title: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials: Comparative Effectiveness and Safety of Direct-Acting Antiviral Agents for Treatment-Naive Hepatitis C Genotype 1.
abstract: All possible direct-acting antiviral agent (DAA) regimens for treatment-naive hepatitis C genotype 1 were evaluated by many randomized controlled trials (RCTs). However, the optimum regimen remains inconclusive. We aim to compare interventions in terms of sustained virological response at 12 (SVR12) and 24 (SVR24) weeks after the end of treatment and adverse effects (AEs) (fatigue, headache, nausea, insomnia). PubMed, Embase, and the Cochrane Library were searched for RCTs until July 31, 2015. We estimated odds ratios (ORs) between treatments on clinical outcomes. Twenty-two eligible RCTs were included. Compared with peginterferon-ribavirin (PR), daclatasvir plus PR (OR 8.90, P < 0.001), faldaprevir plus PR (OR 3.72, P < 0.001), simeprevir plus PR (OR 3.59, P < 0.001), sofosbuvir plus PR (OR 4.69, P < 0.001) yield a significant effect in improving SVR12. Consistently, simeprevir plus PR (OR 3.49, P < 0.001), sofosbuvir plus PR (OR 4.51, P < 0.001), daclatasvir plus PR (OR 4.77, P < 0.001) also improved the rates of SVR24 significantly compared with PR. With respect to AEs, compared with PR, ledipasvir plus sofosbuvir plus PR (OR 2.13, P < 0.001) confer a significant AE in nausea, whereas daclatasvir plus PR (OR 0.20, P < 0.001 and OR 0.18, P < 0.001, respectively) lowered the incidence of fatigue and nausea significantly when compared with ledipasvir plus sofosbuvir plus PR. Daclatasvir plus PR was the most effective in SVR12 and SVR24, but caused an increased AEs profile (headache and insomnia). Combined ledipasvir with sofosbuvir or combination of PR was associated with higher incidence of fatigue and nausea.
authors.affiliation: From the Department of Infection and Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University (G-QZ, J-NZ, D-ZC, T-TZ, K-QS, M-HZ), School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou (G-QZ, J-NZ, T-TZ), Department of Infection Diseases, the First Hospital of Jiaxing, Jiaxing (Z-LZ), Queen Mary Hospital, University of Hong Kong, Hong Kong (D-ZC), and Institute of Hepatology (K-QS, M-HZ), Wenzhou Medical University, Wenzhou, China.
authors.forename: Gui-Qi
authors.initials: GQ
authors.lastname: Zhu
authors.forename: Zhuo-Lin
authors.initials: ZL
authors.lastname: Zou
authors.forename: Ji-Na
authors.initials: JN
authors.lastname: Zheng
authors.forename: Da-Zhi
authors.initials: DZ
authors.lastname: Chen
authors.forename: Tian-Tian
authors.initials: TT
authors.lastname: Zou
authors.forename: Ke-Qing
authors.initials: KQ
authors.lastname: Shi
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Zheng
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D057186:Comparative Effectiveness Research; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents