perinatologyРоссийский вестник перинатологии и педиатрииRossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics)1027-40652500-2228Ltd. “The National Academy of Pediatric Science and Innovation”10.21508/1027-4065-2021-66-1-39-46perinatology-1336Research ArticleОБЗОРЫ ЛИТЕРАТУРЫLITERATURE REVIEWSСклерозирующий холангит и воспалительные заболевания кишечника: что первично?Sclerosing cholangitis and inflammatory bowel disease: which comes first?https://orcid.org/0000-0001-8837-9243НикитинА. А.NikitinA. V.

Никитин Артем Вячеславович – кандидат медицинских наук, ассистент кафедры гастроэнтерологии факультета дополнительного профессионального образования РНИМУ им. Н.И. Пирогова, старший научный сотрудник Научно-исследовательского клинического института педиатрии им. академика Ю.Е. Вельтищева

125412 Москва, ул. Талдомская, д. 2

Moscow

artem_i_am@mail.ruhttps://orcid.org/0000-0002-5413-9599ВолынецГ. В.VolynetsG. V.

Волынец Галина Васильевна – доктор медицинских наук, руководитель отдела  гастроэнтерологии 

125412 Москва, ул. Талдомская, д. 2

Moscow

ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России; ОСП «Научно-исследовательский клинический институт педиатрии им. академика Ю.Е. Вельтищева» ФГАОУ ВО РНИМУ им. Н.И. Пирогова» Минздрава РоссииРоссияPirogov Russian National Research Medical University; Veltischev Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical UniversityRussian FederationОСП «Научно-исследовательский клинический институт педиатрии им. академика Ю.Е. Вельтищева» ФГАОУ ВО РНИМУ им. Н.И. Пирогова» Минздрава РоссииРоссияVeltischev Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical UniversityRussian Federation2021290320216613946Copyright © Ltd. “The National Academy of Pediatric Science and Innovation”, 20212021Ltd. “The National Academy of Pediatric Science and Innovation”Ltd. “The National Academy of Pediatric Science and Innovation”https://www.ped-perinatology.ru/jour/about/submissions#copyrightNoticehttps://www.ped-perinatology.ru/jour/article/view/1336

Склерозирующий холангит – одно из самых частых гепатологических внекишечных проявлений воспалительных заболеваний кишечника. Цель данного обзора – обсуждение фенотипа сочетания склерозирующего холангита и воспалительного заболевания кишечника. Представлены теории этиопатогенеза склерозирующего холангита при воспалительных заболеваниях кишечника, а также некоторые особенности фенотипа как смешанных, так и моногенных форм заболеваний.

Склерозирующий холангит в сочетании с воспалительным заболеванием кишечника обычно ассоциируется с панколитом, однако эндоскопически визуализируемая активность воспалительных заболеваний кишечника в этих случаях значительно ниже, а клинические симптомы менее выражены. Установлено, что существует повышенный риск развития злокачественных новообразований при сочетании склерозирующего холангита с воспалительным заболеванием кишечника. Подчеркивается, что механизмы формирования воспалительного заболевания кишечника в сочетании со склерозирующим холангитом остаются недостаточно изученными, хотя выявлено, что на развитие этой патологии влияют лимфоцитарная перекрестная реактивность, аберрантное распознавание микробиотических эпитопов и дисбаланс микробиоты кишечника. Новые биологические агенты, нацеленные на коррекцию взаимодействия между иммунной системой и органами-мишенями, могут обеспечить новые способы лечения склерозирующего холангита, сочетанного с воспалительным заболеванием кишечника.

Sclerosing cholangitis is one of the most common hepatologic extraintestinal manifestations of inflammatory bowel disease. The article discusses the phenotype of the combination of sclerosing cholangitis and inflammatory bowel disease. The authors present their theories of the etiopathogenesis of sclerosing cholangitis in patients with inflammatory bowel disease, as well as some features of the phenotype of both mixed and monogenic forms of diseases.

Sclerosing cholangitis in combination with inflammatory bowel disease is commonly associated with pancolitis, but the endoscopically visualized activity of inflammatory bowel diseases is significantly lower and clinical symptoms are less pronounced. The authors have established that the patients with the combination of sclerosing cholangitis and inflammatory bowel disease are at the increased risk of developing malignant neoplasms. The formation mechanisms of a combination of inflammatory bowel disease and sclerosing cholangitis remain poorly understood, although this pathology is influenced by lymphocytic cross-reactivity, aberrant recognition of microbiotic epitopes and intestinal microbiota imbalance. New biological agents aimed at correcting the interaction between the immune system and target organs may provide new ways of treatment for sclerosing cholangitis associated with inflammatory bowel disease.

детисклерозирующий холангитвоспалительные заболевания кишечникаболезнь Кронаязвенный колитchildrensclerosing cholangitisinflammatory bowel diseaseCrohn’s diseaseulcerative colitisReferencesde Vries A.B., Janse M., Blokzijl H., Weersma R.K. Distinctive inflammatory bowel disease phenotype in primary sclerosing cholangitis. World J Gastroenterol 2015; 21(6): 1956–1971. DOI: 10.3748/wjg.v21.i6.1956de Vries A.B., Janse M., Blokzijl H., Weersma R.K. Distinctive inflammatory bowel disease phenotype in primary sclerosing cholangitis. World J Gastroenterol 2015; 21(6): 1956–1971. DOI: 10.3748/wjg.v21.i6.1956Rasmussen H.H., Fallingborg J.F., Mortensen P.B., Vyberg M., Tage-Jensen U., Rasmussen S.N. Hepatobiliary dysfunction and primary sclerosing cholangitis in patients with Crohn’s disease. Scand J Gastroenterol 1997; 32(6): 604–610. DOI: 10.3109/00365529709025107Rasmussen H.H., Fallingborg J.F., Mortensen P.B., Vyberg M., Tage-Jensen U., Rasmussen S.N. Hepatobiliary dysfunction and primary sclerosing cholangitis in patients with Crohn’s disease. Scand J Gastroenterol 1997; 32(6): 604–610. DOI: 10.3109/00365529709025107Takikawa H., Takamori Y., Tanaka A., Kurihara H., NakanumaY. Analysis of 388 cases of primary sclerosing cholangitis in Japan; Presence of a subgroup without pancreatic involvement in older patients. Hepatol Res 2004; 29(3): 153–159. DOI: 10.1016/j.hepres.2004.03.006Takikawa H., Takamori Y., Tanaka A., Kurihara H., NakanumaY. Analysis of 388 cases of primary sclerosing cholangitis in Japan; Presence of a subgroup without pancreatic involvement in older patients. Hepatol Res 2004; 29(3): 153–159. DOI: 10.1016/j.hepres.2004.03.006Ang T.L., Fock K.M., Ng T.M., Teo E.K., Chua T.S., Tan J.Y. Clinical profile of primary sclerosing cholangitis in Singapore. J Gastroenterol Hepatol 2002; 17(8): 908–913. DOI: 10.1046/j.1440-1746.2002.02835.xAng T.L., Fock K.M., Ng T.M., Teo E.K., Chua T.S., Tan J.Y. Clinical profile of primary sclerosing cholangitis in Singapore. J Gastroenterol Hepatol 2002; 17(8): 908–913. DOI: 10.1046/j.1440-1746.2002.02835.xNakazawa T., Naitoh I., Hayashi K., Sano H., Miyabe K., Shimizu S. et al. Inflammatory bowel disease of primary sclerosing cholangitis: a distinct entity? World J Gastroenterol 2014; 20(12): 3245–3254. DOI: 10.3748/wjg.v20.i12.3245Nakazawa T., Naitoh I., Hayashi K., Sano H., Miyabe K., Shimizu S. et al. Inflammatory bowel disease of primary sclerosing cholangitis: a distinct entity? World J Gastroenterol 2014; 20(12): 3245–3254. DOI: 10.3748/wjg.v20.i12.3245Eaton J.E., Talwalkar J.A., Lazaridis K.N., Gores G.J., Lindor K.D. Pathogenesis of primary sclerosing cholangitis and advances in diagnosis and management. Gastroenterol 2013; 145(3): 521–536. DOI: 10.1053/j.gastro.2013.06.052Eaton J.E., Talwalkar J.A., Lazaridis K.N., Gores G.J., Lindor K.D. Pathogenesis of primary sclerosing cholangitis and advances in diagnosis and management. Gastroenterol 2013; 145(3): 521–536. DOI: 10.1053/j.gastro.2013.06.052Kornfeld D., Ekbom A., Ihre T. Is there an excess risk for colorectal cancer in patients with ulcerative colitis and concomitant primary sclerosing cholangitis? A population-based study. Gut 1997; 41(4): 522–525. DOI: 10.1136/gut.41.4.522Kornfeld D., Ekbom A., Ihre T. Is there an excess risk for colorectal cancer in patients with ulcerative colitis and concomitant primary sclerosing cholangitis? A population-based study. Gut 1997; 41(4): 522–525. DOI: 10.1136/gut.41.4.522Soetikno R.M., Lin O.S., Heidenreich P.A., Young H.S., Blackstone M.O. Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: a meta-analysis. Gastrointest Endosc 2002; 56(1): 48–54. DOI: 10.1067/mge.2002.125367Soetikno R.M., Lin O.S., Heidenreich P.A., Young H.S., Blackstone M.O. Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: a meta-analysis. Gastrointest Endosc 2002; 56(1): 48–54. DOI: 10.1067/mge.2002.125367Zheng H.H., Jiang X.L. Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease: a meta-analysis of 16 observational studies. Eur J Gastroenterol Hepatol 2016; 28(4): 383–390. DOI: 10.1097/MEG.0000000000000576Zheng H.H., Jiang X.L. Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease: a meta-analysis of 16 observational studies. Eur J Gastroenterol Hepatol 2016; 28(4): 383–390. DOI: 10.1097/MEG.0000000000000576Smith M.P., Loe R.H. Sclerosing cholangitis;review of recent case reports and associated diseases and four new cases. Am J Surg 1965; 110: 239–246. DOI: 10.1016/00029610(65)90018-8Smith M.P., Loe R.H. Sclerosing cholangitis;review of recent case reports and associated diseases and four new cases. Am J Surg 1965; 110: 239–246. DOI: 10.1016/00029610(65)90018-8Loftus E.V., Sandborn W.J., Tremaine W.J., Mahoney D.W., Zinsmeister A.R., Offord K.P. et al. Risk of colorectal neoplasia in patients with primary sclerosing cholangitis. Gastroenterol 1996; 110(2): 432–440. DOI: 10.1053/gast.1996.v110. pm8566590Loftus E.V., Sandborn W.J., Tremaine W.J., Mahoney D.W., Zinsmeister A.R., Offord K.P. et al. Risk of colorectal neoplasia in patients with primary sclerosing cholangitis. Gastroenterol 1996; 110(2): 432–440. DOI: 10.1053/gast.1996.v110. pm8566590Loftus E.V. Jr., Harewood G.C., Loftus C.G., Tremaine W.J., Harmsen W.S., Zinsmeister A.R. et al. PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis. Gut 2005; 54(1): 91–96. DOI: 10.1136/gut.2004.046615Loftus E.V. Jr., Harewood G.C., Loftus C.G., Tremaine W.J., Harmsen W.S., Zinsmeister A.R. et al. PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis. Gut 2005; 54(1): 91–96. DOI: 10.1136/gut.2004.046615Shah S.C., Ten Hove J.R., Castaneda D., Palmela C., Mooiweer E., Colombel J.F. et al. High Risk of Advanced Colorectal Neoplasia in Patients With Primary Sclerosing Cholangitis Associated With Inflammatory Bowel Disease. Clin Gastroenterol Hepatol 2018; 16(7): 1106–1113.e3. DOI: 10.1016/j.cgh.2018.01.023Shah S.C., Ten Hove J.R., Castaneda D., Palmela C., Mooiweer E., Colombel J.F. et al. High Risk of Advanced Colorectal Neoplasia in Patients With Primary Sclerosing Cholangitis Associated With Inflammatory Bowel Disease. Clin Gastroenterol Hepatol 2018; 16(7): 1106–1113.e3. DOI: 10.1016/j.cgh.2018.01.023Sano H., Nakazawa T., Ando T., Hayashi K., Naitoh I., Okumura F. et al. Clinical characteristics of inflammatory bowel disease associated with primary sclerosing cholangitis. J Hepatobiliary Pancreat Sci 2011; 18(2): 154–161. DOI: 10.1007/s00534-010-0319-8Sano H., Nakazawa T., Ando T., Hayashi K., Naitoh I., Okumura F. et al. Clinical characteristics of inflammatory bowel disease associated with primary sclerosing cholangitis. J Hepatobiliary Pancreat Sci 2011; 18(2): 154–161. DOI: 10.1007/s00534-010-0319-8Ngu J.H., Gearry R.B., Wright A.J., Stedman C.A. Inflammatory bowel disease is associated with poor outcomes of patients with primary sclerosing cholangitis. Clin Gastroenterol Hepatol 2011; 9(12): 1092–1097; quiz e135. DOI: 10.1016/j.cgh.2011.08.027Ngu J.H., Gearry R.B., Wright A.J., Stedman C.A. Inflammatory bowel disease is associated with poor outcomes of patients with primary sclerosing cholangitis. Clin Gastroenterol Hepatol 2011; 9(12): 1092–1097; quiz e135. DOI: 10.1016/j.cgh.2011.08.027Lunder A.K., Hov J.R., Borthne A., Gleditsch J., Johannesen G., Tveit K. et al. Prevalence of Sclerosing Cholangitis Detected by Magnetic Resonance Cholangiography in Patients With Long-term Inflammatory Bowel Disease. Gastroenterol 2016; 151(4): 660–669.e4. DOI: 10.1053/j.gastro.2016.06.021Lunder A.K., Hov J.R., Borthne A., Gleditsch J., Johannesen G., Tveit K. et al. Prevalence of Sclerosing Cholangitis Detected by Magnetic Resonance Cholangiography in Patients With Long-term Inflammatory Bowel Disease. Gastroenterol 2016; 151(4): 660–669.e4. DOI: 10.1053/j.gastro.2016.06.021Chapman R., Fevery J., Kalloo A., Nagorney D.M., Boberg K.M., Shneider B. et al. American Association for the Study of Liver Diseases. Diagnosis and management of primary sclerosing cholangitis. Hepatol 2010; 51(2): 660–678. DOI: 10.1002/hep.23294Chapman R., Fevery J., Kalloo A., Nagorney D.M., Boberg K.M., Shneider B. et al. American Association for the Study of Liver Diseases. Diagnosis and management of primary sclerosing cholangitis. Hepatol 2010; 51(2): 660–678. DOI: 10.1002/hep.23294Lakatos L., Kiss L.S., David G., Pandur T., Erdelyi Z., Mester G. et al. Incidence, disease phenotype at diagnosis, and early disease course in inflammatory bowel diseases in Western Hungary, 2002–2006. Inflamm Bowel Dis 2011;17(12):2558–2565. DOI: 10.1002/ibd.21607Lakatos L., Kiss L.S., David G., Pandur T., Erdelyi Z., Mester G. et al. Incidence, disease phenotype at diagnosis, and early disease course in inflammatory bowel diseases in Western Hungary, 2002–2006. Inflamm Bowel Dis 2011;17(12):2558–2565. DOI: 10.1002/ibd.21607Burisch J., Jess T., Martinato M., Lakatos P.L. ECCO-EpiCom.The burden of inflammatory bowel disease in Europe. J Crohns Colitis 2013; 7(4): 322–337. DOI: 10.1016/j.crohns.2013.01.010Burisch J., Jess T., Martinato M., Lakatos P.L. ECCO-EpiCom.The burden of inflammatory bowel disease in Europe. J Crohns Colitis 2013; 7(4): 322–337. DOI: 10.1016/j.crohns.2013.01.010Katsanos K.H., Stamou P., Tatsioni A., Tsianos V.E., Zoumbas S., Kavvadia S. et al. Northwest Greece IBD Study Group. Prevalence of inflammatory bowel disease related dysplasia and cancer in 1500 colonoscopies from a referral center in northwestern Greece. J Crohns Colitis 2011; 5(1): 19–23. DOI: 10.1016/j.crohns.2010.09.001Katsanos K.H., Stamou P., Tatsioni A., Tsianos V.E., Zoumbas S., Kavvadia S. et al. Northwest Greece IBD Study Group. Prevalence of inflammatory bowel disease related dysplasia and cancer in 1500 colonoscopies from a referral center in northwestern Greece. J Crohns Colitis 2011; 5(1): 19–23. DOI: 10.1016/j.crohns.2010.09.001Lazaridis K.N., LaRusso N.F. Primary Sclerosing Cholangitis. New Engl J Med 2016; 375(12): 1161–1170. DOI: 10.1056/NEJMra1506330Lazaridis K.N., LaRusso N.F. Primary Sclerosing Cholangitis. New Engl J Med 2016; 375(12): 1161–1170. DOI: 10.1056/NEJMra1506330Lazaridis K.N., LaRusso N.F. The Cholangiopathies. Mayo Clin Proc 2015; 90(6): 791–800. DOI: 10.1016/j.mayocp.2015.03.017Lazaridis K.N., LaRusso N.F. The Cholangiopathies. Mayo Clin Proc 2015; 90(6): 791–800. DOI: 10.1016/j.mayocp.2015.03.017Hov J.R., Boberg K.M., Karlsen T.H. Autoantibodies in primary sclerosing cholangitis. World J Gastroenterol 2008; 14(24): 3781–3791. DOI: 10.3748/wjg.14.3781Hov J.R., Boberg K.M., Karlsen T.H. Autoantibodies in primary sclerosing cholangitis. World J Gastroenterol 2008; 14(24): 3781–3791. DOI: 10.3748/wjg.14.3781Roozendaal C., de Jong M.A., van den Berg A.P., van Wijk R.T., Limburg P.C., Kallenberg C.G. Clinical significance of anti-neutrophil cytoplasmic antibodies (ANCA) in autoimmune liver diseases. J Hepatol 2000; 32(5): 734–741. DOI: 10.1016/s0168-8278(00)80241-xRoozendaal C., de Jong M.A., van den Berg A.P., van Wijk R.T., Limburg P.C., Kallenberg C.G. Clinical significance of anti-neutrophil cytoplasmic antibodies (ANCA) in autoimmune liver diseases. J Hepatol 2000; 32(5): 734–741. DOI: 10.1016/s0168-8278(00)80241-xTerjung B., Spengler U., Sauerbruch T., Worman H.J. Atypical p-ANCA in IBD and hepatobiliary disorders react with a 50-kilodalton nuclear envelope protein of neutrophils and myeloid cell lines. Gastroenterol 2000; 119(2): 310–322. DOI: 10.1053/gast.2000.9366Terjung B., Spengler U., Sauerbruch T., Worman H.J. Atypical p-ANCA in IBD and hepatobiliary disorders react with a 50-kilodalton nuclear envelope protein of neutrophils and myeloid cell lines. Gastroenterol 2000; 119(2): 310–322. DOI: 10.1053/gast.2000.9366Mitsuyama K., Niwa M., Takedatsu H., Yamasaki H., Kuwaki K., Yoshioka S. et al. Antibody markers in the diagnosis of inflammatory bowel disease. World J Gastroenterol 2016; 22(3): 1304–1310. DOI: 10.3748/wjg.v22.i3.1304Mitsuyama K., Niwa M., Takedatsu H., Yamasaki H., Kuwaki K., Yoshioka S. et al. Antibody markers in the diagnosis of inflammatory bowel disease. World J Gastroenterol 2016; 22(3): 1304–1310. DOI: 10.3748/wjg.v22.i3.1304Targan S.R., Landers C., Vidrich A., Czaja A.J. High-titer antineutrophil cytoplasmic antibodies in type-1 autoimmune hepatitis. Gastroenterol 1995; 108(4): 1159–1166. DOI: 10.1016/0016-5085(95)90215-5Targan S.R., Landers C., Vidrich A., Czaja A.J. High-titer antineutrophil cytoplasmic antibodies in type-1 autoimmune hepatitis. Gastroenterol 1995; 108(4): 1159–1166. DOI: 10.1016/0016-5085(95)90215-5Seibold F., Weber P., Schöning A., Mörk H., Goppel S., Scheurlen M. Neutrophil antibodies (pANCA) in chronic liver disease and inflammatory bowel disease: do they react with different antigens? Eur J Gastroenterol Hepatol 1996;8(11):1095–1100. DOI: 10.1097/00042737199611000-00012Seibold F., Weber P., Schöning A., Mörk H., Goppel S., Scheurlen M. Neutrophil antibodies (pANCA) in chronic liver disease and inflammatory bowel disease: do they react with different antigens? Eur J Gastroenterol Hepatol 1996;8(11):1095–1100. DOI: 10.1097/00042737199611000-00012Høie O., Aamodt G., Vermeire S., Bernklev T., Odes S., Wolters F.L. et al. European Collaborative study group of Inflammatory Bowel Disease (EC-IBD). Serological markers are associated with disease course in ulcerative colitis. A study in an unselected population-based cohort followed for 10 years. J Crohns Colitis 2008; 2(2): 114–122. DOI: 10.1016/j.crohns.2007.10.001Høie O., Aamodt G., Vermeire S., Bernklev T., Odes S., Wolters F.L. et al. European Collaborative study group of Inflammatory Bowel Disease (EC-IBD). Serological markers are associated with disease course in ulcerative colitis. A study in an unselected population-based cohort followed for 10 years. J Crohns Colitis 2008; 2(2): 114–122. DOI: 10.1016/j.crohns.2007.10.001Ruemmele F.M., Targan S.R., Levy G., Dubinsky M., Braun J., Seidman E.G. Diagnostic accuracy of serological assays in pediatric inflammatory bowel disease. Gastroenterol 1998; 115(4): 822–829. DOI: 10.1016/s0016-5085(98)70252-5Ruemmele F.M., Targan S.R., Levy G., Dubinsky M., Braun J., Seidman E.G. Diagnostic accuracy of serological assays in pediatric inflammatory bowel disease. Gastroenterol 1998; 115(4): 822–829. DOI: 10.1016/s0016-5085(98)70252-5Loly C., Belaiche J., Louis E. Predictors of severe Crohn’s disease. Scand J Gastroenterol 2008; 43(8): 948–954. DOI: 10.1080/00365520801957149Loly C., Belaiche J., Louis E. Predictors of severe Crohn’s disease. Scand J Gastroenterol 2008; 43(8): 948–954. DOI: 10.1080/00365520801957149Jostins L., Ripke S., Weersma R.K., Duerr R.H., McGovern D.P., Hui K.Y. et al. International IBD Genetics Consortium (IIBDGC) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012; 491(7422): 119–124. DOI: 10.1038/nature11582Jostins L., Ripke S., Weersma R.K., Duerr R.H., McGovern D.P., Hui K.Y. et al. International IBD Genetics Consortium (IIBDGC) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012; 491(7422): 119–124. DOI: 10.1038/nature11582Liu J.Z., van Sommeren S., Huang H., Ng S.C., Alberts R., Takahashi A. et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet 2015; 47(9): 979– 986. DOI: 10.1038/ng.3359Liu J.Z., van Sommeren S., Huang H., Ng S.C., Alberts R., Takahashi A. et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet 2015; 47(9): 979– 986. DOI: 10.1038/ng.3359Duboc H., Rajca S., Rainteau D., Benarous D., Maubert M.A., Quervain E. et al. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut 2013; 62(4): 531–539. DOI: 10.1136/gutjnl-2012-302578Duboc H., Rajca S., Rainteau D., Benarous D., Maubert M.A., Quervain E. et al. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut 2013; 62(4): 531–539. DOI: 10.1136/gutjnl-2012-302578Greve J.W., Gouma D.J., Buurman W.A. Bile acids inhibit endotoxin-induced release of tumor necrosis factor by monocytes: an in vitro study. Hepatology 1989;10(4):454–458. DOI: 10.1002/hep.1840100409Greve J.W., Gouma D.J., Buurman W.A. Bile acids inhibit endotoxin-induced release of tumor necrosis factor by monocytes: an in vitro study. Hepatology 1989;10(4):454–458. DOI: 10.1002/hep.1840100409Calmus Y., Guechot J., Podevin P., Bonnefis M.T., Giboudeau J., Poupon R. Differential effects of chenodeoxycholic and ursodeoxycholic acids on interleukin 1, interleukin 6 and tumor necrosis factor-alpha production by monocytes. Hepatol 1992; 16(3): 719–723. DOI: 10.1002/hep.1840160317Calmus Y., Guechot J., Podevin P., Bonnefis M.T., Giboudeau J., Poupon R. Differential effects of chenodeoxycholic and ursodeoxycholic acids on interleukin 1, interleukin 6 and tumor necrosis factor-alpha production by monocytes. Hepatol 1992; 16(3): 719–723. DOI: 10.1002/hep.1840160317Bernstein C., Holubec H., Bhattacharyya A.K., Nguyen H., Payne C.M., Zaitlin B. et al. Carcinogenicity of deoxycholate, a secondary bile acid. Arch Toxicol 2011; 85(8): 863–871. DOI: 10.1007/s00204-011-0648-7Bernstein C., Holubec H., Bhattacharyya A.K., Nguyen H., Payne C.M., Zaitlin B. et al. Carcinogenicity of deoxycholate, a secondary bile acid. Arch Toxicol 2011; 85(8): 863–871. DOI: 10.1007/s00204-011-0648-7Bernstein H., Bernstein C., Payne C.M., Dvorakova K., Garewal H. Bile acids as carcinogens in human gastrointestinal cancers. Mutat Res 2005; 589(1): 47–65. DOI: 10.1016/j.mrrev.2004.08.001Bernstein H., Bernstein C., Payne C.M., Dvorakova K., Garewal H. Bile acids as carcinogens in human gastrointestinal cancers. Mutat Res 2005; 589(1): 47–65. DOI: 10.1016/j.mrrev.2004.08.001Torres J., Palmela C., Brito H., Bao X., Ruiqi H., Moura-Santos P. et al. The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease. United Eur Gastroenterol J 2018; 6(1): 112–122. DOI: 10.1177/2050640617708953Torres J., Palmela C., Brito H., Bao X., Ruiqi H., Moura-Santos P. et al. The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease. United Eur Gastroenterol J 2018; 6(1): 112–122. DOI: 10.1177/2050640617708953Tsaitas C., Semertzidou A., Sinakos E. Update on inflammatory bowel disease in patients with primary sclerosing cholangitis. World J Hepatol 2014;6(4):178–187. DOI: 10.4254/wjh.v6.i4.178Tsaitas C., Semertzidou A., Sinakos E. Update on inflammatory bowel disease in patients with primary sclerosing cholangitis. World J Hepatol 2014;6(4):178–187. DOI: 10.4254/wjh.v6.i4.178Chapman R., Cullen S. Etiopathogenesis of primary sclerosing cholangitis. World J Gastroenterol 2008; 14(21): 3350–3359. DOI: 10.3748/wjg.14.3350Chapman R., Cullen S. Etiopathogenesis of primary sclerosing cholangitis. World J Gastroenterol 2008; 14(21): 3350–3359. DOI: 10.3748/wjg.14.3350Chapman R., Fevery J., Kalloo A., Nagorney D.M., Boberg K.M., Shneider B. et al. American Association for the Study of Liver Diseases. Diagnosis and management of primary sclerosing cholangitis. Hepatol 2010; 51(2): 660–678. DOI: 10.1002/hep.23294Chapman R., Fevery J., Kalloo A., Nagorney D.M., Boberg K.M., Shneider B. et al. American Association for the Study of Liver Diseases. Diagnosis and management of primary sclerosing cholangitis. Hepatol 2010; 51(2): 660–678. DOI: 10.1002/hep.23294Christensen B., Micic D., Gibson P.R., Yarur A., Bellaguarda E., Corsello P. et al. Vedolizumab in patients with concurrent primary sclerosing cholangitis and inflammatory bowel disease does not improve liver biochemistry but is safe and effective for the bowel disease. Aliment Pharmacol Ther 2018; 47(6): 753–762. DOI: 10.1111/apt.14525Christensen B., Micic D., Gibson P.R., Yarur A., Bellaguarda E., Corsello P. et al. Vedolizumab in patients with concurrent primary sclerosing cholangitis and inflammatory bowel disease does not improve liver biochemistry but is safe and effective for the bowel disease. Aliment Pharmacol Ther 2018; 47(6): 753–762. DOI: 10.1111/apt.14525Cesaro C., Tiso A., Del Prete A., Cariello R., Tuccillo C., Cotticelli G. et al. Gut microbiota and probiotics in chronic liver diseases. Dig Liver Dis 2011; 43(6): 431–438. DOI: 10.1016/j.dld.2010.10.015Cesaro C., Tiso A., Del Prete A., Cariello R., Tuccillo C., Cotticelli G. et al. Gut microbiota and probiotics in chronic liver diseases. Dig Liver Dis 2011; 43(6): 431–438. DOI: 10.1016/j.dld.2010.10.015Yamada S., Ishii M., Liang L.S., Yamamoto T., Toyota T. Small duct cholangitis induced by N-formyl L-methionine L-leucine L-tyrosine in rats. J Gastroenterol 1994; 29(5): 631–636. DOI: 10.1007/bf02365447Yamada S., Ishii M., Liang L.S., Yamamoto T., Toyota T. Small duct cholangitis induced by N-formyl L-methionine L-leucine L-tyrosine in rats. J Gastroenterol 1994; 29(5): 631–636. DOI: 10.1007/bf02365447Quraishi M.N., Sergeant M., Kay G., Iqbal T., Chan J., Constantinidou C. et al. The gut-adherent microbiota of PSC-IBD is distinct to that of IBD. Gut 2017; 66(2): 386–388. DOI: 10.1136/gutjnl-2016-311915Quraishi M.N., Sergeant M., Kay G., Iqbal T., Chan J., Constantinidou C. et al. The gut-adherent microbiota of PSC-IBD is distinct to that of IBD. Gut 2017; 66(2): 386–388. DOI: 10.1136/gutjnl-2016-311915Kummen M., Holm K., Anmarkrud J.A., Nyg rd S., Vesterhus M., Høivik M.L. et al. The gut microbial profile in patients with primary sclerosing cholangitis is distinct from patients with ulcerative colitis without biliary disease and healthy controls. Gut 2017; 66(4): 611–619. DOI: 10.1136/gutjnl-2015-310500Kummen M., Holm K., Anmarkrud J.A., Nyg rd S., Vesterhus M., Høivik M.L. et al. The gut microbial profile in patients with primary sclerosing cholangitis is distinct from patients with ulcerative colitis without biliary disease and healthy controls. Gut 2017; 66(4): 611–619. DOI: 10.1136/gutjnl-2015-310500Palmela C., Peerani F., Castaneda D., Torres J., Itzkowitz S.H. Inflammatory Bowel Disease and Primary Sclerosing Cholangitis: A Review of the Phenotype and Associated Specific Features. Gut Liver 2018; 12(1): 17–29. DOI: 10.5009/gnl16510Palmela C., Peerani F., Castaneda D., Torres J., Itzkowitz S.H. Inflammatory Bowel Disease and Primary Sclerosing Cholangitis: A Review of the Phenotype and Associated Specific Features. Gut Liver 2018; 12(1): 17–29. DOI: 10.5009/gnl16510Lv L.X., Fang D.Q., Shi D., Chen D.Y., Yan R., Zhu Y.X. et al. Alterations and correlations of the gut microbiome, metabolism and immunity in patients with primary biliary cirrhosis. Environ Microbiol 2016; 18(7): 2272–2286. DOI: 10.1111/1462-2920.13401Lv L.X., Fang D.Q., Shi D., Chen D.Y., Yan R., Zhu Y.X. et al. Alterations and correlations of the gut microbiome, metabolism and immunity in patients with primary biliary cirrhosis. Environ Microbiol 2016; 18(7): 2272–2286. DOI: 10.1111/1462-2920.13401Chen Y., Ji F., Guo J., Shi D., Fang D., Li L. Dysbiosis of small intestinal microbiota in liver cirrhosis and its association with etiology. Sci Rep 2016; 6: 34055. DOI: 10.1038/srep34055Chen Y., Ji F., Guo J., Shi D., Fang D., Li L. Dysbiosis of small intestinal microbiota in liver cirrhosis and its association with etiology. Sci Rep 2016; 6: 34055. DOI: 10.1038/srep34055Wei X., Yan X., Zou D., Yang Z., Wang X., Liu W. et al. Abnormal fecal microbiota community and functions in patients with hepatitis B liver cirrhosis as revealed by a metagenomic approach. BMC Gastroenterol 2013; 13: 175. DOI: 10.1186/1471-230X-13-175Wei X., Yan X., Zou D., Yang Z., Wang X., Liu W. et al. Abnormal fecal microbiota community and functions in patients with hepatitis B liver cirrhosis as revealed by a metagenomic approach. BMC Gastroenterol 2013; 13: 175. DOI: 10.1186/1471-230X-13-175Chalasani N.P., Hayashi P.H., Bonkovsky H.L., Navarro V.J., Lee W.M., Fontana R.J. Practice Parameters Committee of the American College of Gastroenterology. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol 2014; 109(7): 950–966; quiz 967. DOI: 10.1038/ajg.2014.131Chalasani N.P., Hayashi P.H., Bonkovsky H.L., Navarro V.J., Lee W.M., Fontana R.J. Practice Parameters Committee of the American College of Gastroenterology. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol 2014; 109(7): 950–966; quiz 967. DOI: 10.1038/ajg.2014.131Dave M., Elmunzer B.J., Dwamena B.A., Higgins P.D. Primary sclerosing cholangitis: meta-analysis of diagnostic performance of MR cholangiopancreatography. Radiol 2010; 256(2): 387–396. DOI: 10.1148/radiol.10091953Dave M., Elmunzer B.J., Dwamena B.A., Higgins P.D. Primary sclerosing cholangitis: meta-analysis of diagnostic performance of MR cholangiopancreatography. Radiol 2010; 256(2): 387–396. DOI: 10.1148/radiol.10091953Harbord M., Annese V., Vavricka S.R., Allez M., Barreirode Acosta M., Boberg K.M. et al. European Crohn’s and Colitis Organisation. The First European Evidence-based Consensus on Extra-intestinal Manifestations in Inflammatory Bowel Disease. J Crohns Colitis 2016; 10(3): 239–254. DOI: 10.1093/ecco-jcc/jjv213Harbord M., Annese V., Vavricka S.R., Allez M., Barreirode Acosta M., Boberg K.M. et al. European Crohn’s and Colitis Organisation. The First European Evidence-based Consensus on Extra-intestinal Manifestations in Inflammatory Bowel Disease. J Crohns Colitis 2016; 10(3): 239–254. DOI: 10.1093/ecco-jcc/jjv213Aabakken L., Karlsen T.H., Albert J., Arvanitakis M., Chazouilleres O., Dumonceau J.M. et al. Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) Clinical Guideline. Endoscopy 2017; 49(6): 588–608. DOI: 10.1055/s-0043-107029Aabakken L., Karlsen T.H., Albert J., Arvanitakis M., Chazouilleres O., Dumonceau J.M. et al. Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) Clinical Guideline. Endoscopy 2017; 49(6): 588–608. DOI: 10.1055/s-0043-107029Lindor K.D., Kowdley K.V., Harrison ME. American College of Gastroenterology. ACG Clinical Guideline: Primary Sclerosing Cholangitis. Am J Gastroenterol 2015; 110(5): 646– 659; quiz 660. DOI: 10.1038/ajg.2015.112Lindor K.D., Kowdley K.V., Harrison ME. American College of Gastroenterology. ACG Clinical Guideline: Primary Sclerosing Cholangitis. Am J Gastroenterol 2015; 110(5): 646– 659; quiz 660. DOI: 10.1038/ajg.2015.112Sørensen J. ., Nielsen O.H., Andersson M., Ainsworth M.A., Ytting H., Bélard E. et al. Inflammatory bowel disease with primary sclerosing cholangitis: A Danish population-based cohort study 1977–2011. Liver Int 2018; 38(3): 532–541. DOI: 10.1111/liv.13548Sørensen J. ., Nielsen O.H., Andersson M., Ainsworth M.A., Ytting H., Bélard E. et al. Inflammatory bowel disease with primary sclerosing cholangitis: A Danish population-based cohort study 1977–2011. Liver Int 2018; 38(3): 532–541. DOI: 10.1111/liv.13548Nordenvall C., Olén O., Nilsson P.J., von Seth E., Ekbom A., Bottai M. et al. Colectomy prior to diagnosis of primary sclerosing cholangitis is associated with improved prognosis in a nationwide cohort study of 2594 PSC-IBD patients. Aliment Pharmacol Ther 2018; 47(2): 238–245. DOI: 10.1111/apt.14393Nordenvall C., Olén O., Nilsson P.J., von Seth E., Ekbom A., Bottai M. et al. Colectomy prior to diagnosis of primary sclerosing cholangitis is associated with improved prognosis in a nationwide cohort study of 2594 PSC-IBD patients. Aliment Pharmacol Ther 2018; 47(2): 238–245. DOI: 10.1111/apt.14393Riley T.R., Schoen R.E., Lee R.G., Rakela J. A case series of transplant recipients who despite immunosuppression developed inflammatory bowel disease. Am J Gastroenterol 1997; 92(2): 279–282.Riley T.R., Schoen R.E., Lee R.G., Rakela J. A case series of transplant recipients who despite immunosuppression developed inflammatory bowel disease. Am J Gastroenterol 1997; 92(2): 279–282.Joo M., Abreu-e-Lima P., Farraye F., Smith T., Swaroop P., Gardner L. et al. Pathologic features of ulcerative colitis in patients with primary sclerosing cholangitis: a case-control study. Am J Surg Pathol 2009; 33(6): 854–862. DOI: 10.1097/PAS.0b013e318196d018Joo M., Abreu-e-Lima P., Farraye F., Smith T., Swaroop P., Gardner L. et al. Pathologic features of ulcerative colitis in patients with primary sclerosing cholangitis: a case-control study. Am J Surg Pathol 2009; 33(6): 854–862. DOI: 10.1097/PAS.0b013e318196d018Boonstra K., van Erpecum K.J., van Nieuwkerk K.M., Drenth J.P., Poen A.C., Witteman B.J. et al. Primary sclerosing cholangitis is associated with a distinct phenotype of inflammatory bowel disease. Inflamm Bowel Dis 2012; 18(12): 2270–2276. DOI: 10.1002/ibd.22938Boonstra K., van Erpecum K.J., van Nieuwkerk K.M., Drenth J.P., Poen A.C., Witteman B.J. et al. Primary sclerosing cholangitis is associated with a distinct phenotype of inflammatory bowel disease. Inflamm Bowel Dis 2012; 18(12): 2270–2276. DOI: 10.1002/ibd.22938Lindström L., Lapidus A., Ost A., Bergquist A. Increased risk of colorectal cancer and dysplasia in patients with Crohn’s colitis and primary sclerosing cholangitis. Dis Colon Rectum 2011; 54(11): 1392–1397. DOI: 10.1097/DCR.0b013e31822bbcc1Lindström L., Lapidus A., Ost A., Bergquist A. Increased risk of colorectal cancer and dysplasia in patients with Crohn’s colitis and primary sclerosing cholangitis. Dis Colon Rectum 2011; 54(11): 1392–1397. DOI: 10.1097/DCR.0b013e31822bbcc1Shah S.C., Ten Hove J.R., Castaneda D., Palmela C., Mooiweer E., Colombel J.F. et al. High Risk of Advanced Colorectal Neoplasia in Patients With Primary Sclerosing Cholangitis Associated With Inflammatory Bowel Disease. Clin Gastroenterol Hepatol 2018; 16(7): 1106–1113.e3. DOI: 10.1016/j. cgh.2018.01.023Shah S.C., Ten Hove J.R., Castaneda D., Palmela C., Mooiweer E., Colombel J.F. et al. High Risk of Advanced Colorectal Neoplasia in Patients With Primary Sclerosing Cholangitis Associated With Inflammatory Bowel Disease. Clin Gastroenterol Hepatol 2018; 16(7): 1106–1113.e3. DOI: 10.1016/j. cgh.2018.01.023Halliday J.S., Djordjevic J., Lust M., Culver E.L., Braden B., Travis S.P. et al. A unique clinical phenotype of primary sclerosing cholangitis associated withCrohn’s disease. J Crohns Colitis 2012; 6(2): 174–181. DOI: 10.1016/j.crohns.2011.07.015Halliday J.S., Djordjevic J., Lust M., Culver E.L., Braden B., Travis S.P. et al. A unique clinical phenotype of primary sclerosing cholangitis associated withCrohn’s disease. J Crohns Colitis 2012; 6(2): 174–181. DOI: 10.1016/j.crohns.2011.07.015Freeman H.J. Application of the Montreal classification for Crohn’s disease to a single clinician database of 1015 patients. Can J Gastroenterol 2007; 21(6): 363–366. DOI: 10.1155/2007/951526Freeman H.J. Application of the Montreal classification for Crohn’s disease to a single clinician database of 1015 patients. Can J Gastroenterol 2007; 21(6): 363–366. DOI: 10.1155/2007/951526

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