Serum Angiopoietin‐2 Predicts Mortality and Kidney Outcomes in Decompensated Cirrhosis

Allegretti, Andrew S.; Parada, Xavier Vela; Ortiz, Guillermo A.; Long, Joshua D.; Krinsky, Scott; Zhao, Sophia; Fuchs, Bryan C.; Sojoodi, Mozhdeh; Zhang, Dongsheng; Karumanchi, S. Ananth; Kalim, Sahir; Nigwekar, Sagar U.; Thadhani, Ravi; Parikh, Samir M.; Chung, Raymond T.

doi:10.1002/hep.30230

Cited by 34 publications

(41 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, baseline serum Ang2 level might be a significant factor associated with liver fibrosis non‐regression after successful HCV eradication by DAAs, especially in patients with advanced liver fibrosis. In the present study, as well as in a previous report, Ang2 levels were significantly correlated with LSM and spleen size, which are factors associated with portal hypertension (Fig. a–d) .…”

Section: Discussionsupporting

confidence: 91%

“…Angiopoietin‐2 (Ang2) is a context‐dependent antagonist of the Tie2‐mediated signaling that is associated with vessel stabilization; thus, increased Ang2 level causes vascular leak and inflammation. Moreover, elevated serum Ang2 level was observed in patients with advanced liver fibrosis and HCC . Importantly, portal hypertension‐induced slow blood flow could increase Ang2 expression .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Suda

Kimura

et al. 2020

Hepatology Research

View full text Add to dashboard Cite

Aim Factors associated with improvement of liver fibrosis after successful hepatitis C virus (HCV) eradication by interferon (IFN)‐free direct‐acting antiviral agents (DAAs) have been not clarified well. Angiopoietin‐2 (Ang2) is reported to be associated with vascular leak and inflammation observed in patients with advanced liver fibrosis. Methods In this retrospective study, patients treated with IFN‐free DAAs who underwent transient elastography before and at 24‐weeks post‐treatment and achieved sustained viral response were enrolled. Baseline serum Ang2 was measured, and its relationship with other clinical factors was analyzed. Liver fibrosis stage was defined based on liver stiffness according to a previous report. Predictive factors for regression of liver fibrosis stage after DAA therapy were evaluated. Results Overall, 116 patients were analyzed. Baseline serum Ang2 levels were significantly associated with liver stiffness, spleen index, and liver stiffness‐based liver fibrosis stage. Moreover, 75% of patients experienced regression of liver fibrosis stage after DAA therapy. Multivariate analysis revealed that advanced liver fibrosis stage and Ang2 levels were significantly associated with regression of liver fibrosis stage after DAA therapy. In patients with advanced liver fibrosis (F3/4), baseline Ang2 level alone could predict regression of liver fibrosis stage. A baseline Ang2 cut‐off value (354 pg/ML) could predict regression of liver fibrosis stage after DAA therapy with high accuracy (sensitivity 0.882, specificity 0.733). Conclusions Evaluation of serum Ang2 levels before DAA therapy is important. Our results provide a novel mechanistic insight into non‐regression of liver stiffness after DAA therapy. Long‐term and larger studies are required.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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

Suda

Kimura

et al. 2020

Hepatology Research

View full text Add to dashboard Cite

show abstract

“…Increased Ang‐2 serum levels have been observed in various inflammatory conditions and have also been reported as a diagnostic and prognostic marker for HCC and, recently, decompensated cirrhosis . We report elevated Ang‐2 serum levels in patients with NASH compared with those with NAFL or without NAFLD in a well‐characterized cohort of bariatric surgery patients.…”

Section: Discussionmentioning

confidence: 57%

“…Increased Ang-2 serum levels have been observed in various inflammatory conditions and have also been reported as a diagnostic and prognostic marker for HCC and, recently, decompensated cirrhosis. (30)(31)(32) We report elevated Ang-2 serum levels in patients with NASH compared with those with NAFL or without NAFLD in a well-characterized cohort of bariatric surgery patients. Moreover, circulating Ang-2 levels correlated with the histological features of NASH, in particular the grade of lobular inflammation, and associated independently with histological NASH in multivariate analysis.…”

Section: Discussionmentioning

confidence: 76%

Angiopoietin‐2 Promotes Pathological Angiogenesis and Is a Therapeutic Target in Murine Nonalcoholic Fatty Liver Disease

et al. 2019

View full text Add to dashboard Cite

Angiogenesis contributes to the development of nonalcoholic steatohepatitis (NASH) and promotes inflammation, fibrosis, and progression to hepatocellular carcinoma (HCC). Angiopoietin‐2 (Ang‐2) is a key regulator of angiogenesis. We aimed to investigate the role of Ang‐2 and its potential as a therapeutic target in NASH using human samples, in vivo mouse models, and in vitro assays. Serum Ang‐2 levels were determined in 104 obese patients undergoing bariatric surgery and concomitant liver biopsy. The effect of the Ang‐2/Tie2 receptor inhibiting peptibody L1‐10 was evaluated in the methionine‐choline deficient (MCD) and streptozotocin‐western diet nonalcoholic fatty liver disease mouse models, and in vitro on endothelial cells and bone marrow–derived macrophages. The hepatic vasculature was visualized with µCT scans and scanning electron microscopy of vascular casts. Serum Ang‐2 levels were increased in patients with histological NASH compared with patients with simple steatosis and correlated with hepatic CD34 immunoreactivity as a marker of hepatic angiogenesis. Serum and hepatic Ang‐2 levels were similarly increased in mice with steatohepatitis. Both preventive and therapeutic L1‐10 treatment reduced hepatocyte ballooning and fibrosis in MCD diet‐fed mice and was associated with reduced hepatic angiogenesis and normalization of the vascular micro‐architecture. Liver‐isolated endothelial cells and monocytes from MCD‐fed L1‐10–treated mice showed reduced expression of leukocyte adhesion and inflammatory markers, respectively, compared with cells from untreated MCD diet‐fed mice. In the streptozotocin‐western diet model, therapeutic Ang‐2 inhibition was able to reverse NASH and attenuate HCC progression. In vitro, L1‐10 treatment mitigated increased cytokine production in lipopolysaccharide‐stimulated endothelial cells but not in macrophages. Conclusion: Our findings provide evidence for Ang‐2 inhibition as a therapeutic strategy to target pathological angiogenesis in NASH.

show abstract

“…In addition to their established functions in developmental and pathological angiogenesis, angiopoietins serve as a link between angiogenesis and inflammation. The levels of angiopoietin-2 have been reported to be increased in patients with cirrhosis, with the increased levels being correlated with disease prognosis [44,45]. The therapeutic inhibition of angiopoietin-2 has been reported to reduce inflammation and fibrosis in the experimental models of liver fibrosis induced by carbon tetrachloride [46] or those of non-alcoholic steatohepatitis (NASH) [47].…”

Section: Angiopoietin/tie Systemmentioning

confidence: 99%

Pathological Angiogenesis: The New Culprit behind Chronic Liver Disease

Ramirez¹,

Fernández²

2019

obm hg

View full text Add to dashboard Cite

Angiogenesis is the formation of new blood vessels from the existing ones. It is a complex and highly regulated process which plays a role in a wide variety of physiological and pathological processes. Angiogenesis is essential for a variety of functions in chronic liver disease, including the development and establishment of liver inflammation and fibrosis, the formation of portosystemic collaterals, increase in the splanchnic blood flow, and portal hypertension. Angiogenesis involves a sequence of well-coordinated events which are mediated by a number of strictly regulated interactions between the pro-angiogenic factors and their corresponding receptors expressed on the surface of various vascular (e.g., endothelial cells and pericytes) and stromal components constituting the extracellular matrix. The present review provides an overview of the contribution of angiogenesis to the progression of chronic liver disease, and discusses the functional roles of the key growth factors and cytokines that are known to promote angiogenesis in liver disease, including the vascular endothelial growth factor, placental growth factor, platelet-derived endothelial cell growth factor, and the angiopoietin system. Inhibiting the activity of the aforementioned

show abstract

Serum Angiopoietin‐2 Predicts Mortality and Kidney Outcomes in Decompensated Cirrhosis

Cited by 34 publications

References 50 publications

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

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

Angiopoietin‐2 Promotes Pathological Angiogenesis and Is a Therapeutic Target in Murine Nonalcoholic Fatty Liver Disease

Pathological Angiogenesis: The New Culprit behind Chronic Liver Disease

Contact Info

Product

Resources

About