摘要：
目的 探讨慢性乙型肝炎(CHB)患者血清铜蓝蛋白(CP)水平与肝脏炎症活动度分级、纤维化分期的关系,建立肝纤维化分级无创模型并分析其诊断价值.方法 2009年1月至2011年6月于福建医科大学附属第一医院肝病中心确认的CHB患者148例,同步进行肝组织病理学、血清CP及生物化学指标检查.Spearman等级相关分析法判断CP水平与肝脏病理学分级之间的相关性；Logistic回归分析法分析相关指标的诊断意义.构建肝脏纤维化诊断预测模型,受试者工作曲线(ROC)法评价模型的诊断价值.结果 148例CHB患者炎症活动度分级G1、G2、G3、G4的血清CP平均值分别为(212.5±34.9)、(205.5±32.0)、(201.4±37.7)和(172.8±20.4) mg/L,ANOVA分析提示4组炎症活动度分级间CP水平的差异有统计学意义(F=6.309,P＜0.01)；纤维化分期S1、S2、S3、S4的血清CP平均水平分别为(217.4±32.3)、(206.0±37.7)、(194.2±29.8)和(179.7±30.4)mg/L,ANOVA分析提示纤维化分期间CP的差异有统计学意义(F=8.608,P＜0.01).Spearman等级相关分析法分析提示,CP与炎症活动度分级(r=-0.316,P＜0.01)以及纤维化分期(r=-0.404,P＜0.01)均呈负相关关系.应用ROC分别建立CP水平对S≥2、S≥3、S=4的诊断曲线,曲线下面积(AUC)分别为0.71、0.70和0.72.经Logistic回归分析,筛选出模型-1(S≥2)、模型-2(S≥3)、模型-3(S=4)组包括CP、甲胎蛋白、胆碱酯酶、PLT、年龄的肝纤维化独立预测因子,最终构建数学模型并计算肝纤维化评分,模型-1、模型-2、模型-3的AUC分别为0.84、0.83和0.87,准确率分别为71.8％、80.3％和79.2％.结论 CHB患者的血清CP水平与肝脏炎症活动度分级、纤维化分期呈负相关关系,随病理分级的增加而呈阶梯状降低.CP水平可作为无创性判断肝脏纤维化状态的一项重要指标,纳入CP而构建的肝纤维化预测模型对CHB肝纤维化肝硬化有较好的诊断价值.%Objective To investigate the relationship between levels of ceruloplasmin (CP) and inflammation grade,fibrosis stages in liver of patients with chronic hepatitis B (CHB),and to establish liver fibrosis non-invasive model and evaluate its diagnostic value for liver pathological stages.Methods Both liver biopsy samples and sera were collected from 148 consecutive CHB patients in Liver Center,First Affiliated Hospital,Fujian Medical University during January 2009 to June 2011.The relationships between CP and liver pathological stages were analyzed using Spearman rank correlation analysis.Receiver operator characteristic (ROC) curve was used to evaluate the diagnostic value of CP for liver pathological stages.The diagnostic values of relevant indicators were analyzed by Logistic regression.The liver pathology-predicting model was built and the diagnostic value of the model was analyzed by ROC curve.Results The mean values of CP in 148 CHB patients with liver inflammation grades of G1 to G4 were (212.5 ± 34.9),(205.5± 32.0),(201.4 ± 37.7) and (172.8 ± 20.4) mg/L,respectively,which were significantly different by ANOVA test (F=6.309,P＜0.01).Similarly,the mean values of CP in patients with liver fibrosis stages of S1 to S4 were (217.4±32.3),(206.0±37.7),(194.2±29.8) and (179.7±30.4) mg/L,respectively,which were significantly different by ANOVA test (F =8.608,P ＜ 0.01).Spearman rank correlation analysis showed that CP was negatively correlated with liver inflammation grades (r=-0.316,P＜0.01) and fibrosis stages (r=-0.404,P＜0.01).ROC curve analysis revealed that the area under the curves (AUC) were 0.71 (S≥2),0.70 (S≥3) and 0.72 (S=4).Multiple Logistic regression analysis showed that CP,α-fetoprotein,cholesterol,platelet and age were independent predictors for liver fibrosis.ROC curve analysis revealed that AUC were 0.84 in model-1 (S≥2),0.83 in model-2 (S≥3) and 0.87 in model-3 (S=4).The accuracy rates were 71.8％,80.3％ and 79.2％,respectively.Conclusions The CP levels are negatively correlated with inflammation grades and fibrosis stages in the liver of CHB patients.CP could be an important non-invasive indicator for liver fibrosis and the model including CP can be used to predict liver fibrosis in CHB.
