Table 2.
Colesevelam Versus Placebo: Longitudinal Full Liver Fat Mapping Using Magnetic Resonance Imaging Proton Density Fat-Fraction (MRI PDFF) and Magnetic Resonance Spectroscopy (MRS) With Colocalized MRI Measurements
| 2A | Colesevelam (n=24) | Placebo (n=22) | Difference | ||||
|---|---|---|---|---|---|---|---|
| Liver Segments | Baseline | Posttreatment | P-Value | Baseline | Posttreatment | P-Value | (P-Value) |
| 1 | 12.5 (6.2) | 15.1 (6.7) | 0.012 | 16.5 (7.0) | 14.2 (6.2) | 0.114 | 4.8 (0.005) |
| 2 | 13.0 (6.1) | 15.6 (6.9) | 0.017 | 17.2 (7.4) | 14.3 (6.5) | 0.060 | 5.5 (0.003) |
| 3 | 13.9 (6.5) | 16.8 (7.4) | 0.006 | 18.4 (8.5) | 15.2 (6.2) | 0.055 | 6.1 (0.002) |
| 4a | 14.7 (6.4) | 17.4 (6.9) | 0.008 | 18.1 (7.7) | 15.6 (6.1) | 0.100 | 5.2 (0.004) |
| 4b | 14.7 (6.9) | 17.5 (7.5) | 0.012 | 18.1 (7.5) | 15.6 (6.5) | 0.082 | 5.3 (0.003) |
| 5 | 14.5 (6.9) | 17.5 (7.7) | 0.018 | 17.7 (7.9) | 14.9 (6.0) | 0.062 | 5.8 (0.003) |
| 6 | 14.0 (6.4) | 17.1 (7.1) | 0.008 | 17.9 (7.9) | 15.3 (6.0) | 0.082 | 5.8 (0.002) |
| 7 | 15.0 (6.7) | 18.0 (7.6) | 0.019 | 18.6 (8.5) | 15.4 (5.7) | 0.038 | 6.2 (0.002) |
| 8 | 15.4 (6.7) | 18.1 (7.6) | 0.021 | 18.8 (8.6) | 15.9 (6.4) | 0.058 | 5.5 (0.003) |
| MRI PDFF average | 14.2 (6.3) | 17.0 (7.0) | 0.011 | 17.9 (7.7) | 15.2 (6.0) | 0.065 | 5.6 (0.002) |
| 2B | Colesevelam (n=19) | Placebo (n=20) | Difference | ||||
|---|---|---|---|---|---|---|---|
| Baseline | Post-Treatment | P-Value | Baseline | Post-Treatment | P-Value | (P-Value) | |
| MRS | 16.8 (6.4) | 18.7 (7.8) | 0.106 | 18.4 (7.2) | 16.1 (5.1) | 0.127 | 4.3 (0.028) |
| 2C | Colesevelam (n=20) | Placebo (n=21) | Difference | ||||
|---|---|---|---|---|---|---|---|
| MRI-level | Baseline | Post-Treatment | P-Value | Baseline | Post-Treatment | P-Value | (P-Value) |
| MRI-s | 14.8 (7.0) | 17.5 (8.1) | 0.065 | 17.4 (8.1) | 15.2 (5.1) | 0.167 | 4.81 (0.016) |
| MRI-m | 15.2 (6.9) | 17.3 (7.9) | 0.089 | 17.7 (7.8) | 14.5 (5.0) | 0.089 | 4.80 (0.017) |
| MRI-i | 14.9 (6.8) | 17.1 (8.0) | 0.032 | 17.5 (7.8) | 14.5 (5.1) | 0.080 | 5.16 (0.013) |
| MRI average | 15.0 (6.9) | 17.3 (8.0) | 0.056 | 17.4 (7.9) | 14.9 (5.0) | 0.104 | 4.9 (0.014) |
| Pearson r (r2) | 0.984 (0.968) P=0.000 | 0.996 (0.992) P=0.000 | 0.987 (0.974) P=0.000 | 0.961 (0.923) P=0.000 | |||
| Spearman ρ | 0.978 P=0.000 | 0.995 P=0.000 | 0.985 P=0.000 | 0.952 P=0.000 | |||
Data are expressed as means with standard error in parentheses or mean difference with P-value in parentheses.
Correlation coefficient expressed as Pearson coefficient r with r2 in parentheses and corresponding P-value, or as nonparametric Spearman's rho ρ with corresponding P-value.
MRI-PDFF, Magnetic Resonance Imaging Proton Density Fat Fraction; MRS, Magnetic Resonance Spectroscopy; MRI-s, Magnetic Resonance Imaging superior, MRI-m; Magnetic Resonance Imaging middle; MRI-I, Magnetic Resonance Imaging inferior.
Independent sample t test assuming equal variance was performed on all continuous variables for comparisons between groups. Paired-sample t test was performed for comparisons within group. Mean differences reflect comparison between baseline averages minus posttreatment averages.
2A: MRI PDFFs measured in all nine liver segments are used to calculate segmental and overall fat fraction averages at baseline and posttreatment between colesevelam and placebo group. There were three placebo and one Colesevelam dropout patients with no posttreatment MRI. Fat content in each liver segment are calculated by averaging three co-localized regions of interest (ROIs). The MRI total average is calculated using 27 ROIs, three from each liver segment.
2B: Longitudinal changes in MRS measurements from a 2x2x2 cm3 cube (voxel) within the liver at baseline and post-treatment in the colesevelam and placebo groups were used as a reference standard.
2C: Internal validation was performed by colocalizing MR imaging-based PDFF measurements to the reference MR-spectroscopy voxel. Three ROIs were placed on the PDFF maps in the same locations as the spectroscopic voxel (one through the superior third of the voxel[MRI-s], one through the middle third of the voxel[MRI-m], and one through the inferior third of the voxel[MRI-i]). PDFF measurements were averaged and correlation analysis to MR-spectroscopy measurements were performed.