Format

Send to

Choose Destination
See comment in PubMed Commons below
J Hepatol. 2014 Oct;61(4):770-6. doi: 10.1016/j.jhep.2014.05.040. Epub 2014 Jun 4.

Apolipoprotein H expression is associated with IL28B genotype and viral clearance in hepatitis C virus infection.

Author information

1
Laboratory of Dendritic Cell Immunobiology, Institut Pasteur, Paris, France; INSERM U818, Paris, France.
2
Community Medicine Department, National Research Center, Cairo, Egypt.
3
Faculty of Medicine, Ain Shams University, Cairo, Egypt.
4
Emerging Disease Epidemiology Unit, Institut Pasteur, Paris, France.
5
Liver Disease Research Unit, National Hepatology & Tropical Medicine Research Institute, Cairo, Egypt.
6
Liver Disease Research Unit, National Hepatology & Tropical Medicine Research Institute, Cairo, Egypt; Faculty of Medicine, Minia University, Egypt.
7
National Reference Center for Viral Hepatitis B, C, and D, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France; INSERM U955, Créteil, France.
8
INSERM U955, Créteil, France; Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France.
9
Department of Gastroenterology and Hepatology, Hôpital Victor Dupouy, Argenteuil, France.
10
Maladies Infectieuses et Tropicales, Hôpital Tenon (APHP), Paris, France; INSERM U-707, UPMC, Paris, France.
11
Department of Virology, CHU Toulouse, Toulouse, France; INSERM U1043, IFR-BMT, Toulouse, France.
12
Université Paris Descartes, Paris, France; Institut Cochin, INSERM (IMR-S1016), CNRS (UMR 8104), Paris, France; Assistance Publique - Hôpitaux de Paris (APHP), Groupe Hospitalier Cochin Saint-Vincent de Paul, Unité d'Hepatologie, Paris, France.
13
Laboratory of Dendritic Cell Immunobiology, Institut Pasteur, Paris, France; INSERM U818, Paris, France; Assistance Publique - Hôpitaux de Paris (APHP), Groupe Hospitalier Cochin Saint-Vincent de Paul, Unité d'Hepatologie, Paris, France. Electronic address: albertm@pasteur.fr.
14
Emerging Disease Epidemiology Unit, Institut Pasteur, Paris, France; Conservatoire National des Arts et Métiers, Paris, France. Electronic address: fontanet@pasteur.fr.

Abstract

BACKGROUND & AIMS:

HCV requires host lipid metabolism for replication, and apolipoproteins have been implicated in the response to treatment.

METHODS:

We examined plasma apolipoprotein concentrations in three cohorts of patients: mono-infected patients with symptomatic acute hepatitis C (aHCV); those undergoing treatment for chronic hepatitis C (cHCV); and HIV/HCV co-infected patients being treated for their chronic hepatitis C. We also evaluated associations between apolipoproteins and IL28B polymorphisms, a defined genetic determinant of viral clearance.

RESULTS:

Plasma apolipoprotein H (ApoH) levels were significantly higher in patients who achieved spontaneous clearance or responded to pegylated-interferon/ribavirin therapy. Strikingly, patients carrying the IL28B rs12979860 CC SNP correlated with the plasma concentration of ApoH in all three cohorts. Both ApoH and IL28B CC SNP were associated with HCV clearance in univariate analysis. Additional multivariate analysis revealed that the association between IL28B and HCV clearance was closely linked to that of Apo H and HCV clearance, suggesting that both belong to the same biological pathway to clearance. The association between IL28B CC SNP and ApoH was not observed in healthy individuals, suggesting that early post-infection events trigger differential ApoH expression in an IL28B allele dependent manner.

CONCLUSIONS:

This relationship identifies ApoH as the first induced protein quantitative trait associated with IL28B, and characterises a novel host factor implicated in HCV clearance.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00901524.

KEYWORDS:

Apolipoproteins; Hepatitis C virus; IL28B; Lipid metabolism; Quantitative trait loci

PMID:
24905490
DOI:
10.1016/j.jhep.2014.05.040
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center