Effects of HCV eradication by DAA on oxidative stress parameters in patients with chronic hepatitis C

Abstract

Oxidative stress is a feature of chronic hepatitis C (CHC) and it is especially associated with the advanced stages of the disease. In this study we aimed to assess the effects of HCV eradication by direct antiviral agents (DAA) on oxidative stress in a cohort of 92 patients (age 59.8 ± 10.9 years; 56 males) with F3 fibrosis (n = 50) or compensated cirrhosis (n = 42). Redox status was determined by measuring serum lipid hydroperoxides (LOOH), 8-isoprostanes, glutathione peroxidase (GPx) activity, non-proteic thiols and markers of protein, DNA/RNA oxidation at baseline and 12-wk after antiviral treatment. All patients achieved a sustained virologic response (SVR) and SVR was associated with reduction of liver stiffness (15.7 ± 9.3 vs 12.8 ± 8.3 kPa, P < 0.0001), plasma glucose (98 ± 18 vs 92 ± 15 mg/dl, P = 0.045) and carotid intima-media thickness (IMT) (0.82 ± 0.19 vs 0.78 ± 0.19, P = 0.001). At multiple linear regression, higher liver stiffness was associated with higher LOOH (β = 0.272, P = 0.02) and 8-isoprostanes (β = 0.229, P = 0.04), lower GPx (β = −0.212, P = 0.04) and thiols (β = −0.230, P = 0.04). Baseline LOOH levels were also independent predictors of high HOMA-IR (β = 0.301, P = 0.04) and cirrhosis (OR 3.330, 95% CI 1.022–10.854). Carotid IMT was inversely associated with baseline thiols (β = −0.287, P = 0.04) and, consistently, thiols were lower in patients with IMT ≥ 10 mm compared to IMT < 10 mm (22.3 ± 16 vs 14.5 ± 7.9 nmol/μl, P = 0.01). HCV eradication following DAA reduced LOOH (14.6 ± 9.7 vs 7.3 ± 6.8, P < 0.0001), 8-isoprostanes (1397 ± 1926 vs 371 ± 706 pg/ml, P < 0.0001), 8-hydroxy-2′-deoxyguanosine (3451 ± 4499 vs 333 ± 161 pg/ml, P < 0.0001) and thiols (20.8 ± 14.3 vs 3.9 ± 2.5 nmol/μl, P < 0.0001) whereas increased GPx activity (11.3 ± 9.4 vs 16.0 ± 9.3 nmol/min/ml, P = 0.0003). Changes of oxidative stress markers were confirmed in sub-groups stratified for age, metabolic parameters and liver disease severity.