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Path to hepatitis C yields test, clues.

Path to hepatitis C yields test, clues

Last May, researchers announced they had identified and cloned parts of the genetic material of a new virus, which they suggested causes most of the world's cases of non-A, non-B hepatitis (SN: 5/14/88 p.308). The researchers have now disclosed the molecular method that led to the discovery and that has since allowed them to characterize more than 90 percent of the viral genome. They also report developing a test for the virus, designated hepatitis C, which they hope will soon win approval for large-scale blood screening and patient diagnosis, says study leader Michael Houghton of Chiron Corp. in Emeryville, Calif.

The Chiron group's approach to characterizing the hepatitis C virus could prove useful in finding pathogens for other diseases -- such as Alzheimer's or multiple sclerosis -- in which "an infectious agent might be implicated but is not proven [to cause or abet the illness]," Houghton says. "I think several new infectious agents will be discovered."

More than 90 percent of the hepatitis transmitted through blood transfusions represents the non-A, non-B type, an ill-defined ailment diagnosed when non-specific biochemical tests indicate liver injury but the blood bears no indicators of any known hepatitis-causing virus, Houghton says.

The researchers have already used the newly developed hepatitis C test to survey non-A, non-B patients for circulating antibodies to the virus. In a U.S. study, 17 of 24 transfusion-acquired cases and 34 of 59 cases of unknown origin tested positive. "Thus, it appears that hepatitis C virus is a major cause of community-acquired non-A, non-B hepatitis as well as post-transfusion non-A, non-B hepatitis," the researchers write in the April 21 SCIENCE. In addition, they report that 78 percent of chronic cases studied in Japan and 84 percent in Italy tested positive for hepatitis C.

The test probably doesn't pick up all hepatitis C cases in the early, acute stages because the antibody takes months to develop, notes molecular virologist Daniel W. Bradley of the Centers for Disease Control's Hepatitis Branch in Atlanta. Bradley says he and his co-workers are working to develop other assays for the acute disease as well as a vaccine.

To make the test, the Chrion researchers stitched together three hepatitis C viral clones and inserted them into yeast, which then began making a viral protein from the foreign genetic material. Antibodies to the virus bind to the protein and become visible after a color-producing reaction with another antibody, enabling scientists to use the manufactured viral protein to test blood samples for the hepatitis C virus, the team reports.

The test gave a positive result in six out of seven blood samples known to cause non-A, non-B hepatitis in chimpanzees and a negative result in all seven control samples, demonstrating that it detects antibody in infectious samples, Houghton says. And when mixed with blood from 10 prospectively studied transfusion recipients diagnosed with non-A, non-B hepatitis, the test showed that all developed antibodies within a year after infection; for nine, the test picked out a positive blood donor. No such antibodies were detected in blood from 43 people infected with other known hepatitis viruses, he says.

Furthermore use of the test should shed light on whether other agents can cause non-A, non-B hepatitis, Houghton says. Other studies already indicate that a significant portion of the cases may be caused by mutant forms of the hepatitis B virus (SN: 1/28/89, p.52).

The test is now in clinical trials, which should be completed by June, and Chiron plans to apply to the Food and Drug Administration to market the test by the end of the summer, says company spokesman Larry Kurtz.
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Author:Wickelgren, I.
Publication:Science News
Date:Apr 22, 1989
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