Clinical Reviews in Allergy & Immunology

, Volume 45, Issue 1, pp 143–148 | Cite as

Autoimmune Features in Metabolic Liver Disease: A Single-Center Experience and Review of the Literature

  • Koichi Tsuneyama
  • Hayato Baba
  • Kentaro Kikuchi
  • Takeshi Nishida
  • Kazuhiro Nomoto
  • Shinichi Hayashi
  • Shigeharu Miwa
  • Takahiko Nakajima
  • Yuko Nakanishi
  • Shinji Masuda
  • Mitsuhiro Terada
  • Johji Imura
  • Carlo Selmi


Non-alcoholic steatohepatitis (NASH) is the progressive phenotype of non-alcoholic fatty liver disease associated with the metabolic syndrome. The existence of autoimmune features in NASH has been reported, but its significance remains unclear. We herein report the autoantibody profile of 54 patients with histologically proven NASH and further determined the development of autoimmunity in three different murine NASH models (monosodium glutamate, CDAA (choline-deficient l-amino acid-defined), and TSOD (Tsumura Suzuki, Obese Diabetes)) at 48 weeks of age. Forty-eight percent (26/54) of NASH cases were positive for antinuclear (ANA) or antimitochondrial antibody and manifested histological signs of overlap with autoimmune hepatitis and primary biliary cirrhosis, respectively. These patients were significantly older (60 ± 10 versus 50 ± 16 years), more frequently women (81 % versus 43 %), and with more severe portal inflammatory infiltrate compared with patients without autoimmunity. In one third of mice, regardless of the model, we observed a marked lymphoid infiltrate with non-suppurative cholangitis, and several cases were ANA-positive, but none AMA-positive. Our data suggest that autoimmunity may share some pathogenetic traits with the chronic inflammation of NASH, possibly related to advanced age.


Metabolic syndrome Female sex Non-alcoholic fatty liver disease 



Autoimmune hepatitis


Anti-mitochondrial antibodies


Anti-nuclear antibodies


Choline-deficient l-amino acid-defined


Chronic non-suppurative destructive cholangitis




Monosodium glutamate


Non-alcoholic fatty liver disease


Non-alcoholic steatohepatitis


Primary biliary cirrhosis


Tumor necrosis factor-α


Tsumura Suzuki, Obese Diabetes



The authors are thankful to Mr. Tokimasa Kumada and Mr. Hideki Hatta for their help and technical assistance with experiments and to Ms. Yukari Inoue for the excellent support in the manuscript preparation. This work was supported by JSPS KAKENHI Grant Numbers 0293341 and 10293341 and a Research grant of 2010 Takeda Science Foundation.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Koichi Tsuneyama
    • 1
  • Hayato Baba
    • 1
  • Kentaro Kikuchi
    • 2
  • Takeshi Nishida
    • 1
  • Kazuhiro Nomoto
    • 1
  • Shinichi Hayashi
    • 1
  • Shigeharu Miwa
    • 1
  • Takahiko Nakajima
    • 1
  • Yuko Nakanishi
    • 1
  • Shinji Masuda
    • 3
  • Mitsuhiro Terada
    • 4
  • Johji Imura
    • 1
  • Carlo Selmi
    • 5
    • 6
  1. 1.Department of Diagnostic Pathology, Graduate School of Medical and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
  2. 2.Fourth Department of Internal MedicineTeikyo University Mizonokuchi HospitalKanagawaJapan
  3. 3.Department of PathologyKouseiren Takaoka HospitalTakaokaJapan
  4. 4.Department of Internal MedicineKouseiren Takaoka HospitalTakaokaJapan
  5. 5.Division of Rheumatology and Clinical ImmunologyHumanitas Clinical and Research CenterMilanItaly
  6. 6.Division of Rheumatology, Allergy, and Clinical ImmunologyUniversity of CaliforniaDavisUSA

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