title: Early changes in hepatitis C viral quasispecies during interferon therapy predict the therapeutic outcome.
abstract: Despite recent treatment advances, the majority of patients with chronic hepatitis C fail to respond to antiviral therapy. Although the genetic basis for this resistance is unknown, accumulated evidence suggests that changes in the heterogeneous viral population (quasispecies) may be an important determinant of viral persistence and response to therapy. Sequences within hepatitis C virus (HCV) envelope 1 and envelope 2 genes, inclusive of the hypervariable region 1, were analyzed in parallel with the level of viral replication in serial serum samples obtained from 23 patients who exhibited different patterns of response to therapy and from untreated controls. Our study provides evidence that although the viral diversity before treatment does not predict the response to treatment, the early emergence and dominance of a single viral variant distinguishes patients who will have a sustained therapeutic response from those who subsequently will experience a breakthrough or relapse. A dramatic reduction in genetic diversity leading to an increasingly homogeneous viral population was a consistent feature associated with viral clearance in sustained responders and was independent of HCV genotype. The persistence of variants present before treatment in patients who fail to respond or who experience a breakthrough during therapy strongly suggests the preexistence of viral strains with inherent resistance to IFN. Thus, the study of the evolution of the HCV quasispecies provides prognostic information as early as the first 2 weeks after starting therapy and opens perspectives for elucidating the mechanisms of treatment failure in chronic hepatitis C.
authors.affiliation: Department of Medical Sciences, University of Cagliari, 09124 Cagliari, Italy. farcip@pacs.unica.it
authors.forename: Patrizia
authors.initials: P
authors.lastname: Farci
authors.forename: Rita
authors.initials: R
authors.lastname: Strazzera
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Alter
authors.forename: Stefania
authors.initials: S
authors.lastname: Farci
authors.forename: Daniela
authors.initials: D
authors.lastname: Degioannis
authors.forename: Alessandra
authors.initials: A
authors.lastname: Coiana
authors.forename: Giovanna
authors.initials: G
authors.lastname: Peddis
authors.forename: Francesco
authors.initials: F
authors.lastname: Usai
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Serra
authors.forename: Luchino
authors.initials: L
authors.lastname: Chessa
authors.forename: Giacomo
authors.initials: G
authors.lastname: Diaz
authors.forename: Angelo
authors.initials: A
authors.lastname: Balestrieri
authors.forename: Robert H
authors.initials: RH
authors.lastname: Purcell
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D016896:Treatment Outcome; D014759:Viral Envelope Proteins / Q000235:genetics
chemical_list: D000998:Antiviral Agents; C087035:E1 protein, Hepatitis C virus; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus