Attallah A M, Omran D, Omran M M, Albannan M S, Zayed R A, Saif S, Farid A, Hassany M, Yosry A
a Research & Development Dept. , Biotechnology Research Center , New Damietta , Egypt.
b Faculty of Medicine, Dept. of Endemic Medicine and Hepatology , Cairo University , Cairo , Egypt.
Br J Biomed Sci. 2018 Jan;75(1):19-23. doi: 10.1080/09674845.2017.1362950. Epub 2017 Sep 25.
Fibrosis markers are useful for the prediction of cirrhosis but clinical scores such as King's score, AST-Platelet ratio index (APRI), Biotechnology research center (BRC), Fibrosis routine test (FRT), Fibro-α score and Fibro-quotient (FibroQ) have limited accuracy for diagnosing significant fibrosis. We hypothesised that new markers (reflecting the balance between hepatic fibrogenesis and fibrolysis) together with other indirect fibrosis markers would together construct a more sensitive and specific score capable of identifying fibrosis than existing scores.
Collagen IV, hyaluronic acid, platelet-derived growth factor (PDGF) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured by ELISA, and AST, ALT, platelet count, albumin, total bilirubin, INR and AFP by routine methods in 148 patients with hepatitis C induced liver disease. Stepwise linear discriminant analysis and area under receiver-operating characteristic curves (AUCs) were used to create a predictive score and compare it to others.
Patients with significant fibrosis (n = 100, F2-F4) showed 2.08, 2.14, 1.80 and 1.90-fold increase in collagen IV, hyaluronic acid, PDGF and TIMP-1, respectively, over patients with no or mild fibrosis (n = 48, F0/F1)(all p < 0.01). Significant independent predictors of F2-F4 were AFP (AUC 0.79), age (0.76), PDGF (0.74), collagen IV (0.78) and TIMP (0.75), which together formed a five-marker score 'Fibro-Mark' for predicting F2-F4. In comparison with other scores, AUC for Fibro-Mark was 0.89, BRC was 0.83, followed by FRT and King's score (both 0.82), APRI (0.80), Fibro-α (0.70) and finally Fibro Q (0.63).
The Fibro-Mark score provides better discrimination in hepatic-fibrosis staging in chronic hepatitis C patients than existing scores.
纤维化标志物对肝硬化的预测有一定作用,但诸如国王评分、天冬氨酸转氨酶-血小板比率指数(APRI)、生物技术研究中心(BRC)评分、纤维化常规检测(FRT)、Fibro-α评分和纤维化商数(FibroQ)等临床评分在诊断显著纤维化方面准确性有限。我们推测,新的标志物(反映肝纤维化生成与纤溶之间的平衡)与其他间接纤维化标志物共同构建的评分,相较于现有评分,在识别纤维化方面会更敏感、特异。
采用酶联免疫吸附测定法检测148例丙型肝炎所致肝病患者的IV型胶原、透明质酸、血小板衍生生长因子(PDGF)和基质金属蛋白酶-1组织抑制剂(TIMP-1),并通过常规方法检测天冬氨酸转氨酶、丙氨酸转氨酶、血小板计数﹑白蛋白、总胆红素、国际标准化比值(INR)和甲胎蛋白。采用逐步线性判别分析和受试者工作特征曲线下面积(AUC)来创建预测评分并与其他评分进行比较。
显著纤维化患者(n = 100,F2-F4)的IV型胶原、透明质酸、PDGF和TIMP-1分别比无或轻度纤维化患者(n = 48,F0/F1)增加了2.08倍、2.14倍、1.80倍和1.90倍(均p < 0.01)。F2-F4的显著独立预测因子为甲胎蛋白(AUC 0.79)、年龄(0.76)、PDGF(0.74)、IV型胶原(0.78)和TIMP(0.75),它们共同构成了用于预测F2-F4的五标志物评分“Fibro-Mark”。与其他评分相比,Fibro-Mark的AUC为0.89,BRC为0.83,其次是FRT和国王评分(均为0.82),APRI为0.80,Fibro-α为0.70,最后是FibroQ为0.63。
Fibro-Mark评分在慢性丙型肝炎患者肝纤维化分期中的鉴别能力优于现有评分。