Biomarkers over biopsies: A highly accurate and minimally invasive test for liver fibrosis

A team of researchers at the Medical University of South Carolina (MUSC) has developed a new test for detecting liver fibrosis. As reported in Frontiers in Immunology, GlycoFibroTyper (Glycopath Inc., Charleston, South Carolina) detects specially modified antibodies in patient blood samples and uses these measurements as predictors for liver fibrosis. Early detection of this condition can help to identify patients at risk of severe disease while saving others the trouble of undergoing a biopsy, which is a much more invasive test.

“Fibrosis is in essence just scarring,” said Hollings Cancer Center researcher Anand Mehta, D.Phil., SmartState Endowed Chair of Proteomic Biomarkers, who led the study. “Just as your skin can be scarred by scratching, your liver can be scarred by injury.” Mehta is one of the founders of the biotech startup Glycopath.

"One of the most important unmet needs in the clinical care of patients with liver disease is a noninvasive approach to assess fibrosis." -- Don Rockey, M.D.

Injuries capable of producing this scarring in the liver can result from genetic disorders, metabolic diseases or exposure to environmental toxins such as alcohol. While minor fibrosis is often reversible, it can progress to become more severe.

 

“Today you may have a little bit of scar tissue, but three years from now, you may have really bad fibrosis,” said Mehta. “If you are identified as having significant fibrosis or cirrhosis – an extreme form of fibrosis – your risk of developing liver cancer is very high. It’s anywhere from 2% to 7% per year.”

To reduce these risks, it is important that physicians monitor for liver fibrosis in their patients. However, minimally invasive ways of doing so are lacking. Currently, the gold standard for detecting fibrosis is a liver biopsy. During this procedure, a hollow needle is inserted into the patient’s abdomen to collect a sample. While biopsy is extremely accurate, it is also highly invasive.

The idea of adapting Glycopath’s existing liquid biopsy tool, the GlycoTyper, to detect liver fibrosis came from gastroenterologist Don Rockey, M.D., director of the MUSC Digestive Disease Research Core Center and a co-author of the study, who knew firsthand the need for a less invasive test.

“One of the most important unmet needs in the clinical care of patients with liver disease is a noninvasive approach to assess fibrosis,” said Rockey. “Liver biopsy is the time-honored approach, but as new therapies emerge, we desperately need ways to measure fibrosis that don’t require a biopsy.”

Previous research revealed that the attachment of sugar molecules to proteins changed as liver fibrosis progressed. The new fibrosis test was specifically designed to measure changes in sugars attached to IgG, an antibody protein that is found in blood. As a blood draw is much less of an ordeal for patients than a liver biopsy, this was an attractive candidate marker for the test.

“We could classify patients with about 85% to 95% accuracy to fall within those three groups (no fibrosis, early-stage fibrosis, late-stage fibrosis).   -- Anand Mehta, D. Phil.

In the published study, researchers examined blood and biopsy samples provided by Rockey from a group of patients with no, early-stage or late-stage fibrosis. They were able to check the accuracy of the GlycoFibroTyper by comparing its predictions to biopsies from the same patients. The results were very promising.

“We could classify patients with about 85% to 95% accuracy to fall within those three groups,” said Mehta.

“There are other blood tests that people have developed, but they generally don’t work very well – they detect only about 30% to 50% of people with advanced fibrosis,” he said.

GlycoPath is planning to make the test available to clinical and commercial laboratories across the country.

“Glycopath is making the standard reagents and systems that allow anybody to do this in any CLIA (Clinical Laboratory Improvement Amendments)-certified lab, any commercial lab, said Mehta. “While it’s doing that, we’re working to create a clinical network of people who can reproduce this assay in their different places.”

"We listened to the clinician. He got the samples. We did the assay, developed it and published it. This is a good example, in my mind, of what we do and should even do more at MUSC." -- Anand Mehta, D. Phil.

Mehta also noted that the test has drawn the attention of companies conducting clinical trials for drugs to treat liver disease.

“These companies are looking and saying, ‘We have to biopsy patients repeatedly to see if the drug had improvement. That’s not something we want to do. The cost is too much.’ And then, too, patients don’t want to do it. So the trial can’t enroll patients,” said Mehta. “So, drug companies are basically knocking down the door to say, ‘Hey, can we help validate your assay?’”

Such validation by third parties via larger blinded studies will be crucial to help the new test to advance to the clinic, said Mehta.

The collaboration between clinicians and basic science researchers is something that Mehta and Rockey see as invaluable for developing new and useful clinical tests.

“We listened to the clinician. He got the samples. We did the assay, developed it and published it. This is a good example, in my mind, of what we do and should even do more at MUSC,” said Mehta.

“Indeed, this work is an excellent example of collaborative science, where we meld the power of basic science innovation with the clinical arena, and is an approach that I’m extremely excited about,” said Rockey.

Reference

Scott DA, Wang M, Grauzam S, et al. GlycoFibroTyper: A Novel Method for the Glycan Analysis of IgG and the Development of a Biomarker Signature of Liver Fibrosis. Front Immunol. 2022;13:797460. Published 2022 Feb 7. doi:10.3389/fimmu.2022.797460