Hepatitis C Initiative Expands to New Centers

Applying the tools of genome analysis and other advanced technologies, amultidisciplinary scientific coalition is expanding its investigation ofacute and chronic infection caused by the hepatitis C virus (HCV). Largelyunexplored questions, such as why African Americans respond so poorly to thecurrent standard of care, and unresolved issues, such as how diseasepersists unnoticed in the body for decades, will be added to the ongoingstudies of the Hepatitis C Cooperative Research Centers.

The network unites basic and clinical researchers investigating hepatitis Cinfection and the disease process so as to identify new and better means ofprevention and treatment. The National Institute of Allergy and InfectiousDiseases (NIAID), which launched the multicenter program in 1996, todayannounced it will expand the initiative through nearly $6 million offirst-year funding distributed through nine awards.

The grants renew the four existing Centers �� Stanford University inStanford, Calif., the University of Southern California in Los Angeles, theUniversity of Texas Medical Branch at Galveston, and the University ofWashington in Seattle. The funding also adds two new members to theconsortium: the University of Tennessee Health Science Center in Memphis andthe Children's Research Institute, Ohio State University in Columbus. Inaddition, the initiative will fund three new separate studies conductedindependently of the larger centers.

"We are pleased to continue supporting this important cross-cutting researchon HCV infection, which remains a significant emerging infectious diseaseworldwide and one that disproportionately affects minorities in thiscountry," says NIAID Director Anthony S. Fauci, M.D. "Over the years thesecenters have yielded many important findings, and we hope to build on thoseaccomplishments and explore new therapeutic and vaccine strategies."

HCV, first identified little more than a decade ago, is now estimated toinfect about 3 percent of the world's population, including nearly 4 millionAmericans. It is spread primarily through contact with infected blood. Thevirus damages the liver slowly, often without any obvious symptoms. Indeed,many people infected with HCV can remain unaware of their condition fordecades. If not treated, hepatitis C infection can result in devastatingliver damage, which causes nearly 10,000 deaths and leads to about 1,000liver transplants each year in this country alone.

"Current therapy for HCV infection is woefully inadequate, and some studiesestimate that annual deaths from hepatitis C could triple over the next twodecades unless we develop new, more effective interventions," saysvirologist Leslye Johnson, Ph.D., who is chief of NIAID's enteric andhepatic diseases branch and oversees the consortium. "We still need tounderstand why the virus causes disease right away in some people but takesyears or decades to progress in others," she notes. Such knowledge couldhelp researchers develop new ways to stop HCV before it causes disease or ispassed on to others by people who are unaware they have the virus.

The collaboration has already contributed several advances to understandinghepatitis C. Program researchers were the first to clone a copy of HCV thatinfected nonhuman primates, thereby proving the virus alone is sufficient tocause the disease. Another team discovered how genetic differences in oneHCV protein could help predict how well a patient might respond to theimmune substance interferon, one of the standard therapies used currently.The same group developed a new laboratory assay for identifying anti-HCVcompounds. Clinicians at another center discovered that the amount of virusin a patient's bloodstream was a critical factor in how fast the diseaseprogresses.

According to Dr. Johnson, the network will retain a coordinated,multidisciplinary approach, fostering collaboration among scientists invirology, immunology, cell and tissue biology, pathogenesis, animal studies,clinical investigation and allied research. "The new initiative furtherencourages investigators to examine unexplored areas in hepatitis C researchand to increase the application of advanced technologies that monitor thecontribution of host and viral gene activity to disease progression," shesays.

The consortium's basic goals are to identify components of the virus and thebody's immune response as well as individual genetic factors that have acrucial impact on 1) recovery from initial and chronic infection, 2) diseaseprogression and severity, and 3) the influence of cofactors, such as alcoholuse, that amplify HCV damage.

The clinical research emphasizes studies in special populations heavilyaffected by HCV, such as African Americans who respond poorly to standardtherapies. The centers have a mandate, Dr. Johnson notes, to apply newinformation and advances to develop diagnostic tools, therapies andvaccines.

Other National Institutes of Health (NIH) components providing additionalsupport for individual centers include the National Institute of Diabetesand Digestive and Kidney Diseases, the National Institute on Drug Abuse, andthe NIH Office of Research on Minority Health.

The Hepatitis C Cooperative Research Centers are directed by the followinginvestigators:

CALIFORNIAStanford University - Harry Greenberg, M.D.University of Southern California, Los Angeles - Michael Lai, M.D., Ph.D.

OHIOChildren's Research Institute, Ohio State University, Columbus -Christopher Walker, Ph.D.

TENNESSEEUniversity of Tennessee Health Science Center, Memphis - Caroline Riely,M.D.

TEXASUniversity of Texas Medical Branch at Galveston - Stanley Lemon, M.D.

WASHINGTONUniversity of Washington, Seattle - Nelson Fausto, M.D.

The following investigators will conduct individual hepatitis C researchprojects: Kendall A. Smith, M.D., at Weill Medical College of CornellUniversity in New York City; Thomas Chambers, M.D., at Saint LouisUniversity in Missouri; and Michael Gale, Ph.D., at the University of TexasSouthwestern Medical Center in Dallas.

NIAID is a component of the NIH. NIAID supports basic and applied researchto prevent, diagnose and treat infectious and immune-mediated illnesses,including HIV/AIDS and other sexually transmitted diseases, tuberculosis,malaria, autoimmune disorders, asthma and allergies.

Press releases, fact sheets and other NIAID-related materials are availableon the NIAID Web site at http://www.niaid.nih.gov.