Natural history of alcoholic hepatitis. IV. Glycosaminoglycuronans and collagen in the hepatic connective tissue.

The extractable and nonextractable collagen and glycosaminoglycuronans (GAG) were estimated and characterized in 32 dried, defatted human livers obtained at necropsy. 10 had normal livers. 22 of the 32 livers were from patients who drank in excess: 5 had fatty livers, 7 had alcholic hepatitis, and 10 had cirrhosis. Livers with alcoholic hepatitis or cirrhosis had significantly increased total and 1 N NaCl-extractable collagen. Only alcoholic hepatitis livers had significantly increased Tris-buffer-extractable GAG, but the amino acid composition of these GAG (proteoglycans) was no different from that of normal livers. The major fraction of these GAG had isoelectric pH (pI) </= 3.1 in all livers. Livers with alcoholic hepatitis or cirrhosis had significantly increased nonextractable GAG. The major GAG fraction of all livers was chondroitin-4 or -6-SO(4). Alcoholic hepatitis livers had a significant increase of hyaluronic acid and an unidentified hyaluronidase-resistant GAG. Fatty livers showed no differences from normal ones. The data indicates that alcoholic hepatitis is associated with a significantly increased fibroblast activity, but fatty livers of alcoholics are not. The changes in histologically "inactive" micronodular cirrhosis of alcoholic patients indicate continued activity of fibroblasts in the connective tissue of these cirrhotic livers.