Vijayaprakash Suppiah and colleagues show that genotyping hepatitis C patients for the IL28B, HLA-C, and KIR genes improves the ability to predict whether or not patients will respond to antiviral treatment

A Sato

Antonina Smedile

C Dunne

CK Aitken

CS Witt

D Ge

David Dunn

David R. Booth

David Sheridan

DL Thomas

E Ashouri

Elizabeth Powell

Emma Hammond

F Williams

Francesco Negro

G Ahlenstiel

G Askarieh

Gail Matthews

GJ Dore

Golo Ahlenstiel

Graeme J. Stewart

Gregory J. Dore

Jacob George

Jacob Nattermann

JG McHutchison

JH Hoofnagle

JJ Feld

JM Micallef

JR Vidal-Castineira

KA Stegmann

Kate S. O'Connor

M Colonna

M Honda

M Numasaki

Margaret Bassendine

Margaret Hellard

Maria Lorena Abate

Martin Weltman

MM Dring

N Akuta

N Wagtmann

NH Afdhal

Nicola J. Armstrong

Paul Klenerman

Pierre-Yves Bochud

PY Kwo

S Knapp

S Kulkarni

SH Lee

SI Khakoo

Silvana Gaudieri

Simon Mallal

Stephen Riordan

T Marcello

Thomas Berg

Tobias Müller

Ulrich Spengler

V Suppiah

Vijayaprakash Suppiah

William L. Irving

Y Tanaka

PLoS Medicine

English

PubMed

), which have previously been implicated in HCV viral control...Please see later in the article for the Editors' Summar

Suppiah Vijayaprakash

Gaudieri Silvana

Armstrong Nicola J.

O'Connor Kate S.

Berg Thomas

Weltman Martin

Abate Maria Lorena

Spengler Ulrich

Bassendine Margaret

Dore Gregory J.

Irving William L.

Powell Elizabeth

Hellard Margaret

Riordan Stephen

Matthews Gail

Sheridan David

Nattermann Jacob

Smedile Antonina

Müller Tobias

Hammond Emma

Dunn David

Negro Francesco

Bochud Pierre-Yves

Mallal Simon

Ahlenstiel Golo

Stewart Graeme J.

George Jacob

Booth David R.

Public Library of Science (PLOS)

 Variants Additively Predict Response to Therapy in Chronic Hepatitis C Virus Infection in a European Cohort: A Cross-Sectional Study

Background: To date, drug response genes have not proved as useful in clinical practice as was anticipated at the start of the genomic era. An exception is in the treatment of chronic hepatitis C virus (HCV) genotype 1 infection with pegylated interferon-alpha and ribavirin (PegIFN/R). Viral clearance is achieved in 40%–50% of patients. Interleukin 28B (IL28B) genotype predicts treatment-induced and spontaneous clearance. To improve the predictive value of this genotype, we studied the combined effect of variants of IL28B with human leukocyte antigen C (HLA-C), and its ligands the killer immunoglobulin-like receptors (KIR), which have previously been implicated in HCV viral control

Suppiah, Vijay

Gaudieri, Silvana

Armstrong, Nicola J.

O'Connor, Kate S.

Berg, Thomas

Weltman, Martin

Abate, Maria L.

Spengler, Ulrich

Bassendine, Margaret

Dore, Gregory J.

Irving, William L.

Powell, Elizabeth

Hellard, Margaret

Riordan, Stephen

Mathews, Gail

Sheridan, David

Nattermann, Jacob

Smedile, Antonina

Muller, Tobias

Hammond, Emma

Dunn, David

Negro, Francesco

Bochud, Pierre-Yves

Mallai, Simon

Ahlenstiel, Golo (R18999)

Stewart, Graeme J.

George, Jacob

Booth, David R.

Western Sydney ResearchDirect

IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European cohort : a cross-sectional study

null null

Crossref

IL28B, HLA-C, and KIR Variants Additively Predict Response to Therapy in Chronic Hepatitis C Virus Infection in a European Cohort: A Cross-Sectional Study

BackgroundTo date, drug response genes have not proved as useful in clinical practice as was anticipated at the start of the genomic era. An exception is in the treatment of chronic hepatitis C virus (HCV) genotype 1 infection with pegylated interferon-alpha and ribavirin (PegIFN/R). Viral clearance is achieved in 40%-50% of patients. Interleukin 28B (IL28B) genotype predicts treatment-induced and spontaneous clearance. To improve the predictive value of this genotype, we studied the combined effect of variants of IL28B with human leukocyte antigen C (HLA-C), and its ligands the killer immunoglobulin-like receptors (KIR), which have previously been implicated in HCV viral control.Methods and findingsWe genotyped chronic hepatitis C (CHC) genotype 1 patients with PegIFN/R treatment-induced clearance (n = 417) and treatment failure (n = 493), and 234 individuals with spontaneous clearance, for HLA-C C1 versus C2, presence of inhibitory and activating KIR genes, and two IL28B SNPs, rs8099917 and rs12979860. All individuals were Europeans or of European descent. IL28B SNP rs8099917 "G" was associated with absence of treatment-induced clearance (odds ratio [OR] 2.19, p = 1.27×10(-8), 1.67-2.88) and absence of spontaneous clearance (OR 3.83, p = 1.71×10(-14), 2.67-5.48) of HCV, as was rs12979860, with slightly lower ORs. The HLA-C C2C2 genotype was also over-represented in patients who failed treatment (OR 1.52, p = 0.024, 1.05-2.20), but was not associated with spontaneous clearance. Prediction of treatment failure improved from 66% with IL28B to 80% using both genes in this cohort (OR 3.78, p = 8.83×10(-6), 2.03-7.04). There was evidence that KIR2DL3 and KIR2DS2 carriage also altered HCV treatment response in combination with HLA-C and IL28B.ConclusionsGenotyping for IL28B, HLA-C, and KIR genes improves prediction of HCV treatment response. These findings support a role for natural killer (NK) cell activation in PegIFN/R treatment-induced clearance, partially mediated by IL28B

Nicola J Armstrong

Kate S O'Connor

Gregory J Dore

William L Irving

Graeme J Stewart

David R Booth

International Hepatitis C Genetics Consortium (IHCGC)

Directory of Open Access Journals

IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European Cohort: a cross-sectional study.

Abate, Maria Lorena

Institutional Research Information System University of Turin

Background: To date, drug response genes have not proved as useful in clinical practice as was anticipated at the start of the genomic era. An exception is in the treatment of chronic hepatitis C virus (HCV) genotype 1 infection with pegylated interferon-alpha and ribavirin (PegIFN/R). Viral clearance is achieved in 40%-50% of patients. Interleukin 28B (IL28B) genotype predicts treatment-induced and spontaneous clearance. To improve the predictive value of this genotype, we studied the combined effect of variants of IL28B with human leukocyte antigen C (HLA-C), and its ligands the killer immunoglobulin-like receptors (KIR), which have previously been implicated in HCV viral control

Suppiah, Vijayaprakash

Matthews, Gail

Mallal, Simon

Ahlenstiel, Golo

for the International Hepatitis C Genetics Consortium (IHCGC)

University of Queensland eSpace

IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European cohort: A cross-sectional study

To date, drug response genes have not proved as useful in clinical practice as was anticipated at the start of the genomic era. An exception is in the treatment of chronic hepatitis C virus (HCV) genotype 1 infection with pegylated interferon-alpha and ribavirin (PegIFN/R). Viral clearance is achieved in 40%-50% of patients. Interleukin 28B (IL28B) genotype predicts treatment-induced and spontaneous clearance. To improve the predictive value of this genotype, we studied the combined effect of variants of IL28B with human leukocyte antigen C (HLA-C), and its ligands the killer immunoglobulin-like receptors (KIR), which have previously been implicated in HCV viral control

Armstrong, Nicola J

O'Connor, Kate S

Dore, Gregory J

Irving, William L

Müller, Tobias

Stewart, Graeme J

Booth, David R

Archive ouverte UNIGE

IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European Cohort: a cross-sectional study

A novel duplex SSP-PCR typing method for KIR gene profiling.

Amino acid substitution in hepatitis C virus core region and genetic variation near the interleukin 28B gene predict viral response to telaprevir with peginterferon and ribavirin.

Antitumor activity of IFN-lambda in murine tumor models.

Common HLAB8-DR3 haplotype in Northern India is different from that found in Europe.

Consistent beneficial effects of killer cell immunoglobulin-like receptor 2DL3 and group 1 human leukocyte antigen-C following exposure to hepatitis C virus.

Course and outcome of hepatitis C.

Distinct KIR/HLA compound genotypes affect the kinetics of human antiviral natural killer cell responses.

Effect of killer immunoglobulin-like receptors in the response to combined treatment in patients with chronic hepatitis C virus infection.

Effective treatment of injecting drug users with recently acquired hepatitis C virus infection.

Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial.

Genetic variation in IL28B and spontaneous clearance of hepatitis C virus.

Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance.

genetically homogenous Irish population.

Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C.

Hepatic ISG expression is associated with genetic variation in interleukin 28B and the outcome of IFN therapy for chronic hepatitis C.

Hepatitis C pharmacogenetics: state of the art in 2010.

High incidence of hepatitis C virus reinfection in a cohort of injecting drug users.

HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection.

HLA-C is the inhibitory ligand that determines dominant resistance to lysis by NK1- and NK2-specific natural killer cells.

IL-28 elicits antitumor responses against murine fibrosarcoma.

IL28B in hepatitis C virus infection: translating pharmacogenomics into clinical practice.

IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy.

Innate immune genes synergize to predict increased risk of chronic disease in hepatitis C virus infection.

Interferon-alpha-induced TRAIL on natural killer cells is associated with control of hepatitis C virus infection.

Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics.

Keeping NK cells in highly regulated antiviral warfare.

Killer cell inhibitory receptors specific for HLA-C and HLA-B identified by direct binding and by functional transfer.

KIR genotyping by multiplex PCR-SSP.

Mechanism of action of interferon and ribavirin in treatment of hepatitis C.

Molecular diversity of the HLA-C gene identified in a caucasian population.

Natural killer cells are polarized toward cytotoxicity in chronic hepatitis C in an interferonalfa-dependent manner.

Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies.

Systemic and intrahepatic interferon-gamma-inducible protein 10 kDa predicts the first-phase decline in hepatitis C virus RNA and overall viral response to therapy in chronic hepatitis C.

Telaprevir for previously treated chronic HCV infection.

The Human Genome Project provides information about medicine and the new genetics, including a primer on pharmacogenomics Prediction of

file:///data/core-remote/dit/data/public_library_of_science/pdf/f1c/ZnRwOi8vZnRwLm5jYmkubmxtLm5paC5nb3YvcHViL3BtYy9vYV9wYWNrYWdlL2E4L2QzL1BNQzMxNzIyNTEudGFyLmd6.pdf

IL28B, HLA-C, and KIR Variants Additively Predict Response to Therapy in Chronic Hepatitis C Virus Infection in a European Cohort: A Cross-Sectional Study

Abstract

Similar works

Full text

Available Versions

Public Library of Science (PLOS)

Western Sydney ResearchDirect

Crossref

Directory of Open Access Journals

Institutional Research Information System University of Turin

University of Queensland eSpace

Archive ouverte UNIGE

Public Library of Science (PLOS)