Potential conflict of interest: Nothing to report.
The ABCs of viral hepatitis that define biomarker signatures of acute viral hepatitis
Article first published online: 18 FEB 2014
© 2014 by the American Association for the Study of Liver Diseases
Volume 59, Issue 4, pages 1273–1282, April 2014
How to Cite
Duffy, D., Mamdouh, R., Laird, M., Soneson, C., Le Fouler, L., El-Daly, M., Casrouge, A., Decalf, J., Abbas, A., Eldin, N. S., Fontes, M., Abdel-Hamid, M., Mohamed, M. K., Rafik, M., Fontanet, A. and Albert, M. L. (2014), The ABCs of viral hepatitis that define biomarker signatures of acute viral hepatitis. Hepatology, 59: 1273–1282. doi: 10.1002/hep.26901
This work was supported by ANRS grant 12199 (to M.L.A., A.F., and M.R.), the European Research Council Young Investigator Award (to M.L.A.), and the European FP7 project SPHINX (grant reference no.: 261365).
- Issue published online: 24 MAR 2014
- Article first published online: 18 FEB 2014
- Accepted manuscript online: 21 OCT 2013 12:41PM EST
- Manuscript Accepted: 11 OCT 2013
- Manuscript Received: 12 JUL 2013
Viral hepatitis is the leading cause of liver disease worldwide and can be caused by several agents, including hepatitis A (HAV), B (HBV), and C (HCV) virus. We employed multiplexed protein immune assays to identify biomarker signatures of viral hepatitis in order to define unique and common responses for three different acute viral infections of the liver. We performed multianalyte profiling, measuring the concentrations of 182 serum proteins obtained from acute HAV- (18), HBV- (18), and HCV-infected (28) individuals, recruited as part of a hospital-based surveillance program in Cairo, Egypt. Virus-specific biomarker signatures were identified and validation was performed using a unique patient population. A core signature of 46 plasma proteins was commonly modulated in all three infections, as compared to healthy controls. Principle component analysis (PCA) revealed a host response based upon 34 proteins, which could distinguish HCV patients from HAV- and HBV-infected individuals or healthy controls. When HAV and HBV groups were compared directly, 34 differentially expressed serum proteins allowed the separation of these two patient groups. A validation study was performed on an additional 111 patients, confirming the relevance of our initial findings, and defining the 17 analytes that reproducibly segregated the patient populations. Conclusions: This combined discovery and biomarker validation approach revealed a previously unrecognized virus-specific induction of host proteins. The identification of hepatitis virus specific signatures provides a foundation for functional studies and the identification of potential correlates of viral clearance. (Hepatology 2014;59:1273-1282)