NEW YORK ─ Siemens Healthineers is launching the first prognostic test to obtain authorization in the US to assess the risk of liver disease progression from nonalcoholic steatohepatitis (NASH), in order to help reduce disease prevalence and the number of invasive biopsies performed to assess patients for liver conditions.
The company's Enhance Liver Fibrosis (ELF) Test, which runs on its Advia Centaur XP immunoassay system, provides a numeric score based on the presence of three biomarkers in serum ─ tissue inhibitor of metalloproteinases 1, amino-terminal propeptide of type III procollagen, and hyaluronic acid.
Because the test uses a simple blood draw, it can be made broadly available to gastroenterologists, hepatologists, primary care physicians, and other clinicians assessing liver disease due to NASH, Deepak Nath, head of diagnostics at Siemens Healthineers, said in an interview.
NASH is a type of nonalcoholic fatty liver disease (NAFLD) characterized by inflammation of the liver and liver cell damage, which can cause cirrhosis and hepatocellular carcinoma and indicate a need for liver transplantation.
According to Nath, the high prevalence of both NAFLD and NASH made obtaining authorization for the blood test "an important strategic priority" for Siemens Healthineers.
"NASH doesn't manifest with obvious clinical symptoms and can become a silent killer," he said, adding that a blood test that enables routine monitoring and detects the disease early in its progression can lead to early intervention and better treatment.
About 20 million people in the US are candidates to use its ELF test, Nath said, adding it will become available this spring from Laboratory Corporation of America and Quest Diagnostics through an agreement inked with Siemens Healthineers.
For about 10 years, the test has been available in Europe and other countries that accept CE marking for diagnosis "and to aid in fibrosis staging across a variety of liver disease etiologies ─ not just NASH but, more broadly, NAFLD," Nath said. The launch of the ELF assay in the US follows de novo authorization granted by the US Food and Drug Administration during the summer for use of the test as a prognostic tool to assess the risk of liver disease progression from NASH.
To pursue the authorization, Erlangen, Germany-based Siemens Healthineers collaborated with Gilead Sciences and Galectin Therapeutics, which are conducting clinical trials to assess the safety and efficacy of therapies they are developing for liver disease. In all, the collaborators used data from five clinical trials with a total of 517 patients for the de novo submission, according to Siemens Healthineers.
Because no predicate device was available as a comparison diagnostic test for the assay, Siemens Healthineers had to demonstrate that the assay is "objective, repeatable, and accurate," Nath said.
According to Zobair Younossi, a hepatologist and president of Fairfax, Virginia-based Inova Medicine Services, Siemens Healthineers' ELF assay has demonstrated high performance in numerous clinical studies. Younossi is not affiliated with Siemens Healthineers but uses the EFL test and other modalities to diagnose liver fibrosis and related ailments in clinical practice.
In a recent study published in JAMA Network Open, he and his colleagues said the ELF test can be used in gastroenterology, endocrinology, and primary care practices to identify patients with increased risk of nonalcoholic steatohepatitis who would require aggressive treatment.
In the cross-sectional study involving 829 patients with NAFLD, the investigators used different combinations of cutoff values for the ELF test's numeric score to rule in advanced fibrosis, and obtained positive and negative predictive values of 95 percent, Younossi said.
The main advantage of the blood test is that it can be used to reduce the number of biopsies required to access the progression of patients with liver disease, he said. An invasive liver biopsy is the gold standard and has been used historically to assess progression to liver fibrosis from NASH, but patients and their doctors are eager to try alternate ways for monitoring, he noted.
The ELF test, which uses a simple blood draw, makes repeat testing more affordable and enables broader use, Younossi said.
The test has a current procedural terminology (CPT) code for reimbursement and Medicare provides reimbursement at $176 per assay, according to Siemens Healthineers.
While the firm has the advantage that not many other tests for NASH have been commercialized, a few companies are developing diagnostic and prognostic tests for the condition, including Loos, France-based Genfit, which has a licensing agreement to enable Labcorp to develop and commercialize a blood-based molecular diagnostic test using its multianalyte technology.
Also, Charleston, South Carolina-based GlycoPath is developing MALDI-based assays that analyze protein glycosylation patterns for diagnosing liver fibrosis in patients at risk for disease conditions that include hepatitis B and C and NASH. Palo Alto, California-based firm DiscernDx is developing a multiomics diagnostics assay for NASH, and the Massachusetts Institute of Technology spinout Glympse Bio has initiated studies to detect patients' responses to treatments that are in development for NASH.
For clinicians looking to assess liver fibrosis due to NASH, the most popular alternatives to biopsy are not IVD tests, Younossi said, adding that the closest competitors to the ELF assay are elastography tests that measure liver stiffness using radiology. Elastography methods generally perform well in ruling out liver fibrosis but their results can vary with patient differences such as levels of obesity. They are also expensive and not broadly available, Younossi said.
Clinicians also use the Fibrosis-4 (FIB-4) score to assess patents suspected of advanced fibrosis due to NASH. The score, which Younossi said can be combined with the ELF test as part of a clinical workup, is based on a formula that includes measurements of enzymes associated with liver health as well as platelet count and a patient's age to estimate liver scarring.
With no medications currently available to treat NASH, a healthy diet and exercise, the best available treatments options, are "very effective and emphasize the need for a blood test to identify who needs treatment," Younossi said.
Nonetheless, a broad range of medicines are in development for NASH and related liver disease conditions, and if treatments are approved, noninvasive blood tests will also be needed to monitor the progression of patients on such therapies, he added.