LAUSR

Introduction: The efficacy of second generation direct-acting antiviral agents (DAAs-2), in terms of sustained viral response (SVR) 12 weeks after the end of treatment (EOT), has widely been proven; however, long-term efficacy is still controversial due to the low number of available studies with a small number of patients. The objective of this study is to conduct a systematic review and, if possible, a meta-analysis of existing clinical evidence of the long-term efficacy (SVR longer than 12 weeks after EOT) of DAAs-2 for hepatitis C virus (HCV) treatment. Methods: A systematic review was performed with the use of CENTRAL, MEDLINE, Embase, Pubmed and SBBL-CILEA/METACRAWLER databases. Trials were initially screened by the title; secondly, full papers and abstracts were analysed. The meta-analysis included randomised controlled trials (RCTs) with adult patients affected by HCV, treated with DAAs-2 and assessed for longer than 12 weeks after EOT. Study quality assessment was undertaken using the Jadad scale. Heterogeneity analysis of the studies was conducted with chi-square and I2. The statistical analysis of the efficacy rate was performed using the meta package with the R software. The effect estimate was expressed in risk ratio (RR) with 95% confidence interval (CI 95%) and pooled using a random effects model. Results: Of the 106 identified studies, 11 high quality RCTs were included for meta-analysis (25 were duplicate publications, 70 did not meet the inclusion criteria). Considered genotypes were 1 (n = 9), 2 (n = 1), 3 (n = 1). Meta-analysis included 3,720 patients (2,698 treated with DAAs-2; 1,022 treated with placebo or a first generation DAA±Ribavirin±Pegylated interferon). Heterogeneity between studies was high (p<0.001; I2 = 90.2%); however, it was absorbed by the model (τ2 = 0,08). Long-term efficacy was expressed as SVR 24 weeks after EOT, since longer timescales were not available. According to the pooled RR, the incidence of efficacy was 1.5 (CI 95%: 1.24−1.83, p < 0.001). Conclusions: The meta-analysis demonstrated that DAAs-2 for HCV treatment have long-term efficacy at SVR 24 weeks after the EOT; however, the number of studies is mostly based on genotype 1. More RCTs are required to confirm long-term efficacy at more than six months after EOT for all treated genotypes.