The high levels of hyaluronic acid (HA), a glycosaminoglycan of the liver extracellular matrix, which is synthesized and degraded in the liver sinusoidal cells, have been related with a decreased function of the endothelial sinusoidal cells. The relevance of HA in alcoholic liver disease has not been sufficiently evaluated, and therefore the current study was addressed to assess whether serum HA reflects the severity of liver fibrosis and fibrogenesis as well as the potential usefulness of hyaluronic acid as a marker of early fibrosis in alcoholics with liver damage. Serum HA and aminoterminal propeptide of collagen III (PIIIP) 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 plus alcoholic hepatitis = 11). The severity of liver inflammation and fibrosis were scored in liver specimens as: 0, no lesion; 1+ mild; 2+ moderate; and 3+ severe. Twenty-seven patients (60%) had HA above normal 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 damage. Hyaluronic acid levels were higher in those patients with more liver inflammation (0, 128 +/- 38; 1+, 553 +/- 141; 2+, 668 +/- 259; 3+, and 1,073 +/- 419 microg/L; P = .004) and of fibrosis (0, 79 +/- 32; 1+, 156 +/- 70; 2+, 219 +/- 105; and 3+, 695 +/- 114 microg/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+, and 66 +/- 30 ng/mL, P: not significant). Moreover, a direct linear correlation was observed between HA and PIIIP (r = .72, P < .001). A receiver 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). In conclusion, serum HA reflects the severity of liver inflammation, fibrosis, and fibrogenesis in patients with alcoholic liver disease and is useful as a marker of precirrhotic and cirrhotic stages.