Quantitative Ultrasound Biomarkers to Assess Nonalcoholic Fatty Liver Disease

Objectives: Nonalcoholic fatty liver disease (NAFLD) is a high prevalence disorder that is often asymptomatic in the early stages and even in the development of nonalcoholic steatohepatitis (NASH) and compensated Advanced Chronic Liver Disease (cACLD). Non-invasive early detection of NAFLD remains a challenge.
The aim of the study was to assess the diagnostic performance of quantitative ultrasound (QUS) biomarkers in assessing hepatic steatosis and cACLD using magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE) as references.

Methods: After obtaining IRB approval and written informed consent, we prospectively recruited 125 adult volunteers (48 men and 77 women, mean age 54y) who underwent liver QUS, MRI, and laboratory tests within 30 days. Based on MRI-PDFF and MRE, we divided 125 participants into three groups (normal livers, NAFLD, and cACLD). We examined diagnostic performance of ultrasound attenuation coefficient (AC), normalized local variance (NLV), Superb Microvascular Imaging-based vascularity index (SMI-VI) for determining the variable grade of hepatic steatosis, and tested shear wave velocity (SWV) and shear wave dispersion slope (SWD) for determining cACLD using the area under the receiver operating characteristic curve (AUC) analysis. We also analyzed correlations of QUS biomarkers to MRI and biochemical parameters using the Spearman correlation coefficient and tested the differences in QUS biomarkers among the three groups using one-way ANOVA.

Results : There were 22 participants with healthy livers, 78 with NAFLD without fibrosis, and 25 with cACLD. We observed significant differences in AC, NLV, SMI-VI, and SWV among the three groups. The AUC of AC, NLV, and SMI-VI for determining ≥ mild steatotic livers (MRI-PDFF ≥5%) was 0.95, 0.90, and 0.92, respectively. The AUC of SWV and SWD for determining cACLD was 0.93 and 0.66, respectively. Quantitative ultrasound biomarkers (AC, NLV, SMI-VI, SWV) demonstrated positive or negative correlation with MRI-PDFF in the NAFLD group (AC: r= 0.91, NLV: r= -0.74, SMI-VI: r= -0.86, SWV: r= -0.56). There was a significant difference in the regression slope of AC to MRI-PDFF in livers with and without ≥F1 liver fibrosis (p=0.02).

Conclusions: The main limitations of the study included that the number of participants with cACLD was small and liver biopsy pathology was not available for the diagnosis of NASH.
Study results suggest that ultrasound AC, NLV, and SMI-VI have high sensitivity and specificity to determine and grade hepatic steatosis in NAFLD. SWV and SWD have moderate to high sensitivity and specificity to determine ≥F1 liver fibrosis. Liver fibrosis may affect AC in quantifying fat content in the liver.