Serum aspartate aminotransferase isoenzymes in cholestatic infants and children

ABSTRACT

Serum aspartate aminotranferase enzyme [AST] and its isoenzymes; the cytosolic [c-AST] and mitochondrial [m-AST] are usually increased in different liver diseases. The aim of this work is to determine the level of AST isoenzymes in infants with cholestasis and to assess the value of such determination in differentiating intrahepatic from extrahepatic causes and also in predicting disease severity. This study included 50 patients suffering from neonatal cholestasis, admitted to National Liver Institute, Menoufiya University. They were 26 patients with extrahepatic biliary atresia [EHBA]; 13 patients with idiopathic neonatel hepatitis [INH]; 3 patients with paucity of interlobular bile ducts [PILBD]; 3 patients with alpha-one-antitrypsin deficiency [alpha 1-ATD]; 2 patients with septicemia; 1 patient with choledochal cyst; 1 pataient with Niemann Pick disease and 1 patient with primary sclerosing cholangitis [PSC]. Ten normal healthy infants of matched age and sex served as a control group. All patients were subjected to full history taking, thorough clinical examination and appropriate investigations. Aspartate aminoransferase enzyme and its isoenzymes were measured in all groups and it was found that all patient groups had significantly elevated total AST levels in comparison to the normal controls, the total AST level was significantly higher in patients with INH as compared to those with EHBA, the c-AST level in all patient groups was significantly higher than that in normal controls, all patient groups had significantly elevated m-AST levels in comparison to the normal controls, the m-AST level was significantly higher in patients with INH as compared to those with EHBA, in the subgroups of both EHBA and INH, the c-AST was preferentially elevated in subgroup a [fair outcome, Child class B] while the m-AST was preferentially elevated in subgroup b [poor outcome, Child class C], the m-AST/total AST ratio showed a statistically significant difference between EHBA and INH on one hand and between INH and alpha -1ATD on the other hand. In comparative analysis of m-AST/total AST ratio among various patient groups, we found that there was a high statistically significant difference between EHBA and INH [P<0.01] and according to the cut-off point of this ratio, we found that any homeostatic infant having a ratio more than 0.359 is most probably diagnosed as an intrahepatic cholestasis, while any ratio less than 0.359 is most probably diagnosed as an extrahepatic cholestasis. c-AST level is increased in all groups of cholestatic disorders in which there is mild damage of hepatocyte plasma membrane [cases of fair outcome], while the m-AST level is highly increased in severe hepatocellular injury which cause mitochondrial damage [cases of poor outcome]. Also, we conclude that a cut-off point of 0.359 of the m-AST total AST ratio is useful in differentiating between intra-hepatic and extrahepatic cholestasis