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Low Accuracy of FIB-4 and NAFLD Fibrosis Scores for Screening for Liver Fibrosis in the Population

Graupera, Isabel; Thiele, Maja; Serra-Burriel, Miquel; Caballeria, Llorenç; Roulot, Dominique; Wong, Grace Lai-Hung; Fabrellas, Núria; Guha, Indra Neil; Arslanow, Anita; Expósito, Carmen; Hernández, Rosario; Aithal, Guruprasad Padur; Galle, Peter R.; Pera, Guillem; Wong, Vincent Wai-Sun; Lammert, Frank; Ginès, Pere; Castera, Laurent; Krag, Aleksander

Low Accuracy of FIB-4 and NAFLD Fibrosis Scores for Screening for Liver Fibrosis in the Population Thumbnail


Isabel Graupera

Maja Thiele

Miquel Serra-Burriel

Llorenç Caballeria

Dominique Roulot

Grace Lai-Hung Wong

Núria Fabrellas

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Professor of Hepatology

Anita Arslanow

Carmen Expósito

Rosario Hernández

Peter R. Galle

Guillem Pera

Vincent Wai-Sun Wong

Frank Lammert

Pere Ginès

Laurent Castera

Aleksander Krag


Background & Aims

Fibrosis-4 (FIB-4) and the nonalcoholic fatty liver disease fibrosis score (NFS) are the 2 most popular noninvasive blood-based serum tests proposed for widespread fibrosis screening. We therefore aimed to describe the accuracy of FIB-4 and NFS to detect elevated liver stiffness as an indicator of hepatic fibrosis in low-prevalence populations.


This study included a total of 5129 patients with concomitant measurement of FIB-4, NFS, and liver stiffness measurement (LSM) by Fibroscan (Echosens, France) from 5 independent population-based cohorts from Spain, Hong Kong, Denmark, England, and France; 3979 participants from the general population and 1150 from at-risk cohorts due to alcohol, diabetes, or obesity. We correlated LSM with FIB-4 and NFS, and calculated pre- and post-test predictive values of FIB-4 and NFS to detect elevated LSM at 8 kPa and 12 kPa cutoffs. The mean age was 53 ± 12 years, the mean body mass index was 27 ± 5 kg/m2, and 2439 (57%) were women. One in 10 patients (552; 11%) had liver stiffness ≥8 kPa, but 239 of those (43%) had a normal FIB-4, and 171 (31%) had normal NFS. The proportion of false-negatives was higher in at-risk patients than the general population. FIB-4 was false-negative in 11% of diabetic subjects, compared with 2.5% false-negatives with NFS. Waist circumference outperformed FIB-4 and NFS for detecting LSM ≥8 kPa in the general population. Almost one-third (28%–29%) of elevated FIB-4/NFS were false-positive in both the general population and at-risk cohorts.


FIB-4 and NFS are suboptimal for screening purposes due to a high risk of overdiagnosis and a non-negligible percentage of false-negatives, especially in patients with risk factors for chronic liver disease. Waist circumference emerged as a potential first step to identify patients at risk for liver fibrosis in the general population.


Graupera, I., Thiele, M., Serra-Burriel, M., Caballeria, L., Roulot, D., Wong, G. L., …Krag, A. (2022). Low Accuracy of FIB-4 and NAFLD Fibrosis Scores for Screening for Liver Fibrosis in the Population. Clinical Gastroenterology and Hepatology, 20(11), 2567-2576.e6.

Journal Article Type Article
Acceptance Date Jun 5, 2022
Online Publication Date Oct 25, 2022
Publication Date Nov 1, 2022
Deposit Date Nov 19, 2022
Publicly Available Date Nov 29, 2022
Journal Clinical Gastroenterology and Hepatology
Print ISSN 1542-3565
Electronic ISSN 1542-7714
Peer Reviewed Peer Reviewed
Volume 20
Issue 11
Pages 2567-2576.e6
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