title: 'Favourable' IL28B polymorphisms are associated with a marked increase in baseline viral load in hepatitis C virus subtype 3a infection and do not predict a sustained virological response after 24 weeks of therapy.
abstract: IL28B host genetic make-up is known to play a critical role in the outcome of genotype 1 hepatitis C virus (HCV) infection in the context of both primary infection and therapy. However, the role of IL28B in subtype 3a infection remains unclear, and has not yet been assessed in the UK population where subtype 3a is dominant. In this study, we evaluated the role of the IL28B single-nucleotide polymorphism rs8099917 in 201 patients recruited from two well-defined cohorts (from Nottingham and Oxford), treated with the standard-of-care therapy of pegylated interferon and ribavirin for 24 weeks. We showed that the 'favourable' IL28B gene was associated with a rapid virological response to therapy at 4 weeks (P<0.0001), but not with a sustained virological response to therapy. The median viral load at baseline, before therapy, was markedly increased in people with the 'favourable' IL28B genotype [median viral load for the TT allele, 925,961 IU ml(-1) (range 2200-21,116,965 IU ml(-1)), and for the GT or GG allele, 260,284 IU ml(-1) (range 740-7,560,000 IU ml(-1)); P = 0.0010]. Our results suggest that the host genetic response plays an important role in early viral clearance of subtype 3a virus from the blood. However, significant reservoirs of infection must persist, as viral relapse is common, even in those with the favourable host genotype.
authors.affiliation: The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bucci
authors.affiliation: The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: Annette
authors.initials: A
authors.lastname: von Delft
authors.affiliation: John Radcliffe Hospital, Oxford, UK.
authors.forename: Annabel
authors.initials: A
authors.lastname: Christian
authors.affiliation: The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: Vicki M
authors.initials: VM
authors.lastname: Flemming
authors.affiliation: The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: Abby
authors.initials: A
authors.lastname: Harrison
authors.affiliation: The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: John
authors.initials: J
authors.lastname: Halliday
authors.affiliation: John Radcliffe Hospital, Oxford, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Collier
authors.affiliation: John Radcliffe Hospital, Oxford, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Manganis
authors.affiliation: NIHR Oxford Biomedical Research Centre, Oxford, UK.|The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.affiliation: NIHR Nottingham Digestive Diseases Biomedical Research Unit, Nottingham, UK.
authors.forename: William
authors.initials: W
authors.lastname: Irving
authors.affiliation: NIHR Oxford Biomedical Research Centre, Oxford, UK.|The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Barnes
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D006113:United Kingdom; D019562:Viral Load; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda