Early proteomic analysis may allow noninvasive identification of hepatitis C response to treatment with pegylated interferon α-2b and ribavirin

Eur J Gastroenterol Hepatol. 2010 Dec 15. [Epub ahead of print]

Devitt EJ, Power KA, Lawless MW, Browne JA, Gaora PO, Gallagher WM, Crowe J.

aCentre for Liver Disease bSchool of Medicine and Medical Science, Mater Misericordiae University Hospital cUCD School of Biomolecular and Biomedical Science cUCD School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland.

Abstract

BACKGROUND AND AIM: 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.

CONCLUSION: 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.

PMID: 21164346 [PubMed - as supplied by publisher]

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