SERUM HYALURONATE REFLECTS HEPATIC FIBROGENESIS IN ALCOHOLIC LIVER-DISEASE AND IS USEFUL AS A MARKER OF FIBROSIS

The high levels of hyaluronic acid (HA), a glycosaminoglycan of the li ver extracellular matrix, which is synthesized and degraded in the liv er sinusoidal cells, have been related with a decreased function of th e endothelial sinusoidal cells. The relevance of HA in alcoholic liver disease has not been sufficiently evaluated, and therefore the curren t study was addressed to assess whether serum HA reflects the severity of liver fibrosis and fibrogenesis as well as the potential usefulnes s of hyaluronic acid as a marker of early fibrosis in alcoholics with liver damage. Serum HA and aminoterminal propeptide of collagen III (P IIIP) levels, a marker of liver fibrogenesis in alcoholics with liver disease, were assessed in 45 chronic alcoholic patients (31 men and 14 women, age: 44.1 +/- 1.5 years) (normal liver = 7; fatty changes = 8; fibrosis = 7; alcoholic hepatitis = 6; cirrhosis = 6; and cirrhosis p lus alcoholic hepatitis = 11). The severity of liver inflammation and fibrosis were scored in liver specimens as: 0, no lesion; 1+ mild; 2moderate; and 3+ severe. Twenty-seven patients (60%) had HA above norm al values (1 patient with fatty changes, 3 patients with fibrosis, and all patients with alcoholic hepatitis or cirrhosis). Hyaluronic acid and (PIIIP) levels increased in parallel with the severity of liver da mage. Hyaluronic acid levels were higher in those patients with more l iver inflammation (0, 128 +/- 38; 1+, 553 +/- 141; 2+, 668 +/- 259; 3, and 1,073 +/- 419 mu g/L; P = .004) and of fibrosis (0, 79 +/- 32; 1 +, 156 +/- 70; 2+, 219 +/- 105; and 3+, 695 +/- 114 mu g/L; P < .001). Procollagen III peptide levels were related with fibrosis (0, 17 +/- 1; 1+, 25 +/- 6; 2+, 47 +/- 13; 3+, and 55 +/- 9 ng/mL; P = .002) but not with inflammation (0, 29 +/- 7; 1+, 45 +/- 7; 2+, 54 +/- 9; 3+, an d 66 +/- 30 ng/mL, P: not significant). Moreover, a direct linear corr elation was observed between HA and PIIIP (r = .72, P < .001). A recei ver operating characteristic (ROC) curve analysis revealed that HA was similar to PIIIP levels in discriminating between alcoholics without fibrosis and those with fibrosis (area under the ROC curves) .913 +/- .042 vs. .867 +/- .054; P: n.s). hn conclusion, serum HA reacts the se verity of liver inflammation, fibrosis, and fibrogenesis in patients w ith alcoholic liver disease and is useful as a marker of precirrhotic and cirrhotic stages.