The effect of alcohol-induced hepatomegaly on portal hypertension in cirrhotic rats

Abstract

Male Sprague-Dawley rats with CCl 4-induced cirrhosis (confirmed by increased collagen content and light microscopy) were fed either ethanol (Group A, n = 9) or isocaloric carbohydrate diet (Group B, n = 8) for 4 weeks. Histologic and hemodynamic measurements were obtained in the awake state before (time 1) and after the 4 weeks of diet (time 2). Portal-systemic shunts were evaluated using radiolabelled microspheres. Liver weight was increased in Group A (16.5 ± 0.5 vs. 14.2 ± 0.5 g, mean ± SE, p < 0.005) as was the ratio of liver weight over total body weight (3.41 ± 0.05 vs. 2.86 ± 0.09%, p < 0.0001, +19.2%). Hepatocytes surface area was increased in the ethanol group (357 ± 9 vs. 294 ± 7 μm 2, p < 0.0001). In Group B, only 9 ± 2% of hepatocytes had steatosis as opposed to 69 ± 3% of centronodular and 34 ± 3% of perinodular hepatocytes in Group A ( p < 0.001). Portal pressure remained stable in both groups (time 1 (A) 16.9 ± 0.8, (B) 15.8 ± 1.1 mmHg, n.s.; time 2 (A) 15.9 ± 0.7, (B) 15.8 ± 0.6 mmHg, n.s.). Portal-systemic shunts did not change with time or diet (time 1 (A) 10.6 ± 3.7%, (B) 4.1 ± 2.1%, n.s.; time 2 (A) 13.4 ± 5.9%, (B) 10.8 ±4.3%, n.s.). In conclusion, these data show that CCl 4-induced cirrhosis is a stable model over a 4-week period following cessation of CCl 4 exposure; that in cirrhotic rats, steatosis and hepatomegaly can be induced by alcohol; and finally that a 20% increase in hepatomegaly is not associated with change in portal pressure, even in a cirrhotic rat liver.