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 measured miR-122, HMGB1, apoptosis K18, necrosis K18, and GLDH activity in plasma obtained at the point of hospital admission, before AC treatment had begun, but when a timed blood acetaminophen concentration had indicated the requirement for AC therapy. We performed a correlation analysis on values obtained from each individual marker against the peak serum ALT activity during patient hospitalization. The presentation serum miR-122, HMGB1, apoptosis K18, necrosis K18, and GLDH activity values all significantly correlated with peak ALT activity values (P < 0.0001, Fig. 1A-E). The correlation coefficients (R2) were 0.14, 0.67, 0.57, 0.59, and 0.45 and the Pearson R values (95% confidence interval [CI]) were 0.37 (0.21-0.52), 0.82 (0.75-0.87), 0.75 (0.67, 0.82), 0.77 (0.69-0.83), and 0.67 (0.56-0.76) for miR-122, HMGB1, apoptosis K18, necrosis K18, and GLDH activity, respectively.
Affiliation: MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK.