Correlation between liver cell necrosis and circulating alanine aminotransferase after ischaemia/reperfusion injuries in the rat liver.

Abstract

Circulating liver enzymes such as alanine transaminase are often used as markers of hepatocellular damage. Ischaemia/reperfusion (I/R) injury is an inevitable consequence of prolonged liver ischaemia. The aim of this study was to examine the correlation between liver enzymes and volume of liver cell necrosis after ischaemia/reperfusion injuries, using design-unbiased stereological methods. Forty-seven male Wistar rats were subjected to 1h of partial liver ischaemia, followed by either 4 or 24h of reperfusion. Within each group, one-third of animals were subjected to ischaemic preconditioning and one-third to ischaemic postconditioning. At the end of reperfusion, blood and liver samples were collected for analysis. The volume of necrotic liver tissue was subsequently correlated to circulating markers of I/R injury. Correlation between histological findings and circulating markers was performed using Pearson's correlation coefficient. Alanine transferase peaked after 4h of reperfusion; however, at this time-point, only mild necrosis was observed, with a Pearson's correlation coefficient of 0.663 (P=0.001). After 24h of reperfusion, alanine aminotransferase was found to be highly correlated to the degree of hepatocellular necrosis R=0.836 (P=0.000). Furthermore, alkaline phosphatase (R=0.806) and α-2-macroglobulin (R=0.655) levels were also correlated with the degree of necrosis. We show for the first time that there is a close correlation between the volume of hepatocellular necrosis and alanine aminotransferase levels in a model of I/R injury. This is especially apparent after 24h of reperfusion. Similarly, increased levels of alkaline phosphatase and α-2-macroglobulin are correlated to the volume of liver necrosis.