Biochemical markers of hepatic fibrosis.

Most liver diseases lead to a pathobiochemical reaction termed liver fibrosis. This is a dynamic process implying different rates of progression or regression. Thus, histological examination of a liver biopsy is essential for a diagnosis but biochemical tests are necessary for assessing the activity of the process and monitoring its evolution. We review the most important constituents of liver connective tissue and the biochemical tests developed for evaluating liver fibrosis. The aminopeptide of type III procollagen is the most widely used parameter: two different radioimmunoassays have been developed with different affinities for the two circulating forms of the molecule. The determination of serum P3P reveals an elevation of blood levels both in acute and chronic liver diseases. In the first, serum P3P is an index of hepatic necrosis and inflammation which correlates with other biochemical parameters. In the second it is an index of active fibrogenesis. Moreover, in primary biliary cirrhosis this parameter is an independent prognostic variable and an important predictor of survival. Other immunoassays exist for different collagen cleavage products, but their clinical value is not established. Laminin and fibronectin are the principal structural glycoproteins in liver. Fibronectin determination does not seem to be of clinical value in liver disease. In contrast, serum laminin correlates with the severity of portal venous pressure in advanced liver disease. Its concentration parallels the severity of varices and may indicate the risk of bleeding. Hyaluronate is a high molecular weight polysaccharide, raised serum concentrations reflect both its increased synthesis by activated fibroblasts and its impaired catabolism by the liver. Thus, it may be useful for evaluating and monitoring the progression of chronic liver disease. The measurement of the activity of prolyl 4-hydroxylase as well as that of lysine oxidase and other enzymes has been proposed, but their clinical value is not sufficiently demonstrated. A panel of tests (e.g., laminin, hyaluronate and the aminopeptide of type III procollagen) seems to be recommended for a biochemical assessment of liver fibrosis in clinical practice.