慢性肝病患者肝纤维化血清学指标与肝组织纤维化分期的量化关系

目的研究肝纤维化血清学指标与慢性肝病患者肝穿刺活体组织学检查纤维化分期的量化关系。方法用放射免疫法检测118例肝病患者血清层黏连蛋白（LN）、透明质酸（HA），Ⅲ型前胶原蛋白（PCⅢ）、Ⅳ型胶原蛋白（CⅣ）的水平，并与患者的肝组织病理学检查作对比。通过SPSS11．0软件包分析LN、HA、PCⅢ、CⅣ与肝组织纤维化分期及炎症分级的量化关系。结果LN、HA、PCⅢ、CⅣ与肝组织学炎症分级有相关性（r分别为0．394．0．449、0．443、0．35l，P值均〈0．01）；与肝组织纤维化分期也有相关性（r值分别为0．456、0．564、0．476、0．42l，P值均〈0．01）。LN．HA、PCⅢ、CⅣ对S2以上肝纤维化诊断界值分别为110、110、100、70ng／ml，其诊断灵敏度分别为70％、79％、79％、74％，特异度分别为68％，72％、64％、73％。对S4（早期肝硬化）的诊断界值分别为130、140、120．70ng／ml，其诊断灵敏度分别为79％、93％，79％，86％，特异度分别为66％、82％．72％、61％。受试者工作特征曲线分析显示：在这些患者中判断有无肝硬化存在，HA比其它指标更有价值；HA测定值大于l90ng／ml时，其诊断早期肝硬化的准确度为93％。结论慢性肝病患者，血清HA、LN、PCⅢ、CⅣ水平与肝纤维化分期有一定量化关系，其中HA诊断早期肝硬化有重要意义。

A quantitative study of the relationship between levels of liver fibrosis markers in sera and fibrosis stages of liver tissues of patients with chronic hepatic diseases

OBJECTIVES: To study the quantitative relationship between the levels of serum liver fibrosis markers and fibrosis stages of liver tissues in patients with chronic hepatic diseases. METHODS: In 118 patients with chronic hepatitis, fatty liver or cirrhosis, their Serum levels of LN, HA, PCIII and CIV were investigated by EIA and their liver histological changes were studied. The relationship between the levels of serum LN, HA, PCIII and CIV and the degrees of liver tissue fibrosis was analyzed quantitatively by using the SPSS11.0. RESULTS: A correlation between the levels of serum LN, HA, PCIII and CIV and the histologically assessed grades of inflammatory activity was found (r = 0.394, 0.449, 0.443, 0.351, respectively, P <0.01). The correlation between the levels of serum LN, HA, PCIII and CIV and the histological assessed stages of liver fibrosis was strong (r = 0.456, 0.564, 0.476, 0.421 respectively, P <0.01). The levels of serum LN, HA, PCIII and CIV of the patients with a stage 2 liver fibrosis were 110 ng/ml, 110 ng/ml, 100 ng/ml and 70 ng/ml respectively, with sensibilities of diagnosing stage 2 liver fibrosis at 70%, 79%, 79% and 74% respectively. Their specificities in diagnosing stage 2 liver fibrosis were 68%, 72%, 64% and 73% respectively. The levels of LN, HA, PCIII and CIV in serum of these patients diagnosing cut-off value in stage 4 liver fibrosis (early cirrhosis) were 130 ng/ml, 140 ng/ml, 120 ng/ml and 70 ng/ml respectively. Their sensibility of diagnosing liver cirrhosis was 79%, 93%, 79% and 86% respectively. Their specificity of diagnosing liver cirrhosis was 66%, 82%, 72% and 61% respectively. As shown by the ROC curves in these patients, differentiating patients with cirrhosis or without cirrhosis, serum HA level was more valuable than LN, PCIII, CIV (the areas under the curves = 0.938 vs 0.775, 0.787, 0.791 ) When serum HA was higher than 190 ng/ml, the veracity of diagnosing liver cirrhosis was 93%. CONCLUSIONS: There is a certain quantitative relationship between the levels of LN, HA, PCIII and CIV in serum and the degrees of liver tissue fibrosis. The level of HA in serum is an important reference datum for early diagnosing liver cirrhosis.