<?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-2019-14-73-79</article-id><article-id custom-type="elpub" pub-id-type="custom">medsovet-4241</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>ЗАБОЛЕВАНИЯ ПЕЧЕНИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>LIVER DISEASE</subject></subj-group></article-categories><title-group><article-title>Синдром холестаза у коморбидного пациента: трудности диагностики</article-title><trans-title-group xml:lang="en"><trans-title>Cholestasis syndrome in a comorbid patient: diagnostic difficulties</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0344-8375</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Винницкая</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Vinnitskaya</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Винницкая Елена Владимировна, доктор медицинских наук, руководитель научно-исследовательского отдела гепатологии</p><p>111123, Москва, шоссе Энтузиастов, д. 86</p></bio><bio xml:lang="en"><p>Elena V. Vinnitskaya, Dr. of Sci. (Med.), Head of Hepatology Research Department</p><p>86, Shosse Entuziastov, Moscow, 111123</p></bio><email xlink:type="simple">e.vinnitskaya@mknc.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/0000-0002-4599-4040</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Хайменова</surname><given-names>Т. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Khaymenova</surname><given-names>T. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Хайменова Татьяна Юрьевна, кандидат медицинских наук, заведующая отделением заболеваний печени</p><p>111123, Москва, шоссе Энтузиастов, д. 86 </p></bio><bio xml:lang="en"><p>Tatyana Yu. Khaymenova, Cand. of Sci. (Med.), Head of Hepatology Research Department</p><p>86, Shosse Entuziastov, Moscow, 111123</p></bio><email xlink:type="simple">fortatiana@list.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/0000-0002-4581-7052</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Салиев</surname><given-names>К. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Saliev</surname><given-names>K. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Салиев Кирилл Германович, лаборант-исследователь научно-исследовательского отдела гепатологии</p><p>111123, Москва, шоссе Энтузиастов, д. 86 </p></bio><bio xml:lang="en"><p>Kirill G. Saliev, Dr. of Sci. (Med.), Research Assistant of Hepatology Research Department</p><p>86, Shosse Entuziastov, Moscow, 111123</p></bio><email xlink:type="simple">k.saliev@inbox.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/0000-0003-2195-9643</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сбикина</surname><given-names>Е. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Skibkina</surname><given-names>E. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Сбикина Евгения Сергеевна, младший научный сотрудник научно-исследовательского отдела гепатологии</p><p>111123, Москва, шоссе Энтузиастов, д. 86 </p></bio><bio xml:lang="en"><p>Evgeniya S. Sbikina, Junior Researcher, Hepatology Research Department</p><p>86, Shosse Entuziastov, Moscow, 111123</p></bio><email xlink:type="simple">esbikina@gmail.com</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8094-660X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Абсандзе</surname><given-names>К. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Absandze</surname><given-names>K. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Абсандзе Кетован Гелаевна, аспирант научно-исследовательского отдела гепатологии</p><p>111123, Москва, шоссе Энтузиастов, д. 86 </p></bio><bio xml:lang="en"><p>Ketovan G. Absandze, a postgraduate student, Hepatology Research Department</p><p>86, Shosse Entuziastov, Moscow, 111123</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4291-812X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сандлер</surname><given-names>Ю. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Sandler</surname><given-names>Yu. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Сандлер Юлия Григорьевна, кандидат медицинских наук, старший научный сотрудник научно-исследовательского отдела гепатологии</p><p>111123, Москва, шоссе Энтузиастов, д. 86 </p></bio><bio xml:lang="en"><p>Yuliya G. Sandler, Cand. of Sci. (Med.), Senior Researcher, Hepatology Research Department</p><p>86, Shosse Entuziastov, Moscow, 111123</p></bio><email xlink:type="simple">sandlerjulia2012@gmail.com</email><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff xml:lang="ru" id="aff-1"><institution>Московский клинический научно-практический центр имени А.С. Логинова Департамента здравоохранения города Москвы</institution><country>Russian Federation</country></aff><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Московский клинический научно-практический центр имени А.С. Логинова Департамента здравоохранения города Москвы</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Moscow Clinical Scientific and Practical Center named after A.S. Loginov Department of Health of Moscow</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2019</year></pub-date><pub-date pub-type="epub"><day>11</day><month>10</month><year>2019</year></pub-date><volume>0</volume><issue>14</issue><fpage>73</fpage><lpage>79</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Винницкая Е.В., Хайменова Т.Ю., Салиев К.Г., Сбикина Е.С., Абсандзе К.Г., Сандлер Ю.Г., 2019</copyright-statement><copyright-year>2019</copyright-year><copyright-holder xml:lang="ru">Винницкая Е.В., Хайменова Т.Ю., Салиев К.Г., Сбикина Е.С., Абсандзе К.Г., Сандлер Ю.Г.</copyright-holder><copyright-holder xml:lang="en">Vinnitskaya E.V., Khaymenova T.Y., Saliev K.G., Skibkina E.S., Absandze K.G., Sandler Y.G.</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/4241">https://www.med-sovet.pro/jour/article/view/4241</self-uri><abstract><p>Цель обзорной статьи – продемонстрировать обобщенные представления по вопросам классификации и диагностики синдрома холестаза различной этиологии, рассмотреть возможности применения лабораторных и инструментальных методов исследования в реальной клинической практике у коморбидного пациента. Основные положения. По механизму развития холестаз условно подразделяют на внутрипеченочный и внепеченочный, а также смешанного типа. Внепеченочный холестаз развивается при механической обструкции магистральных внепеченочных или главных внутрипеченочных протоков. Внутрипеченочный холестаз – в результате целого ряда заболеваний, таких как острый вирусный гепатит, первичный билиарный холангит, лекарственное повреждение печени, амилоидоз печени. В реальной клинической практике у коморбидного пациента возможно сочетание нескольких этиологических факторов, приводящих к развитию холестаза. Приводится клиническое наблюдение, когда у пациента с желчнокаменной болезнью, меланомой и язвенным колитом после исключения целого ряда возможных причин, вызывающих холестаз, диагностирован аутоиммунный перекрестный синдром – аутоиммунный гепатит и первичный склерозирующий холангит (ПСХ), что позволило приступить к иммуносупрессивной терапии кортикостероидами (метипред 48 мг/сут) и препаратом урсодезоксихолиевой кислоты (УДХК) Эксхол в дозе 1500 мг/сут. Вне зависимости от причины внутрипеченочного холестаза препаратом терапии холестатических поражений первой линии остается УДХК. Заключение. Только последовательный методический подход с учетом всех возможных причин холестаза может привести к правильному диагнозу и своевременному проведению адекватной терапии в каждом конкретном случае.</p></abstract><trans-abstract xml:lang="en"><p>The purpose of the review article is to demonstrate generalized ideas on the classification and diagnosis of cholestasis syndrome of various etiologies, to consider the possibility of using laboratory and instrumental research methods in real clinical practice in a comorbid patient. The main provisions. According to the mechanism of development, cholestasis is conditionally divided into intrahepatic and extrahepatic, as well as a mixed type. Extrahepatic cholestasis develops with mechanical obstruction of the main extrahepatic or main intrahepatic ducts. Intrahepatic cholestasis as a result of a number of diseases, such as acute viral hepatitis, primary biliary cholangitis, drug damage to the liver, amyloidosis of the liver. In real clinical practice, a combination of several etiological factors leading to the development of cholestasis is possible in a comorbid patient. A clinical observation is given when, in a patient with gallstone disease, melanoma and ulcerative colitis, after excluding a number of possible causes of cholestasis, autoimmune cross syndrome, autoimmune hepatitis and primary sclerosing cholangitis (PSC), was diagnosed, which allowed the initiation of immunosuppressive therapy with 48 mg corticosteroid (per day) and the preparation of ursodeoxycholic acid (UDCA) exhol at a dose of 1500 mg per day. Regardless of the cause of intrahepatic cholestasis, UDCA remains the drug for the treatment of first-line cholestatic lesions. Conclusion. Only a consistent methodological approach, taking into account all the possible causes of cholestasis, can lead to a correct diagnosis and timely adequate treatment in each case.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>внепеченочный и внутрипеченочный холестаз</kwd><kwd>биопсия печени</kwd><kwd>урсодезоксихолевая кислота (УДХК)</kwd><kwd>Эксхол</kwd></kwd-group><kwd-group xml:lang="en"><kwd>extrahepatic and intrahepatic cholestasis</kwd><kwd>liver biopsy</kwd><kwd>ursodeoxycholic acid (UDCA)</kwd><kwd>Exhol</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">Подымова С.Д. Болезни печени: Руководство для врачей. Изд. 5-е, перераб. и доп. М.: Медицинское информационное агентство, 2018. 984. с. Режим доступа: https://medknigaservis.ru/wp-content/uploads/2019/01/NF0008638.pdf.</mixed-citation><mixed-citation xml:lang="en">Podymova S.D. Liver diseases: Manual. Ed. 5th, revised and supplemented. Moscow: Medical Informational Agency, 2018. 984 p. (In Russ.) Available at: https://medknigaservis.ru/wpcontent/uploads/2019/01/NF0008638.pdf.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Ивашкин В.Т., Маевская М.В., Павлов Ч.С., Тихонов И.Н., Широкова Е.Н., Буеверов А.О., Драпкина О.М., Шульпекова Ю.О., Цуканов В.В., Маммаев С.Н., Маев И.В., Пальгова Л.К. Клинические рекомендации по диагностике и лечению неалкогольной жировой болезни печени Российского общества по изучению печени и Российской гастроэнтерологической ассоциации. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2016;(2):24-42. doi: 10.22416/1382-43762016-26-2-24-42.</mixed-citation><mixed-citation xml:lang="en">Ivashkin V.T., Mayevskaya M.V., Pavlov C.S., Tikhonov I.N., Shirokova Y.N., Buyeverov A.O., Drapkina O.M., Shulpekova Y.O., Tsukanov V.V., Mammayev S.N., Mayev I.V., Palgova L.K. Diagnostics and treatment of non-alcoholic fatty liver disease: clinical guidelines of the Russian Scientific Liver Society and the Russian gastroenterological association. Rossiyskiy zhurnal gastroehnterologii, gepatologii, koloproktologii = Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2016;(2):24-42. (In Russ.) doi: 10.22416/13824376-2016-26-2-24-42.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Modha K. Clinical Approach to Patients With Obstructive Jaundice. Techniques in Vascular and Interventional Radiology. 2015;18(4):197– 200. doi: 10.1053/j.tvir.2015.07.002.</mixed-citation><mixed-citation xml:lang="en">Modha K. Clinical Approach to Patients With Obstructive Jaundice. Techniques in Vascular and Interventional Radiology. 2015;18(4):197– 200. doi: 10.1053/j.tvir.2015.07.002.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Шамсиев Ж.З., Эгамбердиев А.А. Современное состояние вопросов диагностики и лечения механической желтухи (обзор литературы). Научные исследования. 2018;(4):69-72. Режим доступа: https://cyberleninka.ru/article/n/sovremennoesostoyanievoprosov-diagnostiki-i-lecheniyamehanicheskoyzheltuhi-obzor-literatury.</mixed-citation><mixed-citation xml:lang="en">Shamsiev J.Z., Egamberdiev A.A. Сurrent status of diagnosis and treatment of obstructive jaundice (review of literature). Nauchnye issledovaniya = Scientific Research. 2018;(4):69-72. (In Russ.) Available at: https://cyberleninka.ru/article/n/sovremennoe-sostoyanie-voprosovdiagnostikii-lecheniya-mehanicheskoy-zheltuhiobzor-literatury.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Курбаниязов З.Б., Махмудов Т.Б., Сулаймонов С.У., Давлатов С.С. Хирургическое лечение больных с синдромом Мириззи. Врачаспирант. 2012;(2.1):135-138. Режим доступа: http://www.sbook.ru/vrasp/index.htm.</mixed-citation><mixed-citation xml:lang="en">Kurbananiyazov Z.B., Makhmudov T.B., Sulaymonov S.U., Davlatov S.S. Surgical treatment of patients with Mirizzi syndrome. Vrach-aspirant = Postgraduate Doctor. 2012;(2.1):135-138. (In Russ.) Available at: http://www.sbook.ru/vrasp/index.htm.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Buyukasik K., Toros A.B., Bektas H., Ari A., Deniz M.M. Diagnostic and therapeutic value of ERCP in acute cholangitis. ISRN Gastroenterol. 2013;2013:191729. doi: 10.1155/2013/191729.</mixed-citation><mixed-citation xml:lang="en">Buyukasik K., Toros A.B., Bektas H., Ari A., Deniz M.M. Diagnostic and therapeutic value of ERCP in acute cholangitis. ISRN Gastroenterol. 2013;2013:191729. doi: 10.1155/2013/191729.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Lan Cheong Wah D., Christophi C., Muralidharan V. Acute cholangitis: current concepts. ANZ J Surg. 2017;87(7-8):554-559. doi: 10.1111/ans.13981.</mixed-citation><mixed-citation xml:lang="en">Lan Cheong Wah D., Christophi C., Muralidharan V. Acute cholangitis: current concepts. ANZ J Surg. 2017;87(7-8):554-559. doi: 10.1111/ans.13981.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009;51(2):237-267. doi: 10.1016/j.jhep.2009.04.009.</mixed-citation><mixed-citation xml:lang="en">European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009;51(2):237-267. doi: 10.1016/j.jhep.2009.04.009.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">European Association for the Study of the Liver. EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitisq J Hepatol. 2017;67(1):145-172. doi: 10.1016/j.jhep.2017.03.022.</mixed-citation><mixed-citation xml:lang="en">European Association for the Study of the Liver. EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitisq J Hepatol. 2017;67(1):145-172. doi: 10.1016/j.jhep.2017.03.022.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Miura F., Takada T., Kawarada Y., Nimura Y., Wada K., Hirota M., Nagino M., Tsuyuguchi T., Mayumi T., Yoshida M., Strasberg S.M., Pitt H.A., Belghiti J., de Santibanes E., Gadacz T.R., Gouma D.J., Fan S.T., Chen M.F., Padbury R.T., Bornman P.C., Kim S.W., Liau K.H., Belli G., Dervenis C. Flowcharts for the diagnosis and treatment of acute cholangitis and cholecystitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg. 2007;14(1):27-34. doi: 10.1007/s00534-006-1152-y.</mixed-citation><mixed-citation xml:lang="en">Miura F., Takada T., Kawarada Y., Nimura Y., Wada K., Hirota M., Nagino M., Tsuyuguchi T., Mayumi T., Yoshida M., Strasberg S.M., Pitt H.A., Belghiti J., de Santibanes E., Gadacz T.R., Gouma D.J., Fan S.T., Chen M.F., Padbury R.T., Bornman P.C., Kim S.W., Liau K.H., Belli G., Dervenis C. Flowcharts for the diagnosis and treatment of acute cholangitis and cholecystitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg. 2007;14(1):27-34. doi: 10.1007/s00534006-1152-y.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Romagnuolo J., Bardou M., Rahme E., Joseph L., Reinhold C., Barkun A.N. Magnetic resonance cholangiopancreatography: a meta-analysis of test performance in suspected biliary disease. Ann Intern Med. 2003;139(7):547-57. doi: 10.7326/0003-4819-139-7-200310070-00006.</mixed-citation><mixed-citation xml:lang="en">Romagnuolo J., Bardou M., Rahme E., Joseph L., Reinhold C., Barkun A.N. Magnetic resonance cholangiopancreatography: a metaanalysis of test performance in suspected biliary disease. Ann Intern Med. 2003;139(7):547-57. doi: 10.7326/0003-4819139-7-200310070-00006.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Giadas T., Cabada L. Sarria Octavio de Toledo M.T., Martinez-Berganza Asensio R., Cozcolluela Cabrejas I., Alberdi Ibanez A., Alvarez Lopez, Garcia-Asensio S. Helical CT cholangiography in the evaluation of the biliary tract: application to the diagnosis of choledocholithiasis. Abdom Imaging. 2002;27(1):61-70. doi: 10.1007/s00261-001-0043-6.</mixed-citation><mixed-citation xml:lang="en">Giadas T., Cabada L. Sarria Octavio de Toledo M.T., Martinez-Berganza Asensio R., Cozcolluela Cabrejas I., Alberdi Ibanez A., Alvarez Lopez, Garcia-Asensio S. Helical CT cholangiography in the evaluation of the biliary tract: application to the diagnosis of choledocholithiasis. Abdom Imaging. 2002;27(1):61-70. doi: 10.1007/s00261-001-0043-6.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Chalasani N.P., Hayashi P.H., Bonkovsky H.L., Navarro V.J., Lee W.M., Fontana. ACG Clinical Guide: the diagnosis and management of idiosyncratic druginduced liver injury. Am J Gastroenterol. 2014;109(7):950-966; quiz 967. doi: 10.1038/ajg.2014.131.</mixed-citation><mixed-citation xml:lang="en">Chalasani N.P., Hayashi P.H., Bonkovsky H.L., Navarro V.J., Lee W.M., Fontana. ACG Clinical Guide: the diagnosis and management of idiosyncratic druginduced liver injury. Am J Gastroenterol. 2014;109(7):950-966; quiz 967. doi: 10.1038/ajg.2014.131.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Wen Z., Wang K., Li H., Shi V. A comprehensive study of the association between drug hepatotoxicity and daily dose, liver metabolism, and lipophilicity using 975 oral medications. Oncotarget. 2015;6(19):17031-17038. doi: org/10.18632/oncotarget.4400.</mixed-citation><mixed-citation xml:lang="en">Wen Z., Wang K., Li H., Shi V. A comprehensive study of the association between drug hepatotoxicity and daily dose, liver metabolism, and lipophilicity using 975 oral medications. Oncotarget. 2015;6(19):17031-17038. doi: org/10.18632/oncotarget.4400.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Bjornsson E.S., Bergmann O.M., Bjornsson H.K., Kvaran R.B., Olafsson S. Incidence, presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterol. 2013;144(7):1419–1425.e3. doi: 10.1053/j.gastro.2013.02.006.</mixed-citation><mixed-citation xml:lang="en">Bjornsson E.S., Bergmann O.M., Bjornsson H.K., Kvaran R.B., Olafsson S. Incidence, presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterol. 2013;144(7):1419–1425.e3. doi: 10.1053/j.gastro.2013.02.006.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Sola S., Amaral J.D., Castro R.E., Ramalho R.M., Borralho P.M., Kren B.T., Tanaka H., Steer C.J., Rodrigues C. M. P. Nuclear translocation of UDCA by the glucocorticoid receptor is required to reduce TGF-beta1-induced apoptosis in rat hepatocytes. Hepatology. 2005;42:925–934. doi: 10.1002/hep.20870.</mixed-citation><mixed-citation xml:lang="en">Sola S., Amaral J.D., Castro R.E., Ramalho R.M., Borralho P.M., Kren B.T., Tanaka H., Steer C.J., Rodrigues C. M. P. Nuclear translocation of UDCA by the glucocorticoid receptor is required to reduce TGF-beta1induced apoptosis in rat hepatocytes. Hepatology. 2005;42:925–934. doi: 10.1002/hep.20870.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Rodrigues C.M., Ma X., Linehan-Stieers C., Fan G., Kren B.T., Steer C.J. Ursodeoxycholic acid prevents cytochrome c release in apoptosis by inhibiting mitochondrial membrane depolarization and channel formation. Cell Death Differ. 1999;6(9):842–854. doi: 10.1038/sj.cdd.4400560.</mixed-citation><mixed-citation xml:lang="en">Rodrigues C.M., Ma X., Linehan-Stieers C., Fan G., Kren B.T., Steer C.J. Ursodeoxycholic acid prevents cytochrome c release in apoptosis by inhibiting mitochondrial membrane depolarization and channel formation. Cell Death Differ. 1999;6(9):842–854. doi: 10.1038/sj.cdd.4400560.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Jacquemin E., Hermans D., Myara A., Habes D., Debray D., Hadchouel M., Sokal E.M., Bernard O. Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis. Hepatology. 1997;25:519–523. doi: org/10.1002/hep.510250303.</mixed-citation><mixed-citation xml:lang="en">Jacquemin E., Hermans D., Myara A., Habes D., Debray D., Hadchouel M., Sokal E.M., Bernard O. Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis. Hepatology. 1997;25:519–523. doi: org/10.1002/hep.510250303</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>
