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.

Keywords: direct-acting antivirals; hepatitis C virus; intima-media thickness; small dense low-density lipoprotein cholesterol.

Figure.

Relationship between the changes in the IMT and clinical factors. The changes in the IMT were calculated by subtracting the IMT (mm) before treatment with DAAs from that after a year of treatment. Changes in diameters by 1 unit (0.1 mm) or more were indicated. Error bars represent SD. Differences between pre- and post-treatment values were evaluated by a t-test, and values of p<0.05 were considered statistically significant. a: The max-IMT significantly increased a year after treatment compared to that at the start of treatment (p=0.0058). The Y-axis represents the max-IMT diameter (mm). b: The mean-IMT at the start of treatment did not differ markedly from that after a year. The Y-axis represents the mean-IMT diameter (mm). c: The max-IMT in men (M) was higher than that in women (F) at the start of treatment and a year later (p=0.04 and 0.0015, respectively), and the difference was significant when comparing values after a year with those at the start of treatment (p=0.0034). The difference in the max-IMT (dmax-IMT) was calculated as follows: dmax-IMT=max-IMT after a year - max-IMT at the start of treatment. The dmax-IMT was higher in men than in women (p=0.008). The Y-axis represents the max-IMT and dmax-IMT diameters (mm). d: The %sdLDL was calculated as follows: %sdLDL=sdLDL at the start of treatment/LDL at the start of treatment. The dmax-IMT in women with %sdLDL≥16% was higher than that in women with %sdLDL<16% (p=0.0154), and the dmax-IMT in men with %sdLDL<16% was higher than that in women with %sdLDL<16% (p=0.027). The numbers of women with %sdLDL≥16%, women with %sdLDL<16%, men with %sdLDL ≥16%, and men with %sdLDL<16% were 15, 13, 13, and 7, respectively. The Y-axis represents the dmax-IMT diameter (mm).