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Acute presentation of autoimmune hepatitis: a multicentre study with detailed histological evaluation in a large cohort of patients
  1. Hiep Nguyen Canh1,
  2. Kenichi Harada1,
  3. Hirofumi Ouchi1,
  4. Yasunori Sato1,
  5. Koichi Tsuneyama2,
  6. Masayoshi Kage3,
  7. Masayuki Nakano4,
  8. Kaname Yoshizawa5,
  9. Atsushi Takahashi6,
  10. Masanori Abe7,
  11. Jong-Hon Kang8,
  12. Kazuhiko Koike9,
  13. Ayano Inui10,
  14. Tomoo Fujisawa10,
  15. Akinobu Takaki11,
  16. Teruko Arinaga-Hino12,
  17. Takuji Torimura12,
  18. Yoshiyuki Suzuki13,
  19. Keiichi Fujiwara14,
  20. Mikio Zeniya15,
  21. Hiromasa Ohira6,
  22. Atsushi Tanaka16,
  23. Hajime Takikawa16
  24. Intractable Liver and Biliary Diseases Study Group of Japan
  1. 1Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
  2. 2Department of Pathology Lab. Med., Tokushima University, Graduate School, Tokushima, Japan
  3. 3Kurume University Research Center for Innovative Cancer Therapy, Kurume, Japan
  4. 4Division of Diagnostic Pathology, Shonan Fujisawa Tokushukai Hospital, Fujisawa, Japan
  5. 5Department of Gastroenterology, National Hospital Organization, Shinshu Ueda Medical Center, Ueda, Japan
  6. 6Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
  7. 7Department of Gastroenterology and Metabiology, Ehime University Graduate School of Medicine, Ehime, Japan
  8. 8Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan
  9. 9Department of Gastroenterology and Hepatology, The Third Hospital of Jikei University School of Medicine, Tokyo, Japan
  10. 10Department of Pediatric Hepatology and Gastroenterology, Eastern Yokohama Hospital, Yokohama, Japan
  11. 11Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
  12. 12Department of Medicine, Kurume University School of Medicine, Kurume, Japan
  13. 13Department of Hepatology, Toranomon Hospital, Tokyo, Japan
  14. 14Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
  15. 15Sanno Medical Center, International University of Health and Welfare, Tokyo, Japan
  16. 16Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
  1. Correspondence to Dr Kenichi Harada, Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan; kenichih{at}


Aims Although liver biopsy is crucial to diagnose and guide treatment decisions, a detailed histological analysis of autoimmune hepatitis (AIH) with clinically acute presentations has not yet been performed. This study aimed to characterise the histological features and explore potential histological hallmarks to diagnose the acute presentation of AIH.

Methods We systematically evaluated liver specimens of 87 adult patients with acute presentation of AIH retrospectively enrolled from Japanese multicentre facilities. Each histological feature was predefined by consensus based on the diagnostic criteria.

Results Key findings were that acute presentation of AIH revealed histological features of both acute hepatitis and chronic hepatitis accompanying various degrees of fibrosis. The prominent features were lobular necrosis/inflammation (97.7%), plasma cell infiltration (96.4%), emperipolesis (89.3%), pigmented macrophages (84.5%), cobblestone appearance of hepatocytes (82.6%) and perivenular necroinflammatory activity, including centrilobular necrosis (81.4%).

Conclusions The acute presentation of AIH represents the entire histological spectrum of acute hepatitis and chronic hepatitis with various activity grades and fibrosis stages that clinically correspond to acute-onset AIH and acute exacerbation of classic AIH, respectively. Although there are no pathognomonic features for the pathological diagnosis, the prominent presence of lobular and perivenular necroinflammatory activity, pigmented macrophages and cobblestone appearance of hepatocytes in addition to the classic AIH features, such as plasma cell infiltration and emperipolesis, are useful for the pathological diagnosis of the acute presentation of AIH.


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  • Handling editor Cheok Soon Lee

  • Twitter Follow Hiep Nguyen Canh @Nguyen Canh Hiep

  • Contributors Each of the authors contributed to the manuscript. The concept of this study was created by the Intractable Liver and Biliary Diseases Study Group of Japan. KH, KT, MK and MN developed the protocol. KH, KT, MK, MN, HO, YS and HNC reviewed the slides, collected, analysed and interpreted the data. HNC drafted the manuscript and KH critically revised the manuscript. KY, AT, MA, J-HK, KK, AI, TF, AT, TA-H, TT, YS, KF, MZ, HO, AT and HT identified clinical cases, and collected data. All authors read and approved the final manuscript.

  • Funding This study was conducted and supported by the Health Labour Science Research Grants from Research on Measures for Intractable Diseases, the Intractable Hepato-Biliary Diseases Study Group in Japan and grant No. 26460416 from the Japan Society for the Promotion of Science (KH). HNC received the Japanese Government (Monbukagakusho: MEXT) Scholarship, No. 153345.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Fukushima Medical University Ethics Committee (no.2099).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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