NASH FibroSure® With Reflex to Enhanced Liver Fibrosis (ELF)™ Test

NASH FibroSure® Plus is recommended for patients with suspected nonalcoholic fatty liver disease, now known as metabolic dysfunction-associated steatotic liver disease (MASLD). It is not recommended for patients with other liver diseases. It is also not recommended in patients with Gilbert disease, acute hemolysis, acute viral hepatitis, drug induced hepatitis, genetic liver disease, autoimmune hepatitis and/or extra-hepatic cholestasis. Any of these clinical situations may lead to inaccurate quantitative predictions of fibrosis. This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

Currently, there are no clear screening guidelines for nonalcoholic fatty liver disease (NAFLD), now known as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). The joint EASL-EASD-EASO guideline reviewed the accuracy of a few serum markers including NFS, FIB-4, and ELF™ test for significant and advanced fibrosis, suggesting that "non-invasive tests may be confidently used for first-line risk stratification to exclude severe disease." The NICE (National Institute for Health and Care Excellence) guideline on assessment and management of NAFLD recommended ELF™ as an accurate biomarker and the most cost-effective test to detect advanced fibrosis.² 

Analysis of multiple prevalences showed that using the ELF™ test at a threshold of 10.51 in primary care settings with disease prevalence of 5% to 10% leads to a very low PPV (0.26 and 0.43, respectively). However, the test can lead to PPV exceeding 0.80 in a high-prevalence setting only (>40%). Yet, at this threshold, the summary estimate of sensitivity in detecting advanced fibrosis, at 0.50, is well below the 1.00 mentioned in the NICE guideline.³ This may question the validity of the NICE recommendation, to "explain to people with an ELF™ score below 10.51 that they are unlikely to have advanced liver fibrosis."² 

Although the available research is too limited to address biomarker accuracy in ruling out significant and advanced fibrosis in patients with NAFLD among the general population, the estimations based on one study suggest that the ELF™ test has a high NPV when the prevalence is lower than 30%.³ This highlights the value of the ELF™ test as a first-line test to exclude advanced fibrosis in the primary care setting and hence to avoid further evaluation of specialists.

However, it is important to note that the high sensitivity of the test (>0.90) comes at the expense of limited specificity (0.30), which, given the low prevalence, means there will be a substantial number of false positive results. This needs to be considered, especially when the test is going to be applied in a clinical setting with low prevalence of the disease, as the large number of false positive results might lead patients to have unnecessary invasive and expensive procedures, like biopsy. 

ELF scores may be influenced by age and gender. Even in an apparently healthy cohort of individuals, a small proportion showed ELF scores beyond the 9.8 cut-off value, emphasizing that lower values need to be interpreted with caution.⁴