HCV substitutions and IL28B polymorphisms on outcome of peg-interferon plus ribavirin combination therapy.
OBJECTIVE
A number of recent studies have shown that human polymorphisms near the IL28B type III interferon (IFNλ) gene influence the response to peg-interferon plus ribavirin combination therapy for infection with chronic hepatitis C virus (HCV). Viral polymorphisms, including substitutions within the HCV core and NS5A proteins, have also been shown to influence treatment outcome, but it is not known whether these factors act independently of the IL28B polymorphism or if they reflect the same or a different underlying mechanism. Multiple logistic regression was used to determine whether host and viral polymorphisms independently predict sustained virological response (SVR).


METHODS
Two single nucleotide polymorphisms were genotyped in the IL28B locus (rs12979860 and rs8099917) from 817 patients with chronic HCV infection, and substitutions at amino acids 70 and 91 of the HCV core protein and within the NS5A interferon sensitivity-determining region (ISDR) were analysed.


RESULTS
It was found that independent predictors of an SVR included IL28B rs12979860 CC genotype (OR=4.98; p=4.00E-08), core amino acid 70 substitutions (OR=0.53; p=0.016), age and baseline viral load. For non-virological response, the IL28B rs12979860 CT/TT genotype (OR=0.23; p=1.96E-8) and age were independent predictors. IL28B rs12979860 genotype (p=1.4E-8), core amino acid 70 substitutions (p=0.0013), ISDR substitutions (p=0.0019), baseline viral load, γ-glutamyltranspeptidase, alanine aminotransferase and platelet count were independent predictors for change in viral load by week 4 of treatment.


CONCLUSIONS
IL28B polymorphisms and HCV core amino acid 70 substitutions contribute independently to an SVR to peg-interferon plus ribavirin combination therapy.
Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan.
C Nelson
CN
Hayes
Mariko
M
Kobayashi
Norio
N
Akuta
Fumitaka
F
Suzuki
Hiromitsu
H
Kumada
Hiromi
H
Abe
Daiki
D
Miki
Michio
M
Imamura
Hidenori
H
Ochi
Naoyuki
N
Kamatani
Yusuke
Y
Nakamura
Kazuaki
K
Chayama
D000368:Aged; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b