Assessment of Glutamate Dehydrogenase Enzyme as a New Hepatotoxicity Biomarker
Sarah Ahmad Mohammad El Morsy;
Abstract
Background: Paracetamol toxicity is common. It can lead to liver necrosis and liver failure. The current methods used for diagnosis of paracetamol induced hepatotoxicity have many limitations.Mitochondrial damage is central in paracetamol toxicity. Glutamate dehydrogenase (GLDH), a mitochondrial enzyme found mainly in the liver, is liberated when mitochondria are severely damaged with loss of mitochondrial membrane integrity with high tissue specificity.
The aim of this study:was to assess the role of GLDH in early prediction of paracetamol-induced liver injury, and gaining further insight into paracetamol intracellular mechanisms in acute paracetamol intoxicated patients.
Material and methods: this study was conducted on adult patients with acute paracetamol overdose admitted to Poison Control Centre of Ain-Shams University Hospitals (PCC-ASUH) in the period from August, 2013 till January, 2017. Patients were classified into two groups, group I: with normal liver profile and group II: with abnormal liver profile. All patients had plasma paracetamol level, liver profile, renal function tests, glucose, electrolytes, ABG, and GLDH level measured
Results: 90 adult patients were included in the study, 64 (71%) with normal liver profile and 26 with abnormal liver profile (29%). Females had significant higher risk of hepatotoxicity than males (34% vs 0% respectively). Incidences of vomiting and abdominal pain at presentation were higher in group II (100%, 77%) than group I (78%, 19%) respectively. Mean (SD) on admission GLDH plasma level was significantly higher in group II (98 ±63) than group I (41.7 ± 33). Also, median (IQR) of GLDH on admission plasma level {79.3 (49-128)} was significantly higher than that of AST {32 (27.75-39.25) and ALT {26 (18-77)} serum levels. Mean (SD) GLDH time to peak (8.85 ± 3.82) was shorter than that of other liver profile tests (AST, ALT, INR and total bilirubin) {(42.54 ± 13.88), (45.96 ± 14.41), (37.31 ±15.3),(35.77 ± 6.6)} respectively. On admission plasma GLDH (AUC) = 0.826, P=0.000, 95% CI 0.752 to 0.886. At cut-off value 63 U/L, the presence of hepatotoxicity could be predicted with 70% sensitivity and 85% specificity with PPV 52.5% and NPV of 92%.
Conclusion: plasma GLDH can be used as an early specific mechanistic predictor of paracetamol induced hepatotoxicity in humans.
Keywords: Paracetamol, Drug induced hepatotoxicity, Glutamate dehydrogenase enzyme, Mechanistic biomarkers, Mitochondrial necrosis
The aim of this study:was to assess the role of GLDH in early prediction of paracetamol-induced liver injury, and gaining further insight into paracetamol intracellular mechanisms in acute paracetamol intoxicated patients.
Material and methods: this study was conducted on adult patients with acute paracetamol overdose admitted to Poison Control Centre of Ain-Shams University Hospitals (PCC-ASUH) in the period from August, 2013 till January, 2017. Patients were classified into two groups, group I: with normal liver profile and group II: with abnormal liver profile. All patients had plasma paracetamol level, liver profile, renal function tests, glucose, electrolytes, ABG, and GLDH level measured
Results: 90 adult patients were included in the study, 64 (71%) with normal liver profile and 26 with abnormal liver profile (29%). Females had significant higher risk of hepatotoxicity than males (34% vs 0% respectively). Incidences of vomiting and abdominal pain at presentation were higher in group II (100%, 77%) than group I (78%, 19%) respectively. Mean (SD) on admission GLDH plasma level was significantly higher in group II (98 ±63) than group I (41.7 ± 33). Also, median (IQR) of GLDH on admission plasma level {79.3 (49-128)} was significantly higher than that of AST {32 (27.75-39.25) and ALT {26 (18-77)} serum levels. Mean (SD) GLDH time to peak (8.85 ± 3.82) was shorter than that of other liver profile tests (AST, ALT, INR and total bilirubin) {(42.54 ± 13.88), (45.96 ± 14.41), (37.31 ±15.3),(35.77 ± 6.6)} respectively. On admission plasma GLDH (AUC) = 0.826, P=0.000, 95% CI 0.752 to 0.886. At cut-off value 63 U/L, the presence of hepatotoxicity could be predicted with 70% sensitivity and 85% specificity with PPV 52.5% and NPV of 92%.
Conclusion: plasma GLDH can be used as an early specific mechanistic predictor of paracetamol induced hepatotoxicity in humans.
Keywords: Paracetamol, Drug induced hepatotoxicity, Glutamate dehydrogenase enzyme, Mechanistic biomarkers, Mitochondrial necrosis
Other data
| Title | Assessment of Glutamate Dehydrogenase Enzyme as a New Hepatotoxicity Biomarker | Other Titles | تقييم إنزيم الجلوتامات ديهيدروجيناز كدلالة بيولوجية جديدة لسمية الكبد | Authors | Sarah Ahmad Mohammad El Morsy | Issue Date | 2018 |
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