Test predicts risk of liver scarring after transplant, study shows

October 06, 2005

CHAPEL HILL -- An estimated 20 percent of people with chronic hepatitis C who receive a liver transplant will develop advanced cirrhosis, scarring of the new organ severe enough to impair its ability to function normally within five years of transplantation.

A new study from the University of North Carolina at Chapel Hill School of Medicine may have found a way to identify those at greatest risk, thereby allowing doctors to decide who should receive treatment that could save the transplanted organ. The new findings appear in the October issue of the journal Liver Transplantation.

The research found a laboratory test that shows activation of a certain type of liver cell - hepatic stellate cells - to be useful in determining high risk for developing cirrhosis.

"Right now, there are no reliable tests for identifying the group that's at high risk," said lead author Dr. Mark W. Russo, assistant professor of medicine in the Division of Gastroenterology and Hepatology at UNC. "The reason you want to identify that group is because there are some people who will not go on to develop cirrhosis from hepatitis C after liver transplant and the therapy has a lot of side effects and is also very expensive."

This antiviral drug therapy is effective in only 10 percent to 30 percent of liver transplant recipients, the research team reported. Moreover, side effects, including anemia, cause roughly the same percentage of patients to stop the treatment.

Russo and collaborators from UNC and the University of Florida focused on hepatic stellate cells (HSCs), which normally store vitamin A in the liver. But they produce collagen and other proteins that can lead to fibrosis, or scarring, in patients infected with hepatitis C virus.

The research team hypothesized that a known valid biomarker of HSC activation - alpha smooth muscle actin (alpha-SMA) - could predict which patients would later develop fibrosis.

The study involved 46 patients with hepatitis C virus who received liver transplants between 1997 and 2001. The patients were divided into two groups: those who developed advanced fibrosis within two years of liver transplant and those who developed mild or no fibrosis in the same period.

Liver tissue samples from four months, one year and two years post-transplant were scored in the laboratory for alpha-SMA. The results showed HSC activation to be significantly higher in the four-month biopsies for those who developed advanced fibrosis within two years. "These results are exciting because they suggest for the first time that this biomarker could help us identify liver transplant recipients with hepatitis C who are at high risk for progressing to advanced fibrosis. But it would be important to confirm this in a larger independent, prospective study," Russo said.
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UNC co-authors along with Russo include Dr. Michael Fried and Dr. Roshan Shrestha, professors of medicine within the Division of Gastroenterology and Hepatology; and Robert Schoonhoven, laboratory research specialist in the UNC School of Public Health's department of environmental sciences and engineering. Co-authors from the University of Florida include Dr. Roberto Firpi, clinical assistant professor of medicine, and Dr. David Nelson, assistant professor of medicine.

Support for the research came from the National Institute of Environmental Health Sciences, a component of the National Institutes of Health.

Note: Contact Russo at mark_russo@med.unc.edu.
School of Medicine contact: Leslie Lang, (919) 843-9687

University of North Carolina Health Care

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