肝纤维化血清五项标志物的诊断意义

目的探讨慢性肝炎患者血清透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(CⅣ)、层粘蛋白(LN)和转化生长因子β1(TGFβ1)对肝纤维化的诊断意义.方法检测116例病毒性肝炎患者血清HA、PCⅢ、CⅣ、LN、TGFβ1水平、并与其中87例慢性肝炎患者的肝组织病理作对比.结果血清HA与肝组织炎症活动度呈较弱的正相关(r＝0393,P<0.05),血清HA、PCⅢ、LN、TGFβ1与肝纤维化程度呈中等程度的正相关(r分别为0584、0454、0441和0612,P<005),血清CⅣ与之则呈较弱的正相关(r=0.319,P<0.05).血清HA诊断肝硬化的AUC明显大于血清PCⅢ、CⅣ、LN、TGFβ1者(AUC=0.904vs0.784、0.815、0.805、0828.P<0.05)血清HA、LN、TGFβ1判断S2期以上肝纤维化的ROC曲线下面积(AUC)明显大于血清PCⅢ、CⅣ者(AUC=0849、0.819、0836vs0702、0721,P<0.05).联合五项指标估计肝纤维化程度,判别分析只选人血清HA和TGFβ1.若将肝纤维化程度S1、S2、S3不作区分,判别效果中各期的差异有显著性(P<005).正确预测率为72.90%.结论五项指标均有助于诊断肝硬化和判断S2期以上肝纤维化,前者应选择血清HA.后者则可选择血清HA、LN或TGFβ1;估计肝纤维化程度以血清HA和TGFβ1同时检测为佳,但仅有助于估计慢性肝炎患者是"无肝纤维化”、"处于肝纤维化阶段”或"肝硬化”,而不能对肝纤维化程度进行精确估计.因而不能取代肝组织病理活检.

Diagnostic value of five serum makers for liver fibrosis

OBJECTIVE: To research the diagnostic value of serum hyaluronic acid (HA), type III procollagen (PCIII), type IV collagen (CIV), laminin (LN), and transforming growth factor-beta(1) (TGF-beta(1)) for liver fibrosis in patients with chronic hepatitis. METHODS: Serum levels of HA, PCIII, CIV, LN and TGF-beta(1) in 116 patients with chronic hepatitis and cirrhosis were investigated and compared with hepatic histological findings of 87 patients. RESULTS: The correlation between serum HA and histologically assessed grade of inflammatory activity was weak (r=0.393, P<0.05). The correlation between serum HA, PCIII, LN, TGF-beta(1) and histologically assessed stage of liver fibrosis were all moderate (r=0.584, 0.454, 0.441 and 0.612, respectively, P<0.05), while that between serum CIV and histologically assessed stage of liver fibrosis was weak (r=0.319, P<0.05). As shown by the ROC curves in cases of chronic hepatitis, the ability to differentiate patients with cirrhosis from those without cirrhosis was greater for serum HA than that for serum PCIII, CIV, LN, and TGF-beta(1) (the areas under the curves=0.904 vs 0.784, 0.815, 0.805, 0.828, P<0.05). The ability of serum HA, LN and TGF-beta(1) to differentiate patients with extensive liver fibrosis from those with no or mild liver fibrosis exceeded that of serum PCIII and CIV (the areas under the curves=0.849, 0.819, 0.836 vs 0.702, 0.721, P<0.05). To discriminate the stage of liver fibrosis, serum HA and TGF-beta(1) were selected from the five markers by Bayes discriminate analysis. If S(1), S(2) and S(3) were not required to be discriminated, discrimination between the three stages showed significant difference (P<0.05). The predictive accurate percentage was 72.90%. CONCLUSIONS: The five markers all have the ability not only to judge liver cirrhosis, in which the ability of serum HA is the best, but also to differentiate chronic hepatitis with extensive liver fibrosis from that with no or mild liver fibrosis, in which the ability of serum HA, LN, TGF-beta(1) is stronger than the other two. It is useful for detection of serum HA and TGF-beta(1) at the same time to discriminate the histologically assessed stage of fibrosis. Serum HA and TGF-beta(1) can be helpful in discriminating patients of chronic hepatitis with "no liver fibrosis", "liver fibrosis but no cirrhosis" and "liver cirrhosis", but cannot discriminate them accurately as the histologically assessed stage of fibrosis. They cannot displace liver biopsy for the judgement of liver fibrosis.