Table 2.
Novel biomarkers accurately predicted peak ALT of more than 100 U/L after paracetamol overdose
|
Derivation cohort (MAPP) n/N=105/985 |
Validation cohort (BIOPAR) n/N=26/202 |
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|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ROC–AUC | p value | Specificity | Sensitivity | PPV | NPV | ROC–AUC | p value | Specificity | Sensitivity | PPV | NPV | |
| ALT | 0·84 (0·79–0·89) | <0·0001 | 0·95 | 0·52 (0·42–0·62) | 53·9 | 94·3 | 0·81 (0·71–0·92) | <0·0001 | 0·95 | 0·50 (0·29–0·70) | 61·9 | 92·8 |
| Paracetamol concentration | 0·56 (0·49–0·62) | 0·0569 | 0·95 | 0·09 (0·04–0·16) | 10·4 | 88·6 | 0·50 (0·36–0·63) | 0·9928 | 0·95 | 0·15 (0·04–0·35) | 33·3 | 88·4 |
| miR-122 | 0·97 (0·95–0·98) | <0·0001 | 0·95 | 0·79 (0·70–0·87) | 65·4 | 97·4 | 0·97 (0·95–0·99) | <0·0001 | 0·95 | 0·84 (0·65–0·95) | 71·0 | 97·6 |
| HMGB1 | 0·95 (0·93–0·98) | <0·0001 | 0·95 | 0·82 (0·73–0·88) | 65·7 | 97·8 | 0·98 (0·96–0·99) | <0·0001 | 0·95 | 0·81 (0·61–0·93) | 70·0 | 97·1 |
| Full-length K18 | 0·95 (0·92–0·97) | <0·0001 | 0·95 | 0·56 (0·46–0·66) | 57·3 | 94·8 | 0·93 (0·86–0·99) | <0·0001 | 0·95 | 0·54 (0·33–0·73) | 70·0 | 97·1 |
| Caspase-cleaved K18 | 0·84 (0·78–0·89) | <0·0001 | 0·95 | 0·65 (0·56–0·75) | 61·1 | 95·9 | 0·87 (0·78–0·97) | <0·0001 | 0·95 | 0·69 (0·48–0·86) | 66·7 | 95·4 |
| GLDH | 0·86 (0·82–0·90) | <0·0001 | 0·95 | 0·58 (0·48–0·68) | 58·1 | 95·0 | 0·83 (0·74–0·93) | <0·0001 | 0·95 | 0·54 (0·33–0·73) | 63·6 | 93·3 |
ROC–AUC (95% CI), sensitivity at 95% specificity (95% CI), and PPV and NPV were calculated to identify the potential of novel and established stratification biomarkers to predict the development of acute liver injury (ALT ≥100 U/L). ROC=receiver operator characteristic. AUC=area under the curve. PPV=positive predictive value. NPV=negative predictive value. ALT=alanine aminotransferase. HMGB1=high mobility group box-1. GLDH=glutamate dehydrogenase.