Abstract
Although liver cirrhosis and hepatocellular carcinoma are major consequences of hepatitis C (HCV), there has been an increasing number of studies examining extrahepatic manifestations, especially those caused by systemic chronic inflammation and metabolic complications that might predispose HCV patients to atherosclerosis and ischemic cerebrovascular disease (CVD). The aim of our study was to assess E-selectin, VCAM-1, ICAM-1 and VEGF-A serum levels in patients with chronic HCV infection and to correlate them with cerebrovascular reactivity. A blood sample was taken from eighteen patients with chronic hepatitis C infection and from the same number of healthy blood donors in the control group. The aim was to analyse markers of endothelial dysfunction and to correlate them with cerebrovascular reactivity expressed as breath-holding index (BHI) determined using transcranial color Doppler. The obtained results revealed significant differences between the groups in all endothelial markers except for the E selectin. While the ICAM-1 and sVCAM-1 were significantly increased in the hepatitis group, VEGF-A was significantly decreased. A significant reduction of 0.5 (95% CI 0.2, 0.8) in the mean BHI was found in the hepatitis group (mean BHI 0.64) compared to controls (mean BHI 1.10). No significant association between the BHI and any of the endothelial markers was found in the control group, while in the hepatitis group, the scatter plot of ICAM-1 vs BHI suggested that the association might be present. In conclusion, the results of this study confirm an association between a chronic HCV infection and altered cerebrovascular reactivity as well as higher levels of markers of endothelial activation (ICAM-1, VCAM-1) as possible indicators of an increased CVD risk.
Highlights
Despite the availability of well-tolerated and effective treatments with novel oral antivirals over the last few years, hepatitis C (HCV) still remains a major global health problem
Our study showed that cerebrovascular reactivity values, calculated as the breath-holding index (BHI), were significantly lower in the HCV group than in the healthy control group
Markers of endothelial activation (E-selectin, intracellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1)) and the regulator of angiogenesis vascular endothelial growth factor -A (VEGF-A) were included in our research
Summary
Despite the availability of well-tolerated and effective treatments with novel oral antivirals (direct-acting antivirals, DAA) over the last few years, hepatitis C (HCV) still remains a major global health problem. The major burden of the chronic HCV infection comes from liver cirrhosis, hepatocellular carcinoma and liver transplantation. Some of them are immune mediated and others are driven by systemic chronic inflammation and metabolic complications that might predispose patients to atherosclerosis, including cerebrovascular atherosclerosis (Cacoub et al, 2016). Conventional risk factors for CVD include ageing, smoking, alcohol consumption, obesity, hyperlipidemia, hypertension, atrial fibrillation and diabetes. E-selectin, intracellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1) as markers of endothelial activation, as well as vascular endothelial growth factor -A (VEGF-A) as the regulator of angiogenesis, have been found to be potential indicators of endothelial dysfunction, atherosclerosis and risk of CVD (Stanimirovic et al, 1997; Blann et al, 1999; Poggesi et al, 2016; Billinger et al, 2017; Tchalla et al, 2017; Setyopranoto et al, 2019; Varona et al, 2019)
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