Research

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 McHutchison²

¹  Department of Disease and Biomarker Proteomics, GlaxoSmithKline Pharmaceuticals, Stevenage, UK

²  Division of Gastroenterology, Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA

³  Division of Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, North Carolina, USA

⁴  Infectious Diseases Centre of Excellence for Drug Discovery, Virology, GlaxoSmithKline Pharmaceuticals, Stevenage, UK

⁵  Molecular Discovery Research-Informatics, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, North Carolina, USA

⁶  Department of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, Texas, USA

author email corresponding author email

Journal of Translational Medicine 2007, 5:33doi:10.1186/1479-5876-5-33

Published:	11 July 2007

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 blinded fashion using a 2D polyacrylamide gel electrophoresis/LC-MS/MS platform. Partial least squares discriminant analysis and likelihood ratio statistics were used to rank individual differences in protein expression between the 2 groups.

Results

Seven individual protein spots were identified as either significantly increased (α₂-macroglobulin, haptoglobin, albumin) or decreased (complement C-4, serum retinol binding protein, apolipoprotein A-1, and two isoforms of apolipoprotein A-IV) with advanced fibrosis. Three individual proteins, haptoglobin, apolipoprotein A-1, and α₂-macroglobulin, are included in existing non-invasive serum marker panels.

Conclusion

Biomarkers identified through expression profiling may facilitate the development of more accurate marker algorithms to better quantitate hepatic fibrosis and monitor disease progression.