Changes in type IV collagen content in livers of patients with alcoholic liver disease

Abstract

An increase of serum type IV collagen levels in patients with liver disease has been reported; however, the mechanisms of this increase are not yet well known. We recently developed an assay system for type IV collagen content in liver biopsy specimens. In this study, type IV collagen content in the livers and sera of patients with alcoholic liver disease and nonalcoholic liver disease was determined. Serum and hepatic type IV collagen contents were measured with a one-step sandwich enzyme immunoassay system using monoclonal antibodies for human type IV collagen. Hepatic type IV collagen content increased significantly in liver disease. In alcoholic liver disease, type IV collagen content in patients with mild fibrosis was lower than that in advanced types of alcoholic liver disease. In nonalcoholic liver disease, hepatic type IV collagen content tended to increase with the progression of fibrosis. Type IV collagen content in alcoholic liver disease was significantly higher than that in the corresponding type of nonalcoholic liver disease. Hepatic total collagen content increased significantly in parallel with the progression of fibrosis in both alcoholic liver disease and nonalcoholic liver disease. The total collagen content in each type of alcoholic liver disease was significantly lower than that in the corresponding type of nonalcoholic liver disease. The ratio of type IV collagen to total collagen content was the highest in livers showing mild fibrosis, both in alcoholic liver disease and nonalcoholic liver disease, and decreased in parallel with the progression of fibrosis. The ratio in patients with alcoholic liver disease was significantly higher than that in those with the corresponding nonalcoholic liver disease. Hepatic type IV collagen content correlated with the intensity of the staining reactions for type IV collagen only around the sinusoidal walls in alcoholic liver disease, but not in nonalcoholic liver disease. A significant correlation was found between serum and liver type IV collagen content, although the coefficient value was not very high. These results indicate that the response of type IV collagen synthesis to liver injury is strong in mild fibrosis and reaches a plateau at a relatively early stage of fibrosis; then the content of the other types of collagen increases gradually with the progression of fibrosis. The stimulation for type IV collagen synthesis is more prominent in alcoholic liver disease than in nonalcoholic liver disease, especially at intralobular areas.