Ultrasound-derived fat fraction for the noninvasive quantification of hepatic steatosis: a prospective multicenter study
Liyun Xue, Yuli Zhu, Guangwen Cheng, Hao Han, Nianan He, Lin Chen, Zhe Ma, Haiya Ge, Dong Jiang, Ting He, Rui Shen, Wei Jiang, Liping Sun, Jianxing Zhang, Xiaofeng Cai, Huixiong Xu, Hong Ding
Abstract
Abstract Objectives To prospectively evaluate the diagnostic accuracy of ultrasound-derived fat fraction (UDFF) in quantifying hepatic steatosis, to establish and validate a dual-threshold UDFF classification system, and to investigate its efficacy for risk stratification in body mass index (BMI)-defined subgroups. Materials and methods This prospective multicenter study involved 790 suspected metabolic dysfunction-associated steatotic liver disease (MASLD) participants from April 2023 to November 2024 (derivation: n = 553; validation: n = 237). Liver biopsy histopathology ( n = 342), MRI proton density fat fraction (MRI-PDFF) ( n = 396), or proton magnetic resonance spectroscopy ( 1 H-MRS) ( n = 52) was used as the reference standard. UDFF was compared to noninvasive test Hepatic Steatosis Index (HSI) and Fatty Liver Index (FLI) using area under the curve (AUC). The diagnostic thresholds were optimized to maintain at least 90% sensitivity and specificity in stratifying hepatic steatosis severity. A two-step strategy of UDFF followed by HSI was used to rule in and rule out steatosis at BMI ≥ 23 kg/m 2 subgroup. Results UDFF demonstrated significant correlations with three reference standards (Spearman’s ρ = 0.798–0.847). Comparing with HSI and FLI, UDFF showed higher AUC (0.933, 0.948, and 0.914, respectively) for assessing ≥ S1, ≥ S2 and S3. A clinically practical dual-threshold system effectively classified hepatic steatosis severity. A sequential UDFF/HSI strategy achieved a high positive predictive value (PPV = 95.8%) to rule in hepatic steatosis and lowered the proportion of indeterminate cases (from 18.0 to 7.6%) in patients with BMI ≥ 23 kg/m 2 . Conclusion UDFF is a highly effective noninvasive tool for quantifying hepatic steatosis. A sequential use of UDFF/HSI could improve hepatic steatosis detection in patients with BMI ≥ 23 kg/m 2 . Critical relevance statement The study proposed dual-threshold diagnostic criteria (sensitivity/specificity ≥ 90%) of UDFF for steatosis grading, and established a BMI-stratified risk stratification tool in multi-center cohorts, proving the efficacy of UDFF in noninvasively quantifying liver steatosis. Key Points Early diagnosis of hepatic steatosis holds critical clinical significance. The study proposed dual-threshold ultrasound-derived fat fraction (UDFF) criteria and BMI-stratified steatosis risk prediction strategy. UDFF provided a non-invasive, accurate diagnostic alternative to liver biopsy and MRI. Graphical Abstract