Background: Patients with nonalcoholic fatty liver disease (NAFLD) and fibrosis stage ≥ 2 (F2-F4) are at risk for adverse outcomes and considered to be candidates for clinical trials. We aimed to use two NITs combined to rule in and rule out fibrosis stages F2-F4 among patients with NAFLD.

Methods: Data were collected from patients with NAFLD diagnosis. The Enhanced Liver Fibrosis (ELF) and FIB-4 NITs were calculated. Liver biopsies were read by 1 hepatologist; scored by NASH CRN criteria. Significant fibrosis stage was ≥ F2, advanced fibrosis was ≥ F3.

Results: There were 463 NAFLD patients: 48±13 years old, 31% male, 35% type 2 diabetes, 39% had significant fibrosis and 24% advanced fibrosis. In comparison to those without significant fibrosis, patients with significant fibrosis were older (mean age 52 vs. 45 years) , more commonly male (38% vs. 26%) , and had more components of metabolic syndrome (type 2 diabetes, hypertension, hyperlipidemia) as well as higher ELF and FIB-4 scores; similar trends were observed for patients with vs. without advanced fibrosis (p<0.05) . The performance of the two NITs in identifying NAFLD patients with significant fibrosis was as follows: AUC (95% CI) = 0.78 (0.74-0.82) for ELF, 0.79 (0.75-0.83) for FIB-4; for advanced fibrosis AUC = 0.81 (0.77-0.85) for ELF, 0.83 (0.79 - 0.86) for FIB-4. A combination of ELF score ≥9.8 and FIB-4 ≥1.96 returned PPV of 95% which can reliably rule in significant fibrosis (sensitivity 22%, specificity >99%) , while an ELF score ≥7.7 and FIB-4 ≥0.30 had NPV of 95% which can be used to rule out significant fibrosis (sensitivity 98%, specificity 22%) . For advanced fibrosis, similar rules were ELF ≥9.8 and FIB-4 ≥2.90 (PPV 95%, sensitivity 18%, specificity >99%) to rule in; ELF ≥7.2 and FIB-4 ≥0.74 (NPV 95%, sensitivity 92%, specificity 49%) to rule out.

Conclusions: The combination of ELF and FIB-4 can provide an easy algorithm with high predictive value to detect significant or advanced fibrosis in NAFLD.


Z.Younossi: Consultant; Bristol-Myers Squibb Company, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Quest Diagnostics, Siemens. S.Felix: None. T.Jeffers: Stock/Shareholder; Neurometrix. E.Younossi: None. F.Nader: None. A.Racila: None. B.P.Lam: Consultant; Intercept Pharmaceuticals, Inc. M.Stepanova: None.

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