title: Serum level of IP-10 increases predictive value of IL28B polymorphisms for spontaneous clearance of acute HCV infection.
abstract: OBJECTIVE
  Single nucleotide polymorphisms (SNPs) in IL28B and serum levels of interferon γ inducible protein 10 (IP-10) predict outcomes of antiviral therapy in patients with chronic hepatitis C. We associated IL28B SNPs rs12979860 and rs8099917, along with serum levels of IP-10, with outcomes of patients with acute hepatitis C (AHC).
  
  
  METHODS
  We studied 120 patients with AHC (64 male; 37 ± 16 years old) and 96 healthy individuals (controls). The IL28B SNPs rs12979860 and rs8099917 were detected using real-time polymerase chain reaction; serum concentrations of IP-10 were measured by enzyme-linked immunosorbent assays of 62 patients with AHC.
  
  
  RESULTS
  Hepatitis C virus was cleared spontaneously from 59 patients (49.2%). The IL28B rs12979860 C/C genotype was more frequent among patients with AHC than controls (62.5% vs 39.6%; P < .001) and among patients with spontaneous clearance than those without (74.6% vs 51.7%; P = .02) (positive predictive value, 60.3%). Patients with IL28B rs12979860 C/C more frequently developed jaundice (53.2% vs 27.6%; P = .022) than carriers of the T allele. The median level of IP-10 was lower among patients with AHC and spontaneous clearance (764 [113-2470] pg/mL) than those without spontaneous clearance (1481 [141-4412] pg/mL; P = .006). Based on receiver operating characteristic analysis, 540 pg/mL IP-10 was set as the cutoff for patients most likely to have spontaneous clearance (positive predictive value, 71.4%; negative predictive value, 65.9%). Including data on IP-10 levels increased the ability of the IL28B rs12979860 C/C to identify patients most likely to have spontaneous clearance (83% of those who had an IP-10 level <540 pg/mL and 32% who had an IP-10 level >540 pg/mL) (P < .01).
  
  
  CONCLUSIONS
  The combination of serum level of IP-10 and SNPs in IL28B can identify patients with AHC who are most likely to undergo spontaneous clearance and those in need of early antiviral therapy.
authors.affiliation: Internal Medicine III, Department of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Sandra
authors.initials: S
authors.lastname: Beinhardt
authors.forename: Judith H
authors.initials: JH
authors.lastname: Aberle
authors.forename: Michael
authors.initials: M
authors.lastname: Strasser
authors.forename: Emina
authors.initials: E
authors.lastname: Dulic-Lakovic
authors.forename: Andreas
authors.initials: A
authors.lastname: Maieron
authors.forename: Anna
authors.initials: A
authors.lastname: Kreil
authors.forename: Karoline
authors.initials: K
authors.lastname: Rutter
authors.forename: Albert F
authors.initials: AF
authors.lastname: Staettermayer
authors.forename: Christian
authors.initials: C
authors.lastname: Datz
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Scherzer
authors.forename: Robert
authors.initials: R
authors.lastname: Strassl
authors.forename: Martin
authors.initials: M
authors.lastname: Bischof
authors.forename: Rudolf
authors.initials: R
authors.lastname: Stauber
authors.forename: Gerd
authors.initials: G
authors.lastname: Bodlaj
authors.forename: Hermann
authors.initials: H
authors.lastname: Laferl
authors.forename: Heidemarie
authors.initials: H
authors.lastname: Holzmann
authors.forename: Petra
authors.initials: P
authors.lastname: Steindl-Munda
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.forename: Harald
authors.initials: H
authors.lastname: Hofer
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001317:Austria; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D054357:Chemokine CXCL10 / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000472:pathogenicity*; D006526:Hepatitis C / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D012075:Remission, Spontaneous; D019562:Viral Load; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D015415:Biomarkers; D054357:Chemokine CXCL10; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; C114753:CXCL10 protein, human; C000624353:interferon-lambda, human; D000095022:Interferon Lambda