NEW YORK – London-based startup Metadeq has developed a noninvasive blood test with the goal of bypassing the need for liver biopsies when diagnosing the severity of liver disease.
The test, developed with collaborators from King's College London, is intended to measure and stage nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and liver fibrosis, which can eventually progress to cirrhosis of the liver. According to Giorgio Castagneto Gissey, the founder and president of Metadeq, approximately 150 million people have NASH, but there's no way to know the exact number because the traditional method of testing — using a liver biopsy — isn't scalable.
While liver biopsy is the gold standard for diagnosing and staging NASH, there are hurdles to obtaining one: The procedure must be done in a clinic or hospital, the turnaround time is long, and the cost can be prohibitive, Castagneto Gissey said.
Geltrude Mingrone, a professor of diabetes and nutrition at King's College London who helped develop the test, noted that liver biopsies can be dangerous and lead to complications for the patient. They also require a pathologist to analyze the biopsy, which takes additional time and effort.
Metadeq's test, called Hepar-Q, returns results in less than an hour and doesn't require anything more than a blood draw. Although he declined to give a cost estimate for the test, Castagneto Gissey said it would be "significantly cheaper" than a liver biopsy.
The technology could "completely replace" liver biopsy "as the standard of diagnosis for both NASH and liver fibrosis," he said.
Hepar-Q leverages flow cytometry and uses a monoclonal antibody to target two specific proteins and measure their levels. It then runs the results through a machine learning algorithm to predict the presence or absence of NASH or liver fibrosis and its stages. The diseases are a spectrum, beginning with NAFLD that progresses to NASH, which can then move to liver fibrosis and eventually cirrhosis.
The first biomarker, perilipin-2, is a representation of fat accumulation and inflammation in the liver, and higher PLIN2 levels indicate more severe NASH, Mingrone said. The other biomarker, RAB14, is associated with regulating collagen in the liver, and lower levels of RAB14 correlate to a higher degree of liver fibrosis.
In a study published in Gut last month that focused on the test's performance in NASH and liver fibrosis, the algorithm using PLIN2 combined with other clinical factors to measure NASH showed sensitivity between 88 percent and 95 percent, with specificity between 90 percent and 100 percent.
In the same study, which included 250 patients that had either NAFLD or NASH, the algorithm that included RAB14 with other clinical factors to predict liver fibrosis had sensitivity between 99 percent and 100 percent, with specificity between 90 percent and 96 percent. Both algorithms were compared to liver biopsy results, Castagneto Gissey said.
Although the current test uses flow cytometry to measure the presence of each biomarker, the company is developing an ELISA version, which would make the test more scalable, he added. The current test can perform about 800 diagnoses per day on one machine, but an ELISA kit could allow for "thousands and thousands" of tests per day.
Metadeq isn't the only company working on blood tests for liver disease, however. SomaLogic's SOMAscan proteomics platform was used to quantify serum proteins for liver fibrosis in a paper published last year in Hepatology Communications, while DiscernDx is developing a noninvasive liquid biopsy test to determine which patients with NAFLD are unlikely to progress to NASH. Siemens Healthineers, meantime, received de novo authorization from the US Food and Drug Administration last August for its Enhanced Liver Fibrosis blood test to determine the likelihood that patients with advanced fibrosis will progress to cirrhosis and liver-related clinical events. Laboratory Corporation of America also licensed a blood test from French biotech company Genfit to determine whether patients with high-risk NASH are at risk of progressing to more severe conditions.
Right now, Metadeq's focus is on commercializing the test in Europe and the US, and the company is "progressing" toward submitting the assay for approval from the FDA, along with CE marking, with expectations for approval in the next two to three years, Castagneto Gissey said. However, the company will eventually look to expand to other countries, and the technology behind the test is either patented or has patent applications filed in multiple countries, he noted.
The business model for the US, where Metadeq has a subsidiary, involves setting the company up as a blood test service company, conducting the test in its own laboratory after sending out blood collection kits. Castagneto Gissey said he sees the firm starting off by providing the test to pharmaceutical companies that are developing drugs for liver disease to aid in clinical trials, as well as moving into the hospital and clinical markets. In Europe, however, the firm will likely rely on distribution partners to commercialize the test.
As of now, there are no FDA-approved drugs for NASH, Mingrone added, partially because it is difficult to find patients with severe NASH, since performing liver biopsies on all patients to measure the impact of a drug isn't feasible. Hepar-Q could be useful in determining which patients would be the best candidates for a drug trial, making it possible to find a cure, or at least a treatment, she said.
It would also be particularly helpful in determining the prevalence of NAFLD and NASH. The difficulty of conducting liver biopsies means that only at-risk patients, such as those with obesity or type 2 diabetes, undergo them, leading experts to extrapolate the prevalence of the disease from just those patients. We "probably have the wrong figures in excess or in defect," Mingrone said. With this test, "we can gain information about the real prevalence of NASH and NAFLD in the general population" and monitor the proteins in the same way that cholesterol and triglycerides are monitored to track a patient's risk of developing the disease, she said.
In addition to the Hepar-Q test, which covers the "whole spectrum" of NAFLD, NASH, and liver fibrosis together, the firm is working on three other proprietary tests that focus on NAFLD, NASH, and liver fibrosis individually, he said. The technology could also be applied to other metabolic diseases, Castagneto Gissey said.
"It provides doctors and patients with a way better tool to monitor liver health, and this could well be the future gold standard of NAFLD, NASH, and liver fibrosis diagnosis," Castagneto Gissey added.