Optimization of direct anti‐viral agent treatment schedule: Focus on HCV genotype 3

Abstract

Background and aim: Direct antiviral agents (DAAs) have led to high sustained virological responses (SVR) in hepatitis C virus (HCV) patients. However, genotype 3 patients respond to treatment in a suboptimal way. This study aims to identify which of the several treatment schedules recommended for genotype 3 would constitute the best option. Methods: Twenty-four Italian centers were involved in this real-life study of HCV genotype 3 patients treated with DAAs. To expand the number of cases, we conducted a systematic review of the literature on the outcome of genotype 3 patients treated with DAAs. Results: A total of 233 patients with HCV genotype 3 were enrolled. Cirrhotic patients accounted for 83.7%. Overall, the SVR12 rate was achieved by 205 patients (88.0%); the SVR rates were 78.8% after sofosbuvir/ribavirin, 92.5% after sofosbuvir/daclatasvir AE ribavirin, and 100% after sofosbuvir/ledipasvir (seven patients). No difference in rate of SVR was observed in cirrhotic and non-cirrhotic patients (92.2 vs 94.4) using a combination regimen of NS5A and NS5B inhibitors. The systematic review of the literature provided data of 3311 patients: The mean weighted SVR12 rate was 84.4% (CI: 80.4-87.8); the rates varied from 79.0% (CI: 70.9-85.3) with sofosbuvir/ribavirin, to 83.7% (CI: 66.2-93.1) with sofosbuvir/ ledispavir, and to 88.2% (CI: 83.3-91.7) with sofosbuvir/daclatasvir. Conclusions: Our results reinforce the concept that patients with HCV genotype 3 should no longer be considered difficult-totreat individuals. The optimal therapeutic regimen for these patients appears to be the combination sofosbuvir/daclatasvir, administered for 12 weeks without the use of RBV in non-cirrhotic patients. In cirrhotics the meta-analytic approach suggests extending therapy to 24 weeks.

Systematic Review with Meta-Analysis: Efficacy and Safety of Direct-Acting Antivirals for Chronic Hepatitis C Genotypes 5 and 6

“…First, as regards SOF + RBV regimen, the meta-analysis by Bayatpoor et al [33] reported pooled SVR12 rates on genotypes 2 and 3 at 92% and 55–81% (this depended on treatment duration), respectively, which were lower compared to our analysis for genotype 6 at 100% SVR12 rate. In addition, the meta-analysis by Morisco et al [34] also reported a lower pooled SVR12 rate on genotype 3 at 79%.…”

“…Moreover, regarding the efficacy of SOF/LDV ± RBV regimen, the meta-analysis by Morisco et al [34] reported pooled SVR12 rate at 83.7% for SOF/LDV on genotype 3. In addition, several meta-analyses [37–41] reported pooled SVR12 rates ranging from 95–99.7% of SOF/LDV ± RBV on genotype 1.…”