Removal of hyaluronic acid from the circulation in rheumatoid disease and primary biliary cirrhosis.

Recent evidence from metabolic studies in animals and from measurement of plasma and serum hyaluronic acid (HA) levels in humans indicates that the liver is the organ mainly responsible for the clearance of circulating HA. The clearance of HA from the bloodstream was therefore studied with tritium-labeled material of high specific activity in patients with rheumatoid arthritis or primary biliary cirrhosis (PBC). In patients with rheumatoid arthritis, HA clearance was similar to that reported in normal subjects and approached the range of hepatic blood flow. HA metabolism was also rapid. In patients with PBC, clearance was inversely related to the preexisting plasma HA levels and severity of disease. Renal excretion of HA remained low despite the slower decay of plasma concentrations. Metabolic degradation was not significantly impaired. Most of the injected material was accounted for as tritiated water within 24 hours. Taken with data from other species and with the raised plasma HA levels observed in a variety of liver diseases, our findings indicate that the liver may also be the major site for the uptake of circulating HA in humans. High levels of plasma HA in the absence of hepatic dysfunction can be taken as evidence of an increased input from the tissues.