Autoimmune hepatitis (AIH) is an autoimmune liver disease that is characterized by a progressive destruction of the liver parenchyma and the development of liver fibrosis. We aimed to examine the relationship between circulating cytokines/chemokines and the Mac-2 binding protein glycosylation isomer (M2BPGi) levels in Japanese patients with autoimmune hepatitis (AIH).
We investigated the relationship between circulating cytokines/chemokines and M2BPGi levels in Japanese patients with AIH. Seventy-seven patients with well-documented AIH were enrolled in the National Hospital Organization (NHO)-AIH-liver-network database. We measured the serum levels of 20 cytokines in 31 selected AIH patients before and after steroid treatment using multisuspension cytokine array.
Eleven cytokines and soluble adhesion molecules were increased in untreated AIH patients compared with treated AIH patients. Among these cytokines and soluble adhesion molecules, soluble intercellular adhesion molecule-1 (sICAM-1) and interferon-γ-inducible protein 10 (IP-10) were most downregulated by steroid therapy in AIH patients. We measured serum sICAM-1 and IP-10 by ELISA and found the levels were significantly higher in AIH patients (n = 77) compared with chronic viral hepatitis C patients (n = 32). Furthermore, there was a positive correlation between sICAM-1 or IP-10 and alanine aminotransferase, total bilirubin, and circulating M2BPGi levels. M2BPGi levels were increased in AIH patients with high stages of liver fibrosis. Additionally, M2BPGi levels were correlated with the histological grade of inflammation in AIH. Circulating M2BPGi levels were significantly reduced by steroid treatment in AIH patients.
sICAM-1 and IP-10 are useful markers to assess immune-mediated hepatitis activity in AIH and they correlate with circulating M2BPGi. Serum M2BPGi levels increased in untreated AIH patients with active hepatitis and were decreased by steroid therapy. M2BPGi reflects autoimmune-mediated hepatic inflammation as well as liver fibrosis.
aDepartment of Rheumatology, Fukushima Medical University, Fukushima
bClinical Research Center, Nagasaki Medical Center, Nagasaki
cDepartment of Immunology and Rheumatology, Unit of Translational Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki
dNational Hospital Organization, Takasaki Medical Center, Takasaki
eNational Hospital Organization, Higashihiroshima Medical center, Higashihiroshima, Hiroshima
fNational Hospital Organization, Shinsyu-Ueda Medical Center, Ueda, Nagano
gNational Hospital Organization, Kanazawa Medical Center, Kanazawa, Ishikawa
hNational Hospital Organization, Beppu Medical Center, Beppu, Oita
iNational Hospital Organization, Nagoya Medical Center, Naka-ku, Nagoya, Aichi
jNational Hospital Organization, Asahikawa Medical Center, Asahikawa, Hokkaido
kNational Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba
lNational Hospital Organization, Ureshino Medical Center, Ureshino, Saga
mNational Hospital Organization, Okayama Medical Center, Okayama, Okayama
nNational Hospital Organization, Tokyo National Hospital, Tokyo
oNational Hospital Organization, Kure Medical Center, Kure, Hiroshima
pDepartment of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki
qMolecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba
rDepartment of Gastroenterology, Fukushima Medical University, Fukushima.
Correspondence: Kiyoshi Migita, Department of Rheumatology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan (e-mail: firstname.lastname@example.org).
Abbreviations: AIH = autoimmune hepatitis, IP-10 = interferon-γ-inducible protein 10, M2BPGi = Mac-2 binding protein glycosylation isomer, NHO = National Hospital Organization, sICAM-1 = soluble intercellular adhesion molecule-1.
Ethical Approval and Consent to participate: The study was approved by the Ethics Committee of the NHO Central Internal Review Board and participating NHO liver-network hospitals (H30-0313001). Written informed consent was obtained from each individual.
Consent for publication: Not applicable.
Funding: This work was supported by a grant from the National Hospital Organization.
Conflict of Interest: KM has received research grants from Chugai, Pfizer, and AbbVie. Rest of the authors declares that they have no competing interests.
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Received July 24, 2018
Accepted November 6, 2018