title: Identification of the Best Direct-Acting Antiviral Regimen for Patients With Hepatitis C Virus Genotype 3 Infection: A Systematic Review and Network Meta-analysis.
abstract: Direct-acting antivirals (DAAs) are effective in the treatment of chronic hepatitis C virus (HCV) infection, although results for patients infected with genotype 3 are suboptimal. There are several regimens available, however, direct comparisons have not been made and are unlikely to occur. We aimed to identify the most effective DAA regimen for patients infected with HCV genotype 3 and to assess the role of ribavirin.
  
  
  
  We conducted a systematic search of PubMed, Embase, and Web of Science databases through March 2016. We performed a Bayesian network meta-analysis using a random-effects model to indirectly compare regimens in patients with and without cirrhosis. We calculated mean estimated sustained virologic response (SVR) with 95% credible intervals (95% CrI) per regimen and effect of ribavirin as odds ratio. We focused on current recommended regimens and regimens under evaluation by regulatory authorities.
  
  
  
  Our search identified 2167 articles; 27 studies (comprising 3415 patients) were included. Among patients without cirrhosis, the greatest rates of SVR were estimated for those receiving sofosbuvir + velpatasvir with ribavirin (99%; 95% CrI, 98%-100%) and without ribavirin (97%; 95% CrI, 95%-99%), sofosbuvir + daclatasvir + ribavirin (96%; 95% CrI, 92%-98%), and sofosbuvir + peginterferon + ribavirin (95%; 95% CrI, 91%-98%), all for 12 weeks. Among patients with cirrhosis, the highest rates of SVR were estimated for those receiving sofosbuvir + velpatasvir for 24 weeks (96%; 95% CrI, 92%-99%), sofosbuvir + daclatasvir + ribavirin for 24 weeks (94%; 95% CrI, 87%-98%), and sofosbuvir + velpatasvir + ribavirin for 12 weeks (94%; 95% CrI, 86%-98%). Ribavirin increases efficacy in patients with and without cirrhosis (odds ratio, 2.6-4.5).
  
  
  
  An indirect comparison of DAA-based treatments, using Bayesian network meta-analysis, found regimens containing sofosbuvir and velpatasvir to be the best option for patients with HCV genotype 3 infection. Our analyses indicated that ribavirin significantly increases SVR rates and should be considered if tolerated.
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Floor A C
authors.initials: FA
authors.lastname: Berden
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Bryan R R Z
authors.initials: BR
authors.lastname: Aaldering
authors.affiliation: Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Groenewoud
authors.affiliation: Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Joanna
authors.initials: J
authors.lastname: IntHout
authors.affiliation: Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Wietske
authors.initials: W
authors.lastname: Kievit
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands. Electronic address: joostphdrenth@cs.com.
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000379:methods; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents
keywords: Comparative Effectiveness; Mixed Treatment Comparison; NS5A Inhibitor; NS5B Inhibitor