Enhanced Liver Fibrosis (ELF)™ Test

Serum

2.5 mL

1 mL

Gel-barrier tube or red-top tube

The Enhanced Liver Fibrosis (ELF™) blood test is a simple, accurate, non-invasive test that provides a simple, unitless numeric score that is generated via an algorithm for use in advanced liver fibrosis. It is indicated as a prognostic marker in conjunction with other laboratory findings and clinical assessments in patients with advanced fibrosis (F3 or F4) due to non-hepatitis (NASH) to assess the likelihood of progression to cirrhosis and liver-related clinical events.¹ Because ELF™ uses a blood sample rather than a biopsy, it can be used routinely for the same patient over time.

Currently, there are no clear screening guidelines for Non-Alcoholic Fatty Liver Disease (NAFLD). 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 5-10% 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

The ELF™ test consists of three fully automated, two-site sandwich immunoassays using direct chemiluminometric technology. The component assays use two monoclonal mouse antibodies: The first antibody is an acridinium ester-labeled antibody. The second antibody is a biotin-labeled antibody. The solid phase contains streptavidin-coated paramagnetic particles. The ELF™ score is derived from an algorithm that combines PIIINP, TIMP-1, and HA. ELF™ is a trademark of Siemens Healthcare Diagnostics.

ELF™ Score Interpretation:

Risk cut-offs to assess the likelihood of progression to cirrhosis and liver-related clinical events within 3.9 years following baseline ELF score (IQR: 14.0-22.4 months):⁵

The Enhanced Liver Fibrosis (ELF™) test measures three direct markers of liver fibrosis: hyaluronic acid (HA), Type III procollagen peptide (PIIINP), and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1). HA is a glycosaminoglycan that is produced by hepatic stellate cells, PIIINP is a marker of early fibrogenesis and inflammation, and TIMP-1 is the circulating inhibitor of MMP enzymes that can enhance fibrogenesis. Together, these assays measure qualitative and quantitative changes in the extracellular matrix (ECM). The ECM refers to a set of macromolecules that comprise the extracellular scaffolding of the liver. Some ECM markers reflect fibrogenesis and others reflect fibrosis regression, allowing for a dynamic evaluation of ECM activity.

The ELF™ score is derived from an algorithm that combines for HA, PIIINP, and TIMP-1.