Cincinnati--The University of Cincinnati (UC) College of Medicine
has received a $2.5 million grant from the National Institute of
Allergy and Infectious Diseases of the National Institutes of Health to
study the genomic variability of hepatitis C (HCV) in infected
hemophiliac patients also infected with HIV, the virus that causes
AIDS. Hemophilia is a bleeding disorder in which certain factors in the
blood needed to form a clot are missing or reduced, resulting in
difficulty controlling hemorrhage.
"Hemophiliacs infected with
both hepatitis C and HIV have more rapidly progressive liver failure
than patients with hepatitis C alone," said Kenneth Sherman, MD, PhD,
associate professor of internal medicine and principal investigator of
the study. "We really don't understand the reason for this accelerated
liver disease process. Treating physicians who care for patients with
hemophilia need additional guidance in how to best manage this
complicated group of patients. AIDS and liver diseases, such as
hepatitis C, have now emerged as major causes of death in people with
hemophilia. This grant represents the importance of studying this group
of patients who through no fault of their own got terrible diseases."
blood contains proteins known as clotting factors which are crucial in
preventing excessive bleeding. Hemophiliacs frequently receive
transfusions of clotting factors, called factor concentrates, to
increase levels of the missing factor. The factor concentrates are
pulled and isolated from large pools of human blood donations. Prior to
1987, almost all factor concentrates were contaminated with hepatitis C
and HIV. Beginning in 1987, the heat treatments that were used to pull
factor concentrates from the blood killed hepatitis C. Screening
donated blood for HIV began in 1985. Universal screening of blood
donations for hepatitis C was implemented in 1992.
phase of the four-year grant will involve the study of banked specimens
from the National Cancer Institute (NCI) Hemophilia Cohort Study. The
NCI study is a longitudinal study following patients who have had
hemophilia and AIDS for 20 years or more. Over the course of the NCI
study, patients have had frequent evaluations of their health status
and blood samples taken. All of the data from the study has been
recorded and stored in a large information bank. Sherman and his
colleagues will perform a very detailed study of the specimens from the
bank for factors associated with the progression of liver disease.
two of the study will be a clinical trial with approximately 25
patients enrolled at seven national sites who have hemophilia,
hepatitis C and/or HIV. Patients enrolled in the treatment phase will
include selected hemophiliacs who have never been treated for hepatitis
C and do not yet have end-stage liver disease. These patients will be
treated with a new generation of hepatitis drugs called PEG-Interferon
and Ribavirin and closely followed after their treatment for up to
three years to study long-term treatment effects and immune responses.
are hoping to understand the mechanisms of rapid liver disease
progression and identify features associated with response or lack of
response to treatment in patients with hemophilia," Sherman said.
will serve as the primary study site. The study will be performed in
collaboration with researchers from the National Hemophilia Foundation;
Pennsylvania State University; Harvard Medical College; Tulane
University; Medical College of Wisconsin at Milwaukee; University of
Texas at Houston; Emory University and Georgetown University.