"In previous studies, the response rate to treatment in Caucasians
was about 20 to 40 percent depending on the type of interferon used,
but the response rate in African Americans was less than 5 percent,"
explained Taylor. "There is a growing body of evidence confirming
this difference."
The new study, Viral Resistance to Antiviral Therapy of Chronic
Hepatitis C (Virahep-C), is funded by the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) and coordinated
by the University of Pittsburgh Graduate School of Public Health
Epidemiology Data Center.
Taylor's lab at IU is one of four ancillary labs involved in the
project, the only one not located in a medical school. Eight clinical
centers also will participate in the study, which will enroll 400
patients over a one-year period, 200 African Americans and 200 Caucasians.
Patients will undergo an extensive initial medical evaluation
and return periodically during and following treatment. The goal
will be to determine the differences in response from one group
to another, and also to look at differences between those who do
respond and those who do not in both races. IU and the other three
ancillary labs will investigate what might cause those differences.
"Our job in this large project is to analyze gene expression following
interferon treatment. In other words, we'll look at as many genes
as are expressed at any one time following treatment," said Taylor.
In the past, researchers commonly looked at one gene in one experiment,
but a new technology resulting from the Human Genome Project can
present an array of samples. Referred to as DNA or gene array, this
technology allows researchers to look at the changes in expression
of a number of genes simultaneously.
"We are using DNA chips containing 22,000 genes, or spots, on
arrays. This obviously is not all the genes of an individual, but
most metabolic and physiological pathways are covered, which allows
us to assess which of those may be activated. Preliminary results
indicate that somewhere between 1,000-2,000 of them may be activated
by interferon," he continued.
"Since we are using RNA isolated from the blood of patients before
treatment and also from controls, we should get a picture of what
genes, if any, are actually activated by hepatitis C virus."
Much of Taylor's work is done in collaboration with the Indiana
Genomics Project (INGEN) at the IU School of Medicine. The amount
of data involved in this study is overwhelming, said Taylor, and
requires a great deal of analysis that would not be possible without
the help of INGEN statisticians and bioinfor-maticists.
Taylor has worked in the area of interferon, a natural antiviral
compound, for some time. Most of the work done in his lab, he said,
looks at the molecular activity of interferons, and how it stops
virus infection and inhibits the growth of cancerous cells. In addition
to this study on how interferon works, or doesn't, with hepatitis
C, Taylor has other grants to pursue possible markers in the diagnosis
of breast and other cancers.
Administrative work on Virahep-C began last August, and Taylor
expects the first patient samples to arrive soon.
"We will follow up patient samples before treatment, and at 24,
48 and possibly 72 hours, one week, two weeks and at other time
points up to 48 weeks," explained Taylor. "We should get a complete
picture of what is transpiring after treatment."
HCV has infected an estimated 3.9 million Americans, 2.7 million
of them chronically, according to the National Center for Infectious
Diseases. While the number of new infections each year has dropped
from 240,000 during the 1980s to 40,000 in 1998, it is still a serious
illness. Causing liver disease in about 70 percent of those chronically
infected, hepatitis C is the leading indicator of liver transplant.
"We hope to be able to predict who will respond to treatment and
who will not," said Taylor. "Interferon treatment is very expensive
and there are many side effects. We also hope to learn more about
interferon therapy in general, as well as with hepatitis C. In the
future, it may be possible to decide after a few days whether it
is worth continuing treatment."
Hepatitis what?
"Few of us would know HCV from KFC. Yet this potentially lethal
virus is now four times as widespread as HIV, and few of the nation's
3 million to 4 million carriers have any idea they're infected. HCV,
or hepatitis C virus, was not even discovered until 1988."–from
the April 22 cover stories of "Newsweek"
Read more about hepatitis C at this Newsweek Web site:
http://www.msnbc.com/news/737946.asp#BODY