Liver and Bile

J Hepatol. 2023;79(2):277–86

Kjaergaard M, Prier Lindvig K, Holtz Thorhauge K, Andersen P, Kragh Hansen J, Kastrup N, Møller Jensen J, Dalby Hansen C, Johansen S, Israelsen M, Torp N, Beck Trelle M, Shan S, Detlefsen S, Antonsen S, Ellegaard Andersen J, Graupera I, Ginés P, Thiele M, Krag A

Using the ELF test, FIB-4 and NAFLD fibrosis score to screen the population for liver disease


Background and aims: There is a need for accurate biomarkers of fibrosis for population screening of alcohol-related and non-alcoholic fatty liver disease (ALD, NAFLD). The authors compared the performance of the enhanced liver fibrosis (ELF) test to the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS), using transient elastography (TE) as the reference standard.
Methods: They prospectively included participants from the general population, and people at risk of ALD or NAFLD. Screening positive participants (TE ≥ 8 kPa) were offered a liver biopsy. Concomitant ELF, FIB-4, and NFS were measured using validated cut-offs: ≥ 9.8, ≥ 1.3, ≥ -1.45, respectively.
Results: 3378 participants (1973 general population, 953 at risk of ALD, 452 at risk of NAFLD), with a median age of 57 years (interquartile range, 51–63 years) were included. 242 were screening positive (3.4% in the general population, 12%/14% who were at-risk of ALD/NAFLD, respectively). Most participants with TE < 8 kPa also had ELF < 9.8 (88%) despite a poor overall correlation between ELF and TE (Spearman’s rho = 0.207). ELF was associated with significantly fewer false positives (11%) than FIB-4 and NFS (35% and 45%), while retaining a low rate of false negatives (< 8%). A screening strategy of FIB-4 followed by ELF in indeterminate cases resulted in false positives in 8%, false negatives in 4% and the correct classification in 88% of cases. The authors performed a liver biopsy in 155 of 242 patients (64%) who screened positive, of whom 54 (35%) had advanced fibrosis (≥ F3). ELF diagnosed advanced fibrosis with significantly better diagnostic accuracy than FIB-4 and NFS: AUROC (area under the receiver-operating curve) 0.85 (95% confidence interval [CI]: 0.79–0.92) versus 0.73 (95% CI: 0.64–0.81) and 0.66 (95% CI: 0.57–0.76), respectively.

Conclusion: The enhanced liver fibrosis (ELF) test alone or combined with fibrosis-4 index (FIB-4) for liver fibrosis screening in the general population and at-risk groups reduces the number of futile referrals compared to FIB-4 and NAFLD fibrosis score (NFS), without overlooking true cases.

Prof. Dr. Dr. M. Thiele, FLASH Liver Research Center, Odense University Hospital, Odense C, Denmark, E-Mail: maja.thiele@rsyd.dk

DOI: 10.1016/j.jhep.2023.04.002

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