While
treatment of chronic hepatitis C using pegylated
interferon plus ribavirin leads to sustained HCV clearance and clinical improvement
in approximately half of all patients, response rates are lower in certain "difficult
to treat" groups, including patients with genotype
1 HCV and African-Americans.
It
is unclear why treatment response rates vary by race/ethnicity, but genetic factors
may play a role.
As reported in the January 31, 2007 electronic edition
of the Journal of Virology, researchers used DNA micro-arrays to assess
gene expression in a group of 33 African-American and 36 Caucasian-American patients
with genotype 1 chronic HCV infection during the first 28 days of treatment with
pegylated interferon/ribavirin.
Results
•
Patients
showed a response to treatment at the gene expression level in RNA isolated from
peripheral blood mononuclear cells (PBMCs) regardless of degree of decrease in
HCV RNA levels.
•
Gene
expression responses were relatively blunted in patients with poor virological
response (< 1.5 log10 IU/mL decrease in HCV RNA at 28 days) compared to those
with a marked (> 3.5 log10 decrease) or intermediate (1.5-3.5 log10 decrease)
response.
•
The
number of genes that were up-regulated or down-regulated by pegylated interferon/ribavirin
was fewer in patients with a poor virological response compared to those with
a marked or intermediate response.
•
Induced
levels of known interferon-stimulated genes such as OAS, MX1, IRF-7, and the toll-like
receptor TLR-7 were lower in poor responders compared to patients with marked
or intermediate responses.
•
However,
African-Americans had stronger interferon responses than Caucasian patients overall.
Conclusion
The
authors concluded that, "the relative lack of viral response to interferon
therapy of hepatitis C is associated with blunted interferon cell signaling. No
specific regulatory gene could be identified as responsible for this global blunting
or racial differences." It remains unclear why African-Americans tend
to respond more poorly to interferon-based therapy, given their overall stronger
gene expression response to interferon.
Department of Biology, Indiana
University, Bloomington, IN; Department of Biochemistry and Molecular Biology
and Center for Medical Genomics, Indiana University School of Medicine. Indianapolis,
IN; Institute of Evolution, University of Haifa, Israel; Department of Molecular
Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis,
MO; Department of Medicine, University of Maryland, Baltimore, MD; Graduate School
of Public Health, University of Pittsburgh, Pittsburgh, PA.
02/20/07
Reference M
W Taylor, T Tsukahara, L Brodsky, and others. Changes in gene expression during
peginterferon and ribavirin therapy of chronic hepatitis C distinguish responders
from non responders to antiviral therapy. Journal of Virology. January
31, 2007 [Epub ahead of print].
