INCREASED ASCITIC LEVEL OF HYALURONAN IN LIVER-CIRRHOSIS

Hyaluronan (HA) is a polysaccharide that forms a critical component of extracellular matrixes. It is present in high concentrations in tissu es undergoing remodeling and morphogenesis. Serum HA is elevated in pa tients with chronic liver disease, and this has been considered to be caused by impaired degradation by the liver endothelial cells. We stud ied the level of HA in the ascitic fluid and plasma from 27 patients w ith cirrhotic ascites, These values were compared with peritoneal dial ysate effluent (PDE) and plasma from 33 patients with uremia who were undergoing continuous ambulatory peritoneal dialysis (CAPD), The media n HA levels in ascitic fluid and plasma from our 26 patients with cirr hosis were significantly higher than corresponding PDE and plasma valu es from the 33 CAPD patients (p < 0.0001), The median peritoneal/plasm a ratios of creatinine, albumin, and immunoglobulin G in either cirrho tic or CAPD patients were less than unity. In contrast, the median per itoneal/plasma ratios of HA in both groups of patients exceeded one wi th a higher peritoneal/plasma ratio of HA in patients with cirrhosis ( p = 0.0035). A significant correlation was observed between the asciti c level of HA and interleukin-1 beta, interleukin-6, or transforming g rowth factor-beta. Our in vitro cell culture studies revealed that HA is synthesized by both mesothelial cells and macrophages. We observed an additive effect in the synthesis of HA by mesothelial cells when th e macrophage-conditioned medium was added to the RPMI culture medium. We conclude that a high level of HA is found in ascites from patients with cirrhosis. Our results strongly suggest that simultaneous increas ed synthesis of HA by the peritoneal cells and a reduction of degradat ion by liver endothelial cells occur in these patients with cirrhosis with ascites, This event of increased HA synthesis may be contributory to remodeling and regeneration of the peritoneal lining.