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.
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
Author
Magnus Lindh
University of Gothenburg
Martin Lagging
University of Gothenburg
B Arnholm
Södra Älvsborg Hospital (SÄS)
Anders Eilard
University of Gothenburg
Staffan Nilsson
University of Gothenburg
Chalmers, Mathematical Sciences, Mathematical Statistics
Gunnar Norkrans
University of Gothenburg
Jonas Söderholm
University of Gothenburg
T Wahlberg
Skaraborg Hospital
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
Infectious Medicine
Microbiology in the medical area
DOI
10.1111/j.1365-2893.2010.01425.x
PubMed
21692944