PMID- 36244745
OWN - NLM
STAT- MEDLINE
DCOM- 20230804
LR  - 20230810
IS  - 1880-3873 (Electronic)
IS  - 1340-3478 (Print)
IS  - 1340-3478 (Linking)
VI  - 30
IP  - 8
DP  - 2023 Aug 1
TI  - Plasma Heparin Cofactor II Activity Is Inversely Associated with Hepatic Fibrosis 
      of Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus.
PG  - 871-883
LID - 10.5551/jat.63752 [doi]
AB  - 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. 
      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. 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). 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.
FAU - Hara, Tomoyo
AU  - Hara T
AD  - Department of Hematology, Endocrinology and Metabolism, Tokushima University 
      Graduate School of Biomedical Sciences.
FAU - Uemoto, Ryoko
AU  - Uemoto R
AD  - Department of Community Medicine and Medical Science, Tokushima University 
      Graduate School of Biomedical Sciences.
FAU - Sekine, Akiko
AU  - Sekine A
AD  - Department of Community Medicine and Medical Science, Tokushima University 
      Graduate School of Biomedical Sciences.
FAU - Mitsui, Yukari
AU  - Mitsui Y
AD  - Department of Hematology, Endocrinology and Metabolism, Tokushima University 
      Graduate School of Biomedical Sciences.
FAU - Masuda, Shiho
AU  - Masuda S
AD  - Department of Hematology, Endocrinology and Metabolism, Tokushima University 
      Graduate School of Biomedical Sciences.
FAU - Yamagami, Hiroki
AU  - Yamagami H
AD  - Department of Hematology, Endocrinology and Metabolism, Tokushima University 
      Graduate School of Biomedical Sciences.
FAU - Kurahashi, Kiyoe
AU  - Kurahashi K
AD  - Department of Hematology, Endocrinology and Metabolism, Tokushima University 
      Graduate School of Biomedical Sciences.
FAU - Yoshida, Sumiko
AU  - Yoshida S
AD  - Department of Hematology, Endocrinology and Metabolism, Tokushima University 
      Graduate School of Biomedical Sciences.
FAU - Otoda, Toshiki
AU  - Otoda T
AD  - Department of Community Medicine and Medical Science, Tokushima University 
      Graduate School of Biomedical Sciences.
FAU - Yuasa, Tomoyuki
AU  - Yuasa T
AD  - Department of Community Medicine and Medical Science, Tokushima University 
      Graduate School of Biomedical Sciences.
FAU - Kuroda, Akio
AU  - Kuroda A
AD  - Diabetes Therapeutics and Research Center, Institute of Advanced Medical 
      Sciences, Tokushima University.
FAU - Ikeda, Yasumasa
AU  - Ikeda Y
AD  - Department of Pharmacology, Tokushima University Graduate School of Biomedical 
      Sciences.
FAU - Endo, Itsuro
AU  - Endo I
AD  - Department of Bioregulatory Sciences, Tokushima University Graduate School of 
      Biomedical Sciences.
FAU - Honda, Soichi
AU  - Honda S
AD  - Minami Municipal National Insurance Hospital.
FAU - Yoshimoto, Katsuhiko
AU  - Yoshimoto K
AD  - Department of Medical Pharmacology, Tokushima University Graduate School of 
      Biomedical Sciences.
AD  - Kondo Naika Hospital.
FAU - Kondo, Akira
AU  - Kondo A
AD  - Kondo Naika Hospital.
FAU - Tamaki, Toshiaki
AU  - Tamaki T
AD  - Anan Medical Center.
FAU - Matsumoto, Toshio
AU  - Matsumoto T
AD  - Fujii Memorial Institute of Medical Sciences, Tokushima University.
FAU - Matsuhisa, Munehide
AU  - Matsuhisa M
AD  - Diabetes Therapeutics and Research Center, Institute of Advanced Medical 
      Sciences, Tokushima University.
FAU - Abe, Masahiro
AU  - Abe M
AD  - Department of Hematology, Endocrinology and Metabolism, Tokushima University 
      Graduate School of Biomedical Sciences.
FAU - Aihara, Ken-Ichi
AU  - Aihara KI
AD  - Department of Community Medicine and Medical Science, Tokushima University 
      Graduate School of Biomedical Sciences.
AD  - Anan Medical Center.
LA  - eng
PT  - Journal Article
DEP - 20221014
PL  - Japan
TA  - J Atheroscler Thromb
JT  - Journal of atherosclerosis and thrombosis
JID - 9506298
RN  - 81604-65-1 (Heparin Cofactor II)
RN  - EC 3.4.21.5 (Thrombin)
RN  - 0 (Biomarkers)
SB  - IM
CIN - J Atheroscler Thromb. 2023 Aug 1;30(8):853-854. PMID: 36740275
MH  - Humans
MH  - *Non-alcoholic Fatty Liver Disease
MH  - *Diabetes Mellitus, Type 2/complications
MH  - Heparin Cofactor II
MH  - Cross-Sectional Studies
MH  - Thrombin
MH  - Liver Cirrhosis/diagnosis/complications
MH  - Biomarkers
MH  - Severity of Illness Index
PMC - PMC10406648
OTO - NOTNLM
OT  - Heparin cofactor II
OT  - NAFLD
OT  - Protease-activated receptors
OT  - T2DM
OT  - Thrombin
COIS- K.A. has received research funding and speaker honoraria from Teijin Pharma Ltd., 
      Nippon Boehringer Ingelheim Co., Ltd., and Ono Pharmaceutical Co., Ltd. M.A. 
      received research funding from Teijin Pharma Ltd. and Ono Pharmaceutical Co., 
      Ltd. No other potential conflicts of interest relevant to this article were 
      reported.
EDAT- 2022/10/17 06:00
MHDA- 2023/08/04 06:43
PMCR- 2023/08/01
CRDT- 2022/10/16 21:23
PHST- 2023/08/04 06:43 [medline]
PHST- 2022/10/17 06:00 [pubmed]
PHST- 2022/10/16 21:23 [entrez]
PHST- 2023/08/01 00:00 [pmc-release]
AID - DN/JST.JSTAGE/jat/63752 [pii]
AID - 10.5551/jat.63752 [doi]
PST - ppublish
SO  - J Atheroscler Thromb. 2023 Aug 1;30(8):871-883. doi: 10.5551/jat.63752. Epub 2022 
      Oct 14.