Researchers Discover Genomic Signature for Predicting Acute Rejection in Liver Transplant Patients

May 1, 2017
Researchers Discover Genomic Signature for Predicting Acute Rejection in Liver Transplant Patients
A recently-discovered genomic signature for predicting acute rejection in liver transplant recipients will be detailed tomorrow at the American Transplant Congress in Chicago. (Source: © Sebastian Kaulitzki/Fotolia)

A recently-discovered genomic signature for predicting acute rejection in liver transplant (LT) recipients will be detailed May 2, during a presentation at the American Transplant Congress (ATC) in Chicago.

Josh Levitsky, M.D., professor of medicine (gastroenterology, hepatology) and surgery (organ transplantation) at Northwestern University Feinberg School of Medicine, will present results from a single-center discovery and internal validation study that examined gene expression profiles in the peripheral blood and biopsy tissue of liver transplant recipients.

The study examined 181 patients, of which 45 showed normal function; 45 elevation in liver function tests (LFTs), with a biopsy showing acute rejection (AR); and 91, abnormal LFTs with no clinical or histological evidence of AR.

Using Affymetrix gene expression arrays, the authors showed a significant number of differentially expressed genes in the peripheral blood between the three clinical phenotypes with high predictive accuracy (sensitivity, specificity, PPV, NPV), even when adjusted for prevalent incidence of each phenotype. The researchers performed internal validation via both standard bootstrapping and leave-one-out cross-validation.

“We have identified blood and graft mRNA signatures that can distinguish AR from other major causes of graft injury in LT recipients and may be useful in the monitoring and management of LT recipients,” Dr. Levitsky and colleagues concluded in an abstract of their presentation, titled "Blood and Biopsy Genomic Signatures of Acute Rejection in Liver Transplant Recipients.”

Dr. Levitsky said in a statement that he and colleagues have discovered a “significant” number of genes in the peripheral blood that are differentially expressed between three clinical phenotypes—normal function, elevated liver function tests with a biopsy showing AR, and elevated liver function tests with no clinical symptoms or histological evidence of AR.

“These encouraging results suggest a predictive model for AR in peripheral blood samples, which if further validated, may form the basis for a test that can be used to improve health management of liver transplant recipients and make possible personalized immunosuppression,” Dr. Levitsky said. “Such validation studies are already in process.”

Dr. Levitsky is a clinical advisor to Transplant Genomics Inc. (TGI), which holds an exclusive license to commercialize transplant diagnostic tests based on research by investigators at Northwestern and The Scripps Research Institute.

“TGI is excited about the opportunity to expand our product portfolio from kidney to liver as we strive to bring innovative molecular tests to market that benefit the lives of organ transplant recipients,” stated TGI President and CEO Stan Rose, Ph.D. “Dr. Levitsky's discovery may lead to a new predictive tool that, in the future, can enable improved management of liver transplant patients.”