Interleukin-34 as a fibroblast-derived marker of liver fibrosis in patients with non-alcoholic fatty liver disease

Hirotaka Shoji, Sachiyo Yoshio, Yohei Mano, Erina Kumagai, Masaya Sugiyama, Masaaki Korenaga, Taeang Arai, Norio Itokawa, Masanori Atsukawa, Hiroshi Aikata, Hideyuki Hyogo, Kazuaki Chayama, Tomohiko Ohashi, Kiyoaki Ito, Masashi Yoneda, Yuichi Nozaki, Takumi Kawaguchi, Takuji Torimura, Masanori Abe, Yoichi HiasaMoto Fukai, Toshiya Kamiyama, Akinobu Taketomi, Masashi Mizokami, Tatsuya Kanto

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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.

Original languageEnglish
Article number28814
JournalScientific reports
Volume6
DOIs
Publication statusPublished - Jul 1 2016

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Interleukins
Liver Cirrhosis
Fibroblasts
Fibrosis
Collagen Type IV
Liver
Hepatic Stellate Cells
Macrophage Colony-Stimulating Factor
Macrophage Activation
Non-alcoholic Fatty Liver Disease
Hyaluronic Acid
Serum
Chemokines
ROC Curve
Area Under Curve
Liver Diseases
Biomarkers
Macrophages
Cytokines
Biopsy

All Science Journal Classification (ASJC) codes

  • General

Cite this

Shoji, H., Yoshio, S., Mano, Y., Kumagai, E., Sugiyama, M., Korenaga, M., ... Kanto, T. (2016). Interleukin-34 as a fibroblast-derived marker of liver fibrosis in patients with non-alcoholic fatty liver disease. Scientific reports, 6, [28814]. https://doi.org/10.1038/srep28814

Interleukin-34 as a fibroblast-derived marker of liver fibrosis in patients with non-alcoholic fatty liver disease. / Shoji, Hirotaka; Yoshio, Sachiyo; Mano, Yohei; Kumagai, Erina; Sugiyama, Masaya; Korenaga, Masaaki; Arai, Taeang; Itokawa, Norio; Atsukawa, Masanori; Aikata, Hiroshi; Hyogo, Hideyuki; Chayama, Kazuaki; Ohashi, Tomohiko; Ito, Kiyoaki; Yoneda, Masashi; Nozaki, Yuichi; Kawaguchi, Takumi; Torimura, Takuji; Abe, Masanori; Hiasa, Yoichi; Fukai, Moto; Kamiyama, Toshiya; Taketomi, Akinobu; Mizokami, Masashi; Kanto, Tatsuya.

In: Scientific reports, Vol. 6, 28814, 01.07.2016.

Research output: Contribution to journalArticle

Shoji, H, Yoshio, S, Mano, Y, Kumagai, E, Sugiyama, M, Korenaga, M, Arai, T, Itokawa, N, Atsukawa, M, Aikata, H, Hyogo, H, Chayama, K, Ohashi, T, Ito, K, Yoneda, M, Nozaki, Y, Kawaguchi, T, Torimura, T, Abe, M, Hiasa, Y, Fukai, M, Kamiyama, T, Taketomi, A, Mizokami, M & Kanto, T 2016, 'Interleukin-34 as a fibroblast-derived marker of liver fibrosis in patients with non-alcoholic fatty liver disease', Scientific reports, vol. 6, 28814. https://doi.org/10.1038/srep28814
Shoji, Hirotaka ; Yoshio, Sachiyo ; Mano, Yohei ; Kumagai, Erina ; Sugiyama, Masaya ; Korenaga, Masaaki ; Arai, Taeang ; Itokawa, Norio ; Atsukawa, Masanori ; Aikata, Hiroshi ; Hyogo, Hideyuki ; Chayama, Kazuaki ; Ohashi, Tomohiko ; Ito, Kiyoaki ; Yoneda, Masashi ; Nozaki, Yuichi ; Kawaguchi, Takumi ; Torimura, Takuji ; Abe, Masanori ; Hiasa, Yoichi ; Fukai, Moto ; Kamiyama, Toshiya ; Taketomi, Akinobu ; Mizokami, Masashi ; Kanto, Tatsuya. / Interleukin-34 as a fibroblast-derived marker of liver fibrosis in patients with non-alcoholic fatty liver disease. In: Scientific reports. 2016 ; Vol. 6.
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AU - Kumagai, Erina

AU - Sugiyama, Masaya

AU - Korenaga, Masaaki

AU - Arai, Taeang

AU - Itokawa, Norio

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AU - Aikata, Hiroshi

AU - Hyogo, Hideyuki

AU - Chayama, Kazuaki

AU - Ohashi, Tomohiko

AU - Ito, Kiyoaki

AU - Yoneda, Masashi

AU - Nozaki, Yuichi

AU - Kawaguchi, Takumi

AU - Torimura, Takuji

AU - Abe, Masanori

AU - Hiasa, Yoichi

AU - Fukai, Moto

AU - Kamiyama, Toshiya

AU - Taketomi, Akinobu

AU - Mizokami, Masashi

AU - Kanto, Tatsuya

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N2 - 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.

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