IL28B polymorphisms determine early viral kinetics and treatment outcome in patients receiving peginterferon/ribavirin for chronic hepatitis C genotype 1
Artikel i vetenskaplig tidskrift, 2011

Single nucleotide polymorphisms (SNPs) upstream of IL28B predict the outcome of treatment in chronic hepatitis C virus (HCV) infection, but their impact on viral kinetics and relation to other predictors are not well known. Here, two SNPs, rs12979860 and rs8099917, were analysed and related to early viral kinetics during treatment in 110 patients with HCV genotype 1 infection. The reduction of HCV RNA after 7 days of therapy was more pronounced (P < 0.0001) in patients with CC(rs12979860) or TT(rs8099917) than in patients carrying TT(rs12979860) or GG(rs8099917), respectively. The two SNPs were in linkage disequilibrium (d' = 1, r2 = 0.44), but CC(rs12979860) was less common (43% vs. 71%) than TT(rs8099917). Patients carrying both CC(rs12979860) and TT(rs8099917) genotypes achieved lower levels of HCV RNA at week 4 than those with CT or TT at rs12979860 and TT(rs8099917) (P = 0.0004). The viral elimination was significantly influenced by rs12979860 independently of baseline viral load, age or fibrosis. This translated into high rates of sustained viral response (SVR) among patients carrying CC(rs12979860) despite the presence of high viral load at baseline (SVR 74%), high age (SVR 79%) or severe liver fibrosis (SVR 83%). We conclude that the IL28B variability influences the antiviral efficiency of interferon/ribavirin therapy and has a strong impact on SVR, independently of traditional response predictors. A combined assessment of these SNPs in conjunction with other response predictors may better predict outcome in difficult-to-treat patients.

genetics

administration & dosage

Polymorphism

Recombinant Proteins

administration & dosage

therapeutic use

genetics

physiology

Polyethylene Glycols

Adult

Interleukins

Kinetics

administration & dosage

administration & dosage

Humans

Chronic

Middle Aged

Single Nucleotide

Antiviral Agents

administration & dosage

therapeutic use

Treatment Outcome

Linkage Disequilibrium

therapeutic use

genetics

Ribavirin

Prognosis

drug effects

Genotype

Hepatitis C

therapeutic use

Female

Interferon-alpha

Hepacivirus

drug therapy

therapeutic use

Male

Författare

Magnus Lindh

Göteborgs universitet

Martin Lagging

Göteborgs universitet

B Arnholm

Boras Hospital

Anders Eilard

Göteborgs universitet

Staffan Nilsson

Chalmers, Matematiska vetenskaper, matematisk statistik

Göteborgs universitet

Gunnar Norkrans

Göteborgs universitet

Jonas Söderholm

Göteborgs universitet

T Wahlberg

Central Hospital Skovde

Rune Wejstål

Göteborgs universitet

Johan Westin

Göteborgs universitet

Kristoffer Hellstrand

Göteborgs universitet

Journal of Viral Hepatitis

1352-0504 (ISSN) 1365-2893 (eISSN)

Vol. 18 7 e325-e331

Ämneskategorier

Infektionsmedicin

Mikrobiologi inom det medicinska området

DOI

10.1111/j.1365-2893.2010.01425.x

PubMed

21692944