Determinants of Hepatic Function in Liver Cirrhosis in the Rat Multivariate Analysis

We investigated the determinants of hepatic clearance func-tions in a rat model of liver cirrhosis induced by phenobarbi-tal/CCI4. Aminopyrine N-demethylation (ABT), galactose elimination (GBT), and serum bile acids (SBA) were deter-mined in vivo. The livers were then characterized hemodynami-cally: intrahepatic shunting (IHS) was determined by micro-spheres and sinusoidal capillarization by measuring the extra-vascular albumin space (EVA) by a multiple indicator dilution technique. The intrinsic clearance was determined by assaying the activity of the rate-limiting enzymes in vitro. Hepatocellu-lar volume (HCV) was measured by morphometry. ABT and SBA, but not GBT, differentiated cirrhotic from normal liver. IHS ranged from normal to 10%; all cirrhotic livers showed evidence of sinusoidal capillarization (reduced EVA). The cirrhotic livers showed a bimodal distribution of HCV, HCV being decreased in 50 % of the cirrhotic livers. Multivariate analysis showed EVA and portal flow to be the main determinants of microsomal (ABT) and cytosolic (GBT) clearance function; SBA, by contrast, were determined solely by IHS. We conclude that sinusoidal capillarization is the main de-terminant of hepatic clearance, while serum bile acids reflect intrabepatic shunting. These findings emphasize the impor-tance of alterations of hepatic nutritional flow to explain re-duced clearance function in cirrhosis of the liver