Hepatology International

, Volume 12, Issue 2, pp 191–199 | Cite as

Long-term observation of acute-onset autoimmune hepatitis presenting clinically and radiologically as acute hepatitis

  • Keiichi Fujiwara
  • Yoshihiro Fukuda
  • Katsushi Seza
  • Masaya Saito
  • Shin Yasui
  • Masayuki Nakano
  • Osamu Yokosuka
  • Naoya Kato
Original Article



There is yet no gold standard for the diagnosis of acute-onset autoimmune hepatitis (A-AIH), especially histologically acute AIH. As a result, long-term observation of A-AIH has been difficult and the nature is not well known. We retrospectively analyzed the clinicopathological features of A-AIH over a long prospective follow-up period.


Clinical, biochemical, immunological and pathological features of 30 patients (21 female, mean age 55.1 ± 13.1 years) with non-severe A-AIH “without signs of clinical and radiological chronicity” admitted to a community hospital between 2001 and 2015 who were prospectively followed for more than 2 years were analyzed retrospectively.


Liver histology of 45% showed acute and 55% chronic hepatitis. Mean age was older, prothrombin time activity was higher, AIH scores before treatment were lower in histologically acute hepatitis than histologically chronic hepatitis significantly. Liver fibrosis was not coarse, but delicate with severe activity in most patients showing chronic hepatitis defined by our strict criteria. Median (range) follow-up period was 6.9 (2.1–16.2) years. Six (20%) patients experienced episode of relapses. All were alive at the last follow-up point. Corticosteroid was continued at 2.5–5 mg/day until the study end point without serious side effects in most patients. Serial change of alanine aminotransferase levels, immunoglobulin G levels and anti-nuclear antibody titers did not show statistical difference between histologically acute and chronic hepatitis.


Rapid progression of fibrosis could occur in A-AIH. Treatment response and long-term prognosis were good, and not different between patients with histologically acute and chronic hepatitis.


Autoimmune hepatitis Acute presentation Non-severe Long-term observation Histology 



Autoimmune hepatitis


Acute-onset autoimmune hepatitis


Alanine aminotransferase


Immunoglobulin G


Anti-nuclear antibody





We are indebted to all our colleagues at our liver units who cared for the patients described herein. We thank Nobuyuki Moriya (Chiba Medical Center) for help in the extraction of old data.

Authors contributions

KF designed and performed the research, analyzed the clinical data and wrote the manuscript. KF, YF, KS, MS, SY, OY and NK contributed to the clinical aspects. KF and MN reviewed the histopathological changes. All authors approved the final version of the manuscript.

Compliance with ethical standards

Conflict of interest

Keiichi Fujiwara, Yoshihiro Fukuda, Katsushi Seza, Masaya Saito, Shin Yasui, Masayuki Nakano, Osamu Yokosuka and Naoya Kato declare that they have no conflict of interest.

Ethical approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.

Informed consent

Informed consent was obtained from all patients for being included in the study.

Supplementary material

12072_2018_9848_MOESM1_ESM.tiff (1.5 mb)
Supporting Figure 1. Serial changes of ANA titers of histologically acute (a) and chronic (b) AIH patients after the start of treatment. ANA, anti-nuclear antibody. (TIFF 1521 kb)


  1. 1.
    Nikias GA, Batts KP, Czaja AJ. The nature and prognostic implications of autoimmune hepatitis with an acute presentation. J Hepatol 1994;21:866–871CrossRefPubMedGoogle Scholar
  2. 2.
    Czaja AJ. Acute and acute severe (fulminant) autoimmune hepatitis. Dig Dis Sci 2013;58:897–914CrossRefPubMedGoogle Scholar
  3. 3.
    Fujiwara K, Yasui S, Yokosuka O. Autoimmune acute liver failure: the emerging etiology for acute liver failure (review). Hepatol Int 2013;7:335–346CrossRefPubMedGoogle Scholar
  4. 4.
    Abe M, Mashiba T, Zeniya M, Yamamoto K, Onji M, Tsubouchi H, Autoimmune Hepatitis Study Group-Subgroup of the Intractable Hepato-Biliary Disease Study Group in Japan. Present status of autoimmune hepatitis in Japan: a nationwide survey. J Gastroenterol 2011;46:1136–1141CrossRefPubMedGoogle Scholar
  5. 5.
    Stravitz RT, Lefkowitch JH, Fontana RJ, Acute Liver Failure Study Group, et al. Autoimmune acute liver failure: proposed clinical and histological criteria. Hepatology 2011;53:517–526CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Alvarez F, Berg PA, Bianchi FB, et al. International Autoimmune Hepatitis Group report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 1999;31:929–938CrossRefPubMedGoogle Scholar
  7. 7.
    Okano N, Yamamoto K, Sakaguchi K, et al. Clinicopathological features of acute-onset autoimmune hepatitis. Hepatol Res 2003;25:263–270CrossRefPubMedGoogle Scholar
  8. 8.
    Misdraji J, Thiim M, Graeme-Cook FM. Autoimmune hepatitis with centrilobular necrosis. Am J Surg Pathol 2004;28:471–478CrossRefPubMedGoogle Scholar
  9. 9.
    Hofer H, Oesterreicher C, Wrba F, Ferenci P, Penner E. Centrilobular necrosis in autoimmune hepatitis: a histological feature associated with acute clinical presentation. J Clin Pathol 2006;59:246–249CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Fujiwara K, Fukuda Y, Yokosuka O. Precise histological evaluation of liver biopsy specimen is indispensable for diagnosis and treatment of acute onset autoimmune hepatitis. J Gastroenterol 2008;43:951–958CrossRefPubMedGoogle Scholar
  11. 11.
    Yasui S, Fujiwara K, Yonemitsu Y, Oda S, Nakano M, Yokosuka O. Clinicopathological features of severe and fulminant forms of autoimmune hepatitis. J Gastroenterol 2011;46:378–390CrossRefPubMedGoogle Scholar
  12. 12.
    Fujiwara K, Nakano M, Yasui S, Okitsu K, Yonemitsu Y, Yokosuka O. Advanced histology and impaired liver regeneration are associated with disease severity in acute onset autoimmune hepatitis. Histopathology 2011;58:693–704CrossRefPubMedGoogle Scholar
  13. 13.
    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;31:1013–1020CrossRefPubMedGoogle Scholar
  14. 14.
    Hennes EM, Zeniya M, Czaja AJ, International Autoimmune Hepatitis Group, et al. Simplified diagnostic criteria for autoimmune hepatitis. Hepatology 2008;48:169–176CrossRefPubMedGoogle Scholar
  15. 15.
    Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994;19:1513–1520CrossRefPubMedGoogle Scholar
  16. 16.
    Yasui S, Fujiwara K, Okitsu K, Yonemitsu Y, Ito H, Yokosuka O. Importance of computed tomography imaging features for the diagnosis of autoimmune acute liver failure. Hepatol Res 2012;42:42–50CrossRefPubMedGoogle Scholar
  17. 17.
    Yasui S, Fujiwara K, Yokosuka O. Autoimmune fulminant hepatic failure in chronic hepatitis C during peg-interferon-alfa 2b plus ribavirin treatment showing histological heterogeneity. Dig Liver Dis 2011;43:666–667CrossRefPubMedGoogle Scholar
  18. 18.
    Fujiwara K, Ohtsuka M, Yokosuka O. Radiologic and histologic heterogeneity in a case of autoimmune acute liver failure. Clin Gastroenterol Hepatol 2014;12:e19–e20CrossRefPubMedGoogle Scholar
  19. 19.
    Fujiwara K, Fukuda Y, Seza K, et al. High level of persistent liver injury is one of clinical characteristics in treatment-naïve acute onset autoimmune hepatitis: experience in a community hospital. J Hepatobiliary Pancreat Sci 2016;23:174–180CrossRefPubMedGoogle Scholar
  20. 20.
    Yasui S, Fujiwara K, Tawada A, Fukuda Y, Nakano M, Yokosuka O. Efficacy of intravenous glycyrrhizin in the early stage of acute onset autoimmune hepatitis. Dig Dis Sci 2011;56:3638–3647CrossRefPubMedGoogle Scholar
  21. 21.
    Fujiwara K, Yasui S, Nakano M, et al. Severe and fulminant hepatitis of indeterminate etiology in a Japanese center. Hepatol Res 2015;45:E141–E149CrossRefPubMedGoogle Scholar
  22. 22.
    Scheuer PJ, Maggi G. Hepatic fibrosis and collapse: histological distinction by orcein staining. Histopathology 1980;4:487–490CrossRefPubMedGoogle Scholar
  23. 23.
    Horiuchi R, Uchida T, Karasawa T, Shikata T. Diagnostic significance of elastic fibers in liver diseases. Kanzo 1985;31:1315–1323CrossRefGoogle Scholar
  24. 24.
    Fujiwara K, Yasui S, Yokosuka O. Efforts at making the diagnosis of acute onset autoimmune hepatitis. Hepatology 2011;54:371–372CrossRefPubMedGoogle Scholar
  25. 25.
    Yoshizawa K, Matsumoto A, Ichijo T, et al. Long-term outcome of Japanese patients with type 1 autoimmune hepatitis. Hepatology 2012;56:668–676CrossRefPubMedGoogle Scholar
  26. 26.
    Montano-Loza AJ, Carpenter HA, Czaja AJ. Consequences of treatment withdrawal in type 1 autoimmune hepatitis. Liver Int 2007;27:507–515CrossRefPubMedGoogle Scholar
  27. 27.
    Hoeroldt B, McFarlane E, Dube A, et al. Long-term outcomes of patients with autoimmune hepatitis managed at a nontransplant center. Gastroenterology 2011;140:1980–1989CrossRefPubMedGoogle Scholar
  28. 28.
    Czaja AJ, Ludwig J, Baggenstoss AH, Wolf A. Corticosteroid-treated chronic active hepatitis in remission: uncertain prognosis of chronic persistent hepatitis. N Engl J Med 1981;304:5–9CrossRefPubMedGoogle Scholar
  29. 29.
    Muratori P, Granito A, Quarneti C, et al. Autoimmune hepatitis in Italy: the Bologna experience. J Hepatol 2009;50:1210–1218CrossRefPubMedGoogle Scholar
  30. 30.
    Yeoman AD, Al-Chalabi T, Karani JB, et al. Evaluation of risk factors in the development of hepatocellular carcinoma in autoimmune hepatitis: implications for follow-up and screening. Hepatology 2008;48:863–870CrossRefPubMedGoogle Scholar

Copyright information

© Asian Pacific Association for the Study of the Liver 2018

Authors and Affiliations

  1. 1.Department of Gastroenterology, Graduate School of MedicineChiba UniversityChibaJapan
  2. 2.Department of GastroenterologySeikeikai Chiba Medical CenterChibaJapan
  3. 3.Division of PathologyShonan Fujisawa Tokushukai HospitalFujisawaJapan

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