Correlation of intrahepatic pressure with collagen in the Disse space and hepatomegaly in humans and in the rat

Abstract

In 70 alcoholic patients the amount of collagen in the space of Disse was compared, using an electron microscopic graded score, to the height of the intrahepatic pressure. A highly significant correlation was found between the amount of collagen and intrahepatic pressure in the group as a whole (r = 0.84; p < 10(-6)), as well as in subgroups of 30 alcoholic patients with normal livers or steatosis (r = 0.83; p < 10(-6)), 9 patients with alcoholic hepatitis (r = 0.81; p < 0.01), and 31 with cirrhosis (r = 0.86; p < 10(-6)). A nonparametric correlational analysis for the complete group also showed a significant relationship (rho = 0.85; p < 10(-6)) between collagen scores and intrahepatic pressure. In 60 patients hepatocyte surface area was measured in the biopsies. In these, hepatocyte surface area significantly correlated with intrahepatic pressure (r = 0.68; p < 10(-7)). No correlation was found between intrahepatic pressure and fat, alcoholic hyalin, or terminal hepatic vein sclerosis. Only with necrosis (r = 0.38; p < 0.001) and inflammation (r = 0.29; p < 0.05) was there a significant relationship with intrahepatic pressure. Chronic ethanol administration for 4 wk in liquid diets to young Wistar rats produced a 50% hepatomegaly due to an increase in hepatocyte size. Intrahepatic pressure in the rats receiving alcohol (19.3 +/- 2.3 mmHg) was significantly higher than in the controls on sucrose (10.4 +/- 0.9 mmHg) (p < 0.01). A highly significant correlation was found between hepatocyte surface area and intrahepatic pressure (r = 0.70; p < 0.005). There was no increase in collagen in the Disse space in these animals. Therefore, hepatomegaly in the absence of an increase in collagen in the Disse space may result in increased intrahepatic pressure. These studies may indicate a sequence of events: hepatomegaly, portal hypertension, and collagenization in the Disse space, which could occur in alcoholic liver disease.