DIRECT-ACTING antivirals restore systemic redox homeostasis in chronic HCV patients

Chronic hepatitis C therapy has completely changed in the last years due to the availability of direct-acting antivirals (DAAs). Removing the virus may be not enough since chronic infection deeply modifies immune system and cellular metabolism along decades of inflammation. Oxidative stress plays a significant role in maintaining systemic inflammation during chronic HCV infection. Other than removing the virus, effective therapy could counteract oxidative stress. This study investigated the impact of DAA treatment on circulating markers of oxidative stress and antioxidant defence in a cohort of patients affected by chronic hepatitis C. To this, an observational study on 196 patients who started therapy with DAA for HCV-related hepatitis was performed. Patients were assessed at baseline, 4 weeks after the initiation of therapy (4wks), at the end of treatment (EoT), and 12 weeks after the EoT (SVR12). Circulating oxidative stress was determined by measuring serum hydroxynonenal (HNE)- and malondialdehyde (MDA)-protein adducts, and 8-hydroxydeoxyguanosine (8-OHdG). Antioxidant status was evaluated by measuring the enzymatic activity and mRNA expression of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in peripheral blood mononuclear cells. We observed a reduction of serum 8-OHdG at 4wks, while the circulating level of both HNE- and MDA-protein adducts diminished at EoT; all these markers persisted low at SVR12. On the other side, we reported an increase in the enzymatic activity of all the antioxidant enzymes in PBMC at EoT and SVR12. Taking into account circulating 8-OHdG and antioxidant enzyme activities, patients with high fibrosis stage were those that had the most benefit from DAA therapy. To conclude, this study indicates that treatment with DAAs improves the circulating redox status of patients affected by chronic hepatitis C. This positive impact of DAA therapy may be related to its effectiveness on cutting down viremia and pro-inflammatory markers.

Keywords: Direct-acting antivirals; HCV infection; redox balance.