Predictive value of the IL28B polymorphism on the effect of interferon therapy in chronic hepatitis C patients with genotypes 2a and 2b.
OBJECTIVE
Common IL28B locus polymorphisms (SNPs rs8099917 and rs12979860) have been reported to affect peg-interferon plus ribavirin combination therapy (PEG-RBV) for hepatitis C virus (HCV) genotype 1b, but few reports have examined their effect on other two common genotypes, 2a and 2b.


METHODS
We analyzed predictive factors for sustained virological response (SVR) in a retrospective study of 719 patients with either genotype 2a (530) or 2b (189). Of these patients, 160 were treated with PEG-RBV and 559 were treated with interferon monotherapy. We evaluated predictive factors including HCV RNA, histological findings, IL28B SNP genotypes (rs8099917, rs12979860, and rs12980275), and the effect of treatment regimen and prior treatment history.


RESULTS
HCV RNA viral load, treatment regimen, and rs8099917 genotypes independently contributed to the effect of the therapy. For patients treated with PEG-RBV, rs8099917 and viral load were independent predictive factors for SVR in genotype 2b but not in genotype 2a. Conversely, in patients treated with interferon monotherapy, viral load and rs8099917 were independent predictive factors for SVR in genotype 2a but not in genotype 2b. The favorable rs8099917 genotype is also associated with a steep decline in viral load by the second week of treatment.


CONCLUSIONS
Initial viral load and rs8099917 genotype are significant independent predictors of SVR in genotype 2 patients.
Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN (The Institute of Physical and Chemical Research), 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Tomokazu
T
Kawaoka
C Nelson
CN
Hayes
Waka
W
Ohishi
Hidenori
H
Ochi
Toshiro
T
Maekawa
Hiromi
H
Abe
Masataka
M
Tsuge
Fukiko
F
Mitsui
Nobuhiko
N
Hiraga
Michio
M
Imamura
Shoichi
S
Takahashi
Michaki
M
Kubo
Tatsuhiko
T
Tsunoda
Yusuke
Y
Nakamura
Hiromitsu
H
Kumada
Kazuaki
K
Chayama
D000368:Aged; D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda
D000998:Antiviral Agents; D007370:Interferon Type I; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda