Longitudinal Changes in Lipid Profile After Sustained Virological Response in Patients with Chronic Hepatitis C Treated with Direct-Acting Antivirals

<b>Background:</b> Direct-acting antiviral (DAA) therapy has transformed chronic hepatitis C virus (HCV) infection into a curable disease. Beyond viral eradication, increasing attention has been directed toward metabolic changes following sustained virological response (SVR), particularly alterations in lipid metabolism. This study aimed to assess the long-term evolution of lipid parameters after HCV cure in a real-world clinical cohort. <b>Methods:</b> We conducted a prospective, single-center observational study including 85 patients with chronic HCV infection who achieved SVR after DAA therapy. Lipid parameters, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides, were assessed at baseline and during post-SVR follow-up at 24, 48, and 96 weeks. Body mass index (BMI) and non-invasive fibrosis indices were also evaluated. Longitudinal changes were analyzed using mixed-effects models. <b>Results:</b> Total cholesterol increased from 157.7 ± 35.6 mg/dL at baseline to 179.6 ± 42.9 mg/dL at SVR 24 and further to 189.0 ± 40.3 mg/dL at SVR 48, stabilizing at 177.7 ± 38.3 mg/dL at SVR 96. LDL-C showed a similar trajectory from 94.6 ± 30.8 mg/dL at baseline to 107.5 ± 33.3 mg/dL at SVR 24, further raising to 115.7 ± 36.2 mg/dL at SVR48, and 111.8 ± 39.5 mg/dL at SVR 96. HDL-C showed minimal change, while triglycerides demonstrated greater interindividual variability without a consistent population-level trend. BMI remained stable over follow-up (26.6 ± 4.7 to 27.6 kg/m²). Linear mixed-effects models confirmed a significant effect of time after SVR on total cholesterol and LDL-C (<i>p</i> < 0.05). <b>Conclusions:</b> In this real-world cohort, HCV cure with DAA therapy was associated with sustained long-term changes in lipid metabolism, characterized by increases in total cholesterol and LDL-C independent of major weight changes. These findings support the importance of continued metabolic monitoring after SVR, particularly in patients with additional cardiometabolic risk factors.