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.