title: Interleukin-34 as a fibroblast-derived marker of liver fibrosis in patients with non-alcoholic fatty liver disease.
abstract: Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic non-viral liver disease. Activation of macrophages and hepatic stellate cells is a critical step that promotes liver fibrosis. We aimed to explore the feasibility of interleukin-34 (IL-34), a key regulator of macrophages, as a fibrosis marker in patients with NAFLD. We enrolled 197 liver biopsy-proven NAFLD patients. We evaluated the serum levels of IL-34, macrophage-colony stimulating factor (M-CSF), soluble CD163 (sCD163), 40 cytokines/chemokines, hyaluronic acid, type IV collagen 7s, and clinically-approved fibrosis scores. IL-34 increased with the progression of fibrosis and was an independent marker for liver fibrosis. Immunostaining experiments, using resected liver specimens from NAFLD patients, revealed that IL-34 was mainly expressed on liver fibroblasts. IL-34 based fibrosis score (0.0387*IL-34 (pg/ml) + 0.3623*type IV collagen 7s (ng/ml) + 0.0184*age (year)-1.1850) was a practical predictive model of liver fibrosis. Using receiver-operating characteristic analyses, the area under the curve, sensitivity, and specificity of IL-34 based fibrosis score were superior or comparable to the other fibrosis biomarkers and scores. In conclusion, the IL-34 based fibrosis score, including serum IL-34, type IV collagen 7s and age, is a feasible diagnostic marker of liver fibrosis in NAFLD patients.
authors.affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.|Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Shoji
authors.affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Yoshio
authors.affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Mano
authors.affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
authors.forename: Erina
authors.initials: E
authors.lastname: Kumagai
authors.affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Sugiyama
authors.affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Korenaga
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan.
authors.forename: Taeang
authors.initials: T
authors.lastname: Arai
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Itokawa
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Atsukawa
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical &Health Sciences, Hiroshima University, Hiroshima, Hiroshima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aikata
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical &Health Sciences, Hiroshima University, Hiroshima, Hiroshima, Japan.|Department of Gastroenterology and Hepatology, JA Hiroshima General Hospital, Hatsukaichi, Hiroshima, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hyogo
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical &Health Sciences, Hiroshima University, Hiroshima, Hiroshima, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ohashi
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: Kiyoaki
authors.initials: K
authors.lastname: Ito
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Yoneda
authors.affiliation: Department of Gastroenterology, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nozaki
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Kawaguchi
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Torimura
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Abe
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Hiasa
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Moto
authors.initials: M
authors.lastname: Fukai
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Kamiyama
authors.affiliation: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Taketomi
authors.affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
authors.affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kanto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007378:Interleukins / Q000096:biosynthesis* / Q000097:blood; D008103:Liver Cirrhosis / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications*; D012372:ROC Curve
chemical_list: D015415:Biomarkers; C529076:IL34 protein, human; D007378:Interleukins