乙型肝炎病毒阳性肝硬化患者进展为肝细胞肝癌预测模型的建立及验证

Establishment and validation of a predictive model for HBV-positive hepatocellular carcinoma

目的基于实验室常用检测指标筛选乙型肝炎病毒(HBV)阳性肝硬化患者进展为肝细胞肝癌(HCC)的影响因素,建立预测模型并检验其效能。方法收集2010—2020年于中国医科大学附属第一医院就诊的男性乙型肝炎肝硬化患者661例(肝硬化组)和男性乙型肝炎HCC患者694例(HCC组)的病例资料进行回顾性分析,比较2组间年龄及实验室指标,包括血常规、肝功能(天门冬氨酸氨基转移酶-丙氨酸氨基转移酶比值、谷氨酰胺转移酶、总蛋白、前白蛋白、总胆汁酸、总胆红素、直接胆红素、胆碱酯酶)、HBV指标、甲胎蛋白(AFP)、纤维蛋白原(Fbg)、血钙(Ca^(2+))的差异。采用多因素Logistic回归分析肝硬化进展为HCC的影响因素。以HCC高发病风险相关指标(P<0.05)构建列线图预测模型,并通过受试者工作特征(ROC)曲线及校准曲线对模型进行验证。结果2组患者血常规、肝功能、HBV核心抗体(HBV-cAb)、抗HBc-IgM、AFP、Fbg、Ca^(2+)比较,差异有统计学意义(P<0.05)。多因素分析显示,Ca^(2+)(OR=35.770,95%CI 13.388~99.304)、HBV-cAb(OR=0.878,95%CI 0.816~0.944)、AFP(OR=1.002,95%CI 1.001~1.003)、Fbg(OR=1.369,95%CI 1.202~1.564)为HCC的独立影响因素(P<0.05),用此4个指标构建列线图预测模型,ROC曲线显示模型的曲线下面积为0.750(95%CI 0.720~0.781,P=0.126),验证组ROC曲线下面积为0.752(95%CI 0.705~0.798,P=0.098),与校准曲线贴合良好。结论基于Ca^(2+)、HBV-cAb、AFP、Fbg建立了一个HBV阳性肝硬化进展为HCC的预测模型,该模型经ROC曲线及校准曲线验证,具有良好的区分度和校准度。

Objective The risk factors for hepatocellular carcinoma(HCC)in hepatitis B virus(HBV)-positive cirrhosis patients were screened based on commonly used laboratory indexes for the purpose of establishing a predictive model and the prediction efficacy of established model was validated in a validation patient cohort.Methods The clinical data of 661 male patients with HBV-positive cirrhosis(cirrhosis group)and 694 male patients with HBV-positive HCC admitted to the First Hospital of China Medical University from 2010 to 2020 were retrospectively analyzed,age and complete blood count,liver function index(aspartate transaminase/alanine transaminase,glutamine transpeptidase,total protein,prealbumin,total bile acid,total bilirubin,direct bilirubin,cholinesterase),HBV markers,alpha-fetoprotein(AFP),fibrinogen,calcium were compared between the two groups.Multivariate Logistic regression was used to analyze the independent risk factors of HCC.The prediction model of high risk HCC(P<0.05)was constructed and validated by receiver operating characteristic(ROC)curve and calibration curve.Results There was significant difference in complete blood count,liver function index,HBV core antibody,HBV core antibody IgM,alpha-fetoprotein,fibrinogen,calcium between the two groups(P<0.05).Multivariate analysis showed that calcium(OR=35.770,95%CI 13.39-99.304),HBV core antibody(OR=0.878,95%CI 0.816-0.944),AFP(OR=1.002,95%CI 1.001-1.003),fibrinogen(OR=1.369,95%CI 1.202-1.564)were the independent risk factors for HCC(P<0.05),and were used for the nomogram.The AUC of the nomogram was 0.750(95%CI 0.720-0.781)and the AUC of the validation group was 0.752(95%CI 0.705-0.798).Conclusions Based on calcium,hepatitis B virus core antibody,AFP,fibrinogen,a nomogram of the HCC is established and verified by ROC curve,which could be used to predict the risk of HBV-positive HCC.