Table 3.
Accuracy of biomarkers to predict peak ALT of more than 100 U/L in patients with normal ALT and INR at hospital presentation
Derivation cohort (MAPP) n/N=40/875 |
Validation cohort (BIOPAR) n/N=13/176 |
|||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
ROC–AUC | p value | Specificity | Sensitivity | PPV | NPV | ROC–AUC | p value | Specificity | Sensitivity | PPV | NPV | |
ALT | 0·61 (0·51–0·68) | 0·02015 | 0·95 | 0·22 (0·11–0·36) | 22·0 | 95·3 | 0·63 (0·50–0·76) | 0·0071 | 0·95 | 0·29 (0·15–0·41) | 8·8 | 92·9 |
Paracetamol concentration | 0·58 (0·51–0·66) | 0·03762 | 0·95 | 0·10 (0·03–0·22) | 6·9 | 94·4 | 0·59 (0·40–0·69) | 0·0079 | 0·95 | 0·31 (0·09–0·51) | 33·3 | 94·5 |
miR-122 | 0·96 (0·93–0·99) | <0·0001 | 0·95 | 0·84 (0·71–0·93) | 48·8 | 98·9 | 0·97 (0·94–1·00) | <0·0001 | 0·95 | 0·92 (0·64–0·99) | 70·5 | 99·4 |
HMGB1 | 0·94 (0·89–0·98) | <0·0001 | 0·95 | 0·88 (0·76–0·95) | 45·8 | 99·2 | 0·98 (0·97–1·00) | <0·0001 | 0·95 | 0·92 (0·64–0·99) | 54·5 | 99·4 |
Full-length K18 | 0·94 (0·89–0·99) | <0·0001 | 0·95 | 0·88 (0·76–0·95) | 54·3 | 99·2 | 0·93 (0·81–1·00) | <0·0001 | 0·95 | 0·85 (0·55–0·98) | 61·1 | 98·7 |
Caspase-cleaved K18 | 0·79 (0·70–0·88) | <0·0001 | 0·95 | 0·60 (0·45–0·74) | 51·8 | 97·3 | 0·80 (0·63–0·97) | 0·0003 | 0·95 | 0·69 (0·39–0·90) | 52·9 | 97·5 |
GLDH | 0·74 (0·67–0·82) | <0·0001 | 0·95 | 0·34 (0·21–0·49) | 27·3 | 95·7 | 0·65 (0·49–0·81) | 0·0068 | 0·95 | 0·15 (0·02–0·45) | 20·1 | 93·3 |
ROC–AUC (95% CI), sensitivity at 95% specificity (95% CI), PPV, and NPV were calculated to assess the potential of novel and established stratification biomarkers to predict the development of acute liver injury. 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.