title: Interleukin 28B polymorphism predicts pegylated interferon plus ribavirin treatment outcome in chronic hepatitis C genotype 4.
abstract: Single nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) region are the strongest baseline predictors of a sustained virologic response (SVR) to peg-interferon (PegIFN) and ribavirin (Rbv) in patients with hepatitis C virus (HCV) genotype 1 infection. Whether this holds true for HCV-4 patients too is unknown. The aim was to investigate the predictive power of the rs12979860 IL28B SNP for a response to Peg-IFN and Rbv in HCV-4 patients. All HCV-4 patients consecutively treated between September 2004 and June 2010 with PegIFN and Rbv at two liver centers at the Maggiore Hospital Milan (Italy) underwent TaqMan SNP Genotyping assays for testing rs12979860 genotype. Of 112 treated patients (98 males, 75 of Egyptian descent, 26 with cirrhosis) 103 were included in the final analysis; five discontinued treatment for nonvirologic reasons and four did not consent to genetic testing. Twenty-four (23%) were genotype CC, 65 (63%) CT, and 14 (14%) TT. Overall, 50 (49%) achieved an SVR: 21 (88%) CC patients versus 29 (37%) CT/TT (P < 0.0001). CC patients more often had a rapid virologic response (RVR) than CT/TT patients (12, 50% versus 23, 29%; P = 0.08), while also showing lower relapse rates (0% [0/21] versus 36% [16/45] P = 0.0013). In non-RVR patients, SVR rates were higher in CC than CT/TT patients (9 [75%] versus 13 [23%] P = 0.001). By logistic regression, the IL28B rs12979860 CC genotype was an independent predictor of SVR with an odds ratio of 8.0 (95% confidence interval 2.00-32.01; P = 0.003).
  
  
  CONCLUSIONS
  The IL28B rs12979860 SNP may have an added value in the treatment algorithm of HCV-4 patients because it is the strongest predictor of an SVR to PegIFN/Rbv therapy.
authors.affiliation: Centro AM e A Migliavacca, First Division of Gastroenterology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Università degli Studi di Milano, Milan, Italy.
authors.forename: Stella
authors.initials: S
authors.lastname: De Nicola
authors.forename: Alessio
authors.initials: A
authors.lastname: Aghemo
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Rumi
authors.forename: Enrico
authors.initials: E
authors.lastname: Galmozzi
authors.forename: Luca
authors.initials: L
authors.lastname: Valenti
authors.forename: Roberta
authors.initials: R
authors.lastname: Soffredini
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Francesco
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Prati
authors.forename: Roberta
authors.initials: R
authors.lastname: D'Ambrosio
authors.forename: Cristina
authors.initials: C
authors.lastname: Cheroni
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Donato
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; 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