title: The Efficacy and Safety of 12 Weeks of Sofosbuvir and Ledipasvir versus Sofosbuvir, Ledipasvir, and Ribavirin in Patients with Chronic Hepatitis C, Genotype 1, Who Have Cirrhosis and Have Failed Prior Therapy: A Systematic Review and Meta-Analysis.
abstract: Background.The recommended therapy for patients with chronic hepatitis C (CHC), genotype 1, who have cirrhosis and have failed prior therapy is 12 weeks of sofosbuvir (SOF), ledipasvir (LDV), and ribavirin (RBV). This recommendation is based on expert opinion, and the efficacy of 12 weeks of SOF/LDV compared to SOF/LDV/RBV in this patient population has not yet been established.Methods. We conducted a systematic review and meta-analysis. Two investigators independently searched electronic databases and relevant conference proceedings for randomized controlled trials comparing rates of sustained virologic response 12 weeks after therapy (SVR12) when using 12 weeks of SOF/LDV versus 12 weeks of SOF/LDV/RBV in patients with CHC, genotype 1, who have cirrhosis and failed previous therapy.Results.Our search strategy yielded 596 studies of which four met criteria for inclusion. The pooled RR of not achieving SVR12 with SOF/LDV versus SOF/LDV/RBV was 1.21 (95% CI: 0.42-3.48). Adverse events were lower in the SOF/LDV compared to the SOF/LDV/RBV arms (pooled RR: 0.11, 95% CI: 0.04-0.29).Conclusions.Our findings suggest that 12 weeks of SOF/LDV cannot be considered noninferior to 12 weeks of SOF/LDV/RBV to achieve SVR12 in patients with CHC who have cirrhosis and failed prior therapy.
authors.affiliation: Department of Medicine, University of Calgary, Foothills Medical Centre, 1403 29th St. NW, Calgary, AB, Canada T2N 2T9.
authors.forename: William
authors.identifier: 0000-0002-8684-0494
authors.initials: W
authors.lastname: Stokes
authors.affiliation: Department of Community Health Sciences, University of Calgary, Teaching, Research and Wellness Building, 3280 Hospital Drive NW, Calgary, AB, Canada T2N 4N1.
authors.forename: Carol
authors.initials: C
authors.lastname: Fenton
authors.affiliation: Department of Community Health Sciences, University of Calgary, Teaching, Research and Wellness Building, 3280 Hospital Drive NW, Calgary, AB, Canada T2N 4N1.
authors.forename: Fiona
authors.identifier: 0000-0003-0209-9457
authors.initials: F
authors.lastname: Clement
authors.affiliation: Department of Medicine, University of Calgary, Foothills Medical Centre, 1403 29th St. NW, Calgary, AB, Canada T2N 2T9; Department of Community Health Sciences, University of Calgary, Teaching, Research and Wellness Building, 3280 Hospital Drive NW, Calgary, AB, Canada T2N 4N1.
authors.forename: Matthew
authors.initials: M
authors.lastname: James
authors.affiliation: Department of Community Health Sciences, University of Calgary, Teaching, Research and Wellness Building, 3280 Hospital Drive NW, Calgary, AB, Canada T2N 4N1.
authors.forename: Paul
authors.identifier: 0000-0002-3958-7561
authors.initials: P
authors.lastname: Ronksley
authors.affiliation: Department of Medicine, University of Calgary, Foothills Medical Centre, 1403 29th St. NW, Calgary, AB, Canada T2N 2T9; Department of Community Health Sciences, University of Calgary, Teaching, Research and Wellness Building, 3280 Hospital Drive NW, Calgary, AB, Canada T2N 4N1.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Tang
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D005449:Fluorenes / Q000627:therapeutic use*; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008103:Liver Cirrhosis / Q000821:virology; D012254:Ribavirin / Q000627:therapeutic use*; D000069474:Sofosbuvir / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; C586541:ledipasvir; D012254:Ribavirin; D000069474:Sofosbuvir