CHAPEL HILL -- An estimated 20 percent of people with chronichepatitis C who receive a liver transplant will develop advancedcirrhosis, scarring of the new organ severe enough to impair itsability to function normally within five years of transplantation.
A new study from the University of North Carolina at Chapel Hill Schoolof Medicine may have found a way to identify those at greatest risk,thereby allowing doctors to decide who should receive treatment thatcould save the transplanted organ. The new findings appear in theOctober issue of the journal Liver Transplantation.
The research found a laboratory test that shows activation of a certaintype of liver cell -- hepatic stellate cells -- to be useful indetermining high risk for developing cirrhosis.
"Right now, there are no reliable tests for identifying the groupthat's at high risk," said lead author Dr. Mark W. Russo, assistantprofessor of medicine in the Division of Gastroenterology andHepatology at UNC. "The reason you want to identify that group isbecause there are some people who will not go on to develop cirrhosisfrom hepatitis C after liver transplant and the therapy has a lot ofside effects and is also very expensive."
This antiviral drug therapy is effective in only 10 percent to 30percent of liver transplant recipients, the research team reported.Moreover, side effects, including anemia, cause roughly the samepercentage of patients to stop the treatment.
Russo and collaborators from UNC and the University of Florida focusedon hepatic stellate cells (HSCs), which normally store vitamin A in theliver. But they produce collagen and other proteins that can lead tofibrosis, or scarring, in patients infected with hepatitis C virus.
The research team hypothesized that a known valid biomarker of HSCactivation -- alpha smooth muscle actin (alpha-SMA) -- could predictwhich patients would later develop fibrosis.
The study involved 46 patients with hepatitis C virus who receivedliver transplants between 1997 and 2001. The patients were divided intotwo groups: those who developed advanced fibrosis within two years ofliver transplant and those who developed mild or no fibrosis in thesame period.
Liver tissue samples from four months, one year and two yearspost-transplant were scored in the laboratory for alpha-SMA. Theresults showed HSC activation to be significantly higher in thefour-month biopsies for those who developed advanced fibrosis withintwo years."These results are exciting because they suggest for the first timethat this biomarker could help us identify liver transplant recipientswith hepatitis C who are at high risk for progressing to advancedfibrosis. But it would be important to confirm this in a largerindependent, prospective study," Russo said.
UNC co-authors along with Russo include Dr. Michael Fried and Dr.Roshan Shrestha, professors of medicine within the Division ofGastroenterology and Hepatology; and Robert Schoonhoven, laboratoryresearch specialist in the UNC School of Public Health's department ofenvironmental sciences and engineering. Co-authors from the Universityof Florida include Dr. Roberto Firpi, clinical assistant professor ofmedicine, and Dr. David Nelson, assistant professor of medicine.
Support for the research came from the National Institute ofEnvironmental Health Sciences, a component of the National Institutesof Health.
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