Direct-acting antiviral therapy may help restore HCV-induced impaired redox balance and liver fibrosis process

Abstract

Abstract Objectives The aim of this study was to investigate the changes in thiol/disulfide balance, pro-fibrotic mediators (transforming growth factor-beta [TGF-β] and periostin) and a potential biomarker for the prediction of HCV-induced HCC (3β-hydroxysterol Δ24-reductase [DHCR24]) during direct-acting antiviral (DAA) therapy in chronic hepatitis C (CHC) patients. Methods This prospective cohort study included 56 non-cirrhotic, treatment-naive CHC patients who were treated with DAAs between January and June 2020. Laboratory tests, including serum total/native thiol, TGF-β , $\text{,}$ periostin, DHCR24, total bilirubin and albumin levels were measured and disulfide levels were calculated at baseline, then at 1 month and at the end of therapy (EOT). Results Of the 56 patients, all achieved a sustained virological response after DAA therapy. There was a significant decrease in serum levels of disulfide and TGF-β, (p=0.020 and p<0.001, respectively) and a significant increase in serum levels of native thiol compared with baseline levels (p=0.010). There was no significant change in levels of total thiol, DHCR24 and periostin levels. Serum TGF-β levels were found to be positively correlated with total bilirubin levels (rs=0.470, p=0.001) and negatively with albumin levels (rs=−0.483, p<0.001). A significant moderate positive correlation was determined between baseline serum DHRC24 and disulfide levels (rs=0.356, p=0.007). Conclusions The study results suggest that the DAA therapy may help to restore the impaired thiol/disulfide balance and reduce the pro-fibrotic process in CHC patients by markedly decreasing serum levels of TGF-β, a key player in HCV-induced liver fibrosis.