title: IL28B polymorphism genotyping as predictor of rapid virologic response during interferon plus ribavirin treatment in hepatitis C virus genotype 1 patients.
abstract: OBJECTIVE
  To clarify the association of interleukin-28B (IL28B) single nucleotide polymorphisms (SNPs) with hepatitis C virus (HCV) viremia changes for assessment of interferon (IFN) response.
  
  
  METHODS
  A cohort of 118 Caucasian treatment-naïve HCV-G1 infected patients, treated with pegylated-IFN alpha 2a or 2b associated with ribavirin (53 responders, 65 non-responders) during the period 2010-2012, were genotyped for IL28B SNPs rs12979860 C>T and rs8099917 T>G. Genotyping was performed by real-time allelic discrimination assay. Serum HCV RNA levels were assayed at 2, 4, 12, 24 and 48 wk during therapy. Correlation between IL28B genotypes and serum HCV RNA kinetics was investigated. Multivariable logistic regression analysis was performed to identify predictors of null-response.
  
  
  RESULTS
  Twenty-six out of 118 patients (22%) had no HCV RNA decline ≥ 1 log IU/mL at therapy week 4 (null-responders). IL28B genotype was rs8099917 (G)/rs1297860 in 21/26 (80%) of null-responder patients. Using multivariate analysis, it was shown that the presence of the rs8099917 G allele was the best predictor of null-response (OR = 7.9, 95%CI: 1.99-31.18). The presence of at least one favorable genotype showed a positive predictive value of above 90% for HCV RNA reduction ≥ log at week 4. Analysis of the HCV RNA kinetics during 12 wk of therapy in patients with IL28B rs12979860 CT heterozygosis (n = 73), according to their rs8099917 status, showed that the viremia reduction was significantly different in patients carrying the rs8099917 G allele compared to those with favorable homozygosis.
  
  
  CONCLUSIONS
  Our findings emphasize the association of the IL28B rs8099917 G allele with HCV. Genotyping for both IL28B SNPs is useful in clinical practice for thorough patient risk stratification based on IFN responsiveness.
authors.affiliation: Chiara Rosso, Maria Lorena Abate, Alessia Ciancio, Silvia Strona, Gian Paolo Caviglia, Antonella Olivero, Mario Rizzetto, Antonina Smedile, Department of Medical Science, University of Turin, 10123 Turin, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Rosso
authors.affiliation: Chiara Rosso, Maria Lorena Abate, Alessia Ciancio, Silvia Strona, Gian Paolo Caviglia, Antonella Olivero, Mario Rizzetto, Antonina Smedile, Department of Medical Science, University of Turin, 10123 Turin, Italy.
authors.forename: Maria Lorena
authors.initials: ML
authors.lastname: Abate
authors.affiliation: Chiara Rosso, Maria Lorena Abate, Alessia Ciancio, Silvia Strona, Gian Paolo Caviglia, Antonella Olivero, Mario Rizzetto, Antonina Smedile, Department of Medical Science, University of Turin, 10123 Turin, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Ciancio
authors.affiliation: Chiara Rosso, Maria Lorena Abate, Alessia Ciancio, Silvia Strona, Gian Paolo Caviglia, Antonella Olivero, Mario Rizzetto, Antonina Smedile, Department of Medical Science, University of Turin, 10123 Turin, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Strona
authors.affiliation: Chiara Rosso, Maria Lorena Abate, Alessia Ciancio, Silvia Strona, Gian Paolo Caviglia, Antonella Olivero, Mario Rizzetto, Antonina Smedile, Department of Medical Science, University of Turin, 10123 Turin, Italy.
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Caviglia
authors.affiliation: Chiara Rosso, Maria Lorena Abate, Alessia Ciancio, Silvia Strona, Gian Paolo Caviglia, Antonella Olivero, Mario Rizzetto, Antonina Smedile, Department of Medical Science, University of Turin, 10123 Turin, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Olivero
authors.affiliation: Chiara Rosso, Maria Lorena Abate, Alessia Ciancio, Silvia Strona, Gian Paolo Caviglia, Antonella Olivero, Mario Rizzetto, Antonina Smedile, Department of Medical Science, University of Turin, 10123 Turin, Italy.
authors.forename: Giovanni Antonio
authors.initials: GA
authors.lastname: Touscoz
authors.affiliation: Chiara Rosso, Maria Lorena Abate, Alessia Ciancio, Silvia Strona, Gian Paolo Caviglia, Antonella Olivero, Mario Rizzetto, Antonina Smedile, Department of Medical Science, University of Turin, 10123 Turin, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Rizzetto
authors.affiliation: Chiara Rosso, Maria Lorena Abate, Alessia Ciancio, Silvia Strona, Gian Paolo Caviglia, Antonella Olivero, Mario Rizzetto, Antonina Smedile, Department of Medical Science, University of Turin, 10123 Turin, Italy.
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Pellicano
authors.affiliation: Chiara Rosso, Maria Lorena Abate, Alessia Ciancio, Silvia Strona, Gian Paolo Caviglia, Antonella Olivero, Mario Rizzetto, Antonina Smedile, Department of Medical Science, University of Turin, 10123 Turin, Italy.
authors.forename: Antonina
authors.initials: A
authors.lastname: Smedile
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
keywords: Hepatitis C virus-G1; Interferon sensitivity; Interleukin-28B rs12979860; Interleukin-28B rs8099917; Triple therapy