Carotid Intima-media Thickness and Small Dense Low-density Lipoprotein Cholesterol Increase after One Year of Treatment with Direct-acting Antivirals in Patients with Hepatitis C Virus Infection

Abstract

Objective Direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV) infection exert a significantly high sustained viral response (SVR), and patients experience a rebound increase in low-density lipoprotein cholesterol (LDL) and total cholesterol levels. Carotid intima-media thickness (IMT) is a highly reproducible and non-invasive parameter for assessing the atherosclerotic process, and the small dense (sd) LDL level is useful for clinically evaluating the atherogenic risk. Methods A total of 48 patients with chronic HCV infection were treated with DAAs. All patients exhibited an SVR 24 weeks later. We compared the metabolic profiles of the patients, including the sdLDL and IMT values, at the start of DAA treatment with those after one year of treatment. We verified whether the HCV clearance after the administration of DAAs is associated with the development of atherosclerosis. Results The sdLDL, %sdLDL (sdLDL/LDL), and LDL values were exacerbated after a year of treatment; however, the triglyceride level, glycated hemoglobin level, insulin resistance, and body weight remained unaltered. The max-IMT was increased after a year compared to that at the start of treatment. Differences in the max-IMT (dmax-IMT) were greater in men than in women; however, no correlation was observed between the dmax-IMT and genotype, fibrosis, hypertension, hyperlipidemia, diabetes, obesity, and dialysis status. The %sdLDL at the start and a year later was positively correlated with the dmax-IMT. No correlation was observed among various factors including the LDL, triglyceride, body mass index, insulin resistance and dmax-IMT. In uni- and multivariate analyses, a significant correlation was observed between %sdLDL≥16% at the start of treatment and the sex and dmax-IMT. Conclusion Because the sdLDL and IMT values were exacerbated after a year of DAA treatment, atherosclerosis must be evaluated in patients achieving an SVR.

Systematic review: chronic viral hepatitis and metabolic derangement

“…The authors observed that a small dense LDL-C was associated with the increase in intima thickness. 207 Another report found a significant improvement of tricuspid annular plane systolic excursion and lateral E' velocity relative to baseline values, following SVR to DAA in HCV cirrhotic patients. 208 Central artery stiffness was also increased following HCV clearance as a result of DAA treatment and was related to an increase in LDL-C. 209 Long-term results addressing these paradoxical findings in terms of vascular parameters and the risk of cardiovascular events following viral clearance would be worth investigating.…”

“…It measured intima thickness following DAA treatment and found that the maximal intima thickness was higher after 1 year of treatment than the baseline value. The authors observed that a small dense LDL‐C was associated with the increase in intima thickness . Another report found a significant improvement of tricuspid annular plane systolic excursion and lateral E' velocity relative to baseline values, following SVR to DAA in HCV cirrhotic patients .…”

Unmet needs of chronic hepatitis C in the era of direct-acting antiviral therapy

“…Hypolipidemia during viremic status can be reversed to deteriorate lipid profiles after DAA therapy [ 59 ]. An increase in the small dense low-density lipoprotein cholesterol level corresponding to increased carotid intima-media thickness 1 year after DAA therapy has been reported [ 60 ]. Attention should be paid not only to liver-related complications but also to the extrahepatic consequence of cardio-cerebrovascular disease in the post-SVR period.…”

Effect of new oral direct acting antiviral therapy on sexual function in male patients with hepatitis C virus

“…Atherosclerosis is an important contributor for sexual dysfunction (Gowani et al., 2017; Miner et al., 2019). The DAA therapy had advantage of improvement of atherosclerosis (Butt et al., 2019; Ichikawa et al, 2019) and therefore is beneficial in sexual function in patients with HCV.…”