Chronic HCV infection may affect host lipid metabolism and induce hypocholesterolemia, insulin resistance (IR), diabetes, atherosclerosis and steatosis. Low density cholesterol (LDL-C) is an atherogenic lipoprotein, its oxidated form (oxLDL) is involved in the formation of atherosclerotic plaques and is a marker of cardiovascular disease. We investigated the changes of serum lipids, oxLDL and IR during and after DAA treatment of HCV.
We enrolled 77 HCV pts (57.1% males, age 58.7±11.2 yrs, BMI 24.7±3.9, 74% HCV Genotype 1, 28% with metabolic syndrome, 36% with steatosis) with advanced fibrosis or cirrhosis (liver stiffness 19.1±9.9 KPa) treated with DAA (70% with ribavirin). HOMA-score, total, low and high density cholesterol (TC, LDL-C, HDL-C), tryglicerides (TG) and oxLDL levels have been evaluated at baseline (T0), end-of-treatment (EOT) and after 12-weeks of follow-up (FU).
A significant decrease of HOMA-IR occurred during therapy and remained stable during FU (Table). The baseline proportion of patients with HOMA-IR≥4, diagnostic for a pre-diabetic state, was 45.5% and significantly decreased after treatment to 32.5% (p=0.03). The decline of HOMA-IR during antiviral treatment was gender-related, since men experienced a marked reduction of IR both during treatment and FU while women had no changes. TC and LDL-C levels significantly increased during antiviral therapy and FU (Table). The proportion of pts with optimal TC (TC<200 mg/dL) and LDL-C (LDL-C<129 mg/dL) significantly decreased during the study period from 88.3% to 70% (p=0.0075) and from 89% to 76.2% (p=0.04), respectively. Notably also oxLDL levels increased during the study period (Table), while HDLC did not change and TG levels declined only during treatment.
The improvement of insulin resistance and the significant reduction of the proportion of pts with a pre-diabetic state suggest that DAA treatment might revert HCV related metabolic alterations and prevent the development of diabetes. The modulation of the metabolic changes observed during treatment according to gender is an interesting aspect of the interplay between virus and host and an area of future research. The rapid and significant increase in total, LDL and oxLDL cholesterol levels observed in pts with advanced liver disease treated with DAA might increase their cardiovascular risk, suggesting the potential benefit of statin co-administration during or immediately after DAA therapy.