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

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Abstract

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.

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Abbreviations

AIH:

Autoimmune hepatitis

AMA:

Anti-mitochondrial antibodies

ANA:

Anti-nuclear antibodies

CDAA:

Choline-deficient l-amino acid-defined

CNSDC:

Chronic non-suppurative destructive cholangitis

IL-6:

Interleukin-6

MSG:

Monosodium glutamate

NAFLD:

Non-alcoholic fatty liver disease

NASH:

Non-alcoholic steatohepatitis

PBC:

Primary biliary cirrhosis

TNF-α:

Tumor necrosis factor-α

TSOD:

Tsumura Suzuki, Obese Diabetes

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Acknowledgments

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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Authors and Affiliations

  1. Department of Diagnostic Pathology, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan

    Koichi Tsuneyama, Hayato Baba, Takeshi Nishida, Kazuhiro Nomoto, Shinichi Hayashi, Shigeharu Miwa, Takahiko Nakajima, Yuko Nakanishi & Johji Imura

  2. Fourth Department of Internal Medicine, Teikyo University Mizonokuchi Hospital, Kanagawa, Japan

    Kentaro Kikuchi

  3. Department of Pathology, Kouseiren Takaoka Hospital, Takaoka, Japan

    Shinji Masuda

  4. Department of Internal Medicine, Kouseiren Takaoka Hospital, Takaoka, Japan

    Mitsuhiro Terada

  5. Division of Rheumatology and Clinical Immunology, Humanitas Clinical and Research Center, Milan, Italy

    Carlo Selmi

  6. Division of Rheumatology, Allergy, and Clinical Immunology, University of California, Davis, CA, USA

    Carlo Selmi

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  1. Koichi Tsuneyama
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  2. Hayato Baba
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  13. Carlo Selmi
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Correspondence to Koichi Tsuneyama.

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Tsuneyama, K., Baba, H., Kikuchi, K. et al. Autoimmune Features in Metabolic Liver Disease: A Single-Center Experience and Review of the Literature. Clinic Rev Allerg Immunol 45, 143–148 (2013). https://doi.org/10.1007/s12016-013-8383-x

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