预测HBV相关肝细胞癌生存的列线图模型的建立

陈松海; 王春艳; 郭畅; 张珊; 邓亚; 陆荫英; 纪冬

doi:10.3969/j.issn.1001-5256.2022.07.020

预测HBV相关肝细胞癌生存的列线图模型的建立

DOI: 10.3969/j.issn.1001-5256.2022.07.020

陈松海¹,
王春艳¹,
郭畅¹,
张珊^{1, 2},
邓亚³,
陆荫英^{1, 2, , ,},
纪冬^{1, 2, 3, , ,}

1.
解放军总医院第五医学中心肝病医学部，北京 100039
2.
北京大学三〇二临床医学院，北京 100039
3.
南方医科大学第二临床医学院，广州 510515

基金项目:

解放军总医院医疗大数据与人工智能研发项目 (2019MBD-024);

北京市自然科学基金面上项目 (7222173);

深圳市科技创新委员会可持续发展专项 (KCXFZ202002011006448)

伦理学声明: 本研究于2020年7月14日通过解放军总医院第五医学中心伦理委员会审批，批号为2020055D。

利益冲突声明: 本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明: 纪冬负责课题设计及拟定写作思路；陈松海、王春艳、郭畅进行资料分析及撰写论文；所有作者均参与收集及分析数据；陆荫英指导撰写文章并最后定稿。

详细信息

通信作者:
陆荫英，luyinying1973@163.com

纪冬，jidg302@126.com

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出版历程
- 收稿日期: 2021-11-26
- 录用日期: 2022-01-24
- 出版日期: 2022-07-20

Establishment of a nomogram model for predicting the survival of hepatitis B virus-related hepatocellular carcinoma

Songhai CHEN¹,
Chunyan WANG¹,
Chang GUO¹,
Shan ZHANG^{1, 2},
Ya DENG³,
Yinying LU^{1, 2
, ,
,},
Dong JI^{1, 2, 3
, ,
,}

1.
Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
2.
Peking University 302 Clinical Medical School, Beijing 100039, China
3.
The Second Clinical Medical School of Southern Medical University, Guangzhou 510515, China

Research funding:

Medical Big Data and Artificial Intelligence Development Fund of Chinese PLA General Hospital (2019MBD-024);

Beijing Municipal Natural Science Foundation (7222173);

Science Technology and Innovation Committee of Shenzhen Municipality (KCXFZ202002011006448)

More Information

Corresponding author: LU Yinying, luyinying1973@163.com(ORCID: 0000-0002-7737-2334); JI Dong, jidg302@126.com(ORCID: 0000-0001-8214-462X)

摘要

摘要: 目的筛选HBV相关肝细胞癌(HCC)死亡的危险因素并建立列线图预测模型。方法回顾性分析2010年1月—2020年1月在解放军总医院第五医学中心首次确诊为HBV相关HCC的700例患者的资料并进行随访，起点为HCC的诊断日期，终点为死亡。根据随访结果，分为死亡组(n=407)和生存组(n=293)。计量资料用组间比较采用独立样本t检验或Mann-Whitney U检验；计数资料组间比较采用χ²检验；采用Kaplan-Meier法计算生存率，log-rank检验进行单因素分析，应用多变量Cox比例风险回归筛选独立危险因素，并构建可预测1、3、5年生存率的列线图模型，采用200次10折交叉验证法对模型进行评价。结果两组的性别构成、Alb、TBil、ALT、AFP、CHE、LSM及BCLC分期比较差异均有统计学意义(P值均＜0.05)。多因素分析显示男性[风险比(HR)=1.390，95%CI：1.077~1.794]、CHE(2500~5000 U/L)(HR=1.996，95%CI：1.470~2.710)、CHE＜2500 U/L(HR=3.210，95%CI：2.188~4.709)、AFP≥400 ng/mL(HR=1.803，95%CI：1.412~2.303)、肝弹性值≥17.5 kPa(HR=1.719，95%CI: 1.349~2.190)、巴塞罗那分期B/C(HR=3.811，95%CI：2.994~4.852)、巴塞罗那分期D(HR=3.708，95%CI：2.520~5.455)为死亡的独立危险因素(P值均＜0.05)。基于以上因素建立列线图模型，一致性指数为0.789(95%CI：0.769~0.809)，校准曲线拟合良好，模型预测值与实际观测值之间的差异无统计学意义。结论本研究建立的列线图模型可以个体化预测HBV相关HCC患者的1、3、5年的生存率，有助于准确评估预后。
- 癌, 肝细胞 /
- 乙型肝炎病毒 /
- 列线图
Abstract: Objective To investigate the risk factors for death in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and to establish a nomogram predictive model. Methods A retrospective analysis was performed for the clinical data of 700 patients who were diagnosed with HBV-related HCC for the first time in The Fifth Medical Center of Chinese PLA General Hospital from January 2010 to January 2020, and the starting point of follow-up was the date of HCC diagnosis, with death as the endpoint. According to the results of follow-up, the patients were divided into death group with 407 patients and survival group with 293 patients. The independent samples t-test or the Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was used for univariate analysis. The multivariate Cox proportional-hazards regression model was used to screen out independent risk factors and establish a nomogram model to predict 1-, 3-, and 5-year survival rates, and 10-fold cross validation was performed 200 times to evaluate the model. Results There were significant differences between the two groups in sex composition, albumin, total bilirubin, alanine aminotransferase, alpha-fetoprotein (AFP), cholinesterase (CHE), liver stiffness measurement (LSM), and Barcelona Clinic Liver Cancer (BCLC) stage (all P < 0.05). The multivariate analysis showed that male sex (hazard ratio [HR]=1.390, 95% confidence interval [CI]: 1.077-1.794, P < 0.05), CHE (2500-5000 U/L) (HR=1.996, 95%CI: 1.470-2.710, P < 0.05), CHE < 2500 U/L (HR=3.210, 95%CI: 2.188-4.709, P < 0.05), AFP≥400 ng/mL (HR=1.803, 95%CI: 1.412-2.303, P < 0.05), LSM ≥17.5 kPa (HR=1.719, 95%CI: 1.349-2.190, P < 0.05), BCLC stage B/C (HR=3.811, 95%CI: 2.994-4.852, P < 0.05), and BCLC stage D (HR=3.708, 95%CI: 2.520-5.455, P < 0.05) were independent risk factors for death. The nomogram model established based on the above factors had an index of concordance of 0.789 (95%CI: 0.769-0.809) with well-fitted calibration curves, and there was no significant difference between the predicted value of the model and the actual observed value. Conclusion The nomogram model established in this study can predict the 1-, 3-, and 5-year survival rates of HBV-related HCC patients and help to accurately assess the prognosis of patients.
- Carcinoma, Hepatocellular /
- Hepatitis B virus /
- Nomograms

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图 1 HBV相关HCC死亡的危险因素

注：ULN，正常值上限。各因素的参照(HR=1)：BCLC 0/A期；AFP＜20 ng/mL；CHE≥5000 U/L；女性；LSM＜17.5 kPa；ALT＜1×ULN；TBil＜1×ULN；Alb≥1×ULN。

Figure 1. High-risk factors for the mortality of HBV-related HCC

下载: 全尺寸图片幻灯片

图 2 HBV相关HCC的生存曲线

Figure 2. Survival curve for HBV-related HCC

下载: 全尺寸图片幻灯片

图 3 预测HBV相关HCC生存率的列线图及校正曲线

Figure 3. Nomogram and calibration curve to predict survival rate of HBV-related HCC

下载: 全尺寸图片幻灯片

表 1 纳入患者的基线资料

Table 1. Baseline characteristics of enrolled patients

项目	总体(n=700)	死亡组(n=407)	生存组(n=293)	统计值	P值
男[例(%)]	522(74.6)	332(81.6)	190(64.8)	χ²=25.13	＜0.001
年龄(岁)	53.8±9.3	54.1±9.5	53.6±8.9	t=-0.67	0.501
家族史[例(%)]	385(55.0)	213(52.3)	172(58.7)	χ²=2.79	0.095
糖尿病[例(%)]	90(12.9)	49(12.0)	41(14.0)	χ²=0.58	0.446
HBeAg阳性[例(%)]	241(34.4)	137(33.7)	104(35.5)	χ²=0.25	0.614
HBeAg血清学转换¹⁾[例(%)]	53(13.4)	37(15.7)	16(9.9)	χ²=2.37	0.124
LSM≥17.5 kPa[例(%)]	465(66.4)	315(77.4)	150(51.2)	χ²=52.40	＜0.001
Alb(g/L)	33.20±6.20	31.57±6.10	35.60±5.60	t=8.90	＜0.001
TBil(μmol/L)	19.2(13.2~32.1)	22.0(14.8~41.4)	16.2(11.4~23.4)	Z=-7.18	＜0.001
PLT(×10⁹/L)	94(59~145)	92(58~145)	95(61~146)	Z=-0.43	0.670
ALT(U/L)	34(23~52)	45(30~71)	25(20~33)	Z=-13.09	＜0.001
AFP[例(%)]				χ²=56.06	＜0.001
＜20 ng/mL	319(45.6)	147(36.1)	172(58.7)
20~400 ng/mL	199(28.4)	114(28)	85(29.0)
≥400 ng/mL	182(26.0)	146(35.9)	36(12.3)
CHE[例(%)]				χ²=121.78	＜0.001
≥5000 U/L	241(34.4)	78(19.2)	163(55.6)
2500~5000 U/L	295(42.2)	188(46.2)	107(36.5)
＜2500 U/L	164(23.4)	141(34.6)	23(7.8)
BCLC分期[例(%)]				χ²=174.49	＜0.001
0/A	333(47.6)	109(26.8)	224(76.5)
B/C	305(43.6)	239(58.7)	66(22.5)
D	62(8.8)	59(14.5)	3(1.0)
注：1)定义为经抗病毒治疗后HBeAg阳性转为抗HBe阳性者在HBeAg阳性(397例)中的比例。

下载: 导出CSV

表 2 200次10折交叉验证的AUC值

Table 2. The area under the receiver operating characteristic curves from 200-time 10-fold cross validation

生存率	最小值	Q₂₅	中位值	平均值	Q₇₅	最大值
1年	0.704	0.834	0.864	0.862	0.893	0.968
3年	0.679	0.831	0.863	0.860	0.894	0.981
5年	0.609	0.801	0.844	0.841	0.887	0.994

下载: 导出CSV

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