Albumin and collagen gene regulation in alcohol- and virus-induced human liver disease.

Common features of chronic alcoholic liver disease are progressive hypoalbuminemia and a spectrum of liver fibrosis. The molecular mechanisms that account for these effects are still the subject of controversy. Therefore, in the present study we evaluated albumin and collagen gene expression in livers of alcohol abusers and patients with virus-induced liver disease. Albumin and pro alpha 1(I) collagen messenger RNA levels were determined in 30 patients who underwent diagnostic liver biopsy. Of 14 alcoholics, 7 had alcoholic hepatitis alone and the other 7 had cirrhosis plus alcoholic hepatitis. Of 16 nonalcoholic patients with chronic viral infection, 6 had chronic active hepatitis and 10 had cirrhosis plus chronic active hepatitis. Total RNA was extracted from a portion of each biopsy specimen, hybridized with a human albumin or collagen complementary DNA clone, and compared with 2 normal surgical specimens, which served as controls. The Northern hybridization studies showed that (a) despite the presence of inflammation and fibrosis, the albumin messenger RNA levels of alcoholics were similar to those of the controls; (b) these alcoholics had significantly higher levels of albumin messenger RNA than did patients with similar histological levels of disease due to viral infection; and (c) all the categories of patients had markedly increased procollagen messenger RNA levels compared with controls. Given these results it is tempting to speculate that alcohol may actually increase albumin messenger RNA content in humans as it does in animals. Furthermore, the increased procollagen messenger RNA levels in fibrotic livers suggest that an increase in collagen syntheses may be a significant factor in the pathogenesis of hepatic fibrosis.