title: Mutation frequency of NS5A in patients vertically infected with HCV genotype 1 predicts sustained virological response to peginterferon alfa-2b and ribavirin combination therapy.
abstract: Viral genome analyses performed in adult HCV-patients yielded very inconsistent results and are not transferable to children who are often infected vertically during a state of high immune tolerance. We analysed the mutational frequency in the PKR-binding domain (PKR-BD) of NS5A and PePHD of E2 protein pre- and post-treatment with peginterferon-alfa-2b and ribavirin in children chronically infected with HCV genotype 1. Amino acid sequences of NS5A (2 209-2 274) and E2 (618-681) were determined in serum samples using standard PCR procedures. Concerning the PKR-BD a significant higher number of mutations was observed in vertically compared to horizontally infected patients (2.14 vs 1.24, P-value = 0.03). This difference was exclusively based on the increased number of mutations in responders vs non-responders in vertically infected patients (2.95 vs 1.33; P-value = 0.02). While all patients with at least four mutations (n = 3) did respond to therapy, no other predictive parameters could be identified. In the PePHD no differences could be observed between either of these groups. These findings support the idea that viral properties, mode and therewith time of infection in terms of immune tolerance are equally important factors for predicting SVR in children. However given the low number of cases further studies are required to confirm this hypothesis.
authors.affiliation: Children's Hospital, HELIOS Klinikum Wuppertal, Witten-Herdecke University, Wuppertal, Germany. andreas.jenke@helios-kliniken.de
authors.forename: A C W
authors.initials: AC
authors.lastname: Jenke
authors.forename: S
authors.initials: S
authors.lastname: Moser
authors.forename: V
authors.initials: V
authors.lastname: Orth
authors.forename: M
authors.initials: M
authors.lastname: Zilbauer
authors.forename: P
authors.initials: P
authors.lastname: Gerner
authors.forename: S
authors.initials: S
authors.lastname: Wirth
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018562:Disease Transmission, Infectious; D005260:Female; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000635:transmission / Q000821:virology*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction / Q000379:methods; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D014759:Viral Envelope Proteins / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D055815:Young Adult; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C091015:glycoprotein E2, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C417083:peginterferon alfa-2b