title: Lower response to simeprevir and sofosbuvir in HCV genotype 1 in routine practice compared with clinical trials.
abstract: BACKGROUND
  High sustained virological response at 12 weeks after end of treatment (SVR12) with 12 weeks of simeprevir and sofosbuvir±ribavirin (SMV+SOF±RBV) has been demonstrated in hepatitis C virus genotype 1 (HCV-1) but is based on limited data. Therefore, we performed a meta-analysis of available data evaluating the effectiveness of SMV+SOF±RBV in HCV-1.
  
  
  METHODS
  We performed a comprehensive literature search in June 2015 to identify randomised controlled trials (RCTs) and observational studies of HCV-1 patients treated with 12 weeks of SMV+SOF±RBV. Original studies with SVR12 data in ≥5 HCV-1 patients were included. We excluded studies on liver transplant recipients and/or patients co-infected with HIV or hepatitis B/D. We estimated pooled effect sizes using a random-effects model and evaluated heterogeneity with Cochrane Q-test, p≤0.10 and I(2) statistic ≥50%.
  
  
  RESULTS
  Pooled SVR12 was 85.6% (CI 81.3% to 89.0%) in 1389 HCV-1 patients from 15 studies. On subgroup analysis, SVR12 was 83.9% (CI 79.4% to 87.5%) in observational studies, which was lower than 93.5% (CI 85.7% to 97.2%) in RCTs. A trend showed SVR12 was higher in mild fibrosis, 93.0% (CI 86.2% to 96.6%) compared with advanced fibrosis, 81.5% (CI 75.7% to 86.1%), OR 2.22 (CI 0.79 to 6.25, p=0.131). There was no significant difference in SVR12 rates between HCV-1a, 89.9% (CI 81.9% to 94.6%) and HCV-1b, 89.0% (CI 78.9% to 94.6%) with OR 1.35 (CI 0.75 to 2.42, p=0.322). The most common pooled side effects were: headache 15.2% (n=55/361), fatigue 12.1% (n=78/646), nausea 9.5% (n=50/527) and rash 9.3% (n=68/728).
  
  
  CONCLUSIONS
  SMV+SOF±RBV is an effective regimen in HCV-1 patients. The SVR12 rate in observational studies was lower than that in RCTs, which may reflect the more diverse patient population in real-world settings.
authors.affiliation: Department of Internal Medicine , University of California San Diego Medical Center , San Diego, California , USA.
authors.forename: Brittany E
authors.initials: BE
authors.lastname: Yee
authors.affiliation: Department of Internal Medicine , University of California San Diego Medical Center , San Diego, California , USA.
authors.forename: Nghia H
authors.initials: NH
authors.lastname: Nguyen
authors.affiliation: Department of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA; Department of Epidemiology and Biostatistics, Zhejiang University School of Public Health, Hang Zhou, China.
authors.forename: Minjuan
authors.initials: M
authors.lastname: Jin
authors.affiliation: Department of Gastroenterology and Hepatology , Stanford University Medical Center , Palo Alto, California , USA.
authors.forename: Glen
authors.initials: G
authors.lastname: Lutchman
authors.affiliation: Yale Liver Center, Yale University School of Medicine , New Haven, Connecticut , USA.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Lim
authors.affiliation: Department of Gastroenterology and Hepatology , Stanford University Medical Center , Palo Alto, California , USA.
authors.forename: Mindie H
authors.initials: MH
authors.lastname: Nguyen
keywords: FIBROSIS; GENOTYPE; HEPATITIS C