title: The ABCs of viral hepatitis that define biomarker signatures of acute viral hepatitis.
abstract: 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.
authors: Laboratory of Dendritic Cells Immunobiology, Institut Pasteur, Paris, France; INSERM U818, Paris, France.
authors: Darragh
authors: D
authors: Duffy
authors: Rasha
authors: R
authors: Mamdouh
authors: Melissa
authors: M
authors: Laird
authors: Charlotte
authors: C
authors: Soneson
authors: Lenaig
authors: L
authors: Le Fouler
authors: Maï
authors: M
authors: El-Daly
authors: Armanda
authors: A
authors: Casrouge
authors: Jérémie
authors: J
authors: Decalf
authors: Amal
authors: A
authors: Abbas
authors: Noha Sharaf
authors: NS
authors: Eldin
authors: Magnus
authors: M
authors: Fontes
authors: Mohamed
authors: M
authors: Abdel-Hamid
authors: Mostafa K
authors: MK
authors: Mohamed
authors: Mona
authors: M
authors: Rafik
authors: Arnaud
authors: A
authors: Fontanet
authors: Matthew L
authors: ML
authors: Albert
mesh_terms: D000208:Acute Disease; D000328:Adult; D000465:Algorithms; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004534:Egypt / Q000453:epidemiology; D062665:Epidemiological Monitoring; D005260:Female; D006506:Hepatitis A / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D006509:Hepatitis B / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D006526:Hepatitis C / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000821:virology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis
chemical_list: D015415:Biomarkers