Triglyceride-rich lipoproteins and insulin resistance in patients with chronic hepatitis C receiving direct-acting antivirals

Background & aims: Hepatitis C virus (HCV) interferes with carbohydrate and lipid metabolism causing cardio-vascular disease and insulin resistance (IR). Direct-acting antivirals (DAAs) are highly effective for the eradi-cation 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. Methods: 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). Results: 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. Conclusions: HCV-dependent lipid abnormalities are associated with IR and DAA therapy can reverse this asso-ciation. These findings may have potential clinical implications as the HDL-TG trajectory may inform the evo-lution of glucose tolerance and IR after HCV eradication.