Serum proteomic analysis focused on fibrosis in patients with hepatitis C virus infection

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BioMed Central

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Serum proteomic analysis focused on fibrosis in patients with hepatitis C virus infection Ian R White1, Keyur Patel2, William T Symonds3, Anouk Dev2, Philip Griffin4, Nikos Tsokanas1, Mark Skehel1, Chiang Liu5, Amany Zekry2, Paul Cutler1, Mahanandeeshwar Gattu4, Don C Rockey6, Michelle M Berrey3 and John G McHutchison*2 Address: 1Department of Disease and Biomarker Proteomics, GlaxoSmithKline Pharmaceuticals, Stevenage, UK, 2Division of Gastroenterology, Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA, 3Division of Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, North Carolina, USA, 4Infectious Diseases Centre of Excellence for Drug Discovery, Virology, GlaxoSmithKline Pharmaceuticals, Stevenage, UK, 5Molecular Discovery Research-Informatics, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, North Carolina, USA and 6Department of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, Texas, USA Email: Ian R White - [email protected]; Keyur Patel - [email protected]; William T Symonds - [email protected]; Anouk Dev - [email protected]; Philip Griffin - [email protected]; Nikos Tsokanas - [email protected]; Mark Skehel - [email protected]; Chiang Liu - [email protected]; Amany Zekry - [email protected]; Paul Cutler - [email protected]; Mahanandeeshwar Gattu - [email protected]; Don C Rockey - [email protected]; Michelle M Berrey - [email protected]; John G McHutchison* - [email protected] * Corresponding author

Published: 11 July 2007 Journal of Translational Medicine 2007, 5:33

doi:10.1186/1479-5876-5-33

Received: 16 February 2007 Accepted: 11 July 2007

This article is available from: http://www.translational-medicine.com/content/5/1/33 © 2007 White et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Background: Despite its widespread use to assess fibrosis, liver biopsy has several important drawbacks, including that is it semi-quantitative, invasive, and limited by sampling and observer variability. Non-invasive serum biomarkers may more accurately reflect the fibrogenetic process. To identify potential biomarkers of fibrosis, we compared serum protein expression profiles in patients with chronic hepatitis C (CHC) virus infection and fibrosis. Methods: Twenty-one patients with no or mild fibrosis (METAVIR stage F0, F1) and 23 with advanced fibrosis (F3, F4) were retrospectively identified from a pedigreed database of 1600 CHC patients. All samples were carefully phenotyped and matched for age, gender, race, body mass index, genotype, duration of infection, alcohol use, and viral load. Expression profiling was performed in a bl