title: HCV-GenoFibrotest: a combination of viral, liver and genomic (IL28b, ITPA, UGT1A1) biomarkers for predicting treatment response in patients with chronic hepatitis C.
abstract: OBJECTIVE
  Three gene polymorphisms, interferon-lambda-3 (IL28B), inosinetriphosphatase (ITPA) and bilirubinuridine diphosphate-glucuronosyltransferase (UGT1A1) are associated with treatment (interferon and ribavirin) efficacy and adherence in patients with chronic hepatitis C. The hypothesis was that fibrosis stage estimated with FibroTest instead of biopsy was still an independent predictive factor of sustained virologic response (SVR) when these new polymorphisms were assessed.
  
  
  METHODS
  Patients receiving standard of care treatment were retrospectively analyzed with determination of IL28B, ITPA, and UGT1A1 polymorphisms. Baseline prognostic factors were combined using logistic regression analysis in a training group (157 patients) and validated in avalidation group (79 patients).
  
  
  RESULTS
  The combination of the five most predictive factors (HCV genotype 2/3, IL28B genotype, FibroTest, ActiTest and viral load) in the training population had AUROC for SVR=0.743 (0.655-0.810; P<0.0001 vs. random), which was validated in the validation population, AUROC=0.753 (0.616-849; P=0.0007 vs. random, not different from training P=0.88). FibroTest remained significant [OR=4.20 (2.59-12.50); P=0.03] after assessment of the IL28B CC, HCV genotype and viral load.
  
  
  CONCLUSIONS
  Fibrosis stage assessed by FibroTest is an independent predictor of SVR, after accounting for the IL28B genetic polymorphism. A combination of five baseline biomarkers could simplify the baseline prediction of SVR.
authors.affiliation: Pasteur-Cerba, Cergy-Pontoise, France. jmcosta@lab-cerba.com
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Costa
authors.forename: Dmytro
authors.initials: D
authors.lastname: Telehin
authors.forename: Mona
authors.initials: M
authors.lastname: Munteanu
authors.forename: Tetiana
authors.initials: T
authors.lastname: Kobryn
authors.forename: Yen
authors.initials: Y
authors.lastname: Ngo
authors.forename: Vincent
authors.initials: V
authors.lastname: Thibault
authors.forename: Moussalli
authors.initials: M
authors.lastname: Joseph
authors.forename: Vlad
authors.initials: V
authors.lastname: Ratziu
authors.forename: Yves
authors.initials: Y
authors.lastname: Benhamou
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Koz'ko
authors.forename: Galyna
authors.initials: G
authors.lastname: Dubins'ka
authors.forename: Jean-Dominique
authors.initials: JD
authors.lastname: Poveda
authors.forename: Thierry
authors.initials: T
authors.lastname: Poynard
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D005260:Female; D014453:Glucuronosyltransferase / Q000097:blood*; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011755:Pyrophosphatases / Q000097:blood*; D012189:Retrospective Studies; D000099148:UGT1A1 Enzyme; D000095022:Interferon Lambda; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D014453:Glucuronosyltransferase; D007372:Interferons; D007378:Interleukins; D011755:Pyrophosphatases; D000099148:UGT1A1 Enzyme; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase