Clotting Initiator Blamed for Hepatitis Liver Damage

Researchers have identified a protein that triggers the formation of blood clots in the minute blood vessels of the liver in patients with chronic viral hepatitis and may be the cause of the damage caused to the liver during the infection.

Investigators at the University of Toronto (Canada) genetically engineered a line of mice lacking the gene for production of fg12/fibroleukin prothrombinase. When infected with a mouse hepatitis (corona) virus, these mice failed to generate blood clotting and 40% of the mice were still alive 14 days after being infected. Normal mice infected with the virus experienced blood clotting and died within four to seven days of hepatitis infection.

In addition to the tests on mice, liver biopsies from 23 human patients with severe chronic hepatitis B and 13 patients with minimal chronic hepatitis were examined to determine their fg12/fibroleukin prothombinase concentrations and the severity of clotting in their liver tissue. The results, published in the July 1, 2003, issue of the Journal of Clinical Investigation, showed that patients with severe chronic hepatitis expressed fgl2 protein in their livers in association with fibrin clots resulting in liver cell death. Patients with mild chronic hepatitis B had no evidence of fgl2 expression or clotting within their livers.

"This offers new hope to patients by paving the way for future therapies that will change the course of hepatitis,” said senior author Dr. Philip Marsden, professor of medicine at the University of Toronto. "Our work represents an innovative new approach to combating viral disease. Therapies to date have focused on getting rid of the virus, but this work points the way to blocking the damage the virus does.”




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