Differential role of circulating endothelial progenitor cells in cirrhotic patients with or without hepatocellular carcinoma.
OBJECTIVE
Circulating endothelial progenitor cells have a negative prognostic impact in patients with hepatocellular carcinoma, but may play a different role in portal hypertension according to preclinical data. Here, we address this issue for the first time in cirrhotic patients+/-hepatocellular carcinoma.


METHODS
Portal hypertension in cirrhotic and hepatocellular carcinoma patients was determined by hepatic venous pressure gradient. Blood cells staining positive for CD34/KDR/AC133 using flow cytometry were characterised as endothelial progenitor cells. Vascular endothelial growth factor levels were determined by ELISA.


RESULTS
Endothelial progenitor cells levels in peripheral blood were elevated in cirrhotic (n=23) (mean: 0.12+/-0.06% S.D.) and in hepatocellular carcinoma patients (n=24) (0.14+/-0.09% S.D.) relative to healthy controls (H-group, n=15) (0.06+/-0.04% S.D.) (P=0.056 and P=0.02, respectively). There were higher vascular endothelial growth factor levels in hepatocellular carcinoma patients compared to cirrhotics (P=0.047) and HC (P=0.037). Notably, hepatic venous pressure gradient was positively correlated with vascular endothelial growth factor (r=0.5, P=0.046) but negatively with endothelial progenitor cells levels (r=-0.51, P=0.02) in cirrhotics, but not hepatocellular carcinoma patients.


CONCLUSIONS
Circulating endothelial progenitor cells are increased in patients with portal hypertension+/-hepatocellular carcinoma. The negative correlation of endothelial progenitor cells with hepatic venous pressure gradient suggests a protective role of endothelial progenitor cells in liver cirrhosis whilst vascular endothelial growth factor is associated with high hepatic venous pressure gradient. In contrast, increased endothelial progenitor cells in hepatocellular carcinoma rather reflect tumour specific endothelial progenitor cells mobilisation.
Sieghart
W
W
Department of Internal Medicine III, Division of Gastroenterology/Hepatology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Fellner
S
S
Reiberger
T
T
Ulbrich
G
G
Ferlitsch
A
A
Wacheck
V
V
Peck-Radosavljevic
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000503:physiopathology; D042783:Endothelial Cells / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006975:Hypertension, Portal / Q000378:metabolism / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000503:physiopathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D013234:Stem Cells / Q000166:cytology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D014690:Venous Pressure / Q000502:physiology
D042461:Vascular Endothelial Growth Factor A