Hepatitis C Virus Clearance by Direct-Acting Antivirals Agents Improves Endothelial Dysfunction and Subclinical Atherosclerosis: HEPCAR Study

Abstract

INTRODUCTION: Hepatitis C virus (HCV) infection has been related to increased cardiovascular (CV) risk. The aim of this study was to analyze the impact of sustained virological response (SVR) on endothelial dysfunction and subclinical atherosclerosis in patients with hepatitis C virus treated with direct-acting antiviral agents. METHODS: A total of 114 patients were prospectively recruited and underwent CV risk assessment including (i) endothelial dysfunction determined through laser Doppler flowmetry and (ii) subclinical atherosclerosis, elucidated by the ankle-brachial index (ABI). Atherogenic lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides); markers of oxidative stress (oxidized low-density lipoprotein antibodies [OLAbs]), soluble markers of adhesion (vascular cell adhesion molecule [VCAM], e-selectin, and soluble markers of angiogenesis; and vascular endothelial growth factor, endothelial [EMPs] and platelet [PMPs] apoptotic microparticles, and cell-free DNA [cfDNA]) were measured. All determinations were performed at baseline, 12 weeks (SVR time), and 1 year after treatment. RESULTS: In patients with endothelial dysfunction, area of hyperemia improved after virus clearance ( P = 0.013) and was related to significant decrease in VCAM, e-selectin ( P < 0.001), and cfDNA ( P = 0.017) and to increased OLAb levels ( P = 0.001). In patients with subclinical atherosclerosis at baseline, a significantly improved ABI was seen after HCV clearance ( P < 0.001). Levels of both EMPs and PMPs also decreased after SVR and at follow-up ( P = 0.006 and P = 0.002, respectively). DISCUSSION: HCV clearance improved not only liver function but also endothelial dysfunction and subclinical atherosclerosis promoted by decrease in levels of VCAM, e-selectin, cfDNA, and PMPs and EMPs.

The effect of direct acting antiviral agents on vascular endothelial function in Egyptian patients with chronic hepatitis C virus infection

“…Our results were in line with the recent multicenter and prospective study (HEPCAR Study) of HCV patients treated by DAAs with long follow-up period which demonstrated significant reduction in levels endothelial dysfunction markers VCAM-1 and e-selectin at SVR point in all participants and continued in reduction during follow-up for one year ( Muñoz-Hernández et al 2020 ).…”

“…The same was reported by Muñoz-Hernandez et al . ( Muñoz-Hernández et al 2020 ) where a continuous improvement in vascular function markers at SVR time and 1 year after treatment was observed. Therefore, the effect is unlikely to be associated with the pleiotropic effect of DAA.…”

“…This is in agreement with Muñoz-Hernandez et al . ( Muñoz-Hernández et al 2020 ) who found that successful DAA treatment in HCV patients without a history of CV disease has been shown to decrease the risk of CV disease by improving endothelial function, which showed more improvement in patients with worse baseline status. These results supported by Nicola Coppola et al ( Coppola et al 2019 ) who found that the achievement of SVR12 by DAAs regimens has a significant improvement in renal dysfunction as extrahepatic manifestation of HCV infection more in patients with CKD or cirrhosis than patients without cirrhosis or CKD at baseline.…”

Blood markers of endothelial dysfunction and their correlation to cerebrovascular reactivity in patients with chronic hepatitis C infection

“…The obtained results show that hepatitis C group had significantly higher concentrations of ICAM-1 and sVCAM-1 compared to controls which is in accordance with most results of previous studies dealing with HCV, endothelial dysfunction and higher risk of CVD ( Stanimirovic et al, 1997 ; Blann et al, 1999 ; Martinic-Popovic et al, 2014 ). Authors of some recent studies went a step further alleging that the new DAA treatment reverses these chronic HCV effects and enhances endothelial function ( Schmidt et al, 2018 ; Davis et al, 2018 ; Muñoz Hernández et al, 2020 ). In our research, HCV patients had decreased VEGF-A compared to healthy controls opposing several earlier studies connecting higher levels of VEGF-A with the risk of ischemic CVD ( Shoamanesh et al, 2016 ).…”

Circulating microparticles in patients with chronic hepatitis C and changes during direct-acting antiviral therapy

“…Only a few studies about MPs in patients with hepatitis C undergoing DAA therapy have been performed 33,34 . The aims of the following study were: first, compare MPs level between patients with CHC and control group of healthy volunteers; second, evaluate changes of MPs levels during DAA therapy; third, analyzed MPs changes in subpopulations according to gender, genotypes, and fibrosis stage.…”