Serum level of IP-10 increases predictive value of IL28B polymorphisms for spontaneous clearance of acute HCV infection

Gastroenterology. 2012 Jan;142(1):78-85.e2. doi: 10.1053/j.gastro.2011.09.039. Epub 2011 Sep 24.

Abstract

Background & aims: 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.

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Aged, 80 and over
  • Austria
  • Biomarkers / blood
  • Case-Control Studies
  • Chemokine CXCL10 / blood*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Frequency
  • Genotype
  • Hepacivirus / genetics
  • Hepacivirus / pathogenicity*
  • Hepatitis C / blood
  • Hepatitis C / diagnosis
  • Hepatitis C / genetics*
  • Hepatitis C / immunology
  • Humans
  • Interferons
  • Interleukins / genetics*
  • Logistic Models
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Predictive Value of Tests
  • Prognosis
  • RNA, Viral / blood
  • ROC Curve
  • Real-Time Polymerase Chain Reaction
  • Remission, Spontaneous
  • Viral Load
  • Young Adult

Substances

  • Biomarkers
  • CXCL10 protein, human
  • Chemokine CXCL10
  • interferon-lambda, human
  • Interleukins
  • RNA, Viral
  • Interferons