Serum hyaluronan as a marker of liver fibrosis.

Abstract

Hepatic fibrosis is a complex process that involves changes in the amounts of extracellular matrix components and activation of cells which produce these components. Consequently, interest in the identification and determination of blood substances related to matrix material have increased in the recent past years with the need for markers of fibrosis to monitor chronic liver diseases. However blood levels of these substances depend on both enhanced liver production and other factors such as release from other tissues, hepatic uptake, hepatic degradation or urinary excretion. Hyaluronan (hyaluronate or hyaluronic acid), is an unbranched polysaccharide found in the extracellular spaces. Simple assays for serum hyaluronan determination make it possible to use it as a diagnostic marker for diseases. Because hyaluronan is a component of liver fibrosis and is cleared from the blood by the liver endothelial cells, most investigations have been made in liver diseases and increased serum levels were found in these patients. Although the pathophysiological mechanisms involved are not fully understood, both an increase in hepatic production and a decrease in hepatic removal might be involved. Increases in hyaluronan production may be caused by the induction of Ito cell proliferation and the synthesis of extracellular matrix components by inflammation via cytokines. Decreases in serum hyaluronan uptake and degradation may be caused by endothelial cell injury and by the capillarization of sinusoids induced by fibrosis. The measurement of serum hyaluronan levels has therefore been suggested to monitor the fibrotic process in chronic liver diseases.