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.
administration & dosage
drug effects
Adult
administration & dosage
Prognosis
administration & dosage
administration & dosage
therapeutic use
physiology
drug therapy
Chronic
Hepacivirus
Genotype
genetics
Hepatitis C
Single Nucleotide
Ribavirin
Humans
Polymorphism
administration & dosage
Linkage Disequilibrium
Female
Kinetics
genetics
therapeutic use
therapeutic use
Polyethylene Glycols
Interleukins
Male
Antiviral Agents
Treatment Outcome
therapeutic use
genetics
Interferon-alpha
Middle Aged
Recombinant Proteins
therapeutic use
Författare
Magnus Lindh
Göteborgs universitet
Martin Lagging
Göteborgs universitet
B Arnholm
Södra Älvsborgs Sjukhus (SÄS)
Anders Eilard
Göteborgs universitet
Staffan Nilsson
Göteborgs universitet
Chalmers, Matematiska vetenskaper, Matematisk statistik
Gunnar Norkrans
Göteborgs universitet
Jonas Söderholm
Göteborgs universitet
T Wahlberg
Skaraborgs Sjukhus
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-e331Ämneskategorier
Infektionsmedicin
Mikrobiologi inom det medicinska området
DOI
10.1111/j.1365-2893.2010.01425.x
PubMed
21692944