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Hepatitis C virus eradication by direct antiviral agents abates oxidative stress in patients with advanced liver fibrosis
Author(s) -
Salomone Federico,
Petta Salvatore,
Micek Agnieszka,
Pipitone Rosaria Maria,
Distefano Alfio,
Castruccio Castracani Carlo,
Rini Francesca,
Di Rosa Michelino,
Gardi Concetta,
Calvaruso Vincenza,
Di Marco Vito,
Li Volti Giovanni,
Grimaudo Stefania,
Craxì Antonio
Publication year - 2020
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.14608
Subject(s) - medicine , oxidative stress , cohort , fibrosis , gastroenterology , lipid peroxidation , intima media thickness , hepatitis c virus , hepatitis c , immunology , virus , carotid arteries
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 in systemic oxidative stress after viral clearance. Methods We studied a retrospective cohort of 105 patients (age 62.4 ± 11.2 years; 62 men) with F3/F4 fibrosis, characterized by carotid ultrasonography at baseline and at sustained virologic response (SVR) follow‐up. Levels of 8‐iso‐prostaglandin F 2α (F 2 ‐isoprostanes) and other oxidative stress markers were measured on frozen sera. Association between change (denoted as Δ) in oxidative stress markers (exposures) and change in 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 in cIMT (0.92 ± 0.20 vs 0.83 ± 0.21 mm, P < .001). HCV eradication markedly decreased serum levels of F 2 ‐isoprostanes (620.5 [143.2; 1904.1] vs 119.51 [63.2; 400.6] pg/mL, P < .0001), lipid hydroperoxides (13.8 [6.3; 20.7] vs 4.9 [2.3; 9.6] nmol/μl, P < .0001) and 8‐hydroxy‐2'‐deoxyguanosine (558.9 [321.0; 6301.2] vs 294.51 [215.31; 408.95] pg/mL, P < .0001), whereas increased serum GPx activity (10.44 [4.6; 16.3] vs 13.75 [9.42; 20.63] nmol/min/mL, P = .001). By multiple linear regression analysis ΔcIMT was independently associated with ΔF 2 ‐isoprostanes (β: 1.746 [0.948; 2.543]; P < .0001) after adjustment for age, baseline F 2 ‐isoprostanes and baseline IMT. Conclusions Besides association of lipid peroxidation with severity of liver disease, the reduction in F 2 ‐isoprostanes may be involved in the improvement of atherosclerosis after HCV eradication.