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Updated: Jul 3, 2026
Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen
Published on: November 27, 2019
Serum alpha-NH-butyric acid may predict spontaneous survival in pediatric acute liver failure
David A Rudnick1, Dennis J Dietzen, Yumirle P Turmelle
1Department of Pediatrics, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA. rudnick_d@kids.wustl.edu
Insights
Predicting recovery from acute liver failure (ALF) is challenging. New biomarkers, alpha-NH(2)-butyric acid and its ratio to leucine, show promise in identifying patients likely to survive without liver transplantation.
Area of Science:
- Biochemistry
- Metabolomics
- Hepatology
Background:
- Acute liver failure (ALF) is a critical condition with high mortality.
- Predicting spontaneous recovery in ALF patients is difficult.
- Liver regeneration capacity is crucial for ALF recovery.
Purpose of the Study:
- To identify novel metabolomic biomarkers for hepatic regeneration.
- To investigate the utility of these biomarkers in predicting outcomes for patients with acute liver failure (PALF).
Main Methods:
- Comprehensive amino acid analysis in mice after partial hepatectomy.
- Identification of metabolites increased during liver regeneration.
- Serum biomarker analysis in 40 PALF patients.
Main Results:
- Alpha-NH(2)-adipic acid and alpha-NH(2)-butyric acid (Aab) were elevated in regenerating mouse livers and plasma.
- Increased serum Aab and Aab:leucine (Aab:Leu) ratio were observed in PALF patients who survived without transplantation.
- These markers differentiated between patients with varying clinical outcomes.
Conclusions:
- Aab and the Aab:Leu ratio are potential biomarkers of liver regeneration.
- These biomarkers may predict spontaneous recovery in patients with acute liver failure.
- Further validation is needed for clinical application in PALF prognosis.
Abstract:
ALF is a serious, often fatal condition. Up to half of PALF patients do not survive without liver transplantation; however, early identification of those least likely to survive spontaneously remains difficult. Clinical experience suggests that recovery from ALF depends on the ability of the liver to regenerate. Based on this, we hypothesized that bio-markers of hepatic regeneration could have utility as predictors of recovery from PALF. In the studies reported here, we used comprehensive amino acid analysis to search for novel metabolomic markers of liver regeneration in mice subjected to partial hepatectomy. This analysis identified alpha-NH(2)-adipic acid and alpha-NH(2)-butyric acid as significantly increased in liver and plasma samples from mice subjected to partial hepatectomy compared to controls. Next, we tested whether serum levels of these markers were associated with clinical outcomes in PALF patients. This examination, performed on the initially collected serum samples from 40 randomly selected patients enrolled in the PALF Study Group, showed increased alpha-NH(2)-butyric-acid (Aab) and Aab:leucine (Aab:Leu) ratio in patients who survived without transplantation compared to those who were transplanted or died. These data indicate that Aab and the Aab:Leu ratio may predict clinical outcomes in PALF.
