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

Abstract

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.

Methods

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.

Conclusions

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.

Citation

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. https://doi.org/10.1016/j.cgh.2021.12.034

• 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
• DOI: https://doi.org/10.1016/j.cgh.2021.12.034
• Public URL: https://nottingham-repository.worktribe.com/output/13165934
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S1542356521013586