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Biomarkers predicted mortality in patients with acetaminophen-induced ALF

Specific mitochondrial biomarker serum levels were greater among patients who did not survive acetaminophen-induced acute liver failure compared with those who survived and recovered, according to new study data.

Serum samples of glutamate dehydrogenase (GDH), mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) were taken from patients enrolled in the Acute Liver Failure Study Group network who survived acetaminophen (APAP)-induced acute liver failure (ALF; n=34) and compared with levels of those who died (n=35). A healthy control cohort also was used for comparison.

Researchers found all three biomarkers were significantly greater in serum among AALF patients who did not survive compared with survivors. GDH levels were more than twofold greater (450 ± 73 U/L vs. 930 ± 145 U/L), mtDNA were 1.5- to twofold higher (21 ± 6 ng/mL vs. 48 ± 13 ng/mL; 33 ± 10 ng/mL vs. 43 ± 7 ng/mL for two different genes) and nDNA were 1.6-fold greater (148 ± 13% vs. 210 ± 13% of control) among patients who died.

Receiver operating characteristic curve analysis showed that all three biomarkers predicted death at the time of study admission and at peak alanine aminotransferase (ALT) level, but did not reveal any association between mortality and ALT.

“Overall, our data showed that nDNA fragments, GDH, and mtDNA were significantly elevated in all AALF patients and particularly so in those who did not survive,” the researchers concluded. “These data suggest that mitochondrial damage is a critical part of the mechanisms of APAP hepatotoxicity in humans.”

Disclosure: William M. Lee, MD, received grants from Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Merck, Novartis and GlaxoSmithKline.