Effectiveness and safety of daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: Systematic review and meta-analysis

Background and aim: Daclatasvir plus asunaprevir (DCV + ASV) has demonstrated potent antiviral activity in patients with hepatitis C virus (HCV) genotype 1b infection. A definite conclusion about efficacy and safety of DCV + ASV in patients with HCV genotype 1b is not available. A meta-analysis was conducted to evaluate outcomes of all-oral treatment with DCV + ASV in terms of sustained virological response at 12 (SVR₁₂ ) and 24 (SVR₂₄ ) weeks and adverse effects after the end of treatment.

Methods: PUBMED, MEDLINE, and EMBASE databases were searched in May 2016. The data were analyzed with Review Manager 5.3.

Results: Nine trials (n = 1690) met entry criteria. SVR₁₂ was achieved by 89.9% of treatment-naïve patients, 84.7% of interferon-ineligible/intolerant patients, and 81.9% of nonresponder patients. Moreover, 89.0% of interferon-ineligible/intolerant patients and 83.1% of nonresponder patients achieved SVR₂₄ . Baseline characteristics, including gender, race, advanced age, non-CC IL28B genotype, and cirrhosis, did not appear to impact SVR rates. However, the rate of SVR₁₂ in all patients with viral load < 8 × 10⁵ was higher than that of all those with viral load ≥ 8 × 10⁵ (151/162 vs 625/753). Moreover, pre-existing nonstructural protein 5A resistance-associated variants (RAVs) were associated with virological failure during DCV + ASV therapy, resulting in the emergence of multiple RAVs. Treatment with DCV + ASV was well tolerated, with low incidences of serious adverse effects, discontinuations, and grade 3 or 4 laboratory abnormalities in all patients.

Conclusions: Daclatasvir plus asunaprevir provides a highly effective and well-tolerated treatment option for patients with HCV genotype 1b. However, patients with nonstructural protein 5A RAVs at baseline should be assessed to optimize more potent direct antiviral agent therapies.