title: A comprehensive hepatitis C viral kinetic model explaining cure.
abstract: We propose a model that characterizes and links the complexity and diversity of clinically observed hepatitis C viral kinetics to sustained virologic response (SVR)-the primary clinical end point of hepatitis C treatment, defined as an undetectable viral load at 24 weeks after completion of treatment)-in patients with chronic hepatitis C (CHC) who have received treatment with peginterferon alpha-2a +/- ribavirin. The new attributes of our hepatitis C viral kinetic model are (i) the implementation of a cure/viral eradication boundary, (ii) employment of all hepatitis C virus (HCV) RNA measurements, including those below the lower limit of quantification (LLOQ), and (iii) implementation of a population modeling approach. The model demonstrated excellent positive (99.3%) and negative (97.1%) predictive values for SVR as well as high sensitivity (96.6%) and specificity (99.4%). The proposed viral kinetic model provides a framework for mechanistic exploration of treatment outcome and permits evaluation of alternative CHC treatment options with the ultimate aim of developing and testing hypotheses for personalizing treatments in this disease.
authors.affiliation: Exprimo NV, Mechelen, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Snoeck
authors.forename: P
authors.initials: P
authors.lastname: Chanu
authors.forename: M
authors.initials: M
authors.lastname: Lavielle
authors.forename: P
authors.initials: P
authors.lastname: Jacqmin
authors.forename: E N
authors.initials: EN
authors.lastname: Jonsson
authors.forename: K
authors.initials: K
authors.lastname: Jorga
authors.forename: T
authors.initials: T
authors.lastname: Goggin
authors.forename: J
authors.initials: J
authors.lastname: Grippo
authors.forename: N L
authors.initials: NL
authors.lastname: Jumbe
authors.forename: N
authors.initials: N
authors.lastname: Frey
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007700:Kinetics; D008954:Models, Biological; D011092:Polyethylene Glycols / Q000627:therapeutic use; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a