Plasma Heparin Cofactor II Activity Is Inversely Associated with Hepatic Fibrosis of Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus
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- Hara Tomoyo
- Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences
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- Uemoto Ryoko
- Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences
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- Sekine Akiko
- Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences
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- Mitsui Yukari
- Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences
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- Masuda Shiho
- Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences
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- Yamagami Hiroki
- Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences
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- Kurahashi Kiyoe
- Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences
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- Yoshida Sumiko
- Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences
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- Otoda Toshiki
- Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences
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- Yuasa Tomoyuki
- Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences
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- Kuroda Akio
- Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University
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- Ikeda Yasumasa
- Department of Pharmacology, Tokushima University Graduate School of Biomedical Sciences
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- Endo Itsuro
- Department of Bioregulatory Sciences, Tokushima University Graduate School of Biomedical Sciences
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- Honda Soichi
- Minami Municipal National Insurance Hospital
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- Yoshimoto Katsuhiko
- Department of Medical Pharmacology, Tokushima University Graduate School of Biomedical Sciences Kondo Naika Hospital
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- Kondo Akira
- Kondo Naika Hospital
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- Tamaki Toshiaki
- Anan Medical Center
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- Matsumoto Toshio
- Fujii Memorial Institute of Medical Sciences, Tokushima University
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- Matsuhisa Munehide
- Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University
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- Abe Masahiro
- Department of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical Sciences
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- Aihara Ken-ichi
- Department of Community Medicine and Medical Science, Tokushima University Graduate School of Biomedical Sciences Anan Medical Center
抄録
<p> Aims: Thrombin exerts various pathophysiological functions by activating protease-activated receptors (PARs), and thrombin-induced activation of PARs promotes the development of non-alcoholic fatty liver disease (NAFLD). Since heparin cofactor II (HCII) specifically inactivates thrombin action, we hypothesized that plasma HCII activity correlates with the severity of NAFLD.</p><p>Methods: A cross-sectional study was conducted. Plasma HCII activity and noninvasive clinical markers of hepatic fibrosis including fibrosis-4 (FIB-4) index, NAFLD fibrosis score (NFS) and aspartate aminotransferase-to-platelet ratio index (APRI) were determined in 305 Japanese patients with type 2 diabetes mellitus (T2DM). The relationships between plasma HCII activity and the clinical markers were statistically evaluated.</p><p>Results: Multiple regression analysis including confounding factors showed that plasma HCII activity independently contributed to decreases in FIB-4 index (p＜0.001), NFS (p＜0.001) and APRI (p=0.004). In addition, logistic regression analysis for the prevalence of advanced hepatic fibrosis defined by the cutoff points of the clinical scores showed that plasma HCII activity was the sole and common negative factor for prevalence of advanced hepatic fibrosis (FIB-4 index: p=0.002, NFS: p=0.026 and APRI: p=0.012).</p><p>Conclusions: Plasma HCII activity was inversely associated with clinical hepatic fibrosis indices including FIB-4 index, NFS and APRI and with the prevalence of advanced hepatic fibrosis in patients with T2DM. The results suggest that HCII can serve as a novel biomarker for assessment of hepatic fibrosis of NAFLD in patients with T2DM.</p>
収録刊行物
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- Ｊｏｕｒｎａｌ ｏｆ Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ ａｎｄ Ｔｈｒｏｍｂｏｓｉｓ
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Ｊｏｕｒｎａｌ ｏｆ Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ ａｎｄ Ｔｈｒｏｍｂｏｓｉｓ 30 (8), 871-883, 2023-08-01
一般社団法人 日本動脈硬化学会