血清纤维化指标对肝纤维化诊断价值的研究

目的评价血清纤维化指标透明质酸（HA）、Ⅳ型胶原（CⅣ）、Ⅲ型前胶原肽（PⅢP）、层黏连蛋白（LN）对肝纤维化诊断的价值.方法对确诊的慢性乙型肝炎患者50例和健康人18例,测定血清纤维化指标水平,并进行肝组织纤维化分期.根据受试者工作特征曲线判别4项指标对于肝纤维化分期的诊断价值.结果血清HA、CⅣ、PⅢP和肝脏组织炎症分级呈较弱正相关（r分别为0.430、0.382和0.300,P＜0.05）.血清HA、CⅣ与肝脏组织纤维化分期呈中度正相关（r分别为0.614、0.708,P＜0.05）.血清HA、CⅣ水平随肝纤维化的进展程度而升高.血清HA诊断早期肝硬化（S4）的受试者工作特征曲线下面积（AUC）大于血清CⅣ、PⅢP和LN（AUC=0.967比0.932、0.659、0.403）.血清CⅣ诊断肝纤维化（S1～S4）的AUC大于血清HA、PⅢP和LN（AUC=0.853比0.680、0.536、0.487）.血清LN对于肝组织分级或分期均无统计学意义.联合HA＋CⅣ检测比单一指标有更高的特异度.结论血清纤维化指标对肝纤维化进程有一定的预测意义,但不能对肝纤维化精确分期,因此不能取代肝组织病理活检.联合多项指标检测可在一定程度上提高检测效率.寻找新的血清标志物和联合其他标志物是肝纤维化无创性研究的趋势所在.

Serum fibrosis markers in diagnosing liver fibrosis

OBJECTIVE: To evaluate the clinical value of serum fibrosis markers hyaluronic acid (HA), type IV collagen (CIV), type III procollagen N peptide (PIIIP) and laminin (LN) in the diagnosis of liver fibrosis. METHODS: Detection of the serum levels of these markers including HA, CIV, PIIIP, LN was carried out in 50 patients with chronic hepatitis B and 18 healthy persons. Liver biopsy was performed in all patients. The relationship between the markers and liver fibrosis stage was analyzed and the diagnostic value of the markers in liver fibrosis stage evaluated with receiver operating curve. RESULTS: The correlation between serum HA, CIV, PIIIP and histologically assessed grade of inflammatory activity was weak (r = 0.430, 0.382 and 0.300, respectively, P < 0.05). The correlation between serum HA, CIV and histologically assessed stage of liver fibrosis were moderate (r = 0.614, 0.708, respectively, P < 0.05). The increase in serum HA, CIV was correlated with the progression of liver fibrosis. Based on receiver operating curve, the value of using serum HA to differentiate patients with early cirrhosis (S4) from those without cirrhosis (S0-S3) was greater than that of serum CIV, PIIIP and LN (the areas under the curves = 0.967 vs 0.932, 0.659, 0.403), while the ability of serum CIV to predict liver fibrosis (S1-S4) was superior to that of serum HA, PIIIP and LN (areas under the curves = 0.853 vs 0.680, 0.536, 0.487). Serum LN was found to show limited changes in different pathologic grade and stage. The combined detection of HA and CIV has higher specificity than that of a single marker. CONCLUSIONS: Serum fibrosis markers can be helpful in diagnosis of liver fibrosis even in its early stage, but can not discriminate accurately the stage of fibrosis as accurately as the histological assessment. The combination of fibrosis markers is more valuable than single marker. New fibrosis markers and combination of noninvasive markers are the future trend in liver fibrosis research.