Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital.
Bottom Line: In the first hospital presentation plasma sample from patients (n = 129), we measured microRNA-122 (miR-122; high liver specificity), high mobility group box-1 (HMGB1; marker of necrosis), full-length and caspase-cleaved keratin-18 (K18; markers of necrosis and apoptosis), and glutamate dehydrogenase (GLDH; marker of mitochondrial dysfunction).In all patients, biomarkers at first presentation significantly correlated with peak ALT or INR.The application of such a biomarker panel could improve the speed of clinical decision-making, both in the treatment of ALI and the design/execution of patient-individualized treatment strategies.
Affiliation: MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK.Show MeSH
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Mentions: We performed a correlation analysis from individual marker values at first presentation against the peak INR value during patient hospitalization. The presentation values for plasma miR-122, HMGB1, apoptosis K18, necrosis K18, and GLDH activity all significantly correlated with peak INR values (P < 0.0001, Fig. 2A-E). The correlation coefficients (R2) were 0.24, 0.42, 0.29, 0.34, and 0.13 and the Pearson R values (95% CI) were 0.49 (0.34-0.61), 0.64 (0.53-0.74), 0.54 (0.40, 0.65), 0.59 (0.46-0.69), and 0.37 (0.21-0.51) for miR-122, HMGB1, apoptosis K18, necrosis K18, and GLDH activity, respectively. Presentation and 4-hour back-extrapolated plasma acetaminophen concentration did not significantly correlate with either peak ALT activity or peak INR (Fig. 3).
Affiliation: MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK.