A prospective pilot study of circulating endothelial cells as a potential new biomarker in portal hypertension.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Gastroenterology Research Unit, Department of Physiology, Advanced Liver Disease Study Group, Fiterman Center for Digestive Diseases, Mayo Clinic, Rochester, MN 55905, USA.
Soha S
SS
Abdelmoneim
Jayant
J
Talwalkar
Saurabh
S
Sethi
Patrick
P
Kamath
Mohamed Mahmoud Fahmy
MM
Fathalla
Benjamin R
BR
Kipp
Michael B
MB
Campion
Amy C
AC
Clayton
Kevin C
KC
Halling
Vijay H
VH
Shah
D000368:Aged; D015415:Biomarkers; D001792:Blood Platelets / Q000166:cytology; D003430:Cross-Sectional Studies; D042783:Endothelial Cells / Q000473:pathology*; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000097:blood* / Q000209:etiology; D008103:Liver Cirrhosis / Q000097:blood* / Q000150:complications; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D010865:Pilot Projects; D010976:Platelet Count; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012372:ROC Curve; D015203:Reproducibility of Results
D015415:Biomarkers