиночные камни желчного пузыря, были рандоминизированы на группу А, в которой завершили исследование 47 человек (16 мужчин и 31 женщина, средний возраст 67,6 лет), и группу В – 41 человек 14 мужчин и 27 женщин, средний возраст 68,1 года). Все пациенты группы А на протяжении 5 лет непрерывно получали препарат урсодезоксихолевой кислоты Урсосан в дозе 10 мг на кг веса в сутки. Пациентам группы В не назначался Урсосан, эти лица пери- одически принимали курсы спазмолитиков. Клинический осмотр, лабораторные анализы, трансабдоминальное УЗИ печени и желчных путей осуществлялись до начала исследования, 2 раза в год в течение 5 лет и после окончания работы.</p></sec><sec><title>Результаты</title><p>Результаты. Через 5 лет лечения камни определялись у 10,6% пациентов в группе А. В группе В частота желчных камней через 5 лет терапии не изменилась, то есть конкременты определялись у всех пациентов (p&lt;0,001). В группе А к концу исследования множественные камни не наблюдались ни у одного из пациентов, тогда как в группе В через 5 лет множественные камни регистрировались у 2/3 пациентов. У пациентов в группе А регистрировалось отчетливое снижение частоты болевого синдрома и улучшение сократительной функции желчного пузыря в сравнении с лицами группы В к концу периода наблюдения. Профиль побочных явлений не отличался в группах А и В. Переносимость Урсосана в течение 5 лет непрерывного приема препарата была хорошей.</p></sec><sec><title>Выводы</title><p>Выводы. В 5-летнем проспективном исследовании мы получили 90%-ную эффективность Урсосана для растворения камней в желчном пузыре. Урсосан также предупреждал появление новых конкрементов и снижал частоту болевого синдрома, увеличивал сократительную функцию желчного пузыря и уменьшал потребность в холецистэктомиях к концу периода наблюдения.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Objective of the study</title><p>Objective of the study. A 5-year prospective study was aimed to evaluate the efficacy of Ursosan treatment for dissolving gallstones.</p></sec><sec><title>Material and methods</title><p>Material and methods. Patients who had single gallbladder stones were randomized to group A, in which 47 people completed the study (16 men and 31 women, median age is 67.6 years), and group B – 41 people 14 men and 27 women, median age is 68, 1 years). All patients of group A continuously received continuous treatment with ursodeoxycholic acid drug Ursosan at a dose of 10 mg /kg per day for 5 years. The patients of group D did not receive Ursosan; these individuals received periodic courses of spasmodic drugs. The patients passed clinical examination, laboratory tests, transabdominal ultrasound of the liver and biliary tract before the study, 2 times a year for 5 years and after the study.</p></sec><sec><title>Results</title><p>Results. After 5 years of treatment, stones were detected in 10.6% of patients in group A. In group B, the incidence of gallstones did not change after 5 years of treatment, that is, calculi were detected in all patients (p &lt;0.001). At the end of the study, no muldoi tiple stones were observed in any of the patients of group A, while multiple stones were detected in 2/3 of group B patients after 5 years of treatment. A distinct decrease in pain syndrome frequency and improvement in contractile function of the gallbladder were recorded in patients of group A as compared to the patients of group B by the end of the observation period. The side effect profile did not differ in groups A and B. The study showed good tolerance of Ursosan for 5 years of continuous administration of the drug.</p></sec><sec><title>Findings</title><p>Findings. The 5-year prospective study showed that Ursosan’s efficacy in dissolving gallstones accounted for 90%. Ursosan also prevented the formation of new calculi and reduced the frequency of pain, improved the gall-bladder contractile function and reduced the need for cholecystectomy by the end of the observation period.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>холелитиаз</kwd><kwd>лечение</kwd><kwd>УДХК</kwd><kwd>проспективное исследование</kwd><kwd>профилактика</kwd></kwd-group><kwd-group xml:lang="en"><kwd>cholelithiasis</kwd><kwd>treatment</kwd><kwd>UDCA</kwd><kwd>prospective study</kwd><kwd>prevention</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Baiu I., Hawn M.T. Choledocholithiasis. JAMA. 2018;320(14):1506. doi: 10.1001/jama.2018.11812.</mixed-citation><mixed-citation xml:lang="en">Baiu I., Hawn M.T. Choledocholithiasis. JAMA. 2018;320(14):1506. doi: 10.1001/jama.2018.11812.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Zheng Y., Xu M., Heianza Y., Ma W., Wang T., Sun D., Albert C.M., Hu F.B., Rexrode K.M., Manson J.E., Qi L. Gallstone disease and increased risk of mortality: Two large prospective studies in US men and women. J Gastroenterol Hepatol. 2018;33(11):1925-1931. doi: 10.1111/jgh.14264.</mixed-citation><mixed-citation xml:lang="en">Zheng Y., Xu M., Heianza Y., Ma W., Wang T., Sun D., Albert C.M., Hu F.B., Rexrode K.M., Manson J.E., Qi L. Gallstone disease and increased risk of mortality: Two large prospective studies in US men and women. J Gastroenterol Hepatol. 2018;33(11):1925-1931. doi: 10.1111/jgh.14264.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Nassar Y., Richter S. Management of complicated gallstones in the elderly: comparing surgical and non-surgical treatment options. Gastroenterol Rep (Oxf). 2019;7(3):205-211. doi: 10.1093/gastro/goy046.</mixed-citation><mixed-citation xml:lang="en">Nassar Y., Richter S. Management of complicated gallstones in the elderly: comparing surgical and non-surgical treatment options. Gastroenterol Rep (Oxf). 2019;7(3):205-211. doi: 10.1093/gastro/goy046.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Portincasa P., Ciaula A.D., Bonfrate L., Wang D.Q. Therapy of gallstone disease: What it was, what it is, what it will be. World J Gastrointest Pharmacol Ther. 2012,3(2):7-20. doi: 10.4292/wjgpt.v3.i2.7.</mixed-citation><mixed-citation xml:lang="en">Portincasa P., Ciaula A.D., Bonfrate L., Wang D.Q. Therapy of gallstone disease: What it was, what it is, what it will be. World J Gastrointest Pharmacol Ther. 2012,3(2):7-20. doi: 10.4292/wjgpt.v3.i2.7.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Tomida S., Abei M., Yamaguchi T., Matsuzaki Y., Shoda J., Tanaka N., Osuga T. Long-term ursodeoxycholic acid therapy is associated with reduced risk of biliary pain and acute cholecystitis in patients with gallbladder stones: a cohort analysis. Hepatology. 1999;30(1):6-13. doi: 10.1002/hep.510300108.</mixed-citation><mixed-citation xml:lang="en">Tomida S., Abei M., Yamaguchi T., Matsuzaki Y., Shoda J., Tanaka N., Osuga T. Long-term ursodeoxycholic acid therapy is associated with reduced risk of biliary pain and acute cholecystitis in patients with gallbladder stones: a cohort analysis. Hepatology. 1999;30(1):6-13. doi: 10.1002/hep.510300108.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Guarino M.P., Cong P., Cicala M., Alloni R., Carotti S., Behar J. Ursodeoxycholic acid improves muscle contractility and inflammation in symptomatic gallbladders with cholesterol gallstones. Gut. 2007;56(6):815-820. doi: 10.1136/gut.2006.109934.</mixed-citation><mixed-citation xml:lang="en">Guarino M.P., Cong P., Cicala M., Alloni R., Carotti S., Behar J. Ursodeoxycholic acid improves muscle contractility and inflammation in symptomatic gallbladders with cholesterol gallstones. Gut. 2007;56(6):815-820. doi: 10.1136/gut.2006.109934.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Chen X., Yan X.R., Zhang L.P. Ursodeoxycholic acid after common bile duct stones removal for prevention of recurrence: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2018;97(45): e13086. doi: 10.1097/MD.0000000000013086.</mixed-citation><mixed-citation xml:lang="en">Chen X., Yan X.R., Zhang L.P. Ursodeoxycholic acid after common bile duct stones removal for prevention of recurrence: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2018;97(45): e13086. doi: 10.1097/MD.0000000000013086.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Nabil T.M., Khalil A.H., Gamal K. Effect of oral ursodeoxycholic acid on cholelithiasis following laparoscopic sleeve gastrectomy for morbid obesity. Surg Obes Relat Dis. 2019;15(6):827-831. doi: 10.1016/j.soard.2019.03.028.</mixed-citation><mixed-citation xml:lang="en">Nabil T.M., Khalil A.H., Gamal K. Effect of oral ursodeoxycholic acid on cholelithiasis following laparoscopic sleeve gastrectomy for morbid obesity. Surg Obes Relat Dis. 2019;15(6):827-831. doi: 10.1016/j.soard.2019.03.028.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Della Penna A., Lange J., Hilbert J., Archid R., Königsrainer A., Quante M. Ursodeoxycholic Acid for 6 Months After Bariatric Surgery Is Impacting Gallstone Associated Morbidity in Patients with Preoperative Asymptomatic Gallstones. Obes Surg. 2019;29(4):1216-1221. doi: 10.1007/s11695-018-03651-0.</mixed-citation><mixed-citation xml:lang="en">Della Penna A., Lange J., Hilbert J., Archid R., Königsrainer A., Quante M. Ursodeoxycholic Acid for 6 Months After Bariatric Surgery Is Impacting Gallstone Associated Morbidity in Patients with Preoperative Asymptomatic Gallstones. Obes Surg. 2019;29(4):1216-1221. doi: 10.1007/s11695-018-03651-0.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Dosch A.R., Imagawa D.K., Jutric Z. Bile Metabolism and Lithogenesis: An Update. Surg Clin North Am. 2019;99(2):215-229. doi: 10.1016/j.suc.2018.12.003.</mixed-citation><mixed-citation xml:lang="en">Dosch A.R., Imagawa D.K., Jutric Z. Bile Metabolism and Lithogenesis: An Update. Surg Clin North Am. 2019;99(2):215-229. doi: 10.1016/j.suc.2018.12.003.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Цуканов В.В., Селиверстова Е.В., Догадин С.А. Показатели липидного состава сыворотки крови и желчи при заболеваниях желчевыводящих путей у больных сахарным диабетом. Режим доступа: https://elibrary.ru/item.asp?id=9133822.</mixed-citation><mixed-citation xml:lang="en">Tsukanov V.V., Seliverstova Е.V., Dogadin S.A. Lipid composition of blood serum and bile in biliary diseases in patients with diabetes mellitus. Terapevticheskiy arkhiv = Therapeutic Archive. 2005;77(2):15-18. (In Russ.) Available at: https://elibrary.ru/item.asp?id=9133822.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Цуканов В.В., Тонких Ю.Л., Бронникова Е.П., Манчук В.Т. Механизм нормолипидемии у северных народностей. Клиническая медицина. 1999;77(2):38-39.</mixed-citation><mixed-citation xml:lang="en">Tsukanov V.V., Tonkikh Yu.L., Bronnikova E.P., Manchuk V.T. The mechanism of normolipidemia in northerners. Klinicheskaya meditsina = Clinical Medicine. 1999;77(2):38-39. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Di Ciaula A., Wang D.Q., Portincasa P. Cholesterol cholelithiasis: part of a systemic metabolic disease, prone to primary prevention. Expert Rev Gastroenterol Hepatol. 2019;13(2):157-171. doi: 10.1080/17474124.2019.1549988.</mixed-citation><mixed-citation xml:lang="en">Di Ciaula A., Wang D.Q., Portincasa P. Cholesterol cholelithiasis: part of a systemic metabolic disease, prone to primary prevention. Expert Rev Gastroenterol Hepatol. 2019;13(2):157-171. doi: 10.1080/17474124.2019.1549988.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang Y., Jiang R., Zheng X., Lei S., Huang F., Xie G., Kwee S., Yu H., Farrar C., Sun B, Zhao A., Jia W. Ursodeoxycholic acid accelerates bile acid enterohepatic circulation. Br J Pharmacol. 2019;176(16):2848-2863. doi: 10.1111/bph.14705.</mixed-citation><mixed-citation xml:lang="en">Zhang Y., Jiang R., Zheng X., Lei S., Huang F., Xie G., Kwee S., Yu H., Farrar C., Sun B, Zhao A., Jia W. Ursodeoxycholic acid accelerates bile acid enterohepatic circulation. Br J Pharmacol. 2019;176(16):2848-2863. doi: 10.1111/bph.14705.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Simental-Mendía L.E., Simental-Mendía M., Sánchez-García A., Banach M., Serban M.C., Cicero A.F.G., Sahebkar A. Impact of ursodeoxycholic acid on circulating lipid concentrations: a systematic review and meta-analysis of randomized placebo-controlled trials. Lipids Health Dis. 2019;18(1):88. doi: 10.1186/s12944-019-1041-4.</mixed-citation><mixed-citation xml:lang="en">Simental-Mendía L.E., Simental-Mendía M., Sánchez-García A., Banach M., Serban M.C., Cicero A.F.G., Sahebkar A. Impact of ursodeoxycholic acid on circulating lipid concentrations: a systematic review and meta-analysis of randomized placebo-controlled trials. Lipids Health Dis. 2019;18(1):88. doi: 10.1186/s12944-019-1041-4.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Kim D.J., Chung H., Ji S.C., Lee S., Yu K.S., Jang I.J., Cho J.Y. Ursodeoxycholic acid exerts hepatoprotective effects by regulating amino acid, flavonoid, and fatty acid metabolic pathways. Metabolomics. 2019;15(3):30. doi: 10.1007/s11306-019-1494-5.</mixed-citation><mixed-citation xml:lang="en">Kim D.J., Chung H., Ji S.C., Lee S., Yu K.S., Jang I.J., Cho J.Y. Ursodeoxycholic acid exerts hepatoprotective effects by regulating amino acid, flavonoid, and fatty acid metabolic pathways. Metabolomics. 2019;15(3):30. doi: 10.1007/s11306-019-1494-5.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Liu T., Song X., Khan S., Li Y., Guo Z., Li C., Wang S., Dong W., Liu W., Wang B., Cao H. The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing. Int J Cancer. 2019. doi: 10.1002/ijc.32563.</mixed-citation><mixed-citation xml:lang="en">Liu T., Song X., Khan S., Li Y., Guo Z., Li C., Wang S., Dong W., Liu W., Wang B., Cao H. The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing. Int J Cancer. 2019. doi: 10.1002/ijc.32563.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Pearson T., Caporaso J.G., Yellowhair M., Bokulich N.A., Padi M., Roe D.J., Wertheim B.C., Linhart M., Martinez J.A., Bilagody C., Hornstra H., Alberts D.S., Lance P., Thompson P.A. Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development. Cancer Med. 2019;8(2):617-628. doi: 10.1002/cam4.1965.</mixed-citation><mixed-citation xml:lang="en">Pearson T., Caporaso J.G., Yellowhair M., Bokulich N.A., Padi M., Roe D.J., Wertheim B.C., Linhart M., Martinez J.A., Bilagody C., Hornstra H., Alberts D.S., Lance P., Thompson P.A. Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development. Cancer Med. 2019;8(2):617-628. doi: 10.1002/cam4.1965.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Goossens J.F., Bailly C. Ursodeoxycholic acid and cancer: From chemoprevention to chemotherapy. Pharmacol Ther. 2019;203:107396. doi: 10.1016/j.pharmthera.2019.107396.</mixed-citation><mixed-citation xml:lang="en">Goossens J.F., Bailly C. Ursodeoxycholic acid and cancer: From chemoprevention to chemotherapy. Pharmacol Ther. 2019;203:107396. doi: 10.1016/j.pharmthera.2019.107396.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Маевская М.В., Ивашкин В.Т., Ивашкин К.В., Луньков В.Д., Люсина Е.О., Зозуля В.Н., Лещенко В.И. Неалкогольная жировая болезнь печени как причина и следствие кардиометаболических осложнений. Особенности фармакотерапии. Место урсодезоксихолевой кислоты. Терапевтический архив. 2019;91(2):109-117. doi: 10.26442/00403660.2019.02.000122.</mixed-citation><mixed-citation xml:lang="en">Maevskaya M.V., Ivashkin V.T., Ivashkin K.V., Lunkov V.D., Liusina E.O., Zozula V.N., Leshchenko V.I. Non-alcoholic fatty liver disease as a cause and consequence of cardio- metabolic complications. Role of the ursodeoxicholic acid in the pharmacotherapy. Terapevticheskiy arkhiv = Therapeutic Archive. 2019;91(2):109-117. doi: 10.26442/00403660.2019.02.000122.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Chappell L.C., Bell J.L., Smith A., Linsell L., Juszczak E., Dixon P.H., Chambers J., Hunter R., Dorling J., Williamson C., Thornton J.G.; PITCHES study group. Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial. Lancet. 2019;394(10201):849-860. doi: 10.1016/S0140-6736(19)31270-X.</mixed-citation><mixed-citation xml:lang="en">Chappell L.C., Bell J.L., Smith A., Linsell L., Juszczak E., Dixon P.H., Chambers J., Hunter R., Dorling J., Williamson C., Thornton J.G.; PITCHES study group. Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial. Lancet. 2019;394(10201):849-860. doi: 10.1016/S0140-6736(19)31270-X.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Goet J.C., Hirschfield G.M. Guideline review: British Society of Gastroenterology/UK-PBC Primary Biliary Cholangitis treatment and management guidelines. Frontline Gastroenterol. 2019;10(3):316-319. doi: 10.1136/flgastro-2018-101109.</mixed-citation><mixed-citation xml:lang="en">Goet J.C., Hirschfield G.M. Guideline review: British Society of Gastroenterology/UK-PBC Primary Biliary Cholangitis treatment and management guidelines. Frontline Gastroenterol. 2019;10(3):316-319. doi: 10.1136/flgastro-2018-101109.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Örnolfsson K.T., Lund S.H., Olafsson S., Bergmann O.M., Björnsson E.S. Biochemical response to ursodeoxycholic acid among PBC patients: a nationwide population-based study. Scand J Gastroenterol. 2019;54(5):609-616. doi: 10.1080/00365521.2019.1606931.</mixed-citation><mixed-citation xml:lang="en">Örnolfsson K.T., Lund S.H., Olafsson S., Bergmann O.M., Björnsson E.S. Biochemical response to ursodeoxycholic acid among PBC patients: a nationwide population-based study. Scand J Gastroenterol. 2019;54(5):609-616. doi: 10.1080/00365521.2019.1606931.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
