Достижима ли гистологическая ремиссия язвенного колита? - Журнал Терапевтический архив №8 Вопросы лечения 2021

Достижима ли гистологическая ремиссия язвенного колита?

Князев О.В., Каграманова А.В., Хомерики С.Г., Парфенов А.И. Достижима ли гистологическая ремиссия язвенного колита? Терапевтический архив. 2021; 93 (8): 975–981. DOI: 10.26442/00403660.2021.08.200981

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Knyazev OV, Kagramanova AV, Khomeriki SG, Parfenov AI. Is histological remission of ulcerative colitis achievable? Terapevticheskii Arkhiv (Ter. Arkh.). 2021; 93 (8): 975–981. DOI: 10.26442/00403660.2021.08.200981

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Аннотация

В настоящее время в концепцию глубокой ремиссии у пациентов с язвенным колитом (ЯК) включены не только достижение клинической ремиссии, но и эндоскопическое заживление слизистой оболочки толстой кишки и нормализация лабораторных маркеров воспаления. Гистологическая ремиссия в настоящее время не является конечной мишенью терапии ЯК, но должна оцениваться как показатель глубины ремиссии. Тенденция современной терапии ЯК должна быть направлена на эндоскопическое заживление слизистой оболочки кишки, уменьшение активности воспалительного процесса, увеличение продолжительности ремиссии, уменьшение частоты рецидивов заболевания, а также на гистологическую ремиссию ЯК. Тем не менее еще не определено согласованное понятие гистологической ремиссии и ни один из предлагаемых гистологических индексов не стандартизирован. Необходима единая унифицированная формулировка понятия «гистологическая ремиссия» на основании анализа многоцентровых исследований и принятия консенсуса по данному вопросу. Возможность полного восстановления нормальной структуры слизистой оболочки толстой кишки является трудновыполнимой задачей, и, как показали результаты многочисленных исследований, критерии оценки морфологической диагностики гистологической ремиссии достаточно противоречивы и вполне справедливо являются предметом дальнейшей дискуссии.

Ключевые слова: гистологический индекс, гистологическая ремиссия, язвенный колит

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Current conception of deep remission in patients with ulcerative colitis (UC) consists of clinical remission, endoscopic mucosal healing and normalization of laboratory markers. Histological remission should not be used as a primary end point for therapeutic efficacy, but instead should be considered as a marker of deep remission. The main goal of UC treatment should be focused on endoscopic healing of colon mucosa, decrease of inflammation activity, prolonged remission, absence of disease recurrence, and also histologic remission. Nevertheless, the term histologic remission has not yet been fully validated and no histologic indexes have been standardized. We need single unified definition for remission, based on multicentral studies analysis. One of important challenge is restoration of normal colon mucosal and results of multiple studies showed contradictory tests for assessing histologic remission, thus remaining an issue for further discussion.

Keywords: histological index, histological remission, ulcerative colitis

Список литературы

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4. Ungaro R, Colombel JF, Lissoos T, Peyrin-Biroulet L. A Treat-to-Target Update in Ulcerative Colitis: A Systematic Review. Am J Gastroenterol. 2019;114(6):874-83. DOI:10.14309/ajg.0000000000000183
5. Ardizzone S, Cassinotti A, Duca P, et al. Mucosal healing predicts late outcomes after the first course of corticosteroids for newly diagnosed ulcerative colitis. Clin Gastroenterol Hepatol. 2011;9(6):483-9.e3. DOI:10.1016/j.cgh.2010.12.028
6. Zenlea T, Yee EU, Rosenberg L, et al. Histology grade is independently associated with relapse risk in patients with ulcerative colitis in clinical remission: a prospective study. Am J Gastroenterol. 2016;111:685-90. DOI:10.1038/ajg.2016.50
7. Bopanna S, Roy M, Das P, et al. Role of random biopsies in surveillance of dysplasia in ulcerative colitis patients with high risk of colorectal cancer. Intest Res. 2016;14:264-9. DOI:10.5217/ir.2016.14.3.264
8. Colman RJ, Rubin DT. Histological inflammation increases the risk of colorectal neoplasia in ulcerative colitis: a systematic review. Intest Res. 2016;14:202-10. DOI:10.5217/ir.2016.14.3.202
9. Bryant RV, Burger DC, Delo J, et al. Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up. Gut. 2016;65:408-14. DOI:10.5217/ir.2016.14.3.202
10. Тертычный А.С., Ахриева Х.М., Маев И.В., и др. Проблемы диагностики гистологической ремиссии у больных с воспалительными заболеваниями кишечника. Архив патологии. 2017;79(3):3-9 [Tertychnyi AS, Akhrieva KhM, Maev IV, et al. Problemy diagnostiki gistologicheskoi remissii u bol'nykh s vospalitel'nymi zabolevaniiami kishechnika. Arkhiv patologii. 2017;79(3):3-9 (in Russian)]. DOI:10.17116/patol20177933-9
11. Magro F, Langner C, Driessen A, et al. European consensus on the histopathology of inflammatory bowel disease. J Crohns Colitis. 2013;7(10):827-51. DOI:10.1016/j.crohns.2013.06.001
12. Narang V, Kaur R, Garg B, et al. Association of endoscopic and histological remission with clinical course in patients of ulcerative colitis. Intest Res. 2018;16:55-61. DOI:10.5217/ir.2018.16.1.55
13. Geboes K, Riddell R, Ost A, et al. A reproducible grading scale for histological assessment of inflammation in ulcerative colitis. Gut. 2000;47:404-9. DOI:10.1136/gut.47.3.404
14. Mosli MH, Feagan BG, Zou G, et al. Development and validation of a histological index for UC. Gut. 2017;66:50-8. DOI:10.1136/gutjnl-2015-310393
15. Truelove SC, Richards WC. Biopsy studies in ulcerative colitis. Br Med J. 1956;1:1315-18. DOI:10.1136/bmj.1.4979.1315
16. Mosli MH, Feagan BG, Sandborn WJ, et al. Histologic evaluation of ulcerative colitis: a systematic review of disease activity indices. Inflamm Bowel Dis. 2014;20:564-75. DOI:10.1097/01.MIB.0000437986.00190.71
17. Marchal-Bressenot A, Salleron J, Boulagnon-Rombi C, et al. Development and validation of the Nancy histological index for UC. Gut. 2017;66:43-9. DOI:10.1136/gutjnl-2015-310187
18. Christensen B, Hanauer SB, Erlich J, et al. Histologic normalization occurs in ulcerative colitis and is associated with improved clinical outcomes. Clin Gastroenterol Hepatol. 2017;15:1557-64.e1. DOI:10.1016/j.cgh.2017.02.016
19. Löwenberg M, Vermeire S, Mostafavi N, et al. Vedolizumab Induces Endoscopic and Histologic Remission in Patients With Crohn’s Disease. Gastroenterology.
2019;157(4):997-1006.e6. DOI:10.1053/j.gastro.2019.05.067
20. Li K, Marano C, Zhang H, et al. Relationship Between Combined Histologic and Endoscopic Endpoints and Efficacy of Ustekinumab Treatment in Patients With Ulcerative Colitis. Gastroenterology. 2020;159(6):2052-64. DOI:10.1053/j.gastro.2020.08.037
21. Li K, Friedman JR, Chan D, et al. Effects of Ustekinumab on Histologic Disease Activity in Patients With Crohn’s Disease. Gastroenterology. 2019;157(4):1019-31.e7. DOI:10.1053/j.gastro.2019.06.037
22. Knyazev O, Kagramanova A, Kulakov D, et al. Combined therapy with adalimumab and mesenchymal stromal cells contributes to reduction in the degree of inflammation in ulcerative colitis. J Crohns Colitis. 2019;13(Suppl. 1):S350. DOI:10.1093/ecco-jcc/jjy222.600
23. Knyazev O, Kagramanova A, Lishchinskaya A, et al. Combined therapy with mesenchymal stromal cells and vedolizumab contributes to deep remission in ulcerative colitis. United European Gastroenterol J. 2019;7(8S):628. DOI:10.1177/2050640619854663/journals.sagepub.com/home/ueg
24. Князев О.В., Парфенов А.И. Клеточные технологии и биологическая терапия хронических воспалительных заболеваний кишечника. М.: Вита-ПРЕСС, 2020 [Kniazev OV, Parfenov AI. Cell technologies and biological therapy of chronic inflammatory bowel diseases. Moscow: Vita-PRESS, 2020 (in Russian)].
25. Malvão LD, Madi K, Esberard BC, et al. Fecal calprotectin as a noninvasive test to predict deep remission in patients with ulcerative colitis. Medicine. 2021;100:3(e24058). DOI:10.1097/MD.0000000000024058
26. Щукина О.Б., Кондрашина Э.А., Харитидис А.М., и др. Оценка гистологических показателей у больных с клинической ремиссией язвенного колита. Acta Biomedica Scientifica. 2014;6:39-43 [Shchukina OB, Kondrashina EA, Kharitidis AM, et al. Assessment of histological parameters in patients with clinical remission of ulcerative colitis. Acta Biomedica Scientifica. 2014;6:39-43 (in Russian)]
27. Wright R, Truelove SR. Serial rectal biopsy in ulcerative colitis during the course of a controlled therapeutic trial of various diets. Am J Dig Dis. 1966;11:847-57. DOI:10.1007/BF02233941
28. D’Haens G, Sandborn WJ, Feagan BG, et al. A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology. 2007;132:763-86. DOI:10.1053/j.gastro.2006.12.038

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1. Khat'kov IE, Parfenov AI, Kniazev OV, et al. Inflammatory bowel diseases in the practice of a therapist and surgeon. Moscow: Vita-PRESS, 2017 (in Russian)
2. Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol. 2015;110:1324-38. DOI:10.1038/ajg.2015.233
3. Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021;160(5):1570-83. DOI:10.1053/j.gastro.2020.12.031
4. Ungaro R, Colombel JF, Lissoos T, Peyrin-Biroulet L. A Treat-to-Target Update in Ulcerative Colitis: A Systematic Review. Am J Gastroenterol. 2019;114(6):874-83. DOI:10.14309/ajg.0000000000000183
5. Ardizzone S, Cassinotti A, Duca P, et al. Mucosal healing predicts late outcomes after the first course of corticosteroids for newly diagnosed ulcerative colitis. Clin Gastroenterol Hepatol. 2011;9(6):483-9.e3. DOI:10.1016/j.cgh.2010.12.028
6. Zenlea T, Yee EU, Rosenberg L, et al. Histology grade is independently associated with relapse risk in patients with ulcerative colitis in clinical remission: a prospective study. Am J Gastroenterol. 2016;111:685-90. DOI:10.1038/ajg.2016.50
7. Bopanna S, Roy M, Das P, et al. Role of random biopsies in surveillance of dysplasia in ulcerative colitis patients with high risk of colorectal cancer. Intest Res. 2016;14:264-9. DOI:10.5217/ir.2016.14.3.264
8. Colman RJ, Rubin DT. Histological inflammation increases the risk of colorectal neoplasia in ulcerative colitis: a systematic review. Intest Res. 2016;14:202-10. DOI:10.5217/ir.2016.14.3.202
9. Bryant RV, Burger DC, Delo J, et al. Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up. Gut. 2016;65:408-14. DOI:10.5217/ir.2016.14.3.202
10. Tertychnyi AS, Akhrieva KhM, Maev IV, et al. Problemy diagnostiki gistologicheskoi remissii u bol'nykh s vospalitel'nymi zabolevaniiami kishechnika. Arkhiv patologii. 2017;79(3):3-9 (in Russian) DOI:10.17116/patol20177933-9
11. Magro F, Langner C, Driessen A, et al. European consensus on the histopathology of inflammatory bowel disease. J Crohns Colitis. 2013;7(10):827-51. DOI:10.1016/j.crohns.2013.06.001
12. Narang V, Kaur R, Garg B, et al. Association of endoscopic and histological remission with clinical course in patients of ulcerative colitis. Intest Res. 2018;16:55-61. DOI:10.5217/ir.2018.16.1.55
13. Geboes K, Riddell R, Ost A, et al. A reproducible grading scale for histological assessment of inflammation in ulcerative colitis. Gut. 2000;47:404-9. DOI:10.1136/gut.47.3.404
14. Mosli MH, Feagan BG, Zou G, et al. Development and validation of a histological index for UC. Gut. 2017;66:50-8. DOI:10.1136/gutjnl-2015-310393
15. Truelove SC, Richards WC. Biopsy studies in ulcerative colitis. Br Med J. 1956;1:1315-18. DOI:10.1136/bmj.1.4979.1315
16. Mosli MH, Feagan BG, Sandborn WJ, et al. Histologic evaluation of ulcerative colitis: a systematic review of disease activity indices. Inflamm Bowel Dis. 2014;20:564-75. DOI:10.1097/01.MIB.0000437986.00190.71
17. Marchal-Bressenot A, Salleron J, Boulagnon-Rombi C, et al. Development and validation of the Nancy histological index for UC. Gut. 2017;66:43-9. DOI:10.1136/gutjnl-2015-310187
18. Christensen B, Hanauer SB, Erlich J, et al. Histologic normalization occurs in ulcerative colitis and is associated with improved clinical outcomes. Clin Gastroenterol Hepatol. 2017;15:1557-64.e1. DOI:10.1016/j.cgh.2017.02.016
19. Löwenberg M, Vermeire S, Mostafavi N, et al. Vedolizumab Induces Endoscopic and Histologic Remission in Patients With Crohn’s Disease. Gastroenterology.
2019;157(4):997-1006.e6. DOI:10.1053/j.gastro.2019.05.067
20. Li K, Marano C, Zhang H, et al. Relationship Between Combined Histologic and Endoscopic Endpoints and Efficacy of Ustekinumab Treatment in Patients With Ulcerative Colitis. Gastroenterology. 2020;159(6):2052-64. DOI:10.1053/j.gastro.2020.08.037
21. Li K, Friedman JR, Chan D, et al. Effects of Ustekinumab on Histologic Disease Activity in Patients With Crohn’s Disease. Gastroenterology. 2019;157(4):1019-31.e7. DOI:10.1053/j.gastro.2019.06.037
22. Knyazev O, Kagramanova A, Kulakov D, et al. Combined therapy with adalimumab and mesenchymal stromal cells contributes to reduction in the degree of inflammation in ulcerative colitis. J Crohns Colitis. 2019;13(Suppl. 1):S350. DOI:10.1093/ecco-jcc/jjy222.600
23. Knyazev O, Kagramanova A, Lishchinskaya A, et al. Combined therapy with mesenchymal stromal cells and vedolizumab contributes to deep remission in ulcerative colitis. United European Gastroenterol J. 2019;7(8S):628. DOI:10.1177/2050640619854663/journals.sagepub.com/home/ueg
24. Kniazev OV, Parfenov AI. Cell technologies and biological therapy of chronic inflammatory bowel diseases. Moscow: Vita-PRESS, 2020 (in Russian)
25. Malvão LD, Madi K, Esberard BC, et al. Fecal calprotectin as a noninvasive test to predict deep remission in patients with ulcerative colitis. Medicine. 2021;100:3(e24058). DOI:10.1097/MD.0000000000024058
26. Shchukina OB, Kondrashina EA, Kharitidis AM, et al. Assessment of histological parameters in patients with clinical remission of ulcerative colitis. Acta Biomedica Scientifica. 2014;6:39-43 (in Russian)
27. Wright R, Truelove SR. Serial rectal biopsy in ulcerative colitis during the course of a controlled therapeutic trial of various diets. Am J Dig Dis. 1966;11:847-57. DOI:10.1007/BF02233941
28. D’Haens G, Sandborn WJ, Feagan BG, et al. A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology. 2007;132:763-86. DOI:10.1053/j.gastro.2006.12.038

Авторы

О.В. Князев1–3, А.В. Каграманова1, С.Г. Хомерики1, А.И. Парфенов*1

1 ГБУЗ «Московский клинический научно-практический центр им. А.С. Логинова» Департамента здравоохранения г. Москвы, Москва, Россия;
2 ФГБУ «Государственный научный центр колопроктологии им. А.Н. Рыжих» Минздрава России, Москва, Россия;
3 ГБУ «Научно-исследовательский институт организации здравоохранения и медицинского менеджмента» Департамента здравоохранения г. Москвы, Москва, Россия
*asfold@mail.ru

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Oleg V. Knyazev1–3, Anna V. Kagramanova1, Sergei G. Khomeriki1, Asfold I. Parfenov*1

1 Loginov Moscow Clinical Scientific Centre, Moscow, Russia;
2 Ryzikh State Scientific Center for Coloproctology, Moscow, Russia;
3 Research Institute for Healthcare Organization and Medical Management, Moscow, Russia
*asfold@mail.ru

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