title: Early proteomic analysis may allow noninvasive identification of hepatitis C response to treatment with pegylated interferon α-2b and ribavirin.
abstract: OBJECTIVE
  Chronic hepatitis C virus (HCV) infection represents a significant disease burden worldwide. Approximately 170 million people are chronically infected. HCV can lead to liver fibrosis, cirrhosis and hepatocellular carcinoma. Current standard treatment with pegylated interferon and ribavirin is suboptimal and up to 60% of patients fail to respond. Week 4 and 12 HCV RNA is used as a marker of response with nonresponders at 12 weeks discontinuing treatment. Earlier identification of nonresponders using novel biomarkers would be beneficial in preventing unnecessary toxicities and cost. This study profiled the proteomic response to treatment in HCV patients within the first 24 h using surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS).
  
  
  METHODS
  Serum from 25 HCV infected individuals during the initial 24 h of treatment was profiled using SELDI-TOF MS. Arrays were analyzed on the ProteinChip Reader and time-of-flight spectra were generated. Peak detection was performed by Biomarker Wizard software and analyzed using BioConductor packages.
  
  
  RESULTS
  Significant differences were seen between the proteomic profiles of responders and nonresponders to treatment. Overall 70 peaks differentiated responders from nonresponders. A random forest classifier identified a panel of 20 peaks, which differentiated responders from nonresponders with 87.4% accuracy. The CM10 chip revealed 16 peaks identifying genotype 1 responders from nonresponders.
  
  
  CONCLUSIONS
  This study identifies early proteomic spectra as potential predictors of HCV treatment response using SELDI-TOF MS. This illustrates the importance of early biomarkers in the prediction of response within the first 24 h, which may aid in tailoring HCV treatment regimens.
authors.affiliation: Centre for Liver Disease, Mater Misericordiae University Hospital, Dublin, Ireland. emma.devitt@ucd.ie
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Devitt
authors.forename: Karen A
authors.initials: KA
authors.lastname: Power
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Lawless
authors.forename: John A
authors.initials: JA
authors.lastname: Browne
authors.forename: Peadar O
authors.initials: PO
authors.lastname: Gaora
authors.forename: William M
authors.initials: WM
authors.lastname: Gallagher
authors.forename: John
authors.initials: J
authors.lastname: Crowe
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D016903:Drug Monitoring / Q000379:methods*; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D040901:Proteomics; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b