SYSTEMATIC REVIEW AND META – ANALYSIS
Efficacy and Safety of Sofosbuvir-containing Regimens in Chronic Hepatitis C Patients with Genotype 2 and 3: a Comprehensive Analysis of 18 Randomized Controlled Trials
Haozhi Fan1*, Peng Huang1,2*, Ting Tian1, Jingjing Wu1, Xueshan Xia3, Yue Feng3, Jie Wang4, Rongbin Yu1, Yun Zhang1,2, Ming Yue5
1) Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing;
2) Institute of Epidemiology and Microbiology, Huadong Research Institute for Medicine and Biotechnics, Nanjing;
3) Faculty of Life Science and Technology, Kunming University of Science and Technology, Yunnan;
4) Department of Basic and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing;
5) Department of Infectious Diseases, the First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China
Background and Aim: Sofosbuvir is a hepatitis C virus (HCV) NS5B polymerase inhibitor. The objective of this study was to explore the efficacy and safety of sofosbuvir for HCV genotype (GT) 2 and 3 infected patients.
Method: We searched randomized controlled trials (RCTs) which analyzed the efficacy and safety of sofosbuvircontaining regimens for HCV GT 2/3 infected patients and collected data. The endpoints were sustained virological response 12- and 24-weeks after the cessation of therapy (SVR12 and SVR24), the adverse events (AEs) and the severe adverse events (SAEs).
Results: Eighteen trials comprising 2,975 HCV GT 2/3 infected patients were included. The pooled estimate SVR12, SVR24, AEs and SAEs rates were 84.6% (95% CI: 83.2-86.0), 83.7% (95% CI: 82.0-85.2), 83.8 (95% CI: 82.3-85.3) and 3.9 (95% CI: 3.2-4.8). The SVR12 rate of sofosbuvir-containing regimens for HCV GT 2 infection was higher than that for HCV GT 3 infection (95.7% vs. 80.8%). The sofosbuvir combined with velpatasvir (with or without ribavirin) regimen presented a higher SVR12 rate and lower AEs rate than the sofosbuvir combined with ribavirin (with or without peg-IFN) regimen (94.9% vs. 80.7% for SVR12 rate; 69.3% vs. 87.7% for AEs rate).
Conclusions: The sofosbuvir-containing regimens in patients with HCV GT 2 infection have better efficacy than in patients with HCV GT 3 infection.
Key words: hepatitis C virus – sofosbuvir – sustained virological response – combination therapy.
Abbreviations: AE: adverse effect; CHC: chronic hepatitis C; DAA: direct-acting antiviral agent; FDC: Fixed Dose Combination; GT: genotype; HCV: hepatitis C virus; IL28B: interleukin 28B; LLOQ: lower limit of quantitation; Peg IFN: Peg-interferon; RBV: ribavirin; P+R: peg-interferon alfa + ribavirin; RCT: randomized controlled trial; SAE: severe adverse effect; SVR: sustained virological response; S+D+(R): sofosbuvir + daclatasvir (with or without RBV); S+G+E: sofosbuvir + grazoprevir/elbasvir; S+L+(R): sofosbuvir + ledipasvir (with or without RBV) S+R+(P): sofosbuvir + RBV (with or without peg-IFN); S+V+(R): sofosbuvir + velpatasvir (with or without RBV); TE: treatment experienced; TN: treatment-naïve.