Head-to-head comparison of magnetic resonance elastography-based liver stiffness, fat fraction, and T1 relaxation time in identifying at-risk NASH

Abstract

Background and aims: The presence of at-risk NASH is associated with an increased risk of cirrhosis and complications. Therefore, noninvasive identification of at-risk NASH with an accurate biomarker is a critical need for pharmacologic therapy. We aim to explore the performance of several magnetic resonance (MR)-based imaging parameters in diagnosing at-risk NASH.

Approach and results: This prospective clinical trial (NCT02565446) includes 104 paired MR examinations and liver biopsies performed in patients with suspected or diagnosed NAFLD. Magnetic resonance elastography-assessed liver stiffness (LS), 6-point Dixon-derived proton density fat fraction (PDFF), and single-point saturation-recovery acquisition-calculated T1 relaxation time were explored. Among all predictors, LS showed the significantly highest accuracy in diagnosing at-risk NASH [AUC LS : 0.89 (0.82, 0.95), AUC PDFF : 0.70 (0.58, 0.81), AUC T1 : 0.72 (0.61, 0.82), z -score test z >1.96 for LS vs any of others]. The optimal cutoff value of LS to identify at-risk NASH patients was 3.3 kPa (sensitivity: 79%, specificity: 82%, negative predictive value: 91%), whereas the optimal cutoff value of T1 was 850 ms (sensitivity: 75%, specificity: 63%, and negative predictive value: 87%). PDFF had the highest performance in diagnosing NASH with any fibrosis stage [AUC PDFF : 0.82 (0.72, 0.91), AUC LS : 0.73 (0.63, 0.84), AUC T1 : 0.72 (0.61, 0.83), |z| <1.96 for all].

Conclusion: Magnetic resonance elastography-assessed LS alone outperformed PDFF, and T1 in identifying patients with at-risk NASH for therapeutic trials.

Graphical abstract

FIGURE 1

Example images. The first row represents images from a patient with non-NASH (female, 45 y, BMI = 30.2 kg/m²): PDFF = 2.1%, LS = 1.69 kPa, T1 = 794 ms. The second row represents images from a patient with NASH (female, 48 y, BMI = 32.8 kg/m²): PDFF = 20.4%, LS = 2.43 kPa, T1 = 1004 ms. The third row represents images from a patient with at-risk NASH (male, 60 y, BMI = 27.5 kg/m²): PDFF = 10.6%, LS = 3.94 kPa, T1 = 858 ms. The white dotted line illustrates the contour of the liver not the ROI for measurements. Abbreviations: BMI, body mass index; LS, liver stiffness; ROI, regions of interest; PDFF, proton density fat fraction.

FIGURE 2

Scatter plots of PDFF and T1 for differentiating steatosis grades and NASH. The black line indicates the median value. *p < 0.05; **p < 0.01; ***p < 0.0001. Abbreviation: PDFF, proton density fat fraction.

FIGURE 3

Scatter plots of LS and T1 for differentiating clinically significant fibrosis (≥stage 2) and at-risk NASH. The black line indicates the median value. *p < 0.05; **p < 0.01; ***p < 0.0001. Abbreviation: LS, liver stiffness.

FIGURE 4

Correlations between PDFF and T1/LS. **p < 0.01. Abbreviations: LS, liver stiffness; PDFF, proton density fat fraction.

FIGURE 5

Summary of AUC for nominal logistic models for distinguishing NASH and at-risk NASH. *z > 1.96 when compared with LS in diagnosing at-risk NASH. Abbreviations: LS, liver stiffness; PDFF, proton density fat fraction.