Table 1. Performance of non-invasive tests for the diagnosis of fibrotic NASH.
| Test | Prevalence of fibrotic NASH | AUROC (95% CI) |
Cut-offs | Sensitivity (95% CI) |
Specificity (95% CI) |
PPV (%) (95% CI) | NPV (%) (95% CI) |
|---|---|---|---|---|---|---|---|
| MACK-3 (HOMA-IR, AST, CK-18): Original study (5) | 23.3% | 0.85±0.02 | ≤0.134 (rule-out fibrotic NASH) | 90% at cut-off ≤0.134 |
94.2% at cut-off ≥0.550 |
83.4 | 96.9 |
| ≥0.550 (rule-in fibrotic NASH) | |||||||
| MACK-3: External validation cohort (6) | 21.4% | 0.80 (0.74–0.87) | ≤0.134 (rule-out fibrotic NASH) | 100% at cut-off ≤0.134 |
43.8% at cut-off ≥0.550 |
43.1 | 100 |
| ≥0.550 (rule-in fibrotic NASH) | |||||||
| NIS4 algorithm (miR-34a-5p, alpha-2-macroglobulin, YKL-40, and HbA1C) (7) | 44–49% | 0.80 (0.77–0.84) | <0.36 to rule-out fibrotic NASH; | 81.5% (76.9–85.3) at <0.36 cutoff |
87.1% (83.1–90.3) at ≥0.63 cutoff |
79.2 (73.1–84.2) |
77.9 (72.5–82.4) |
| ≥0.63 to rule-in fibrotic NASH | |||||||
| Proteomic-based classification model (4 circulating proteins, BMI, HbA1C) | NA | Discovery cohort: 0.88 (±0.03) | >−0.4491 to rule-in fibrotic NASH | NA | NA | 79.0 | 85.0 |
| Validation cohort: 0.80 (±0.04) | <−0.4491 to rule-out fibrotic NASH | ||||||
| SomaSignal test (composed of 35 different proteins) (8) | 46% | 0.81 (0.75–0.86) | Threshold 0.06 to rule-in fibrotic NASH | 67.0% (59.0–75.0) |
82.0% (59.0–75.0) |
NA | NA |
| MAST score (9) | Derivation cohort: 17.5% | 0.86 (0.78–0.93) | <0.165 rule-out fibrotic NASH | 94.4% | 72.9% | 42.5 | 98.4 |
| >0.242 rule-in fibrotic NASH | 61.1% | 89.4% | 55.0 | 91.6 | |||
| Validation cohort: 11.5% | 0.93 (0.88–0.97) | <0.165 rule-out fibrotic NASH | 89.3% | 72.2% | 29.4 | 98.1 | |
| >0.242 rule-in fibrotic NASH | 75.0% | 90.3% | 50.0 | 96.5 |
NASH, non-alcoholic steatohepatitis; AUROC, areas under the receiver operating characteristic curves; CI, confidence interval; PPV, positive predictive value; NPV, negative predictive value; HOMA-IR, homeostasis model assessment for insulin resistance; AST, aspartate aminotransferase; CK-18, cytokeratin-18 fragments; BMI, body mass index; MAST, MRI-AST score; HbA1C, glycosylated hemoglobin; NA, not available.