Assessment of treatment response in non-alcoholic steatohepatitis using advanced magnetic resonance imaging

Abstract

Background: Magnetic resonance imaging-derived measures of liver fat and volume are emerging as accurate, non-invasive imaging biomarkers in non-alcoholic steatohepatitis (NASH). Little is known about these measures in relation to histology longitudinally.

Aim: To examine any relationship between MRI-derived proton-density fat-fraction (PDFF), total liver volume (TLV), total liver fat index (TLFI), vs. histology in a NASH trial.

Methods: This is a secondary analysis of a 24-week randomised, double-blind, placebo-controlled trial of 50 patients with biopsy-proven NASH randomised to oral ezetimibe 10 mg daily (n = 25) vs. placebo (n = 25). Baseline and post-treatment anthropometrics, biochemical profiling, MRI and biopsies were obtained.

Results: Baseline mean PDFF correlated strongly with TLFI (Spearman's ρ = 0.94, n = 45, P < 0.0001) and had good correlation with TLV (ρ = 0.57, n = 45, P < 0.0001). Mean TLV correlated strongly with TLFI (ρ = 0.78, n = 45, P < 0.0001). After 24 weeks, PDFF remained strongly correlated with TLFI (ρ = 0.94, n = 45, P < 0.0001), maintaining good correlation with TLV (ρ = 0.51, n = 45, P = 0.0004). TLV remained strongly correlated with TLFI (ρ = 0.74, n = 45, P < 0.0001). Patients with Grade 1 vs. 3 steatosis had lower PDFF, TLV, and TLFI (P < 0.0001, P = 0.0003, P < 0.0001 respectively). Regression analysis of changes in MRI-PDFF vs. TLV indicates that 10% reduction in MRI-PDFF predicts 257 mL reduction in TLV.

Conclusions: The MRI-PDFF and TLV strongly correlated with TLFI. Decreases in steatosis were associated with an improvement in hepatomegaly. Lower values of these measures reflect lower histologic steatosis grades. MRI-derived measures of liver fat and volume may be used as dynamic and more responsive imaging biomarkers in a NASH trial, than histology.

Conflict of interest statement

Conflict of Interest: None disclosed.

© 2017 John Wiley & Sons Ltd.

Figures

Figure 1. Cross-sectional relationships between advanced MRI-derived measures at baseline and week 24

At baseline, mean PDFF correlated strongly with TLFI (Spearman’s ρ = 0.94, n=45, P

Figure 2. Relationship of advanced MRI-derived measures and histologic steatosis grade at baseline and week 24

At baseline, patients with Grade 1 steatosis (n=14) on histology had a median PDFF (%) of 9.0 (3.3), versus 13.5 (6.8) in Grade 2 steatosis (n=13), and 22.4 (10.0) in those with Grade steatosis (n=23), P

Figure 3. Mean MRI-PDFF and TLV by fibrosis stage at baseline and week 24

(a) At baseline, mean MRI-PDFF % (±SD) with fibrosis stage 0, 1, 2, 3, 4 were 17.8 (9.3), 18.2 (9.3), 17.5 (8.5), 15.7 (5.5), and 8.1 (2.2), respectively. Mean TLV mL (±SD) were 1733.9 (579.0), 1770.5 (398.9), 2112.4 (588.5), 1967.9 (583.7), and 1569.2 (23.0), respectively. (b) At week 24, the trend was similar. Mean MRI-PDFF (%) with fibrosis stage 0, 1, 2, 3, 4 were 11.8 (8.0), 17.4 (5.2), 19.0 (7.0), 13.0 (5.7), 9.2 (0.0), respectively. Mean TLV (mL) were 1710.8 (632.9), 1745.7 (359.1), 1930.8 (399.1), 2057.4 (570.2), and 1862.2 (0.0), respectively.

Figure 4. Longitudinal changes in TLV versus MRI-PDFF

Over 24 weeks, strong correlation was observed between changes in MRI-PDFF vs. changes in TLV, in a pooled analysis, with Spearman’s ρ=0.64, PΔTLV = 25.7(ΔMRI-PDFF) + 50.3.