Exploring ELF’s Potential for Predicting Fibrosis Severity, With Cecilia Katzenstein

New real-world data are providing clinicians with an overview of the Enhanced Liver Fibrosis (ELF) test’s viability for predicting liver stiffness, supporting its potential use to identify patients eligible for metabolic dysfunction-associated steatohepatitis (MASH) therapies.

The research was presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025 by Cecilia Katzenstein, an MD/MPH student at Icahn School of Medicine at Mount Sinai. In the study, ELF outperformed vibration-controlled transient elastography (VCTE) and FIB-4 in predicting liver stiffness and performed most consistently across all subgroups, adding predictive value when FIB-4 was inconclusive.

Noninvasive tests (NITs) serve as alternative options to liver biopsy for the diagnosis of hepatic fibrosis. Current guidelines support the use of FIB-4, aspartate platelet ratio index, and liver stiffness measurement by transient and magnetic resonance elastography for noninvasive liver disease assessment, but these tools can be limited by indeterminate ranges and varying diagnostic performance among different patient populations.

“For us, usually in a primary care setting, we'll start thinking first about FIB-4, which uses common lab components that primary care physicians have access to,” Katzenstein explained about currently used NITs. “Escalating down the pathway, next, we would think about FibroScan or VCTE, which requires machinery and personnel to operate it, and then we think a little bit about ELF, which is what we are looking into in our study.”

To test the real-world utility of ELF for identifying patients with at-risk MASH, investigators conducted a prospective study of patients evaluated for MASH at an urban, academic center who underwent FIB-4, VCTE, ELF, and MRE as part of routine care. Due to right-skewness and nonlinearity, ELF and MRE values were log-transformed to improve model fit, and model assumptions were confirmed via regression diagnostics.

Spearman’s correlation assessed ELF–MRE association. Investigators used univariable linear regression on log-transformed values, with β interpreted as percent change in stiffness per 1% change in ELF, an approach applied consistently in subgroup analyses by diabetes status, sex, age, and indeterminate FIB-4 value.

Among the cohort (n = 57), the mean age was 57.5 years (SE, 2.0); 57% were female, and 60% were Hispanic. MRE stiffness averaged 3.8 kPa (SE, 0.20) and ELF 9.5 (SE, 0.17). Investigators noted ELF was strongly correlated with MRE (ρ = 0.68; P <.001).

In a log-log regression, a 1% increase in ELF was associated with a 2.01% increase in liver stiffness, explaining 50% of the variance. VCTE and FIB-4 explained 48% and 23% of variance, respectively.

Subgroup analyses confirmed ELF’s strong predictive power. In patients with diabetes, ELF explained 51% variance. In males, this was 54%. Predictive strength was greatest in younger patients and declined with age.

ELF additionally outperformed FIB-4 in all groups and VCTE in women and patients < 40 years of age. In those with indeterminate FIB-4, ELF showed a stronger association with MRE than VCTE.

“Our study is ongoing and we're continuing to recruit patients, so having a bigger sample size will let us dive more into demographic groups, different comorbidities,” Katzenstein said. “I think it could also be interesting to look at ELF in conjunction with FIB-4. Presumably, in all of the patients who you'd be getting the ELF test on, you'd also have the common lab components to calculate their FIB-4 and seeing how these 2 scores maybe work together to prognosticate and predict fibrosis progression, and whether or not patients have F2 or F3 fibrosis and might be candidates for treatment, could be an interesting future direction.”

Editors’ note: Katzenstein has no relevant disclosures.

References

1. Katzenstein C, Mageras A, Miller M, et al. Enhanced Liver Fibrosis (ELF) Test Correlates Better with MRE than VCTE in a Real-World Cohort of Patients with Suspected MASH. Presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2025. Washington, DC. November 7-11, 2025.

2. Grady JT, Cyrus JW, Sterling RK. Novel Noninvasive Tests for Liver Fibrosis: Moving Beyond Simple Tests in Metabolic Dysfunction-associated Steatotic Liver Disease. Clinical Gastroenterology and Hepatology. doi:10.1016/j.cgh.2025.02.035