title: How to optimize current therapy in hepatitis C virus genotype 1 patients. Predictors of response to interferon-based therapy with second wave direct acting antivirals.
abstract: Second wave direct acting antivirals such as sofosbuvir, simeprevir and daclatasvir can be combined with pegylated interferon alpha and ribavirin (PEG-IFN/RBV) as triple therapy in patients with hepatitis C virus (HCV) infection. In patients with HCV genotype 1 (HCV-1), a PEG-IFN/RBV-based regimen with sofosbuvir is highly effective but the presence of cirrhosis and the non-CC IFNL3 genotype have been associated with a poorer response. A PEG-IFN/RBV-based regimen with simeprevir or daclatasvir is based on response-guided therapy and its efficacy depends on predictors of response to IFN. HCV-1 subtype is also a major predictor of response. In HCV-1a infected patients, the K80Q mutation in NS3 or the presence of NS5A variants at baseline are associated with poor response with simeprevir- or daclatasvir-containing regimens respectively. Thus, these regimens should be only used in HCV-1b patients with good predictors of response to IFN.
authors.affiliation: Service d'Hépatologie, Hôpital Saint-Antoine, APHP, UPMC Paris 6, Paris, France.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Serfaty
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D002219:Carbamates; D004359:Drug Therapy, Combination / Q000379:methods*; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics; D006575:Heterocyclic Compounds, 3-Ring / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D016898:Interferon-alpha / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011759:Pyrrolidines; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D000069616:Simeprevir; D000069474:Sofosbuvir; D013449:Sulfonamides / Q000627:therapeutic use; D014542:Uridine Monophosphate / Q000031:analogs & derivatives / Q000627:therapeutic use; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D006575:Heterocyclic Compounds, 3-Ring; D007093:Imidazoles; D016898:Interferon-alpha; D011759:Pyrrolidines; D011994:Recombinant Proteins; D013449:Sulfonamides; D011092:Polyethylene Glycols; D012254:Ribavirin; D000069616:Simeprevir; D014542:Uridine Monophosphate; D014633:Valine; C549273:daclatasvir; C100416:peginterferon alfa-2a; D000069474:Sofosbuvir
keywords: IFNL3; cirrhosis; daclatasvir; genotype 1 subtype; pegylated interferon; response-guided therapy; ribavirin; simeprevir; sofosbuvir