High serum angiopoietin‐2 level predicts non‐regression of liver stiffness measurement‐based liver fibrosis stage after direct‐acting antiviral therapy for hepatitis C

Kawagishi, Naoki; Suda, Goki; Kimura, Megumi; Maehara, Osamu; Shimazaki, Tomoe; Yamada, Ryoichi; Kitagataya, Takashi; Shigesawa, Taku; Suzuki, Kazuharu; Nakamura, Akihisa; Ohara, Masatsugu; Umemura, Machiko; Nakai, Masato; Sho, Takuya; Natsuizaka, Mitsuteru; Morikawa, Kenichi; Ogawa, Koji; Kudo, Yusuke; Nishida, Mutsumi; Sakamoto, Naoya

doi:10.1111/hepr.13490

Cited by 22 publications

(44 citation statements)

References 25 publications

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“…It has been reported that ANGP-2 blood levels are associated with liver brosis in CHC patients [14]. In this study, blood levels of ANGP-2 were correlated with CD31 expression and liver brosis.…”

Section: Discussionsupporting

confidence: 53%

“…Serum ANGP-2 levels have been observed to be signi cantly higher in patients with chronic hepatitis C (CHC) than in healthy controls while VEGF levels were comparable between the two groups [12,13]. Serum ANGP-2 levels appear to be correlated with liver stiffness in CHC patients [14] and increase based on stage progression from chronic hepatitis to cirrhosis [15]. In patients with decompensated cirrhosis, serum ANGP-2 may be a predictor of mortality [16].…”

Section: Introductionmentioning

confidence: 99%

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Blood angiopoietin-2 predicts liver angiogenesis and fibrosis in hepatitis C patients

Osawa

Yoshio

Aoki

et al. 2020

Preprint

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BackgroundPathological angiogenesis is involved in the development of hepatocellular carcinoma (HCC). 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.MethodsPlasma 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).ResultsThe 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. ConclusionsANGP-2 may serve as a useful biomarker for liver angiogenesis and fibrosis in CHC patients. In addition, angiogenesis and fibrosis may be closely related.

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Section: Discussionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Blood angiopoietin-2 predicts liver angiogenesis and fibrosis in hepatitis C patients

Osawa

Yoshio

Aoki

et al. 2020

Preprint

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“…In this study, we included patients with Child‐Pugh grade B, while Chuma's study did not. We and other groups reported that not only the tumor itself but also advanced liver fibrosis could cause serum ANG2 elevation . Thus, the difference in liver fibrosis and HCC condition might affect the results.…”

Section: Discussionmentioning

confidence: 85%

“…We and other groups reported that not only the tumor itself 31 but also advanced liver fibrosis could cause serum ANG2 elevation. 32,33 Thus, the difference in liver fibrosis and HCC condition might affect the results. Therefore, further analysis is required.…”

Section: Discussionmentioning

confidence: 99%

Baseline angiopoietin‐2 and FGF19 levels predict treatment response in patients receiving multikinase inhibitors for hepatocellular carcinoma

et al. 2020

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Background: Sorafenib and lenvatinib are first-line systemic therapies for unresectable hepatocellular carcinoma (HCC). However, the criteria for their selection remain unclear. Methods: We identified patients with unresectable HCC who were treated with sorafenib or lenvatinib between August 2009 and January 2019 at the Hokkaido University Hospital. Patients who continued treatment for >2 months, underwent evaluation by computed tomography every 2-3 months, and had complete clinical data were included. Responders were patients with objective response (OR) for lenvatinib and patients with stable disease (SD) exceeding 6 months (long-SD) or OR for sorafenib. The predictive factors for treatment response, including fibroblast growth factor (FGF)19 and 21, angiopoietin 2 (ANG2), hepatocyte growth factor, and vascular endothelial growth factor, were evaluated. Results: Overall, 27 and 29 patients treated with lenvatinib and sorafenib, respectively, were included. The responders for lenvatinib and sorafenib were 63% (17/27) and 38% (11/29), respectively. No significant predictive factors for treatment response were identified in patients treated with sorafenib. However, baseline serum FGF19 and ANG2 levels were significantly associated with treatment response to lenvatinib. All (9/9) patients with low baseline ANG2 and FGF19 levels who received lenvatinib achieved OR. Conversely, the OR was low (13%; 1/9) in patients with high baseline ANG2 and FGF19 levels. Responder rate was 40% (2/5) in patients with high baseline ANG2 and FGF19 levels who received sorafenib. Conclusion: This study is, to our knowledge, the first to demonstrate that baseline ANG2 and FGF19 levels may aid in selecting optimal systemic therapy for patients with unresectable HCC.

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“…Serum ANGP-2 levels have been observed to be significantly higher in patients with chronic hepatitis C (CHC) than in healthy controls while VEGF levels were comparable between the two groups [12,13]. Serum ANGP-2 levels appear to be correlated with liver stiffness in CHC patients [14] and increase based on stage progression from chronic hepatitis to cirrhosis [15]. In patients with decompensated cirrhosis, serum ANGP-2 may be a predictor of mortality [16].…”

Section: Introductionmentioning

confidence: 99%

Blood angiopoietin-2 predicts liver angiogenesis and fibrosis in hepatitis C patients

et al. 2021

View full text Add to dashboard Cite

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.

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High serum angiopoietin‐2 level predicts non‐regression of liver stiffness measurement‐based liver fibrosis stage after direct‐acting antiviral therapy for hepatitis C

Cited by 22 publications

References 25 publications

Blood angiopoietin-2 predicts liver angiogenesis and fibrosis in hepatitis C patients

Blood angiopoietin-2 predicts liver angiogenesis and fibrosis in hepatitis C patients

Baseline angiopoietin‐2 and FGF19 levels predict treatment response in patients receiving multikinase inhibitors for hepatocellular carcinoma

Blood angiopoietin-2 predicts liver angiogenesis and fibrosis in hepatitis C patients

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