Первичный склерозирующий холангит (ПСХ) – хроническое прогрессирующее холестатическое заболевание печени неизвестной этиологии. В последние годы отмечается неуклонный рост заболеваемости ПСХ. При этом данная нозологическая форма плохо известна практикующим врачам. За последние 10 лет ведущие гепатологические ассоциации разработали или обновили уже существующие рекомендации по ПСХ, что во многом позволило стандартизировать подходы к диагностике и лечению заболевания. Однако в понимании данной нозологии остается больше нерешенных вопросов, чем ответов. Наиболее остро стоят вопросы первичной диагностики и лечения заболевания. Целью обзора явилось обобщение современных и перспективных представлений по диагностике и лечению заболевания. Проведен анализ рекомендаций ведущих гастроэнтерологических/гепатологических ассоциаций по ведению ПСХ. В результате получены наиболее полные представления об особенностях диагностики и возможностях терапии ПСХ на современном этапе развития медицины. В настоящее время влияние ни одного лекарственного препарата на выживаемость пациентов с ПСХ не доказано, и единственным методом лечения, улучшающим прогноз больных, остается трансплантация печени. В то же время неоднократно описаны случаи эффективной терапии ПСХ урсодезоксихолиевой кислотой, что обусловливает ее широкое применение в группе этих пациентов. Также представлен собственный опыт диагностики ПСХ и лечения пациента с данной нозологией.
Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic liver disease with unknown etiology. In recent years, there is steady increase in the incidence of PSC. However, this disease is poorly known to practitioners still. Within last 10 years, leading hepatological associations have developed or updated the current recommendations on PSC. That allowed to standardize approaches to diagnosis and treatment of the disease. However, there are still more questions than answers in the understanding of PSC, and it remains a scientific and clinical problem. Primary diagnosis and treatment of the disease are the sharpest issues. The purpose of this review was to summarize current and advanced concepts in the diagnosis and treatment of the disease. We analyzed recommendations of the leading gastroenterological (hepatological) associations on PSC. As a result, we have received the most complete comprehension on the features of diagnosis and treatment modalities for PSC at the present stage of the development of medicine. Currently, none of the medicinal products are proved to be effective on patient's survival rate, and liver transplantation remains the only treatment that improves prognosis of the patients with PSC. At the same time, there are many observations on effectiveness of ursodeoxycholic acid in PSC, which explains its wide use in this group of patients. We also presented our own experience in diagnosing and treating of a patient with PSC.
1. Navaneethan U, Parasa S, Venkatesh PG. Impact of inflammatory bowel disease on post-cholecystectomy complications and hospitalization costs: a Nationwide Inpatient Sample study. J Crohns Colitis 2013; 7 (5): 164–70.
2. Ngu JH, Gearry RB, Wright AJ et al. Inflammatory bowel disease is associated with poor outcomes of patients with primary sclerosing cholangitis. Clin Gastroenterol Hepatol 2011; 9 (12): 1092–7.
3. Boonstra K, Beuers U, Ponsioen CY. Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: a systematic review. J Hepatol 2012; 56 (5): 1181–8.
4. Keith D, Lindor MD, Kris V et al. ACG Clinical Guideline: Primary Sclerosing Cholangitis. Gastroenterology 2015; 110 (5): 646–59.
5. European Society of Gastrointestinal Endoscopy, European Association for the Study of the Liver. 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. J Hepatol 2017; 66 (6): 1265–81.
6. Lunder AK, Hov JR, Borthne A et al. Prevalence of sclerosing cholangitis, detected by magnetic resonance cholangiography, in patients with longterm inflammatory bowel disease. Gastroenterology 2016; 151: 660–9, e4.
7. Ивашкин В.Т., Широкова В.Т., Маевская М.В. и др. Клинические рекомендации Российской гастроэнтерологической ассоциации и Российского общества по изучению печени по диагностике и лечению холестаза. Рос. журн. гастроэнтерологии, гепатологии, колопроктологии. 2015; 2: 41–57. / Ivashkin V.T., Shirokova V.T., Maevskaia M.V. i dr. Klinicheskie rekomendatsii Rossiiskoi gastroenterologicheskoi assotsiatsii i Rossiiskogo obshchestva po izucheniiu pecheni po diagnostike i lecheniiu kholestaza. Ros. zhurn. gastroenterologii, gepatologii, koloproktologii. 2015; 2: 41–57. [in Russian]
8. EASL Clinical Practice Guidelines. Management of cholestatic liver diseases. J Hepatol 2009; 51 (2): 237–67.
9. Ang TL, Tischendorf J, Hecker H et al. Clinical profile of primary sclerosing cholangitis in Singapore. J Gastroenterol Hepatol 2002; 17 (8): 908–13.
10. Schrumpf E, Abdelnoor M, Fausa O et al. Risk factors in primary sclerosing cholangitis. J Hepatol 1994; 21: 1061–6.
11. Chapman R, Fevery J, Kallo A et al. Diagnosis and management of primary sclerosing cholangitis. J Hepatol 2010; 51 (2): 660–8.
12. Boberg KM, Chapman RW, Hirschfield GM et al. Overlap syndromes: The International Autoimmune Hepatitis Group (IAIHG) position statement on a controversial issue on behalf of the International Autoimmune Hepatitis Group. J Hepatol 2011; 54 (2): 374–85.
13. Hirschfield GM, Karlsen TH, Lindor KD et al. Primary sclerosing cholangitis. Lancet 2013; 382: 1587–99.
14. Karlsen TH, Franke A, Melum E et al. Genome-wide association analysis in primary sclerosing cholangitis. Gastroenterology 2010; 138: 1102–11.
15. Melum E, Franke A, Schramm C et al. Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci. Nat Genet. 2011; 43: 17–9.
16. Harbord M, Annese V, Vavricka SR et al. The First European Evidence-based Consensus on Extra-intestinal Manifestations in Inflammatory Bowel Disease. J Crohns Colitis 2016; 10 (3): 239–54.
17. Meagher S, Yusoff I, Kennedy W et al. The roles of magnetic resonance and endoscopic retrograde cholangiopancreatography (MRCP and ERCP) in the diagnosis of patients with suspected sclerosing cholangitis: a cost-effectiveness analysis. Endoscopy 2007; 39: 222–8.
18. Райхельсон К.Л., Карев В.Е., Марченко Н.В. и др. Морфологическая дифференциальная диагностика аутоиммунных заболеваний печени в клинической практике. Профилакт. и клин. медицина. 2013; 2 (47): 43–9. / Raikhel'son K.L., Karev V.E., Marchenko N.V. i dr. Morfologicheskaia differentsial'naia diagnostika autoimmunnykh zabolevanii pecheni v klinicheskoi praktike. Profilakt. i klin. meditsina. 2013; 2 (47): 43–9. [in Russian]
19. Van Hoogstraten HJ, Wolfhagen FH, van de Meeberg PC et al. Ursodeoxycholic acid therapy for primary sclerosing cholangitis: results of a 2-year randomized controlled trial to evaluate single versus multiple daily doses. J Hepatol 1998; 29 (3): 417–23.
20. Lindor KD. Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis–Ursodeoxycholic Acid Study Group. N Engl J Med 1997; 336: 691–5.
21. Olsson R, Boberg KM, de Muckadell OS et al. High-dose ursodeoxycholic acid in primary sclerosing cholangitis: a 5-year multicenter, randomized, controlled study. Gastroenterology 2005; 129: 1464–72.
22. Mitchell SA, Bansi DS, Hunt N et al. A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis. Gastroenterology 2001; 121: 900–7.
23. Poropat G, Giljaca V, Stimac D et al. Bile acids for primary sclerosing cholangitis. Cochrane Database Syst Rev 2011; 19 (1): CD003626. DOI: 10.1002/14651858. CD003626.pub2.
24. Hansen JD, Kumar S, Lo WK et al. Ursodiol and colorectal cancer or dysplasia risk in primary sclerosing cholangitis and inflammatory bowel disease: a meta-analysis. Dig Dis Sci 2013; 58 (11): 3079–87.
25. Cullen SN, Rust C, Fleming K et al. High dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis is safe and effective. J Hepatol 2008; 48 (5): 792–800.
26. Lindor KD, Enders FB, Schmoll JA et al. Randomized, double-blind controlled trial of high dose ursodeoxycholic acid for primary sclerosing cholangitis. J Hepatol 2008; 48: 378A.
27. Пигарова Е.А., Рожинская Л.Я., Белая Ж.Е. и др. Клинические рекомендации Российской ассоциации эндокринологов по диагностике, лечению и профилактике дефицита витамина D у взрослых. Проблемы эндокринологии. 2016; 62 (4): 60–84. / Pigarova E.A., Rozhinskaia L.Ia., Belaia Zh.E. i dr. Klinicheskie rekomendatsii Rossiiskoi assotsiatsii endokrinologov po diagnostike, lecheniiu i profilaktike defitsita vitamina D u vzroslykh. Problemy endokrinologii. 2016; 62 (4): 60–84. [in Russian]
28. Dickson ER, Murtaugh PA, Wiesner RH et al. Primary sclerosing cholangitis: refinement and validation of survival models. Gastroenterology. 1992; 103 (6): 1893–901.
29. Farrant JM. Natural history and prognostic variables in primary sclerosing cholangitis. Gastroenterology 1991; 100 (6): 1710–7.
30. OPTN/UNOS Liver and Intestinal Organ Transplantation Committee. Redesigning liver distribution to reduce variation in access to liver transplantation. [February 8, 2016].
31. Райхельсон К.Л., Прашнова М.К. Урсодезоксихолевая кислота: существующие рекомендации и перспективы применения. Доктор.ру. 2015; 12 (113): 50–6. / Raikhel`son K.L., Prashnova M.K. Ursodesoxikholevaia kislota: sushchestvuiushchie rekomendatsii i perspektivy primeneniia. Docktor.ru. 2015: 12 (113): 50–6. [in Russian]
32. Плотникова Е.Ю., Сухих А.С. Урсодезоксихолевая кислота вчера и сегодня. Терапевт. 2012; 7: 23–32. / Plotnikova E.Iu., Sukhikh A.S. Ursodesoxikholevaia kislota vchera i segodnia. Terapevt. 2012; 7: 23–32. [in Russian]
33. Багишева Н.В., Трухан Д.И., Гришечкина И.А. и др. Эффективность урсодезоксихолевой кислоты при билиарном сладже у женщин. Современные наукоемкие технологии. 2014; 12 (1): 98–9. / Bagisheva N.V., Trukhan D.I., Grishechkina I.A. Effektivnost` ursodesoxikholevoi kisloty pri biliarnom sladzhe u zhenshchin. Sovremennye naukoiomkie tekhnologii. 2014; 12 (1): 98–9. [in Russian]
34. Эсауленко Е.В., Никитина О.Е., Дунаева Н.В. и др. Опыт применения урсодеоксихолевой кислоты («Урдокса») в комплексной терапии хронического вирусного гепатита. Журн. инфектологии. 2011; 3 (3): 42–5. / Esailenko E.V., Nikitina O.E., Dunaeva N.V. Opyt primeneniia ursodesoxikholevoi kisloty (“Urdoxa”) v komplexnoi terapii khronicheskogo virusnogo gepatita. Zhurn. infektologii. 2011; 3 (3): 42–5. [in Russian]
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1. Navaneethan U, Parasa S, Venkatesh PG. Impact of inflammatory bowel disease on post-cholecystectomy complications and hospitalization costs: a Nationwide Inpatient Sample study. J Crohns Colitis 2013; 7 (5): 164–70.
2. Ngu JH, Gearry RB, Wright AJ et al. Inflammatory bowel disease is associated with poor outcomes of patients with primary sclerosing cholangitis. Clin Gastroenterol Hepatol 2011; 9 (12): 1092–7.
3. Boonstra K, Beuers U, Ponsioen CY. Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: a systematic review. J Hepatol 2012; 56 (5): 1181–8.
4. Keith D, Lindor MD, Kris V et al. ACG Clinical Guideline: Primary Sclerosing Cholangitis. Gastroenterology 2015; 110 (5): 646–59.
5. European Society of Gastrointestinal Endoscopy, European Association for the Study of the Liver. 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. J Hepatol 2017; 66 (6): 1265–81.
6. Lunder AK, Hov JR, Borthne A et al. Prevalence of sclerosing cholangitis, detected by magnetic resonance cholangiography, in patients with longterm inflammatory bowel disease. Gastroenterology 2016; 151: 660–9, e4.
7. Ivashkin V.T., Shirokova V.T., Maevskaia M.V. i dr. Klinicheskie rekomendatsii Rossiiskoi gastroenterologicheskoi assotsiatsii i Rossiiskogo obshchestva po izucheniiu pecheni po diagnostike i lecheniiu kholestaza. Ros. zhurn. gastroenterologii, gepatologii, koloproktologii. 2015; 2: 41–57. [in Russian]
8. EASL Clinical Practice Guidelines. Management of cholestatic liver diseases. J Hepatol 2009; 51 (2): 237–67.
9. Ang TL, Tischendorf J, Hecker H et al. Clinical profile of primary sclerosing cholangitis in Singapore. J Gastroenterol Hepatol 2002; 17 (8): 908–13.
10. Schrumpf E, Abdelnoor M, Fausa O et al. Risk factors in primary sclerosing cholangitis. J Hepatol 1994; 21: 1061–6.
11. Chapman R, Fevery J, Kallo A et al. Diagnosis and management of primary sclerosing cholangitis. J Hepatol 2010; 51 (2): 660–8.
12. Boberg KM, Chapman RW, Hirschfield GM et al. Overlap syndromes: The International Autoimmune Hepatitis Group (IAIHG) position statement on a controversial issue on behalf of the International Autoimmune Hepatitis Group. J Hepatol 2011; 54 (2): 374–85.
13. Hirschfield GM, Karlsen TH, Lindor KD et al. Primary sclerosing cholangitis. Lancet 2013; 382: 1587–99.
14. Karlsen TH, Franke A, Melum E et al. Genome-wide association analysis in primary sclerosing cholangitis. Gastroenterology 2010; 138: 1102–11.
15. Melum E, Franke A, Schramm C et al. Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci. Nat Genet. 2011; 43: 17–9.
16. Harbord M, Annese V, Vavricka SR et al. The First European Evidence-based Consensus on Extra-intestinal Manifestations in Inflammatory Bowel Disease. J Crohns Colitis 2016; 10 (3): 239–54.
17. Meagher S, Yusoff I, Kennedy W et al. The roles of magnetic resonance and endoscopic retrograde cholangiopancreatography (MRCP and ERCP) in the diagnosis of patients with suspected sclerosing cholangitis: a cost-effectiveness analysis. Endoscopy 2007; 39: 222–8.
18. Raikhel'son K.L., Karev V.E., Marchenko N.V. i dr. Morfologicheskaia differentsial'naia diagnostika autoimmunnykh zabolevanii pecheni v klinicheskoi praktike. Profilakt. i klin. meditsina. 2013; 2 (47): 43–9. [in Russian]
19. Van Hoogstraten HJ, Wolfhagen FH, van de Meeberg PC et al. Ursodeoxycholic acid therapy for primary sclerosing cholangitis: results of a 2-year randomized controlled trial to evaluate single versus multiple daily doses. J Hepatol 1998; 29 (3): 417–23.
20. Lindor KD. Ursodiol for primary sclerosing cholangitis. Mayo Primary Sclerosing Cholangitis–Ursodeoxycholic Acid Study Group. N Engl J Med 1997; 336: 691–5.
21. Olsson R, Boberg KM, de Muckadell OS et al. High-dose ursodeoxycholic acid in primary sclerosing cholangitis: a 5-year multicenter, randomized, controlled study. Gastroenterology 2005; 129: 1464–72.
22. Mitchell SA, Bansi DS, Hunt N et al. A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis. Gastroenterology 2001; 121: 900–7.
23. Poropat G, Giljaca V, Stimac D et al. Bile acids for primary sclerosing cholangitis. Cochrane Database Syst Rev 2011; 19 (1): CD003626. DOI: 10.1002/14651858. CD003626.pub2.
24. Hansen JD, Kumar S, Lo WK et al. Ursodiol and colorectal cancer or dysplasia risk in primary sclerosing cholangitis and inflammatory bowel disease: a meta-analysis. Dig Dis Sci 2013; 58 (11): 3079–87.
25. Cullen SN, Rust C, Fleming K et al. High dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis is safe and effective. J Hepatol 2008; 48 (5): 792–800.
26. Lindor KD, Enders FB, Schmoll JA et al. Randomized, double-blind controlled trial of high dose ursodeoxycholic acid for primary sclerosing cholangitis. J Hepatol 2008; 48: 378A.
27. Pigarova E.A., Rozhinskaia L.Ia., Belaia Zh.E. i dr. Klinicheskie rekomendatsii Rossiiskoi assotsiatsii endokrinologov po diagnostike, lecheniiu i profilaktike defitsita vitamina D u vzroslykh. Problemy endokrinologii. 2016; 62 (4): 60–84. [in Russian]
28. Dickson ER, Murtaugh PA, Wiesner RH et al. Primary sclerosing cholangitis: refinement and validation of survival models. Gastroenterology. 1992; 103 (6): 1893–901.
29. Farrant JM. Natural history and prognostic variables in primary sclerosing cholangitis. Gastroenterology 1991; 100 (6): 1710–7.
30. OPTN/UNOS Liver and Intestinal Organ Transplantation Committee. Redesigning liver distribution to reduce variation in access to liver transplantation. [February 8, 2016].
31. Raikhel`son K.L., Prashnova M.K. Ursodesoxikholevaia kislota: sushchestvuiushchie rekomendatsii i perspektivy primeneniia. Docktor.ru. 2015: 12 (113): 50–6. [in Russian]
32. Plotnikova E.Iu., Sukhikh A.S. Ursodesoxikholevaia kislota vchera i segodnia. Terapevt. 2012; 7: 23–32. [in Russian]
33. Bagisheva N.V., Trukhan D.I., Grishechkina I.A. Effektivnost` ursodesoxikholevoi kisloty pri biliarnom sladzhe u zhenshchin. Sovremennye naukoiomkie tekhnologii. 2014; 12 (1): 98–9. [in Russian]
34. Esailenko E.V., Nikitina O.E., Dunaeva N.V. Opyt primeneniia ursodesoxikholevoi kisloty (“Urdoxa”) v komplexnoi terapii khronicheskogo virusnogo gepatita. Zhurn. infektologii. 2011; 3 (3): 42–5. [in Russian]
Авторы
К.Л.Райхельсон*, Е.В.Пазенко, Н.В.Марченко
ФГБОУ ВО «Санкт-Петербургский государственный университет». 199034, Санкт-Петербург, Университетская наб., д. 7/9 *kraikhelson@mail.ru
________________________________________________
K.L.Raikhelson*, E.V.Pazenko, N.V.Marchenko
Saint Petersburg State University. 199034, Russian Federation, Saint Petersburg, Universitetskaia nab., d. 7/9 *kraikhelson@mail.ru