- •Hepatitis C virus (HCV) causes extra-hepatic conditions such as insulin resistance (IR).
- •IR was associated with total circulating triglycerides (TG) but not with cholesterol.
- •Direct-acting antivirals (DAAs) are highly effective for the eradication of HCV.
- •HCV eradication with DAAs decreased in IR and HDL-TG after one-year follow-up.
Background & aims
Hepatitis C virus (HCV) interferes with carbohydrate and lipid metabolism causing cardiovascular disease and insulin resistance (IR). Direct-acting antivirals (DAAs) are highly effective for the eradication of HCV, with positive effects on metabolic health although paradoxically associated with increased total and LDL-cholesterol. The aims of this study were 1) to characterize dyslipidemia (lipoprotein content, number, and size) in naive HCV-infected individuals and 2) to evaluate the longitudinal association of metabolic changes and lipoparticle characteristics after DAA therapy.
We conducted a prospective study with one-year follow-up. 83 naive outpatients treated with DAAs were included. Those co-infected with HBV or HIV were excluded. IR was analyzed using the HOMA index. Lipoproteins were studied by fast-protein liquid chromatography (FPLC) and Nuclear Magnetic Resonance Spectroscopy (NMR).
FPLC analysis showed that lipoprotein-borne HCV was only present in the VLDL region most enriched in APOE. There was a lack of association between HOMA and total cholesterol or cholesterol carried by LDL or HDL at baseline. Alternatively, a positive association was found between HOMA and total circulating triglycerides (TG), as well as with TG transported in VLDL, LDL, and HDL. HCV eradication with DAAs resulted in a strong and significant decrease in HOMA (−22%) and HDL-TG (−18%) after one-year follow-up.
HCV-dependent lipid abnormalities are associated with IR and DAA therapy can reverse this association. These findings may have potential clinical implications as the HDL-TG trajectory may inform the evolution of glucose tolerance and IR after HCV eradication.
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Published online: May 16, 2023
Accepted: May 3, 2023
Received in revised form: May 3, 2023
Received: January 27, 2023
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