Nomogram modeling of hepatocellular carcinoma in patients with sustained HCV antiviral response
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摘要:
目的 探究影响丙型肝炎病毒(HCV)抗病毒持续应答患者发生肝细胞癌的因素，并以此绘制列线图，为临床该类患者发生肝细胞癌的预防提供更为简便直观的预测工具。 方法 选取2020年6月—2022年6月浙江大学医学院附属第二医院临平院区收治的97例HCV感染患者为研究对象，经过治疗后均达到抗病毒持续应答。对患者进行为期2年的随访，根据随访结果分为发生肝细胞癌组(20例)和未发生肝细胞癌组(77例)。分析HCV抗病毒持续应答患者发生肝细胞癌的影响因素，构建列线图模型，并对模型进行评估和验证。 结果 发生肝细胞癌组患者的年龄、饮酒、糖尿病史、肝硬化、总胆红素(TBIL)、甲胎蛋白(AFP)与未发生肝细胞癌组患者比较，差异均有统计学意义(P < 0.05)。多因素logistic回归分析结果显示，年龄、饮酒、糖尿病史、肝硬化、AFP均为HCV抗病毒持续应答患者发生肝细胞癌的影响因素(P < 0.05)。ROC曲线显示，构建的列线图模型ROC曲线下面积为0.862(95% CI：0.805~0.939)，Hosmer-Lemeshow检验结果显示，χ2=5.028，P=0.670。 结论 HCV抗病毒持续应答患者发生肝细胞癌与年龄、饮酒、糖尿病史、肝硬化、AFP等有关，基于以上因素构建的列线图模型具有较好的准确度和一致性。 Abstract:Objective To explore the factors influencing the development of hepatocellular carcinoma (HCC) in patients with a sustained response to hepatitis C virus (HCV) therapy, and to construct a nomogram as a simple and intuitive tool for HCC risk prediction and prevention in these patients. Methods A total of ninety-seven patients with hepatitis C infection admitted to the Second Affiliated Hospital of Zhejiang University Medical College from June 2020 to June 2022, were selected as study subjects. A two-year follow-up was conducted, and the patients were divided into a hepatocellular carcinoma group (20 cases) and a hepatocellular carcinoma group (77 cases) according to the follow-up results. The factors associated with the development of hepatocellular carcinoma in patients with sustained HCV antiviral response were analyzed, and a nomogram model was constructed, evaluated, and validated. Results The age, alcohol consumption, history of diabetes mellitus, cirrhosis, total bilirubin (TBIL), and alpha fetoprotein (AFP) levels differed significantly between patients who developed hepatocellular carcinoma and those who did not develop hepatocellular carcinoma (P < 0.05). The results of multifactorial logistic regression analysis showed that age, alcohol consumption, history of diabetes, liver cirrhosis, and AFP were independent risk factors for the development of hepatocellular carcinoma in patients with sustained HCV antiviral response (P < 0.05). The ROC curves showed that the area under the curve of the nomogram model constructed in this study were 0.862 (95% CI: 0.805-0.939). The Hosmer-Lemeshow test showed that (χ2=5.028, P=0.670). Conclusion The development of hepatocellular carcinoma in patients with sustained HCV antiviral response is related to age, alcohol consumption, history of diabetes, cirrhosis, and AFP. The nomograph model based on these factors shows high accuracy and consistency. -
图 1 HCV抗病毒持续应答患者发生肝细胞癌的列线图模型
Figure 1. A nomogram model of hepatocellular carcinoma in patients with sustained HCV antiviral response
图 2 HCV抗病毒持续应答患者发生肝细胞癌列线图模型的ROC曲线分析
Figure 2. ROC curve analysis of the nomogram model of hepatocellular carcinoma in patients with sustained HCV antiviral response
图 3 列线图模型预测HCV抗病毒持续应答患者发生肝细胞癌的矫正曲线
Figure 3. Calibration curve of the nomogram for assessing hepatocellular carcinoma prediction in patients with sustained HCV antiviral response
表 1 2组HCV患者一般资料比较
Table 1. Comparison of general data in HCV patients between two groups
项目 发生肝细胞癌组(n=20) 未发生肝细胞癌组(n=77) 统计量 P值 年龄(x±s，岁) 60.25±5.31 55.64±5.02 3.616a ＜0.001 性别[例(%)] 0.292b 0.589 男性 12(60.00) 41(53.25) 女性 8(40.00) 36(46.75) 吸烟[例(%)] 1.753b 0.186 是 5(25.00) 10(12.99) 否 15(75.00) 67(87.01) 饮酒[例(%)] 6.264b 0.012 是 7(35.00) 9(11.69) 否 13(65.00) 68(88.31) 糖尿病史[例(%)] 7.576b 0.006 是 12(60.00) 21(27.27) 否 8(40.00) 56(72.73) 高血压史[例(%)] 1.121b 0.290 是 7(35.00) 18(23.38) 否 13(65.00) 59(76.62) 冠心病史[例(%)] 1.353b 0.245 是 9(45.00) 24(31.17) 否 11(55.00) 53(68.83) 肝病家族史[例(%)] 1.355b 0.244 是 6(30.00) 14(18.18) 否 14(70.00) 63(81.82) 肝硬化[例(%)] 13.636b ＜0.001 是 11(55.00) 12(15.58) 否 9(45.00) 65(84.42) Child-Pugh分级[例(%)] 0.336b 0.562 A级 17(85.00) 69(89.61) B级 3(15.00) 8(10.39) 实验室指标 HGB(x±s，g/L) 134.62±15.30 130.58±15.64 1.034a 0.304 ALB(x±s，g/L) 45.62±6.78 45.07±6.38 0.339a 0.735 PLT(x±s，×109/L) 125.88±10.54 123.23±10.15 1.032a 0.305 TBIL(x±s，μmol/L) 25.26±5.49 22.41±5.22 2.153a 0.034 Cr(x±s，μmol/L) 66.57±11.95 66.33±11.63 0.082a 0.935 ALT(x±s，U/L) 46.85±7.65 46.36±7.19 0.268a 0.789 AST(x±s，U/L) 37.64±6.20 38.22±6.87 0.343a 0.732 AFP(x±s，ng/mL) 7.69±1.67 4.85±1.15 8.902a ＜0.001 注：a为t值，b为χ2值。 
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表 2 变量赋值情况
Table 2. Variable assignment
变量 赋值方法 年龄 连续变量，以实际值赋值 饮酒 否=1，是=2 糖尿病史 否=1，是=2 肝硬化 否=1，是=2 TBIL 连续变量，以实际值赋值 AFP 连续变量，以实际值赋值
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表 3 HCV抗病毒持续应答患者发生肝细胞癌影响因素的多因素logistic分析
Table 3. Multivariate logistic analysis of factors influencing hepatocellular carcinoma in patients with sustained antiviral response to HCV
变量 B SE Waldχ2 P值 OR值 95% CI 年龄 0.897 0.348 6.644 ＜0.001 2.452 1.215~3.689 饮酒 0.728 0.258 7.962 ＜0.001 2.071 1.489~2.653 糖尿病史 0.944 0.399 5.598 ＜0.001 2.570 1.877~3.263 肝硬化 1.285 0.457 7.906 ＜0.001 3.615 2.298~4.931 TBIL 0.689 0.572 1.451 0.429 0.502 0.318~0.686 AFP 1.397 0.604 5.350 ＜0.001 4.043 2.972~5.114
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