Early Findings Indicate Aggressive Treatment for Hepatitis C May Be Needed to Arrest Disease Development.

SANTA FE, N.M.--(BUSINESS WIRE)--Oct. 1, 1998--Researchers from Los Alamos National Laboratory, University of Illinois, University of Washington, Bar-Ilan University, and the Santa Fe Institute have demonstrated in short-term clinical trials that the drug interferon-alpha-2b given in doses of 10-15 mIUs (million international units) per day, can block up to 95% of Hepatitis C virus production.

Current treatment level approved by the Federal Drug Administration is 3mIUs three times per week, which is less effective.

Hepatitis C is a chronic illness that over time can result in cirrhosis or liver cancer. It is a difficult virus to study in a laboratory setting as it cannot be grown in a cell culture, and animal studies, to date, have not been effective.

"With the recent success of patient response to HIV therapy that included mathematical modeling of the kinetics of virus replication, experimentalists and theorists once again came together to see if a similar approach to studying and treating Hepatitis C might provide similar beneficial results," said Avidan Neumann, Department of Life Sciences, Bar-Ilan University and External Faculty Member, Santa Fe Institute.

The analysis shows that Hepatitis C virus is more rapidly produced than HIV with approximately a trillion virus particles produced and cleared each day.

The study consisted of twenty-three untreated patients infected with Hepatitis C randomly assigned to take one of three dose regimens from 5, 10 or 15 mIUs daily for 14 days, followed by treatment with 5 mIU daily. Blood

samples were collected every few hours the first two days and then daily for two weeks.

For those patients taking either 10 or 15 mIUs the first two days showed dramatic clearing of the virus followed by a slower stabilized decline for the remaining test period. The rate of this slower stabilized decline appears predictive of whether the virus level in the blood becomes sufficiently low that it is undetectable by current technology after three-months.

"These results show that Hepatitis C infection like HIV infection is highly dynamic with large amounts of virus being rapidly produced in infected individuals. Modifying the current treatment of hepatitis C with increased dosages of interferon given daily helps the body rapidly clear the virus from the blood.

"While the long term effects on disease progression are unknown, these findings suggest that more effective treatment for individuals inflicted with this disease may be possible," said Dr. Alan Perelson, Group Leader, Theoretical Biology and Biophysics Group, Laboratory Fellow at Los Alamos National Laboratory; and Director of the Joseph P. and Jeanne M. Sullivan Theoretical Immunology Program at the Santa Fe Institute.

The report, published today in the scientific journal Science, was released after following the subjects for three months. More longitudinal studies, as well as studies with more subjects are needed to verify results.

However, initial results support the hypothesis that interferon works in combating the disease by blocking infected cells from either producing or releasing the virus; the data and analysis show that the degree of blockage is dependent on the dose; and that doses higher than the 3 mIUs currently given may be needed to combat the disease effectively.

The Santa Fe Institute (SFI) is a private, independent, non-profit 501(c)(3) research and education center. Since its founding, SFI has devoted itself to creating a new kind of scientific research community, focusing on emergent behavior and pattern formation in science.

The Joseph P. and Jeanne M. Sullivan Theoretical Program in Immunology provided partial funding for this project, along with support from the University of Washington, University of Illinois, and Bal-Ilan University in Israel.