Hepatitis C virus eradication by direct antiviral agents abates oxidative stress in patients with advanced liver fibrosis

BACKGROUND AND AIMS HCV eradication improves non-hepatic outcomes such as cardiovascular diseases although without clearly defined mechanisms. In this study we aimed to assess whether improvement of carotid atherosclerosis may be linked to a reduction of systemic oxidative stress after viral clearance. METHODS We studied a retrospective cohort of 105 patients (age 62.4±11.2 years; 62 males) with F3/F4 fibrosis, characterized by carotid ultrasonography at baseline and at sustained virologic response (SVR) follow-up. Levels of 8-iso-prostaglandin F2α (F2 -isoprostanes) and other oxidative stress markers were measured on frozen sera. Association between change (denoted as Δ) of oxidative stress markers (exposures) and change of carotid intima-media thickness (cIMT) (outcome) was examined using multiple linear regression. RESULTS Subclinical atherosclerosis, defined as the presence of carotid plaque and/or cIMT≥0.9, was present in 72% of the cohort. All patients achieved SVR that led to reduction of cIMT (0.92±0.20 vs 0.83±0.21 mm, P<0.001). HCV eradication markedly decreased serum levels of F2 -isoprostanes (620.5 [143.2; 1904.1] vs 119.51 [63.2; 400.6] pg/ml, P<0.0001), lipid hydroperoxides (13.8 [6.3; 20.7] vs 4.9 [2.3; 9.6] nmol/μl, P<0.0001) and 8-hydroxy-2'-deoxyguanosine (558.9 [321.0; 6301.2] vs 294.51 [215.31; 408.95] pg/ml, P<0.0001) whereas increased serum GPx activity (10.44 [4.6; 16.3] vs 13.75 [9.42; 20.63] nmol/min/ml, P=0.001). By multiple linear regression analysis ΔcIMT was independently associated with ΔF2 -isoprostanes (β: 1.746 [0.948; 2.543]; P<0.0001) after adjustment for age, baseline F2 -isoprostanes and baseline IMT. CONCLUSIONS Besides association of lipid peroxidation with severity of liver disease, the reduction of F2 -isoprostanes may be involved in the improvement of atherosclerosis after HCV eradication.