title: Efficacy and Safety of Ledipasvir/Sofosbuvir with and without Ribavirin in Patients with Chronic Hepatitis C Virus Genotype 1 Infection: a meta-analysis.
abstract: BACKGROUND
  The addition of ribavirin (RBV) to the combination treatment of Ledipasvir (LDV) and Sofosbuvir (SOF) remains controversial in the treatment of hepatitis C virus (HCV) infection. We performed a meta-analysis to assess the efficacy and safety of the LDV-SOF with and without RBV in treating HCV genotype 1 patients.
  
  
  METHODS
  The electronical databases of PubMed Medline, EMBASE database, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov website with registered trials were searched. Eligible studies were randomized controlled trials (RCTs) and prospective cohort studies that assessed the efficacy and safety of LDV-SOF with or without RBV in patients with HCV genotype 1 (GT 1). Two reviewers independently screened studies, extracted data and assessed methodology quality. Review Manager 5.3 software was used to analyze the data.
  
  
  RESULTS
  Seven studies involving 2,626 patients with HCV GT 1 - some of whom had cirrhosis - were included in this meta-analysis. The addition of RBV to LDV- SOF regimen neither significantly improved sustained viral response at 12 weeks (SVR12) after the last dose of treatment (RR=1.00, 95%CI 0.99-1.01, p=0.99) nor decreased virologic breakthrough (RR=1.01, 95%CI 0.14-7.19, p=0.99) and relapse (RR=1.36, 95% CI 0.81-2.29, p=0.24). There was no significant difference in the incidence of discontinuation (RR=0.61, 95%CI 0.25-1.53, p=0.30) between LDV- SOF therapy and LDV- SOF plus RBV. LDV- SOF plus RBV therapy had significantly higher rate of the overall adverse events (RR=0.88, 95%CI=0.84- 0.92, p<0.00001). LDV - SOF therapy had higher incidence of serious adverse events (RR=1.60, 95%CI=1.00-2.56, p=0.05) than LDV-SOF plus RBV.
  
  
  CONCLUSIONS
  This meta-analysis suggests that LDV-SOF based therapy is a safe and effective treatment for patients with GT 1 HCV. The addition of RBV to LDV-SOF may increase toxicity without achieving improved efficacy. However, due to the relatively small sample sizes and moderate risk of bias of included studies, large-scale and high-quality clinical research is still needed to confirm the results.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Tao
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Eli Lilly and Company, Suzhou, Jiangzu, People's Republic of China.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Song
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000627:therapeutic use*; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000821:virology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; C586541:ledipasvir; D012254:Ribavirin; D000069474:Sofosbuvir
keywords: Hepatitis C virus infection; Ledipasvir; Meta-analysis; Ribavirin; Sofosbuvir