IL28B polymorphisms determine early viral kinetics and treatment outcome in patients receiving peginterferon/ribavirin for chronic hepatitis C genotype 1
Journal article, 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
Author
Magnus Lindh
University of Gothenburg
Martin Lagging
University of Gothenburg
B Arnholm
Boras Hospital
Anders Eilard
University of Gothenburg
Staffan Nilsson
Chalmers, Mathematical Sciences, Mathematical Statistics
University of Gothenburg
Gunnar Norkrans
University of Gothenburg
Jonas Söderholm
University of Gothenburg
T Wahlberg
Central Hospital Skovde
Rune Wejstål
University of Gothenburg
Johan Westin
University of Gothenburg
Kristoffer Hellstrand
University of Gothenburg
Journal of Viral Hepatitis
1352-0504 (ISSN) 1365-2893 (eISSN)
Vol. 18 7 e325-e331Subject Categories (SSIF 2011)
Infectious Medicine
Microbiology in the medical area
DOI
10.1111/j.1365-2893.2010.01425.x
PubMed
21692944