TY - JOUR
T1 - Interleukin-34 as a fibroblast-derived marker of liver fibrosis in patients with non-alcoholic fatty liver disease
AU - Shoji, Hirotaka
AU - Yoshio, Sachiyo
AU - Mano, Yohei
AU - Kumagai, Erina
AU - Sugiyama, Masaya
AU - Korenaga, Masaaki
AU - Arai, Taeang
AU - Itokawa, Norio
AU - Atsukawa, Masanori
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
PY - 2016/7/1
Y1 - 2016/7/1
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.
AB - 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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U2 - 10.1038/srep28814
DO - 10.1038/srep28814
M3 - Article
C2 - 27363523
AN - SCOPUS:84976871484
VL - 6
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 28814
ER -