title: IL28B genotype is not useful for predicting treatment outcome in Asian chronic hepatitis B patients treated with pegylated interferon-α.
abstract: OBJECTIVE
  IL28B genotype predicts response to pegylated interferon (peg-IFN)-based therapy in chronic hepatitis C. However, the utility of IL28B genotyping in chronic hepatitis B (CHB) cohorts treated with peg-IFN is unclear. It was investigated whether IL28B genotype is associated with peg-IFN treatment outcomes in a predominantly Asian CHB cohort.
  
  
  METHODS
  This was a retrospective analysis of CHB patients treated with 48 weeks of peg-IFN monotherapy. IL28B genotype (rs12979860) was determined (TaqMan allelic discrimination kit). Baseline hepatitis B virus (HBV)-DNA, alanine aminotransferase, and liver histology were available. The primary end-points were HBV e antigen (HBeAg) seroconversion with HBV-DNA < 2000 IU/mL 24 weeks post-therapy (HBeAg-positive patients) and HBV-DNA < 2000 IU/mL 24 weeks after peg-IFN (HBeAg-negative patients). The association between IL28B genotype and peg-IFN outcomes was analyzed.
  
  
  RESULTS
  IL28B genotype was determined for 96 patients. Eighty-eight percent were Asian, 62% were HBeAg positive, and 13% were METAVIR stage F3-4. Median follow-up time was 39.3 months. The majority of patients carried the CC IL28B genotype (84%). IL28B genotype did not differ according to HBeAg status. The primary end-points were achieved in 27% of HBeAg-positive and 61% of HBeAg-negative patients. There was no association between IL28B genotype and the primary end-point in either group. Furthermore, there was no difference in HBeAg loss alone, HBV surface antigen, alanine aminotransferase normalization, or on-treatment HBV-DNA levels according to IL28B genotype.
  
  
  CONCLUSIONS
  In the context of a small possible effect size and high frequency in Asian populations, IL28B genotyping is likely to have, at best, limited clinical utility for predicting peg-IFN treatment outcome for CHB patients in the Asia-Pacific region.
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, University of Melbourne, Melbourne, Australia. jacinta.HOLMES@svhm.org.au
authors.forename: Jacinta A
authors.initials: JA
authors.lastname: Holmes
authors.forename: Tin
authors.initials: T
authors.lastname: Nguyen
authors.forename: Dilip
authors.initials: D
authors.lastname: Ratnam
authors.forename: Neel M
authors.initials: NM
authors.lastname: Heerasing
authors.forename: Jane V
authors.initials: JV
authors.lastname: Tehan
authors.forename: Sara
authors.initials: S
authors.lastname: Bonanzinga
authors.forename: Anouk
authors.initials: A
authors.lastname: Dev
authors.forename: Sally
authors.initials: S
authors.lastname: Bell
authors.forename: Stephen
authors.initials: S
authors.lastname: Pianko
authors.forename: Robert
authors.initials: R
authors.lastname: Chen
authors.forename: Kumar
authors.initials: K
authors.lastname: Visvanathan
authors.forename: Rachel
authors.initials: R
authors.lastname: Hammond
authors.forename: David
authors.initials: D
authors.lastname: Iser
authors.forename: Ferry
authors.initials: F
authors.lastname: Rusli
authors.forename: William
authors.initials: W
authors.lastname: Sievert
authors.forename: Paul V
authors.initials: PV
authors.lastname: Desmond
authors.forename: D Scott
authors.initials: DS
authors.lastname: Bowden
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Thompson
mesh_terms: D000328:Adult; D044466:Asian People; D015331:Cohort Studies; D004279:DNA, Viral / Q000378:metabolism; D023381:Endpoint Determination; D005544:Forecasting; D005838:Genotype; D060005:Genotyping Techniques; D006513:Hepatitis B e Antigens; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a