title: Screening for IL28B gene variants identifies predictors of hepatitis C therapy success.
abstract: BACKGROUND
  Recent research has shown that genetic variation in the IL28B gene predicts both chronicity of HCV infection and sustained virological response (SVR) to antiviral standard therapy. Because HCV affects 170 million people worldwide and is a leading cause of cirrhosis and hepatocellular carcinoma, screening for prognostic factors in routine clinical practice requires rapid and reliable assays.
  
  
  METHODS
  The frequencies of gene polymorphisms IL28B rs8099917, rs12979860 and rs12980275 were investigated in two cohorts of 89 and 187 unrelated HCV-infected Caucasian patients and 195 non-infected participants. This was carried out by means of newly developed sensitive Pyrosequencing™ screening assays.
  
  
  RESULTS
  The minor alleles were more frequent in patients (n=276) than in controls (n=195), with odds ratios (recessive hereditary model) of 2.2-11.6, indicating a moderate to large genotype effect size. The positive predictive values of the minor alleles for chronicity of HCV infection were 68.3%, 64.8% and 65.8% for rs8099917, rs12979860 and rs12980275, respectively. The minor alleles were also more frequent in patients who had a non-SVR (n=49) than in SVR patients (n=40), with odds ratios of 1.1-3.5 showing a small to moderate genotype effect size. The positive predictive values for non-SVR were 56.9%, 79.2% and 74% for rs8099917, rs12979860 and rs12980275, respectively.
  
  
  CONCLUSIONS
  With the screening for IL28B polymorphisms rs12980275, rs8099917 and rs12979860, which are associated with HCV chronicity and with reduced SVR rates, an important prognostic factor of the therapy of chronic hepatitis C can be easily diagnosed.
authors.affiliation: pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University, Frankfurt, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Doehring
authors.forename: Wolf Peter
authors.initials: WP
authors.lastname: Hofmann
authors.forename: Christina
authors.initials: C
authors.lastname: Schlecker
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Simone
authors.initials: S
authors.lastname: Susser
authors.forename: Gerd
authors.initials: G
authors.lastname: Geisslinger
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.forename: Jörn
authors.initials: J
authors.lastname: Lötsch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001483:Base Sequence; D016022:Case-Control Studies; D015331:Cohort Studies; D016001:Confidence Intervals; D004359:Drug Therapy, Combination; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D005858:Germany; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D044465:White People; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b