High predictive accuracy of an unbiased proteomic profile for sustained virologic response in chronic hepatitis C patients

Hepatology. 2011 Jun;53(6):1809-18. doi: 10.1002/hep.24284. Epub 2011 May 14.

Abstract

Chronic hepatitis C (CHC) infection is a leading cause of endstage liver disease. Current standard-of-care (SOC) interferon-based therapy results in sustained virological response (SVR) in only one-half of patients, and is associated with significant side effects. Accurate host predictors of virologic response are needed to individualize treatment regimens. We applied a label-free liquid chromatography mass spectrometry (LC-MS)-based proteomics discovery platform to pretreatment sera from a well-characterized and matched training cohort of 55 CHC patients, and an independent validation set of 41 CHC genotype 1 patients with characterized IL28B genotype. Accurate mass and retention time methods aligned samples to generate quantitative peptide data, with predictive modeling using Bayesian sparse latent factor regression. We identified 105 proteins of interest with two or more peptides, and a total of 3,768 peptides. Regression modeling selected three identified metaproteins, vitamin D binding protein, alpha 2 HS glycoprotein, and Complement C5, with a high predictive area under the receiver operator characteristic curve (AUROC) of 0.90 for SVR in the training cohort. A model averaging approach for identified peptides resulted in an AUROC of 0.86 in the validation cohort, and correctly identified virologic response in 71% of patients without the favorable IL28B "responder" genotype.

Conclusion: Our preliminary data indicate that a serum-based protein signature can accurately predict treatment response to current SOC in most CHC patients.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Blood Proteins / metabolism
  • Cohort Studies
  • Complement C5 / metabolism
  • Genotype
  • Hepatitis C, Chronic / blood*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Humans
  • Interferons / therapeutic use*
  • Interleukins / genetics
  • Models, Statistical
  • Protein Array Analysis*
  • Proteomics*
  • ROC Curve
  • Regression Analysis
  • Sensitivity and Specificity
  • Treatment Outcome
  • Vitamin D-Binding Protein / blood
  • alpha-2-HS-Glycoprotein

Substances

  • AHSG protein, human
  • Antiviral Agents
  • Blood Proteins
  • Complement C5
  • IFNL3 protein, human
  • Interleukins
  • Vitamin D-Binding Protein
  • alpha-2-HS-Glycoprotein
  • Interferons