Impact of Sofosbuvir and Daclatasvir therapy on the expression levels of inflammasomes in chronic hepatitis C infected patients

Abstract

Background and Aim:  Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis. Inflammasomes are multi-protein complexes that sense specific microbial molecules and trigger signaling cascades, leading to caspase1 activation and generation of pro-inflammatory cytokines, including IL-1β and IL-18. We aimed to investigate the expression levels of NLRP3, AIM2 and IFI16 inflammasome genes and serum levels of IL-18 in chronic HCV infected patients before treatment and after SVR12. Methods: The study included 30 chronic HCV infected patients and 30 healthy controls. The expression levels of inflammasome genes were evaluated by Quantitative real-time PCR (qPCR) and serum levels of IL-18 were evaluated by ELISA at baseline and after SVR12 with three months regimen of Sofosbuvir and Daclatasvir. Results: At baseline, the expression level of NLRP3, AIM2 and IFI16 inflammasome genes were higher in comparison to controls (p < /em> = 0.018, 0.000 and 0.155 respectively). In addition, the level of serum IL-18 was up regulated in comparison to controls (p < /em> = 0.000). After treatment, there was a statically significant decrease in the expression level of NLRP3, AIM2 and IFI16 inflammasome genes (p < /em> < 0.0001 for all). Also, there was a statically significant down regulation in the level of serum IL-18 (p < /em> = 0.000). Conclusion: Direct acting antiviral (DAA) therapy not only cause viral eradication but also has an immunological restitution effect as it decreases the expression level of NLRP3, AIM2 and IFI16 inflammasome genes and serum level of IL-18. This down regulation may decrease the risk of HCC development in chronic HCV infected patients.