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

• Published in: Clinical gastroenterology and hepatology Vol. 20; no. 11; pp. 2567 - 2576.e6
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2022
• Subjects: Adult; Aged; Alcoholic Liver Disease; Biopsy - adverse effects; Female; Fibrosis; Gastroenterology and Hepatology; Humans; Liver - pathology; Liver Cirrhosis - etiology; Liver Fibrosis; Male; Middle Aged; NITs; Non-alcoholic Fatty Liver Disease - complications; Nonalcoholic Fatty Liver Disease; Noninvasive Fibrosis Scores; Prevalence; Screening; Severity of Illness Index; Transient Elastography; NAFLD; HK; DK; ALT; FR; AUC; Liver Fibrosis; NPV; UK; ULN; PPV; Noninvasive Fibrosis Scores; NFS; BMI; Transient Elastography; LSM; ES; Screening; TE; Alcoholic Liver Disease; Nonalcoholic Fatty Liver Disease; NIT; ALD; FIB-4; NITs; positive predictive value; Fibrosis-4 test; Hong Kong; alanine aminotransferase; non-invasive tests; France; liver stiffness measurement; area under the receiving operating characteristics curve; body mass index; NAFLD fibrosis score; United Kingdom; Spain; upper limit of normal; Denmark; negative predictive value
• ISSN: 1542-3565; 1542-7714; 1542-7714
• DOI: 10.1016/j.cgh.2021.12.034

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.