Peripheral blood gene expression profile associated with sustained virologic response after peginterferon plus ribavirin therapy for chronic hepatitis-C genotype 1.
We investigated the relationship between global gene expression in peripheral blood mononuclear cells (PBMCs) during the first 4 weeks of peginterferon alfa and ribavirin therapy and long-term eradication of hepatitis-C genotype 1 infections in 23 patients. A sustained virologic response (SVR), defined as an undetected serum HCV ribonucleic acid (RNA) at week 72, was the virologic response endpoint. PBMC RNA was prepared at week 0 and week 4 from 23 patients (17 black and 6 white Americans), and hybridized to Affymetrix GeneChip HG-U133 plus 2.0 arrays. Compared to week 0, 269 genes were differentially expressed at week 4 of treatment, including many genes regulated by alpha interferons and associated with host immunity (p<0.0001), cell signal transduction (p<0.001) and cellular protein metabolism (p<0.001). Expression of these 269 genes at week 0 and week 4 did not differ significantly between patients with and without a SVR. In contrast, SVR was associated with differential expression of 98 genes at week 4 (false discovery rate <0.01). Many of the genes have been implicated in control of HCV lifecycle and thus may play important roles in HCV clearance during peginterferon and ribavirin therapy.
Huang
Chao
C
Department of Medicine, Baltimore, MD, USA.
Chen
Hegang
H
Cassidy
William
W
Howell
Charles D
CD
D000328:Adult; D005260:Female; D020869:Gene Expression Profiling; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a