Test Details
Result Turnaround Time
8 - 12 days
Turnaround time is defined as the usual number of days from the date of pickup of a specimen for testing to when the result is released to the ordering provider. In some cases, additional time should be allowed for additional confirmatory or additional reflex tests. Testing schedules may vary.
Use
NASH FibroSure® Plus is a noninvasive assessment of liver status in patients with nonalcoholic fatty liver disease (NAFLD). Quantitative results of 10 biochemicals in combination with age and gender are analyzed using a computational algorithm to provide a quantitative surrogate marker (0.0-1.0) of liver fibrosis (Metavir F0-F4), hepatic steatosis (0.0-1.0, S0-S3) and nonalcoholic steatohepatitis (NASH) (0.0-0.75, N0-N2). The absence of steatosis (S<0.41) precludes the diagnosis of NASH, now known as metabolic dysfunction-associated steatohepatitis (MASH).
The Enhanced Liver Fibrosis (ELF™) blood test is a simple, accurate, noninvasive 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 nonalcoholic steatohepatitis (NASH), now called metabolic dysfunction- associated steatohepatitis (MASH), 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 across time.
Special Instructions
The patient's age and gender must be submitted, but the patient's height and weight are not required for NASH FibroSure® Plus testing.
Limitations
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 5-10% 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
Custom Additional Information
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.
Specimen Requirements
Specimen
Serum
Volume
4 mL
Minimum Volume
3 mL
Container
Gel-barrier tube or red-top tube
Collection Instructions
Complete clot formation should take place before centrifugation. Serum should be physically separated from cells as soon as possible with a maximum limit of two hours from the time of collection. Transfer serum to a transfer tube.
Stability Requirements
| Temperature | Period |
|---|---|
| Room temperature | 48 hours (stability provided by manufacturer or literature reference) |
| Refrigerated | NASH: 72 hours (stability provided by manufacturer or literature reference) ELF reflex: 7 days (stability provided by manufacturer or literature reference) |
| Frozen | 7 days (stability provided by manufacturer or literature reference) |
| Freeze/thaw cycles | Stable x1 (stability provided by manufacturer or literature reference) |
Storage Instructions
Refrigerate.
Patient Preparation
Patient should be fasting for at least eight hours.
Causes for Rejection
Plasma specimen; gross hemolysis; gross lipemia; improper labeling; nonfasting specimen; patient younger than 14 years of age. Heterophilic antibodies in human serum can react with reagent immunoglobulins and interfere with immunoassays.
References
Poynard T, Munteanu M, Charlotte F, et al. Diagnostic performance of a new noninvasive test for nonalcoholic steatohepatitis using a simplified histological reference. Eur J Gastroenterol Hepatol. 2018 May;30(5):569-577. PubMed 29406435
Poynard T, Peta V, Munteanu M, et al. The diagnostic performance of a simplified blood test (SteatoTest-2) for the prediction of liver steatosis. Eur J Gastroenterol Hepatol. 2019 Mar;31(3):393-402. PubMed 30516570
Ratziu V, Massard J, Charlotte F, et al. Diagnostic value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol. 2006 Feb 14;6:6. PubMed 16503961
Footnotes
1. Day J, Patel P, Parkes J, Rosenberg W. Derivation and performance of standardized Enhanced Liver Fibrosis (ELF) test thresholds for the detection and prognosis of liver fibrosis. J Appl Lab Med. 2019 Mar;3(5):815-826. PubMed 31639756
2. National Guideline Centre (UK). Non-Alcoholic Fatty Liver Disease: Assessment and Management. London: National Institute for Health and Care Excellence (UK); July 2016.
3. Vali Y, Lee J, Boursier J, et al. Enhanced liver fibrosis test for the non-invasive diagnosis of fibrosis in patients with NAFLD: A systematic review and meta-analysis. J Hepatol. 2020 Aug;73(2):252-262. PubMed 32275982
4. Lichtinghagen R, Pietsch D, Bantel H, Manns MP, Brand K, Bahr MJ. The Enhanced Liver Fibrosis (ELF) score: normal values, influence factors and proposed cut-off values. J Hepatol. 2013 Aug;59(2):236-242. PubMed 23523583