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Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital.

Antoine DJ, Dear JW, Lewis PS, Platt V, Coyle J, Masson M, Thanacoody RH, Gray AJ, Webb DJ, Moggs JG, Bateman DN, Goldring CE, Park BK - Hepatology (2013)

Bottom Line: In all patients, biomarkers at first presentation significantly correlated with peak ALT or INR.In patients presenting with normal ALT or INR, miR-122, HMGB1, and necrosis K18 identified the development of liver injury (n = 15) or not (n = 84) with a high degree of accuracy and significantly outperformed ALT, INR, and plasma acetaminophen concentration for the prediction of subsequent ALI (n = 11) compared with no ALI (n = 52) in patients presenting within 8 hours of overdose.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.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK.

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Plasma biomarker values at presentation to the hospital emergency department correlate with peak ALT activity. (A) miR-122, (B) total HMGB1, (C) apoptosis K18, (D) necrosis K18, and (E) GLDH activity were correlated against peak ALT activity in patients who presented early after acetaminophen overdose (<24 hours, n = 129).
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fig01: Plasma biomarker values at presentation to the hospital emergency department correlate with peak ALT activity. (A) miR-122, (B) total HMGB1, (C) apoptosis K18, (D) necrosis K18, and (E) GLDH activity were correlated against peak ALT activity in patients who presented early after acetaminophen overdose (<24 hours, n = 129).

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.


Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital.

Antoine DJ, Dear JW, Lewis PS, Platt V, Coyle J, Masson M, Thanacoody RH, Gray AJ, Webb DJ, Moggs JG, Bateman DN, Goldring CE, Park BK - Hepatology (2013)

Plasma biomarker values at presentation to the hospital emergency department correlate with peak ALT activity. (A) miR-122, (B) total HMGB1, (C) apoptosis K18, (D) necrosis K18, and (E) GLDH activity were correlated against peak ALT activity in patients who presented early after acetaminophen overdose (<24 hours, n = 129).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842113&req=5

fig01: Plasma biomarker values at presentation to the hospital emergency department correlate with peak ALT activity. (A) miR-122, (B) total HMGB1, (C) apoptosis K18, (D) necrosis K18, and (E) GLDH activity were correlated against peak ALT activity in patients who presented early after acetaminophen overdose (<24 hours, n = 129).
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.

Bottom Line: In all patients, biomarkers at first presentation significantly correlated with peak ALT or INR.In patients presenting with normal ALT or INR, miR-122, HMGB1, and necrosis K18 identified the development of liver injury (n = 15) or not (n = 84) with a high degree of accuracy and significantly outperformed ALT, INR, and plasma acetaminophen concentration for the prediction of subsequent ALI (n = 11) compared with no ALI (n = 52) in patients presenting within 8 hours of overdose.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.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Drug Safety Science, Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK.

Show MeSH
Related in: MedlinePlus