title: Kinetic of Virologic Response to Pegylated Interferon and Ribavirin in Children With Chronic Hepatitis C Predicts the Effect of Treatment.
abstract: Chronic hepatitis C is a global health problem. Although new, highly effective and safe direct-acting antivirals have been approved for adults, the only drugs currently registered for children are pegylated interferon and ribavirin. The timelines for the pediatric approval of the new treatment regimens are far off. Three phase II-III pediatric trials with direct-acting antivirals are recruiting, and the estimated dates of completion of these studies range between April 2018 and January 2023.
  
  
  
  The aim of this study was to evaluate the value of on-treatment virologic response (VR) as predictor of sustained virologic response (SVR) in a cohort of Italian children with chronic hepatitis C and to establish possible stopping rules.
  
  
  
  Sixty-four children were enrolled (January 2012 to December 2015). SVR rate was 79.7% (51/64). VR at weeks 2 to 12 were shown to be robust predictors for the attainment of SVR. The positive predictive values of VR at weeks 8 and 12 were 98% and 92.7%, respectively. The negative predictive values at the same treatment weeks were 92.9% and 100%, indicating that no child who did not achieve VR at week 12 obtained SVR and that the likelihood of achieving SVR if still positive at week 8 was very low.
  
  
  
  Our results suggest for the first time that VR at week 8 could be considered a reliable predictor of SVR. Monitoring viral kinetics is useful for predicting the success of pegylated interferon and ribavirin therapy in children.
authors.affiliation: From the *Paediatric and Liver Unit, Meyer Children's University Hospital of Florence, Firenze, Italy; †Servizio di Epatologia e Nutrizione Pediatrica, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy; ‡Unit of Gastroenterology, Digestive Endoscopy, Hepatology and Care of the Child with Liver Transplantation, Department of Woman and Child Health, University Hospital of Padova, Padova, Italy; §Dipartimento di Medicina Interna e Terapia Medica-Sezione Malattie Infettive, Università degli Studi di Pavia, Pavia, Italy; ¶Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy; ‖Department of Statistics, Informatics and Applications "G. Parenti," University of Florence, Florence, Italy; and **Department of Health Sciences, University of Florence, Firenze, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Indolfi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Nebbia
authors.forename: Mara
authors.initials: M
authors.lastname: Cananzi
authors.forename: Anna
authors.initials: A
authors.lastname: Maccabruni
authors.forename: Marco
authors.initials: M
authors.lastname: Zaramella
authors.forename: Lorenzo
authors.initials: L
authors.lastname: D'Antiga
authors.forename: Laura
authors.initials: L
authors.lastname: Grisotto
authors.forename: Chiara
authors.initials: C
authors.lastname: Azzari
authors.forename: Massimo
authors.initials: M
authors.lastname: Resti
mesh_terms: D000293:Adolescent; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D011092:Polyethylene Glycols / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D012254:Ribavirin / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b