Efficacy and safety of direct-acting antivirals in hepatitis c virus-infected patients taking proton pump inhibitors

Abstract

Background and Aims: Direct-acting antiviral (DAA) therapy is the cornerstone of the treatment of chronic hepatitis C virus (HCV) infection. Eradication of HCV, predicted by the attainment of a sustained virologic response (SVR) 12 weeks following DAA therapy, is the goal of this treatment. Interest-ingly, recent studies have reported the possible association between HCV-infected patients with DAA therapy concomitant use of proton pump inhibitors (PPIs) and lower odds of achieving SVR. This meta-analysis was conducted to summarize all available data and to estimate this potential association. Methods: Comprehensive literature review was conducted by first searching the Medline and Embase data-bases through March 2017 to identify all studies that inves-tigated the safety and efficacy of DAAs in patients with HCV infection taking PPIs versus those without PPIs. Adjusted point estimates from each study were combined by the ge-neric inverse variance method of DerSimonian and Laird. Results: Nine cohort studies with 32,684 participants met the eligibility criteria and were included in the meta-analysis. The use of PPIs concomitant with DAAs among HCV-infected patients was associated with lower odds of achieving SVR compared with non-PPI users (pooled odds ratio (OR): 0.74, 95% confidence interval (CI): 0.63–0.88, I2 = 24%). Sub-group analysis addressed the association between PPIs use and SVR12 demonstrated the association of PPI users show-ing lower odds of achieving SVR12 compared with those with no use of PPIs (pooled OR: 0.68, 95% CI: 0.51–0.9, I2 = 33%). Conclusions: This study demonstrated a significantly increased risk of failure to achieve SVR in HCV-infected patients taking DAA with PPIs compared to non-PPI users. Providers should consider whether PPI therapy is indicated for patients and withdraw of PPI therapy in the absence of indications, especially while on DAA therapy.