Yosuke Osawa1,2,3, Sachiyo Yoshio4, Yoshihiko Aoki5, Masaaki Korenaga5, Masatoshi Imamura5, Takashi Oide6, Miku Okawara4, Hironari Kawai4, Yuriko Tsutsui4, Yuichi Yoshida4, Shiori Yoshikawa4, Taizo Mori4, Taiji Yamazoe4, Tatsuya Kanto7,8. 1. The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba, 272-8516, Japan. osawa-gif@umin.ac.jp. 2. Department of Gastroenterology, International University of Health and Welfare Hospital, 537-3 Iguchi, Nasushiobara, Tochigi, 239-2763, Japan. osawa-gif@umin.ac.jp. 3. Department of Gastroenterology and Hepatology, Kohnodai Hospital, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba, 272-8516, Japan. osawa-gif@umin.ac.jp. 4. The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba, 272-8516, Japan. 5. Department of Gastroenterology and Hepatology, Kohnodai Hospital, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba, 272-8516, Japan. 6. Department of Pathology and Laboratory Medicine, Kohnodai Hospital, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba, 272-8516, Japan. 7. The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba, 272-8516, Japan. kantot@hospk.ncgm.go.jp. 8. Department of Gastroenterology and Hepatology, Kohnodai Hospital, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba, 272-8516, Japan. kantot@hospk.ncgm.go.jp.
Abstract
BACKGROUND: Pathological angiogenesis is involved in the development of hepatocellular carcinoma. In patients with chronic hepatitis C (CHC), the level of angiogenic factor angiopoietin (ANGP)-2 is reported to be increased in the blood, correlating with fibrosis. In this study, we aimed to clarify whether blood ANGP-2 is useful as a biomarker for liver angiogenesis and fibrosis in CHC patients and to further reveal the relationship between such pathology in a carbon tetrachloride (CCl4)-treated liver fibrosis mouse model. METHODS: Plasma levels of ANGP-2, expression of a liver sinusoidal endothelial cell (LSEC) marker (CD31), collagen deposition (Sirius Red staining) in the liver, clinical fibrosis markers (Mac-2 binding protein glycosylation isomer, virtual touch quantification, and liver stiffness measurement), and liver function (albumin bilirubin score) were examined in CHC patients. To determine the effects of an anti-angiogenic agent on liver fibrosis in vivo, sorafenib was administered to the CCl4-treated mice (BALB/c male). RESULTS: The plasma levels of ANGP-2 were increased in CHC patients compared to healthy volunteers and decreased by the eradication of hepatitis C with direct-acting antivirals. In addition, plasma ANGP-2 levels were correlated with CD31 expression, collagen deposition, clinical fibrosis markers, and liver function. Sorafenib inhibited liver angiogenesis and fibrosis in the CCl4-treated mice and was accompanied by decreased ANGP-2 expression in LSECs. CONCLUSIONS: ANGP-2 may serve as a useful biomarker for liver angiogenesis and fibrosis in CHC patients. In addition, angiogenesis and fibrosis may be closely related.
BACKGROUND: Pathological angiogenesis is involved in the development of hepatocellular carcinoma. In patients with chronic hepatitis C (CHC), the level of angiogenic factor angiopoietin (ANGP)-2 is reported to be increased in the blood, correlating with fibrosis. In this study, we aimed to clarify whether blood ANGP-2 is useful as a biomarker for liver angiogenesis and fibrosis in CHC patients and to further reveal the relationship between such pathology in a carbon tetrachloride (CCl4)-treated liver fibrosis mouse model. METHODS: Plasma levels of ANGP-2, expression of a liver sinusoidal endothelial cell (LSEC) marker (CD31), collagen deposition (Sirius Red staining) in the liver, clinical fibrosis markers (Mac-2 binding protein glycosylation isomer, virtual touch quantification, and liver stiffness measurement), and liver function (albumin bilirubin score) were examined in CHC patients. To determine the effects of an anti-angiogenic agent on liver fibrosis in vivo, sorafenib was administered to the CCl4-treated mice (BALB/c male). RESULTS: The plasma levels of ANGP-2 were increased in CHC patients compared to healthy volunteers and decreased by the eradication of hepatitis C with direct-acting antivirals. In addition, plasma ANGP-2 levels were correlated with CD31 expression, collagen deposition, clinical fibrosis markers, and liver function. Sorafenib inhibited liver angiogenesis and fibrosis in the CCl4-treated mice and was accompanied by decreased ANGP-2 expression in LSECs. CONCLUSIONS: ANGP-2 may serve as a useful biomarker for liver angiogenesis and fibrosis in CHC patients. In addition, angiogenesis and fibrosis may be closely related.
Authors: Andrew S Allegretti; Xavier Vela Parada; Guillermo A Ortiz; Joshua Long; Scott Krinsky; Sophia Zhao; Bryan C Fuchs; Mozhdeh Sojoodi; Dongsheng Zhang; S Ananth Karumanchi; Sahir Kalim; Sagar U Nigwekar; Ravi I Thadhani; Samir M Parikh; Raymond T Chung Journal: Hepatology Date: 2019-01-04 Impact factor: 17.425
Authors: Sander Lefere; Frederique Van de Velde; Anne Hoorens; Sarah Raevens; Sanne Van Campenhout; Astrid Vandierendonck; Sara Neyt; Bert Vandeghinste; Christian Vanhove; Charlotte Debbaut; Xavier Verhelst; Jo Van Dorpe; Christophe Van Steenkiste; Christophe Casteleyn; Bruno Lapauw; Hans Van Vlierberghe; Anja Geerts; Lindsey Devisscher Journal: Hepatology Date: 2019-02-12 Impact factor: 17.425