Parés A, Deulofeu R, Giménez A, Caballería L, Bruguera M, Caballería J, Ballesta A M, Rodés J
Alcohol and Liver Units, and Laboratory of Biochemistry, Hospital Clínic i Provincial, University of Barcelona, Spain.
Hepatology. 1996 Dec;24(6):1399-403. doi: 10.1002/hep.510240615.
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.
透明质酸（HA）是肝脏细胞外基质的一种糖胺聚糖，在肝窦状细胞中合成和降解，其高水平与肝窦状内皮细胞功能降低有关。HA在酒精性肝病中的相关性尚未得到充分评估，因此本研究旨在评估血清HA是否反映肝纤维化和纤维生成的严重程度，以及透明质酸作为肝损伤酒精患者早期纤维化标志物的潜在用途。对45例慢性酒精患者（31例男性和14例女性，年龄：44.1±1.5岁）（正常肝脏=7例；脂肪变性=8例；纤维化=7例；酒精性肝炎=6例；肝硬化=6例；肝硬化加酒精性肝炎=11例）评估血清HA和III型胶原氨基端前肽（PIIIP）水平，PIIIP是肝病酒精患者肝纤维生成的标志物。肝组织标本中肝脏炎症和纤维化的严重程度评分如下：0，无病变；1+，轻度；2+，中度；3+，重度。27例患者（60%）的HA高于正常值（1例脂肪变性患者，3例纤维化患者，所有酒精性肝炎或肝硬化患者）。透明质酸和（PIIIP）水平随肝损伤严重程度平行升高。肝炎症更严重的患者透明质酸水平更高（0，128±38；1+，553±141；2+，668±259；3+，1073±419μg/L；P = 0.004），纤维化更严重的患者也是如此（0，79±32；1+，156±70；2+，219±105；3+，695±114μg/L；P < 0.001）。前胶原III肽水平与纤维化有关（0，17±1；1+，25±6；2+，47±13；3+，55±9 ng/mL；P = 0.002），但与炎症无关（0，29±7；1+，45±7；2+，54±9；3+，66±30 ng/mL，P：无显著性）。此外，观察到HA与PIIIP之间存在直接线性相关性（r = 0.72，P < 0.001）。受试者工作特征（ROC）曲线分析显示，在区分无纤维化和有纤维化的酒精患者方面，HA与PIIIP水平相似（ROC曲线下面积）0.913±0.042对0.867±0.054；P：无显著性）。总之，血清HA反映酒精性肝病患者肝脏炎症、纤维化和纤维生成的严重程度，可作为肝硬化前期和肝硬化阶段的标志物。
