vtioВестник трансплантологии и искусственных органовRussian Journal of Transplantology and Artificial Organs1995-1191Academician V.I.Shumakov National Medical Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation10.15825/1995-1191-2022-2-39-50vtio-1474Research ArticleКлиническая трансплантологияClinical TransplantologyИсторические аспекты и современное представление об аутоиммунном гепатите. Когда показана трансплантация печени? (Обзор литературы)Historical aspects and current understanding of autoimmune hepatitis. When is liver transplantation indicated? (Review)ИльинскийИ. М.IljinskyI. M.

Ильинский Игорь Михайлович

123182, Москва, ул. Щукинская, д. 1Тел. (999) 877-60-95

Igor Iljinsky

1, Shchukinskaya str., Moscow, 123182Phone: (999) 877-60-95

iiljinsky@mail.ruЦирульниковаО. М.TsirulnikovaO. M.

Москва

Moscow

tsiroulnikova@mail.ruФГБУ «Национальный медицинский исследовательский центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава РоссииРоссияShumakov National Medical Research Center of Transplantology and Artificial OrgansRussian FederationФГБУ «Национальный медицинский исследовательский центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава России; ФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова Минздрава России (Сеченовский университет)РоссияShumakov National Medical Research Center of Transplantology and Artificial Organs; Sechenov UniversityRussian Federation2022250420222423950Copyright © Ильинский И.М., Цирульникова О.М., 20222022Ильинский И.М., Цирульникова О.М.Iljinsky I.M., Tsirulnikova O.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.transpl.ru/vtio/article/view/1474

Аутоиммунный гепатит (АИГ) может возникнуть в любом возрасте, более распространен у женщин, чем у мужчин. Болезнь является проявлением аутоиммунной предрасположенности, вызванной у генетически восприимчивых людей, подверженных экологическим факторам. Патогенез АИГ до конца не изучен, но в нем участвует агрессивный клеточный иммунный ответ. Различные цитокины также влияют на патогенез и тяжесть АИГ. Это заболевание характеризуется повышенным уровнем трансаминаз: аспартат- и аланинаминотрансферазы. Гистология печени имеет решающее значение для диагностики и контроля эффективности лечения АИГ. Диагностика АИГ остается сложной проблемой в клинической практике. Аутоиммунный гепатит является одним из немногих заболеваний печени, при котором медикаментозное лечение улучшает выживаемость пациентов. Стандартные схемы лечения включают относительно высокие дозы преднизолона или преднизолона с добавлением азатиоприна. Положительный эффект при лечении стероидами наблюдается у 80–90% больных. Примерно 20% пациентов не отвечают на лечение стероидными препаратами, и для их лечения используют иммуносупрессивные препараты второй линии: микофенолата мофетил, будесонид, циклоспорин, такролимус, эверолимус и сиролимус. Опубликован опыт применения инфликсимаба и ритуксимаба. При естественном течении АИГ и резистентности к терапии имеется тенденция развития цирроза печени и прогрессирования заболевания до терминальной стадии. Этим пациентам, а также тем, у кого при постановке диагноза обнаружена фульминантная печеночная недостаточность, требуется трансплантация печени.

Autoimmune hepatitis (AIH) can occur at any age and is more common in women. The disease is a manifestation of autoimmune predisposition caused in genetically susceptible people exposed to certain environmental factors. The pathogenetic mechanism of AIH is not yet fully understood, but it involves an aggressive cellular immune response. The pathogenesis and severity of AIH also depend on various cytokines. This disease is characterized by elevated levels of transaminases – aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Liver histology plays a crucial role in confirming or supporting the clinical diagnosis of AIH. Diagnosis of AIH remains a challenge in clinical practice. AIH is one of the few liver diseases for which pharmacologic treatment has been shown to improve survival. Standard treatment is based on high-dose prednisone alone or prednisolone plus azathioprine. It leads to disease remission in 80%-90% of patients. Approximately 20% of patients do not respond to the standard steroid treatment and are treated with second-line immunosuppressive drugs: mycophenolate mofetil, budesonide, cyclosporine, tacrolimus, everolimus, and sirolimus. There have been reports on the use of infliximab and rituximab. In the natural course of AIH and resistance to therapy, there is a tendency for cirrhosis to develop and for the disease to progress to an end stage. These patients, as well as those diagnosed with fulminant liver failure, require liver transplantation.

аутоиммунный гепатитАИГпатогенезгистологиялечениеautoimmune hepatitisAIHpathogenesishistologytreatmentReferencesMieli-Vergani G, Vergani D. Autoimmune hepatitis. Nat Rev Gastroenterol Hepatol. 2011 Jun; 8 (6): 320–329. doi: 10.1038/nrgastro.2011.69.Mieli-Vergani G, Vergani D. Autoimmune hepatitis. Nat Rev Gastroenterol Hepatol. 2011 Jun; 8 (6): 320–329. doi: 10.1038/nrgastro.2011.69.Готье СВ, Константинов БА, Цирульникова ОМ. Трансплантация печени: Руководство для врачей. М.: Медицинское информационное агентство, 2008. 248.Gautier SV, Konstantinov BA, Tsirulnikova OM. Liver transplantation: Guide for doctors. M.: Medical Information Agency, 2008. 248.Manns MP, Czaja AJ, Gorham JD et al. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010; 51: 2193–213. doi: 10.1002/hep.23584.Manns MP, Czaja AJ, Gorham JD et al. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010; 51: 2193–213. doi: 10.1002/hep.23584.Vergani D, Mieli-Vergani G. Cutting edge issues in autoimmune hepatitis. Clin Rev Allergy Immunol. 2012 Jun; 42 (3): 309–321. doi: 10.1007/s12016-010-8236-9.Vergani D, Mieli-Vergani G. Cutting edge issues in autoimmune hepatitis. Clin Rev Allergy Immunol. 2012 Jun; 42 (3): 309–321. doi: 10.1007/s12016-010-8236-9.Weiler-Normann C, Schramm C, Quaas A, Wiegard C, Glaubke C, Pannicke N et al. Infliximab as a rescue treatment in difficult-to-treat autoimmune hepatitis. J Hepatol. 2013 Mar; 58 (3): 529–534. doi: 10.1016/j.jhep.2012.11.010.Weiler-Normann C, Schramm C, Quaas A, Wiegard C, Glaubke C, Pannicke N et al. Infliximab as a rescue treatment in difficult-to-treat autoimmune hepatitis. J Hepatol. 2013 Mar; 58 (3): 529–534. doi: 10.1016/j.jhep.2012.11.010.Vierling JM. Autoimmune hepatitis and overlap syndromes: diagnosis and management. Clin Gastro Hep. 2015; 13: 2088–2108. doi: 10.1016/j.cgh.2015.08.012.Vierling JM. Autoimmune hepatitis and overlap syndromes: diagnosis and management. Clin Gastro Hep. 2015; 13: 2088–2108. doi: 10.1016/j.cgh.2015.08.012.Liberal R, Krawitt EL, Vierling JM, Manns MP, MieliVergani G, Vergani D. Cutting edge issues in autoimmune hepatitis. J Autoimmun. 2016; 75: 6–19. doi: 10.1016/j.jaut.2016.07.005.Liberal R, Krawitt EL, Vierling JM, Manns MP, MieliVergani G, Vergani D. Cutting edge issues in autoimmune hepatitis. J Autoimmun. 2016; 75: 6–19. doi: 10.1016/j.jaut.2016.07.005.Webb GJ, Hirschfield GM, Krawitt EL, Gershwin ME. Cellular and Molecular Mechanisms of Autoimmune Hepatitis. Annu Rev Pathol. 2018 Jan 24; 13: 247–292. doi: 10.1146/annurev-pathol-020117-043534.Webb GJ, Hirschfield GM, Krawitt EL, Gershwin ME. Cellular and Molecular Mechanisms of Autoimmune Hepatitis. Annu Rev Pathol. 2018 Jan 24; 13: 247–292. doi: 10.1146/annurev-pathol-020117-043534.Vergani D, Mieli-Vergani G. Pharmacological management of autoimmune hepatitis. Expert Opin Pharmacother. 2011; 12: 607–613. doi: 10.1517/14656566.2011.524206.Vergani D, Mieli-Vergani G. Pharmacological management of autoimmune hepatitis. Expert Opin Pharmacother. 2011; 12: 607–613. doi: 10.1517/14656566.2011.524206.Zhao XY, Rakhda MI, Wang TI, Jia JD. Immunoglobulin G4-associated de novo autoimmune hepatitis after liver transplantation for chronic hepatitis B- and C-related cirrhosis and hepatocellular carcinoma: a case report with literature review. Transplant Proc. 2013; 45 (2): 824–827. doi: 10.1016/j.transproceed.2012.02.049.Zhao XY, Rakhda MI, Wang TI, Jia JD. Immunoglobulin G4-associated de novo autoimmune hepatitis after liver transplantation for chronic hepatitis B- and C-related cirrhosis and hepatocellular carcinoma: a case report with literature review. Transplant Proc. 2013; 45 (2): 824–827. doi: 10.1016/j.transproceed.2012.02.049.Abe K, Takahashi A, Imaizumi H, Hayashi M, Okai K et al. Interleukin-21 plays a critical role in the pathogenesis and severity of type I autoimmune hepatitis. Springerplus. 2016 Jun 18; 5 (1): 777. doi: 10.1186/s40064-016-2512-y.Abe K, Takahashi A, Imaizumi H, Hayashi M, Okai K et al. Interleukin-21 plays a critical role in the pathogenesis and severity of type I autoimmune hepatitis. Springerplus. 2016 Jun 18; 5 (1): 777. doi: 10.1186/s40064-016-2512-y.Takahashi A, Arinaga-Hino T, Ohira H, Torimura T, Zeniya M et al. Autoimmune hepatitis in Japan: trends in a nationwide survey. J Gastroenterol. 2017 May; 52 (5): 631–640. doi: 10.1007/s00535-016-1267-0.Takahashi A, Arinaga-Hino T, Ohira H, Torimura T, Zeniya M et al. Autoimmune hepatitis in Japan: trends in a nationwide survey. J Gastroenterol. 2017 May; 52 (5): 631–640. doi: 10.1007/s00535-016-1267-0.Kim BH, Kim YJ, Jeong SH, Tak WY, Ahn SH et al. Clinical features of autoimmune hepatitis and comparison of two diagnostic criteria in Korea: a nationwide, multicenter study. J Gastroenterol Hepatol. 2013 Jan; 28 (1): 128–134. doi: 10.1111/j.1440-1746.2012.07292.x.Kim BH, Kim YJ, Jeong SH, Tak WY, Ahn SH et al. Clinical features of autoimmune hepatitis and comparison of two diagnostic criteria in Korea: a nationwide, multicenter study. J Gastroenterol Hepatol. 2013 Jan; 28 (1): 128–134. doi: 10.1111/j.1440-1746.2012.07292.x.Kerkar N, Yanni G. ‘De novo’ and ‘recurrent’ autoimmune hepatitis after liver transplantation: A comprehensive review. J Autoimmun. 2016 Jan; 66: 17–24. doi: 10.1016/j.jaut.2015.08.017.Kerkar N, Yanni G. ‘De novo’ and ‘recurrent’ autoimmune hepatitis after liver transplantation: A comprehensive review. J Autoimmun. 2016 Jan; 66: 17–24. doi: 10.1016/j.jaut.2015.08.017.Werner M, Prytz H, Ohlsson B, Almer S, Bjornsson E et al. Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: a nationwide study. Scand J Gastroenterol. 2008; 43 (10): 1232–1240. doi: 10.1080/00365520802130183.Werner M, Prytz H, Ohlsson B, Almer S, Bjornsson E et al. Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: a nationwide study. Scand J Gastroenterol. 2008; 43 (10): 1232–1240. doi: 10.1080/00365520802130183.Grønbæk L, Vilstrup H, Jepsen P. Autoimmune hepatitis in Denmark: incidence, prevalence, prognosis, and causes of death. A nationwide registry-based cohort study. J Hepatol. 2014 Mar; 60 (3): 612–617. doi: 10.1016/j.jhep.2013.10.020.Grønbæk L, Vilstrup H, Jepsen P. Autoimmune hepatitis in Denmark: incidence, prevalence, prognosis, and causes of death. A nationwide registry-based cohort study. J Hepatol. 2014 Mar; 60 (3): 612–617. doi: 10.1016/j.jhep.2013.10.020.Yang F, Wang Q, Bian Z, Ren LL, Jia J, Ma X. Autoimmune hepatitis: East meets west. J Gastroenterol Hepatol. 2015; 30: 1230–1236. doi: 10.1111/jgh.12952.Yang F, Wang Q, Bian Z, Ren LL, Jia J, Ma X. Autoimmune hepatitis: East meets west. J Gastroenterol Hepatol. 2015; 30: 1230–1236. doi: 10.1111/jgh.12952.Abe K, Takahashi A, Fujita M, Hayashi M, Okai K et al. Interleukin-33/ST2-Mediated Inflammation Plays a Critical Role in the Pathogenesis and Severity of Type I Autoimmune Hepatitis. Hepatol Commun. 2019 Feb 25; 3 (5): 670–684. doi: 10.1002/hep4.1326.Abe K, Takahashi A, Fujita M, Hayashi M, Okai K et al. Interleukin-33/ST2-Mediated Inflammation Plays a Critical Role in the Pathogenesis and Severity of Type I Autoimmune Hepatitis. Hepatol Commun. 2019 Feb 25; 3 (5): 670–684. doi: 10.1002/hep4.1326.Corrigan M, Hirschfield GM, Oo YH, Adams DH. Autoimmune hepatitis: an approach to disease understanding and management. Br Med Bull. 2015 Jun; 114 (1): 181–191. doi: 10.1093/bmb/ldv021.Corrigan M, Hirschfield GM, Oo YH, Adams DH. Autoimmune hepatitis: an approach to disease understanding and management. Br Med Bull. 2015 Jun; 114 (1): 181–191. doi: 10.1093/bmb/ldv021.Vergani D, Mieli-Vergani G. Aetiopathogenesis of autoimmune hepatitis. World J Gastroenterol. 2008 Jun 7; 14 (21): 3306–3312. doi: 10.3748/wjg.14.3306.Vergani D, Mieli-Vergani G. Aetiopathogenesis of autoimmune hepatitis. World J Gastroenterol. 2008 Jun 7; 14 (21): 3306–3312. doi: 10.3748/wjg.14.3306.Agarwal K, Czaja AJ, Donaldson PT. A functional Fas promoter polymorphism is associated with a severe phenotype in type 1 autoimmune hepatitis characterized by early development of cirrhosis. Tissue Antigens. 2007 Mar; 69 (3): 227–235. doi: 10.1111/j.1399-0039.2006.00794.x.Agarwal K, Czaja AJ, Donaldson PT. A functional Fas promoter polymorphism is associated with a severe phenotype in type 1 autoimmune hepatitis characterized by early development of cirrhosis. Tissue Antigens. 2007 Mar; 69 (3): 227–235. doi: 10.1111/j.1399-0039.2006.00794.x.Ma Y, Bogdanos DP, Hussain MJ, Underhill J, Bansal S et al. Polyclonal T-cell responses to cytochrome P450I-ID6 are associated with disease activity in autoimmune hepatitis type 2. Gastroenterology. 2006; 130: 868–882. doi: 10.1053/j.gastro.2005.12.020.Ma Y, Bogdanos DP, Hussain MJ, Underhill J, Bansal S et al. Polyclonal T-cell responses to cytochrome P450I-ID6 are associated with disease activity in autoimmune hepatitis type 2. Gastroenterology. 2006; 130: 868–882. doi: 10.1053/j.gastro.2005.12.020.Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D. Autoimmune hepatitis: Standard treatment and systematic review of alternative treatments. World J Gastroenterol. 2017 Sep 7; 23 (33): 6030–6048. doi: 10.3748/wjg.v23.i33.6030.Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D. Autoimmune hepatitis: Standard treatment and systematic review of alternative treatments. World J Gastroenterol. 2017 Sep 7; 23 (33): 6030–6048. doi: 10.3748/wjg.v23.i33.6030.Kamijo A, Yoshizawa K, Joshita S, Yoneda S, Umemura T et al. Cytokine profiles affecting the pathogenesis of autoimmune hepatitis in Japanese patients. Hepatol Res. 2011 Apr; 41 (4): 350–357. doi: 10.1111/j.1872-034X.2011.00773.x.Kamijo A, Yoshizawa K, Joshita S, Yoneda S, Umemura T et al. Cytokine profiles affecting the pathogenesis of autoimmune hepatitis in Japanese patients. Hepatol Res. 2011 Apr; 41 (4): 350–357. doi: 10.1111/j.1872-034X.2011.00773.x.Liang M, Liwen Z, Yun Z, Yanbo D, Jianping C. Serum Levels of IL-33 and Correlation with IL-4, IL-17A, and Hypergammaglobulinemia in Patients with Autoimmune Hepatitis. Mediators Inflamm. 2018 Jun 24; 2018: 7964654. doi: 10.1155/2018/7964654.Liang M, Liwen Z, Yun Z, Yanbo D, Jianping C. Serum Levels of IL-33 and Correlation with IL-4, IL-17A, and Hypergammaglobulinemia in Patients with Autoimmune Hepatitis. Mediators Inflamm. 2018 Jun 24; 2018: 7964654. doi: 10.1155/2018/7964654.Wobser H, Paur T, Schnoy E, Hartl J, Kirchner GI. Suitability of the simplified autoimmune hepatitis score for the diagnosis of autoimmune hepatitis in a German cohort. United European Gastroenterol J. 2018 Mar; 6 (2): 247–254. doi: 10.1177/2050640617711632.Wobser H, Paur T, Schnoy E, Hartl J, Kirchner GI. Suitability of the simplified autoimmune hepatitis score for the diagnosis of autoimmune hepatitis in a German cohort. United European Gastroenterol J. 2018 Mar; 6 (2): 247–254. doi: 10.1177/2050640617711632.Dohmen K, Tanaka H, Haruno M, Aishima S. Immunoserological and histological differences between autoimmune hepatitis with acute presentation and chronic autoimmune hepatitis. Hepatol Res. 2017 Dec; 47 (13): 1375–1382. doi: 10.1111/hepr.12875.Dohmen K, Tanaka H, Haruno M, Aishima S. Immunoserological and histological differences between autoimmune hepatitis with acute presentation and chronic autoimmune hepatitis. Hepatol Res. 2017 Dec; 47 (13): 1375–1382. doi: 10.1111/hepr.12875.Lohse AW, Mieli-Vergani G. Autoimmune hepatitis. J Hepatol. 2011 Jul; 55 (1): 171–182. doi: 10.1016/j.jhep.2010.12.012.Lohse AW, Mieli-Vergani G. Autoimmune hepatitis. J Hepatol. 2011 Jul; 55 (1): 171–182. doi: 10.1016/j.jhep.2010.12.012.Longhi MS, Ma Y, Mieli-Vergani G, Vergani D. Adaptive immunity in autoimmune hepatitis. Dig Dis. 2010; 28(1): 63–69. doi: 10.1159/000282066.Longhi MS, Ma Y, Mieli-Vergani G, Vergani D. Adaptive immunity in autoimmune hepatitis. Dig Dis. 2010; 28(1): 63–69. doi: 10.1159/000282066.Muratori L, Longhi MS. The interplay between regulatory and effector T cells in autoimmune hepatitis: Implications for innovative treatment strategies. J Autoimmun. 2013 Oct; 46: 74–80. doi: 10.1016/j.jaut.2013.06.016.Muratori L, Longhi MS. The interplay between regulatory and effector T cells in autoimmune hepatitis: Implications for innovative treatment strategies. J Autoimmun. 2013 Oct; 46: 74–80. doi: 10.1016/j.jaut.2013.06.016.Ma L, Qin J, Ji H, Zhao P, Jiang Y. Tfh and plasma cells are correlated with hypergammaglobulinaemia in patients with autoimmune hepatitis. Liver Int. 2014 Mar; 34(3): 405–415. doi: 10.1111/liv.12245.Ma L, Qin J, Ji H, Zhao P, Jiang Y. Tfh and plasma cells are correlated with hypergammaglobulinaemia in patients with autoimmune hepatitis. Liver Int. 2014 Mar; 34(3): 405–415. doi: 10.1111/liv.12245.Qiu D, Wang Q, Wang H, Xie Q, Zang G et al. Validation of the simplified criteria for diagnosis of autoimmune hepatitis in Chinese patients. J Hepatol. 2011 Feb; 54(2): 340–347. doi: 10.1016/j.jhep.2010.06.032.Qiu D, Wang Q, Wang H, Xie Q, Zang G et al. Validation of the simplified criteria for diagnosis of autoimmune hepatitis in Chinese patients. J Hepatol. 2011 Feb; 54(2): 340–347. doi: 10.1016/j.jhep.2010.06.032.Bjornsson E, Talwalkar J, Treeprasertsuk S, Neuhauser M, Lindor K. Patients with typical laboratory features of autoimmune hepatitis rarely need a liver biopsy for diagnosis. Clin Gastroenterol Hepatol. 2011 Jan; 9 (1): 57–63. doi: 10.1016/j.cgh.2010.07.016.Bjornsson E, Talwalkar J, Treeprasertsuk S, Neuhauser M, Lindor K. Patients with typical laboratory features of autoimmune hepatitis rarely need a liver biopsy for diagnosis. Clin Gastroenterol Hepatol. 2011 Jan; 9 (1): 57–63. doi: 10.1016/j.cgh.2010.07.016.Harada K., Hiep N.C., Ohira H. Challenges and Difficulties in Pathological Diagnosis of Autoimmune Hepatitis. Hepatol Res. 2017; 47 (10): 963–971. doi: 10.1111/hepr.12931.Harada K., Hiep N.C., Ohira H. Challenges and Difficulties in Pathological Diagnosis of Autoimmune Hepatitis. Hepatol Res. 2017; 47 (10): 963–971. doi: 10.1111/hepr.12931.Сандлер ЮГ, Салиев КГ, Бацких СН, Хомерики СГ, Хайменова ТЮ, Дорофеев АС и др. Клинико-иммунологические и морфологические особенности различных вариантов аутоиммунного гепатита. Терапевтический архив. 2020; 92 (2): 43–47. doi: 10.26442/00403660.2020.02.000536.Sandler YuG, Saliev KG, Batskikh SN, Khomeriki SG, Khaimenova TYu, Dorofeev AS et al. Clinical, immunological and morphological features of various variants of autoimmune hepatitis. Therapeutic archive. 2020; 92 (2): 43–47. doi: 10.26442/00403660.2020.02.000536.Werner M, Prytz H, Ohlsson B, Almer S, Bjornsson E et al. Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: a nationwide study. Scand J Gastroenterol. 2008; 43 (10): 1232–1240. doi:10.1080/00365520802130183.Werner M, Prytz H, Ohlsson B, Almer S, Bjornsson E et al. Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: a nationwide study. Scand J Gastroenterol. 2008; 43 (10): 1232–1240. doi:10.1080/00365520802130183.Czaja AJ. Cholestatic phenotypes of autoimmune hepatitis. Clin Gastroenterol Hepatol. 2014 Sep; 12 (9): 1430–1438. doi: 10.1016/j.cgh.2013.08.039.Czaja AJ. Cholestatic phenotypes of autoimmune hepatitis. Clin Gastroenterol Hepatol. 2014 Sep; 12 (9): 1430–1438. doi: 10.1016/j.cgh.2013.08.039.Dhaliwal HK, Hoeroldt BS, Dube AK, McFarlane E, Underwood JC et al. Long-Term Prognostic Significance of Persisting Histological Activity Despite Biochemical Remission in Autoimmune Hepatitis. Am J Gastroenterol. 2015 Jul; 110 (7): 993–999. doi: 10.1038/ajg.2015.139.Dhaliwal HK, Hoeroldt BS, Dube AK, McFarlane E, Underwood JC et al. Long-Term Prognostic Significance of Persisting Histological Activity Despite Biochemical Remission in Autoimmune Hepatitis. Am J Gastroenterol. 2015 Jul; 110 (7): 993–999. doi: 10.1038/ajg.2015.139.Gatselis NK, Zachou K, Papamichalis P, Koukoulis GK, Gabeta S et al. Comparison of simplified score with the revised original score for the diagnosis of autoimmune hepatitis: a new or a complementary diagnostic score? Dig Liver Dis. 2010 Nov; 42 (11): 807–812. doi:10.1016/j.dld.2010.03.005.Gatselis NK, Zachou K, Papamichalis P, Koukoulis GK, Gabeta S et al. Comparison of simplified score with the revised original score for the diagnosis of autoimmune hepatitis: a new or a complementary diagnostic score? Dig Liver Dis. 2010 Nov; 42 (11): 807–812. doi:10.1016/j.dld.2010.03.005.Arinaga-Hino T, Ide T, Miyajima I, Ogata K, Kuwahara R et al. Kurume Autoimmune Hepatitis Study Group. Risk of malignancies in autoimmune hepatitis type 1 patients with a long-term follow-up in Japan. Hepatol Res. 2017 Aug 25. doi: 10.1111/hepr.12973.Arinaga-Hino T, Ide T, Miyajima I, Ogata K, Kuwahara R et al. Kurume Autoimmune Hepatitis Study Group. Risk of malignancies in autoimmune hepatitis type 1 patients with a long-term follow-up in Japan. Hepatol Res. 2017 Aug 25. doi: 10.1111/hepr.12973.Johnson PJ, McFarlane IG. Meeting report: International Autoimmune Hepatitis Group. Hepatology. 1993 Oct; 18 (4): 998–1005. doi: 10.1002/hep.1840180435.Johnson PJ, McFarlane IG. Meeting report: International Autoimmune Hepatitis Group. Hepatology. 1993 Oct; 18 (4): 998–1005. doi: 10.1002/hep.1840180435.Alvarez F, Berg PA, Bianchi FB et al. International Autoimmune Hepatitis Group report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999; 31: 929–938. doi: 10.1016/s0168-8278(99)80297-9.Alvarez F, Berg PA, Bianchi FB et al. International Autoimmune Hepatitis Group report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999; 31: 929–938. doi: 10.1016/s0168-8278(99)80297-9.Choi G, Peters MG. The challenge of diagnosing autoimmune hepatitis: less is more. Hepatology. 2008 Jul; 48 (1): 10–12. doi: 10.1002/hep.22438.Choi G, Peters MG. The challenge of diagnosing autoimmune hepatitis: less is more. Hepatology. 2008 Jul; 48 (1): 10–12. doi: 10.1002/hep.22438.Hennes EM, Zeniya M, Czaja AJ, Parés A, Dalekos GN, Krawitt EL et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology. 2008 Jul; 48 (1): 169–176. doi: 10.1002/hep.22322.Hennes EM, Zeniya M, Czaja AJ, Parés A, Dalekos GN, Krawitt EL et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology. 2008 Jul; 48 (1): 169–176. doi: 10.1002/hep.22322.Muratori P, Granito A, Pappas G, Muratori L. Validation of simplified diagnostic criteria for autoimmune hepatitis in Italian patients. Hepatology. 2009; 49: 1782–1783. doi: 10.1002/hep.22825.Muratori P, Granito A, Pappas G, Muratori L. Validation of simplified diagnostic criteria for autoimmune hepatitis in Italian patients. Hepatology. 2009; 49: 1782–1783. doi: 10.1002/hep.22825.Fujiwara K, Yasui S, Tawada A, Fukuda Y, Nakano M, Yokosuka O. Diagnostic value and utility of the simplified International Autoimmune Hepatitis Group criteria in acute-onset autoimmune hepatitis. Liver Int. 2011 Aug; 31 (7): 1013–1020. doi: 10.1111/j.1478-3231.2011.02524.x.Fujiwara K, Yasui S, Tawada A, Fukuda Y, Nakano M, Yokosuka O. Diagnostic value and utility of the simplified International Autoimmune Hepatitis Group criteria in acute-onset autoimmune hepatitis. Liver Int. 2011 Aug; 31 (7): 1013–1020. doi: 10.1111/j.1478-3231.2011.02524.x.Li Y, Peng M, Gong G. Evaluation of the revised versus the simplified scoring system in patients with autoimmune hepatitis. Exp Ther Med. 2014 Jan; 7 (1): 131–136. doi: 10.3892/etm.2013.1366.Li Y, Peng M, Gong G. Evaluation of the revised versus the simplified scoring system in patients with autoimmune hepatitis. Exp Ther Med. 2014 Jan; 7 (1): 131–136. doi: 10.3892/etm.2013.1366.Yeoman AD, Westbrook RH, Al-Chalabi T, Carey I, Heaton ND, Portmann BC et al. Diagnostic value and utility of the simplified International Autoimmune Hepatitis Group (IAIHG) criteria in acute and chronic liver disease. Hepatology. 2009; 50: 538–545. doi: 10.1002/hep.23042.Yeoman AD, Westbrook RH, Al-Chalabi T, Carey I, Heaton ND, Portmann BC et al. Diagnostic value and utility of the simplified International Autoimmune Hepatitis Group (IAIHG) criteria in acute and chronic liver disease. Hepatology. 2009; 50: 538–545. doi: 10.1002/hep.23042.Hiejima E, Komatsu H, Sogo T, Inui A, Fujisawa T. Utility of simplified criteria for the diagnosis of autoimmune hepatitis in children. J Pediatr Gastroenterol Nutr. 2011 Apr; 52 (4): 470–473. doi: 10.1097/MPG.0b013e3181fc1e0b.Hiejima E, Komatsu H, Sogo T, Inui A, Fujisawa T. Utility of simplified criteria for the diagnosis of autoimmune hepatitis in children. J Pediatr Gastroenterol Nutr. 2011 Apr; 52 (4): 470–473. doi: 10.1097/MPG.0b013e3181fc1e0b.Mileti E, Rosenthal P, Peters MG. Validation and modification of simplified diagnostic criteria for autoimmune hepatitis in children. Clin Gastroenterol Hepatol. 2012 Apr; 10 (4): 417-21.e1-2. doi: 10.1016/j.cgh.2011.11.030.Mileti E, Rosenthal P, Peters MG. Validation and modification of simplified diagnostic criteria for autoimmune hepatitis in children. Clin Gastroenterol Hepatol. 2012 Apr; 10 (4): 417-21.e1-2. doi: 10.1016/j.cgh.2011.11.030.Liu F, Pan ZG, Ye J, Xu D, Guo H et al. Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: simplified criteria may be effective in the diagnosis in Chinese patients. J Dig Dis. 2014 Dec; 15 (12): 660–668. doi:10.1111/1751-2980.12196.Liu F, Pan ZG, Ye J, Xu D, Guo H et al. Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: simplified criteria may be effective in the diagnosis in Chinese patients. J Dig Dis. 2014 Dec; 15 (12): 660–668. doi:10.1111/1751-2980.12196.Munoz-Espinosa L, Alarcon G, Mercado-Moreira A, Cordero P, Caballero E et al. Performance of the international classifications criteria for autoimmune hepatitis diagnosis in Mexican patients. Autoimmunity. 2011 Nov; 44 (7): 543–548. doi: 10.3109/08916934.2011.592884.Munoz-Espinosa L, Alarcon G, Mercado-Moreira A, Cordero P, Caballero E et al. Performance of the international classifications criteria for autoimmune hepatitis diagnosis in Mexican patients. Autoimmunity. 2011 Nov; 44 (7): 543–548. doi: 10.3109/08916934.2011.592884.Yatsuji S, Hashimoto E, Kaneda H, Taniai M, Tokushige K, Shiratori K. Diagnosing autoimmune hepatitis in nonalcoholic fatty liver disease: is the International Autoimmune Hepatitis Group scoring system useful? J Gastroenterol. 2005 Dec; 40 (12): 1130–1138. doi:10.1007/s00535-005-1711-z.Yatsuji S, Hashimoto E, Kaneda H, Taniai M, Tokushige K, Shiratori K. Diagnosing autoimmune hepatitis in nonalcoholic fatty liver disease: is the International Autoimmune Hepatitis Group scoring system useful? J Gastroenterol. 2005 Dec; 40 (12): 1130–1138. doi:10.1007/s00535-005-1711-z.DeLemos AS, Foureau DM, Jacobs C, Ahrens W, Russo MW, Bonkovsky HL. Drug-induced liver injury with autoimmune features. Semin Liver Dis. 2014 May; 34(2): 194–204. doi: 10.1055/s-0034-1375959. Epub 2014 May 31.DeLemos AS, Foureau DM, Jacobs C, Ahrens W, Russo MW, Bonkovsky HL. Drug-induced liver injury with autoimmune features. Semin Liver Dis. 2014 May; 34(2): 194–204. doi: 10.1055/s-0034-1375959. Epub 2014 May 31.Boberg KM, Chapman RW, Hirschfield GM, Lohse AW, Manns MP, Schrumpf E. International Autoimmune Hepatitis Group. Overlap syndromes: the International Autoimmune Hepatitis Group (IAIHG) position statement on a controversial issue. J Hepatol. 2011 Feb; 54 (2): 374–385. doi: 10.1016/j.jhep.2010.09.002.Boberg KM, Chapman RW, Hirschfield GM, Lohse AW, Manns MP, Schrumpf E. International Autoimmune Hepatitis Group. Overlap syndromes: the International Autoimmune Hepatitis Group (IAIHG) position statement on a controversial issue. J Hepatol. 2011 Feb; 54 (2): 374–385. doi: 10.1016/j.jhep.2010.09.002.Chandok N, Silveira MG, Lindor KD. Comparing the simplified and international autoimmune hepatitis group criteria in primary sclerosing cholangitis. Gastroenterol Hepatol (NY). 2010 Feb; 6 (2): 108–112.Chandok N, Silveira MG, Lindor KD. Comparing the simplified and international autoimmune hepatitis group criteria in primary sclerosing cholangitis. Gastroenterol Hepatol (NY). 2010 Feb; 6 (2): 108–112.Krawitt EL. Autoimmune hepatitis. N Engl J Med. 2006 Jan 5; 354 (1): 54–66. doi: 10.1056/NEJMra050408.Krawitt EL. Autoimmune hepatitis. N Engl J Med. 2006 Jan 5; 354 (1): 54–66. doi: 10.1056/NEJMra050408.Мациевич МВ, Буеверов АО, Петраченкова МЮ. Альтернативные схемы терапии аутоиммунного гепатита: насколько обоснован их выбор? Альманах клинической медицины. 2018; 46 (5): 504–513. doi: 10.18786/2072-0505-2018-46-5-504-513.Matsievich MV, Bueverov AO, Petrachenkova MYu. Alternative treatment regimens for autoimmune hepatitis: how justified is their choice? Almanac of Clinical Medicine. 2018; 46 (5): 504–513. doi: 10.18786/2072-0505-2018-46-5-504-513.Krawitt EL. Clinical features and management of autoimmune hepatitis. World J Gastroenterol. 2008 Jun 7; 14 (21): 3301–3305. doi: 10.3748/wjg.14.3301.Krawitt EL. Clinical features and management of autoimmune hepatitis. World J Gastroenterol. 2008 Jun 7; 14 (21): 3301–3305. doi: 10.3748/wjg.14.3301.Arcos-Machancoses JV, Molera Busoms C, Julio Tatis E, Victoria Bovo M, Quintero Bernabeu J et al. Accuracy of the 2008 Simplified Criteria for the Diagnosis of Autoimmune Hepatitis in Children. Pediatr Gastroenterol Hepatol Nutr. 2018 Apr; 21 (2): 118–126. doi: 10.5223/pghn.2018.21.2.118.Arcos-Machancoses JV, Molera Busoms C, Julio Tatis E, Victoria Bovo M, Quintero Bernabeu J et al. Accuracy of the 2008 Simplified Criteria for the Diagnosis of Autoimmune Hepatitis in Children. Pediatr Gastroenterol Hepatol Nutr. 2018 Apr; 21 (2): 118–126. doi: 10.5223/pghn.2018.21.2.118.Joshita S, Yoshizawa K, Umemura T, Ohira H, Takahashi A et al. Clinical features of autoimmune hepatitis with acute presentation: a Japanese nationwide survey. J Gastroenterol. 2018 Sep; 53 (9): 1079–1088. doi: 10.1007/s00535-018-1444-4.Joshita S, Yoshizawa K, Umemura T, Ohira H, Takahashi A et al. Clinical features of autoimmune hepatitis with acute presentation: a Japanese nationwide survey. J Gastroenterol. 2018 Sep; 53 (9): 1079–1088. doi: 10.1007/s00535-018-1444-4.Czaja AJ. Autoimmune hepatitis in diverse ethnic populations and geographical regions. Expert Rev Gastroenterol Hepatol. 2013 May; 7 (4): 365–385. doi: 10.1586/egh.13.21.Czaja AJ. Autoimmune hepatitis in diverse ethnic populations and geographical regions. Expert Rev Gastroenterol Hepatol. 2013 May; 7 (4): 365–385. doi: 10.1586/egh.13.21.Vergani D, Longhi MS, Bogdanos DP, Ma Y, Mieli-Vergani G. Autoimmune hepatitis. Semin Immunopathol. 2009 Sep; 31 (3): 421–435. doi: 10.1007/s00281-009-0170-7.Vergani D, Longhi MS, Bogdanos DP, Ma Y, Mieli-Vergani G. Autoimmune hepatitis. Semin Immunopathol. 2009 Sep; 31 (3): 421–435. doi: 10.1007/s00281-009-0170-7.Liberal R, Mieli-Vergani G, Vergani D. Autoimmune hepatitis: From mechanisms to therapy. Rev Clin Esp. 2016, 216 (7), 372–383. doi: 10.1016/j.rce.2016.04.003.Liberal R, Mieli-Vergani G, Vergani D. Autoimmune hepatitis: From mechanisms to therapy. Rev Clin Esp. 2016, 216 (7), 372–383. doi: 10.1016/j.rce.2016.04.003.Zachou K, Gatselis NK, Arvaniti P, Gabeta S, Rigopoulou EI et al. A real-world study focused on the long-term efficacy of mycophenolate mofetil as first-line treatment of autoimmune hepatitis. Aliment Pharmacol Ther. 2016; 43: 1035–1047. doi: 10.1111/apt.13584.Zachou K, Gatselis NK, Arvaniti P, Gabeta S, Rigopoulou EI et al. A real-world study focused on the long-term efficacy of mycophenolate mofetil as first-line treatment of autoimmune hepatitis. Aliment Pharmacol Ther. 2016; 43: 1035–1047. doi: 10.1111/apt.13584.Chen J, Eslick GD, Weltman M. Systematic review with metaanalysis: clinical manifestations and management of autoimmune hepatitis in the elderly. Aliment Pharmacol Ther. 2014; 39: 117–124.Chen J, Eslick GD, Weltman M. Systematic review with metaanalysis: clinical manifestations and management of autoimmune hepatitis in the elderly. Aliment Pharmacol Ther. 2014; 39: 117–124.Cropley A, Weltman M. The use of immunosuppression in autoimmune hepatitis: A current literature review. Clin Mol Hepatol. 2017 Mar; 23 (1): 22–26. doi: 10.3350/cmh.2016.0089.Cropley A, Weltman M. The use of immunosuppression in autoimmune hepatitis: A current literature review. Clin Mol Hepatol. 2017 Mar; 23 (1): 22–26. doi: 10.3350/cmh.2016.0089.Sebode M, Schramm C. Which Alternative for Difficultto-Treat Patients? Dig Dis. 2015; 33 (Suppl 1): 83–87. doi: 10.1159/000440752.Sebode M, Schramm C. Which Alternative for Difficultto-Treat Patients? Dig Dis. 2015; 33 (Suppl 1): 83–87. doi: 10.1159/000440752.Della Corte C, Sartorelli MR, Sindoni CD, Girolami E, Giovannelli L et al. Autoimmune hepatitis in children: an overview of the disease focusing on current therapies. Eur J Gastroenterol Hepatol. 2012 Jul; 24 (7): 739–746. doi: 10.1097/MEG.0b013e328353750c.Della Corte C, Sartorelli MR, Sindoni CD, Girolami E, Giovannelli L et al. Autoimmune hepatitis in children: an overview of the disease focusing on current therapies. Eur J Gastroenterol Hepatol. 2012 Jul; 24 (7): 739–746. doi: 10.1097/MEG.0b013e328353750c.Гордей ЕВ, Фролова МА, Комяк НН, Штурич ИП, Коротков СВ, Федорук АМ и др. Трансплантация печени и аутоиммунные гепатиты. Вестник трансплантологии и искусственных органов. 2019; 21 (S):69.Gordey EV, Frolova MA, Komyak NN, Shturich IP, Korotkov SV, Fedoruk AM et al. Liver transplantation and autoimmune hepatitis. Bulletin of Transplantology and Artificial organs. 2019; 21 (S): 69.Werner M, Wallerstedt S, Lindgren S, Almer S, Björnsson E et al. Characteristics and long-term outcome of patients with autoimmune hepatitis related to the initial treatment response. Scand J Gastroenterol. 2010 Apr; 45(4): 457–467. doi: 10.3109/00365520903555861.Werner M, Wallerstedt S, Lindgren S, Almer S, Björnsson E et al. Characteristics and long-term outcome of patients with autoimmune hepatitis related to the initial treatment response. Scand J Gastroenterol. 2010 Apr; 45(4): 457–467. doi: 10.3109/00365520903555861.Gleeson D, Heneghan MA. British Society of Gastroenterology (BSG) guidelines for management of autoimmune hepatitis. Gut. 2011 Dec; 60 (12): 1611–1629. doi:10.1136/gut.2010.235259.Gleeson D, Heneghan MA. British Society of Gastroenterology (BSG) guidelines for management of autoimmune hepatitis. Gut. 2011 Dec; 60 (12): 1611–1629. doi:10.1136/gut.2010.235259.Borssen AD, Palmqvist R, Kechagias S, Marschall H-U, Bergquist A et al. Histological improvement of liver fibrosis in well-treated patients with autoimmune hepatitis. Medicine (Baltimore). 2017 Aug; 96 (34): e7708. doi:10.1097/MD.0000000000007708.Borssen AD, Palmqvist R, Kechagias S, Marschall H-U, Bergquist A et al. Histological improvement of liver fibrosis in well-treated patients with autoimmune hepatitis. Medicine (Baltimore). 2017 Aug; 96 (34): e7708. doi:10.1097/MD.0000000000007708.Ngu JH, Gearry RB, Frampton CM, Stedman CA. Predictors of poor outcome in patients with autoimmune hepatitis: a population-based study. Hepatology. 2013 Jun; 57 (6): 2399–2406. doi: 10.1002/hep.26290.Ngu JH, Gearry RB, Frampton CM, Stedman CA. Predictors of poor outcome in patients with autoimmune hepatitis: a population-based study. Hepatology. 2013 Jun; 57 (6): 2399–2406. doi: 10.1002/hep.26290.

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