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Published on: September 15, 2017
A prospective pilot study of circulating endothelial cells as a potential new biomarker in portal hypertension
Soha S Abdelmoneim1, Jayant Talwalkar, Saurabh Sethi
1Gastroenterology Research Unit, Department of Physiology, Advanced Liver Disease Study Group, Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, MN 55905, USA.
Insights
Circulating endothelial cell (CEC) counts are higher in cirrhosis patients, with the CEC to platelet ratio (CEC/PC) also elevated in decompensated cirrhosis. These findings suggest CEC may be a useful prognostic marker in liver disease.
Area of Science:
- Vascular biology
- Hepatology
- Biomarker discovery
Background:
- Peripheral circulating endothelial cells (CECs) are potential prognostic markers in cardiovascular disease.
- Vascular injury is associated with cirrhosis and portal hypertension, but CEC levels in these conditions are not well understood.
Purpose of the Study:
- To evaluate CEC count in patients with cirrhosis and portal hypertension.
- To correlate CEC count with markers of portal hypertension and disease severity.
Main Methods:
- Prospective recruitment of 15 patients with cirrhosis/portal hypertension and 15 matched controls.
- Enumeration of peripheral blood CECs using an automated rare cell analysis system.
- Correlation of CEC counts with clinical features and disease severity markers.
Main Results:
- Median CEC levels were significantly higher in cirrhosis patients (73.7 cells/4 ml) compared to controls (28.7 cells/4 ml) (P=0.021).
- The CEC to platelet count ratio (CEC/PC) was significantly higher in cirrhosis patients (0.723) than controls (0.126) (P<0.001).
- CEC/PC ratio at 0.21 demonstrated high sensitivity (100%) and specificity (73%) for differentiating cirrhosis (AUC: 0.89), and was elevated in decompensated cirrhosis (Child B/C).
Conclusions:
- CEC count and CEC/PC ratio are elevated in cirrhosis patients.
- CEC/PC ratio is further increased in decompensated cirrhosis.
- These findings support further research into the prognostic utility of CECs in cirrhosis and portal hypertension.
Background/Aims:
Peripheral circulating endothelial cells (CEC) have been proposed as a prognostic marker in cardiovascular diseases. Cirrhosis and portal hypertension are associated with vascular injury yet little is known about CEC count in these conditions. Therefore, we evaluated CEC count in patients with cirrhosis, and correlated it with markers of portal hypertension/disease severity.
Patients/Methods:
Fifteen patients with cirrhosis/portal hypertension and 15 matched controls were prospectively recruited for study participation. An automated rare cell analysis system was used to enumerate CEC from peripheral blood and correlated with clinical features.
Results:
Median CEC levels were significantly higher in patients with cirrhosis as compared with controls (median [interquartile range (IQR)]; cirrhosis: 73.7 cells/4 ml [53.7-140.3]; controls: 28.7 cells/4 ml [21-58.7]; P=0.021). Ratio of CEC to platelet count (CEC/PC) also distinguished patients with cirrhosis from controls (IQR; cirrhosis: 0.723 [0.396-1.672]; controls: 0.126 [0.103-0.333]; P<0.001). Receiver operator characteristic analysis revealed that CEC cut-off of 42 cells/4 ml showed sensitivity of 87% and specificity of 74% for differentiating cirrhosis from controls (AUC: 0.74), while CEC/PC ratio at 0.21 showed sensitivity of 100% and specificity of 73% (AUC: 0.89). Furthermore, CEC/PC index was significantly elevated in patients with hepatic decompensation as defined by Child B/C (P<0.05). The intra- and interobserver variability correlation coefficients for CEC measurement were 0.9989 and 0.9986 respectively.
Conclusion:
Median CEC count and CEC/PC ratio are significantly elevated in patients with cirrhosis, with CEC/PC also increased in patients with decompensated cirrhosis. These data provide rationale for larger validation studies to assess if CEC may have prognostic utility in patients with cirrhosis and portal hypertension.

