Accuracy of the Enhanced Liver Fibrosis test, and combination of the Enhanced Liver Fibrosis and non‐invasive tests for the diagnosis of advanced liver fibrosis in patients with non‐alcoholic fatty liver disease

Abstract

Aim The Enhanced Liver Fibrosis (ELF) test comprises a logarithmic algorithm combining three serum markers of hepatic extracellular matrix metabolism. We aimed to evaluate the performance of ELF for the diagnosis of liver fibrosis and to compare it with that of liver stiffness measurement (LSM) by FibroScan in non‐alcoholic fatty liver disease. Methods ELF cut‐off values for the diagnosis of advanced fibrosis were obtained using receiver operating characteristic analysis in patients with biopsy‐confirmed non‐alcoholic fatty liver disease (training set; n = 200). Diagnostic performance was analyzed in the training set and in a validation set (n = 166), and compared with that of LSM in the FibroScan cohort (n = 224). Results The area under receiver operating characteristic curve was 0.81 for the diagnosis of advanced fibrosis, and the ELF cut‐off values were 9.34 with 90.4% sensitivity and 10.83 with 90.6% specificity in the training set, and 89.8% sensitivity and 85.5% specificity in the validation set. There was no significant difference in the area under the receiver operating characteristic curve between ELF and LSM (0.812 and 0.839). A combination of ELF (cut‐off 10.83) and LSM (cut‐off 11.45) increased the specificity to 97.9% and the positive predictive value, versus ELF alone. Sequential use of the Fibrosis‐4 index (cut‐off 2.67) and ELF (cut‐off 9.34) increased the sensitivity to 95.9%. Conclusions ELF can identify advanced liver fibrosis in non‐alcoholic fatty liver disease, and its diagnostic accuracy is comparable to that of FibroScan. According to the clinical setting, combinations or sequential procedures using other non‐invasive tests complement the diagnostic performance of ELF for the identification of advanced fibrosis.

Surveillance of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease

“…In Europe, the ELF (enhanced liver fibrosis) test, involving hyaluronic acid and a tissue inhibitor of matrix metalloproteinase type 1 (TIMP-1) along with P3NP (aminoterminal propeptide of type 3 procollagen) is used as the second step [41] (Table 1). A validation study for the efficacy of ELF test was conducted in Japan [42]. In Japan, liver fibrosis markers such as type IV collagen 7S and Mac-2 binding protein glycosylation isomer (M2BPGi) are generally used by hepatologists.…”

The diagnostic conundrum in non-alcoholic fatty liver disease

“…The use in serial combination of TE, NFS and FIB-4 in patients in the grey area of the first test or in those with high values of liver median stiffness (> 9.6 kPa) or low NFS or FIB-4 value (< -1.45 and < 1.3 respectively), increased the diagnostic performance and reduced the diagnostic uncertainty area compared to the use of these tests alone [122]. The combination of ELF test and TE has shown higher diagnostic accuracy for the diagnosis of AF (Sp 97.9%) compared to ELF test alone (Sp 90.6%) [124]. The FibroScan-AST (FAST) score is a novel model (composed of Liver Median Stiffness, controlled attenuated parameter and AST), that showed a good diagnostic performance in identifying NASH with a Nash Activity Score > 4 + F > 2 with a PPV of 0.83-0.81 and an NPV of 0.85-0.71, respectively in derivation and validation cohort [125].…”

Protocol for a phase IV, open-label feasibility study investigating non-invasive markers of hepatic fibrosis in people living with HIV-1 and non-alcoholic fatty liver disease randomised to receiving optimised background therapy (OBT) plus maraviroc or OBT alone

“…24 Other studies have confirmed the accuracy of the ELF score in the assessment of hepatic fibrosis in PLWH and in those with NAFLD. [25][26][27][28] Assuming the SD of the ELF score is 1.12, with 20 patients in each group for the analysis, a difference in ELF of 1 point can be estimated with a 95% CI from 0.6 to 1.4. Assuming an attrition rate of 33%, a target of 30 individuals will be recruited per group.…”