83 QUANTITATIVE HISTOCHEMISTRY: A MEANS OF DETERMINING THE SITE OF INITIAL HEPATOCYTE DAMAGE IN CIRRHOSIS?

Abstract

Cirrhosis is the endscage of liver disease of whatever etiology. Once established, it may be impossible to determine the site of the initial lesion. We have investigated whether periportal area (PPA) & perivenular zones(PVZ) can be identified within cirrhotic nodules by determining hepatocyte specific enzyme activities. Quantitative histochemistry(QH) was used to determine the activity of the microsomal enzymes glucose 6 phosphatase (GP), which has highest activity in the PPA, and NAOPH diaphorase (ND), highest in the PVZ. Results in 5 normal rats & 2 histologically normal child livers where compared with those obtained in 5 rats with CCI4 induced cirrhosis & 3 children with extrahepatic biliary atresia (EHBA),the former being initial PVZ damage & the latter PPA. Both in normal rat & human liver, highest CP activity was detected in the PPA (PPA:PVZ mean ratio 1.7 & 1.8 respectively), while highest ND activity was found in the PVZ(PPA:PVZ 0.5 & 0.85). In CC14 induced cirrhosis, GP activity was greater at the centre of the nodule than at its periphery(centre:periphery 1.8) while ND was higher at its periphery (ratio 0.58), suggesting that the centre of the nodule is of periportal and the periphery of perivenular origin. In contrast, the reverse was found in EHBA, with a centre:periphery ratio of 0.6 for GP & 1.3 for ND. Our data indicate that the enzymatic activity in the cells at the periphery of the cirrhotic nodule are similar to that in the cells initially injured. Although adaptive changes may account for these observations, QH determination of microsomal enzymes may identify the site of initial damage in cryptogenic cirrhosis.