Biomarker signatures tag liver transplant failure

A researcher preserves a section of a liver biopsy.--Courtesy of the University of Washington

Researchers at the University of Washington have found profiles of proteins and gene expression that could point out early signs of hepatitis C-induced liver damage. The profiles could also suggest the need for a liver transplant. Both studies were published in Hepatology.

Hepatitis C is the leading cause of liver failure leading to a need for a liver transplant. The underlying infection can spread to the healthy liver after transplantation. While many patients will see slow damage over years or decades, around a third of patients will experience this in as little as one or two years, potentially leading to early failure of the transplanted organ. To monitor this, transplant patients repeatedly undergo invasive liver biopsies to check the status of their organ and take more aggressive antiviral therapies to control the infection. By identifying those patients at risk of early liver damage, biomarker-based tests could cut the need for repeat biopsies and give the option of lower potency drug treatments with fewer side effects for the majority.

To find potential biomarkers, one team carried out protein analyses of liver biopsies taken at 6 months and a year, and found a panel of 250 proteins that were linked with faster development of fibrosis in the liver, and could be used to predict early-onset liver fibrosis.

The other team looked at the transcriptome (all the RNA molecules) in liver samples taken from hepatitis C-infected patients who had undergone liver transplant surgery to find patterns of gene expression. A gene-expression signature was found that pinpointed those patients at risk of developing severe fibrosis in their transplanted livers, and could be spotted even before there was evidence in the liver tissue of disease progression.

"That suggested to us that events that occur during the early stages when the transplanted liver is becoming infected with the patient's hepatitis C virus influence the course of the disease," said Angela Rasmussen, who led the gene-expression project. The researchers also spotted changes that were in common for a number of different, severe clinical outcomes.

Liver transplants are costly and traumatic, and having biomarkers that could predict those that are likely to fail could allow treatment to begin before symptoms emerge, potentially improving the outcomes for patients. As well as helping to identify patients at risk of failure, this research could also point the way to treatments that protect patients' livers from hepatitis C-induced damage and reduce the need for transplants. However, this is still at an early stage and more studies are needed.

- read the press release
- see the abstract for the proteomics study
- check out the abstract for the transcriptomics study

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