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Gene expression of Peg-interferon alfa-2b plus ribavirin in hepatitis C patients during the first 10 weeks of treatment

ABSTRACT: Study of PBMC gene expression during the first 10 weeks of therapy with Pegylated-interferon-alfa2b (PegIntronTM) and ribavirin (administered by weight) in HCV patients. This study compared the kinetics of gene expression during the first 10 weeks of therapy with Pegylated-interferon-alfa2b (PegIntronTM) and ribavirin (administered by weight) in HCV patients with the recently completed Virahep C study (9999) in which Peginterferon-alfa2a and ribavirin was administered. RNA was isolated from peripheral blood monocytes from twenty treatment-naïve patients just before treatment (day 0,) and at days 3, 6, 10, 13, 27, 42 and 70 days after treatment. Gene expression at each time was compared to that of day 0 using Affymetrix DNA-micro-arrays. Focusing upon genes that changed at least 1.5-fold and p<0.001, the numbers were high at day 3 (300 probes) and 10 (255) but dropped at days 6 (128) and 13 (142) but were steady at later time points. A large number of genes continued to be up regulated throughout the trial period. A second group of genes, including CXCL10, chemokine receptor 1, TRAIL, IL1 R and genes associated with complement and lipid metabolism, were transiently induced. CDKN1C (cyclin kinase inhibitor 1) was induced early but repressed at later times. Genes induced at later times were mostly related to blood chemistry and oxygen transport. Genes down regulated were related to ribosomal proteins and eukaryotic translation complexes. By week 10, 50% of the patients demonstrated a positive response to therapy. Conclusions: The response to pegintron/ribavirin was similar to that reported for Pegasys/ribavirin, although the extent of gene induction was less. No differences were found between patients responding to treatment or non-responders during this period. Our data suggest that more than once a week dosing might be desirable early on during treatment. Keywords: Time Course, gene expression Overall design: Time course, 20 individuals, samples taken before first treatment (day 0) and days 3, 6, 10, 13, 27, 42 and 70.

INSTRUMENT(S): [HG-U133A] Affymetrix Human Genome U133A Array

ORGANISM(S): Homo sapiens  

SUBMITTER: Milton W Taylor  

PROVIDER: GSE11342 | GEO | 2009-04-21



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