Table 2.
Comparison of NRs by Histologic Characteristics Sorted by Dissimilarity Measure From Cluster Analysis
| Steatosis | Ballooning | Lobular Inflammation | Fibrosis | Type of NAFLD | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| <33% (n = 22) | 34%+ (n = 18) | P * | None (n = 23) | Any (n = 17) | P * | None/Mild (n = 27) | Mod/Severe (n = 13) | P * | None (n = 12) | Any (n = 28) | P * | Not NASH (n = 21) | NASH (n = 19) | P * | |
| Median† | Median† | Median† | Median† | Median† | |||||||||||
| Cluster IA | |||||||||||||||
| CAR | 19.9 | 19.9 | 0.91 | 19.9 | 19.8 | 1.00 | 19.9 | 19.8 | 0.26 | 20.5 | 19.7 | 0.02 | 19.9 | 19.8 | 0.46 |
| FXRα | 21.8 | 20.9 | 0.03 | 21.5 | 21.6 | 1.00 | 21.7 | 21.3 | 0.76 | 21.2 | 21.6 | 0.35 | 21.7 | 21.3 | 0.70 |
| LRH1 | 21.1 | 20.4 | 0.14 | 20.7 | 20.9 | 0.61 | 20.7 | 20.6 | 0.95 | 20.5 | 20.8 | 0.92 | 20.7 | 20.7 | 0.94 |
| Global test | 0.06 | 0.99 | 0.43 | 0.02 | 0.63 | ||||||||||
| Cluster IB | |||||||||||||||
| COUP‐TFI | 26.6 | 26.9 | 0.85 | 27.2 | 26.6 | 0.35 | 27.0 | 26.6 | 0.24 | 28.6 | 26.3 | 0.003 | 27.2 | 26.6 | 0.07 |
| LXRα | 27.9 | 27.6 | 0.43 | 27.9 | 27.9 | 0.32 | 27.9 | 27.9 | 0.69 | 28.1 | 27.4 | 0.21 | 27.9 | 27.9 | 0.33 |
| TR2 | 27.6 | 27.0 | 0.37 | 27.5 | 27.1 | 0.55 | 27.5 | 27.2 | 0.96 | 27.9 | 27.2 | 0.23 | 27.5 | 27.1 | 0.48 |
| SHP | 26.6 | 27.0 | 0.61 | 26.6 | 27.0 | 0.88 | 26.7 | 27.0 | 0.93 | 27.1 | 26.6 | 0.42 | 26.7 | 26.8 | 0.60 |
| REV‐ERBAα | 28.0 | 27.3 | 0.85 | 28.3 | 27.2 | 0.08 | 27.3 | 27.5 | 0.74 | 28.3 | 27.3 | 0.17 | 28.2 | 27.4 | 0.34 |
| RARα | 26.6 | 26.5 | 0.47 | 27.0 | 26.4 | 0.89 | 26.6 | 26.4 | 0.62 | 27.8 | 26.1 | 0.005 | 27.0 | 26.4 | 0.68 |
| TRα | 26.0 | 26.0 | 0.89 | 26.1 | 25.8 | 0.94 | 26.0 | 25.9 | 0.82 | 26.7 | 25.7 | 0.05 | 26.0 | 26.0 | 0.58 |
| Global test | 0.40 | 0.55 | 0.56 | 0.006 | 0.04 | ||||||||||
| Cluster IC | |||||||||||||||
| COUP‐TFII | 23.8 | 23.7 | 0.37 | 23.9 | 23.6 | 0.43 | 23.9 | 23.6 | 0.26 | 24.2 | 23.5 | 0.06 | 23.9 | 23.6 | 0.12 |
| RORα | 25.3 | 24.6 | 0.12 | 25.0 | 25.0 | 0.83 | 25.0 | 25.2 | 0.77 | 24.8 | 25.1 | 0.59 | 25.0 | 25.2 | 0.95 |
| GR | 25.1 | 24.7 | 0.21 | 24.9 | 24.8 | 0.34 | 24.9 | 24.6 | 0.20 | 24.9 | 24.9 | 0.71 | 24.9 | 24.8 | 0.26 |
| RXRβ | 25.0 | 25.0 | 0.91 | 24.9 | 25.2 | 0.55 | 25.0 | 24.8 | 0.76 | 25.5 | 24.7 | 0.02 | 25.0 | 24.9 | 0.91 |
| PXR | 25.2 | 25.0 | 0.92 | 25.7 | 25.0 | 0.63 | 25.7 | 24.9 | 0.33 | 26.2 | 24.9 | 0.005 | 25.7 | 25.0 | 0.41 |
| RORγ | 25.4 | 25.5 | 0.90 | 25.6 | 25.4 | 0.59 | 25.5 | 25.0 | 0.82 | 26.1 | 25.2 | 0.06 | 25.6 | 25.4 | 0.62 |
| RXRα | 25.7 | 25.3 | 0.28 | 25.7 | 25.4 | 0.30 | 25.5 | 26.0 | 0.60 | 25.7 | 25.5 | 0.72 | 25.7 | 25.3 | 0.32 |
| PPARα | 26.1 | 25.4 | 0.93 | 26.0 | 26.0 | 0.94 | 26.1 | 25.5 | 0.45 | 27.2 | 25.4 | 0.007 | 26.1 | 25.5 | 0.26 |
| TRβ | 26.1 | 25.3 | 0.85 | 26.1 | 25.4 | 0.53 | 26.1 | 25.3 | 0.33 | 27.0 | 25.7 | 0.05 | 26.1 | 25.3 | 0.34 |
| Global test | 0.14 | 0.50 | 0.03 | 0.09 | 0.21 | ||||||||||
| Cluster IIA | |||||||||||||||
| VDR | 32.0 | 32.1 | 0.65 | 33.0 | 32.0 | 0.39 | 32.9 | 32.0 | 0.97 | 31.9 | 32.9 | 0.22 | 33.0 | 32.1 | 0.58 |
| GCNF | 31.4 | 31.8 | 0.65 | 31.8 | 31.7 | 0.86 | 33.1 | 31.3 | 0.17 | 33.9 | 31.4 | 0.02 | 32.8 | 31.5 | 0.41 |
| PR | 32.4 | 32.6 | 0.84 | 32.6 | 32.6 | 0.81 | 32.6 | 32.5 | 0.80 | 33.4 | 32.2 | 0.16 | 32.6 | 32.5 | 0.71 |
| RARγ | 32.3 | 31.3 | 0.54 | 32.3 | 31.3 | 0.20 | 32.3 | 31.3 | 0.15 | 32.4 | 31.4 | 0.20 | 32.9 | 30.9 | 0.02 |
| PPARδ | 31.6 | 31.4 | 0.85 | 31.6 | 31.0 | 0.20 | 31.7 | 30.8 | 0.08 | 32.6 | 31.2 | 0.006 | 31.7 | 30.8 | 0.06 |
| ERα | 31.6 | 30.9 | 0.28 | 31.5 | 30.9 | 0.05 | 31.5 | 30.7 | 0.02 | 32.2 | 30.9 | 0.009 | 31.6 | 30.9 | 0.02 |
| LXRβ | 30.5 | 30.8 | 0.76 | 30.8 | 30.5 | 0.51 | 30.8 | 30.5 | 0.54 | 31.1 | 30.5 | 0.05 | 30.9 | 30.5 | 0.55 |
| PPARδ2 | 31.2 | 30.8 | 0.70 | 30.7 | 31.0 | 0.78 | 30.9 | 31.7 | 0.78 | 30.9 | 31.0 | 0.94 | 30.9 | 31.2 | 0.75 |
| NURR1 | 31.1 | 30.7 | 0.40 | 31.6 | 30.6 | 0.36 | 31.6 | 30.6 | 0.27 | 33.0 | 30.9 | 0.04 | 31.8 | 30.6 | 0.16 |
| Global test | NC§ | 0.42 | 0.18 | 0.21 | 0.01 | ||||||||||
| Cluster IIB | |||||||||||||||
| MR | 29.7 | 29.2 | 0.24 | 29.4 | 29.6 | 0.65 | 29.6 | 29.6 | 0.53 | 30.1 | 29.4 | 0.33 | 29.6 | 29.6 | 0.49 |
| RARβ | 29.6 | 28.4 | 0.05 | 29.5 | 29.0 | 0.21 | 29.4 | 29.0 | 0.64 | 29.2 | 29.4 | 0.73 | 29.5 | 28.3 | 0.05 |
| ERR1 | 29.7 | 29.2 | 0.50 | 29.1 | 29.7 | 0.48 | 29.4 | 29.5 | 0.90 | 29.2 | 29.6 | 0.86 | 29.1 | 29.7 | 0.91 |
| RARβ1 | 30.0 | 28.4 | 0.02 | 30.0 | 29.1 | 0.26 | 30.0 | 28.7 | 0.10 | 31.6 | 29.1 | 0.01 | 30.1 | 28.7 | 0.03 |
| RARβ2 | 27.8 | 27.0 | 0.20 | 27.9 | 27.6 | 0.61 | 27.9 | 27.1 | 0.52 | 28.7 | 27.3 | 0.09 | 27.9 | 27.1 | 0.41 |
| PPARγ1 | 29.6 | 29.1 | 0.48 | 29.0 | 29.7 | 0.78 | 29.6 | 29.0 | 0.33 | 31.8 | 28.9 | 0.001 | 29.7 | 29.0 | 0.20 |
| PPARγ2 | 29.2 | 26.9 | 0.07 | 28.3 | 29.3 | 0.44 | 29.3 | 26.7 | 0.003 | 30.8 | 28.2 | 0.04 | 29.1 | 27.9 | 0.10 |
| PPARγ3 | 27.3 | 27.6 | 0.93 | 27.1 | 27.8 | 0.003 | 27.6 | 26.8 | 0.07 | 27.5 | 27.4 | 0.75 | 27.4 | 27.5 | 0.48 |
| Global test | 0.03 | 0.06 | 0.09 | 0.11 | 0.08 | ||||||||||
Abbreviations: ERR, estrogen‐related receptor; GR, glucocorticoid receptor; LRH1, liver receptor homolog 1; MR, mineralocorticoid receptor; PR, progesterone receptor; REV‐ERBa‐α, nuclear receptor subfamily 1 group D member 1; RORα, RAR‐related orphan receptor alpha; SHP, small heterodimer partner.
*
Based on robust linear regression.
†
Normalized mRNA levels.
‡
P values from global test regressing presence of more severe histologic feature on set of NRs in each cluster.
§
Not calculable, regression did not converge.