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浙江大学学报(医学版)  2020, Vol. 49 Issue (3): 375-382    DOI: 10.3785/j.issn.1008-9292.2020.06.04
原著     
基于白蛋白胆红素指数的肝细胞癌根治性手术患者中期死亡风险预测模型评估
王晓波1(),张兆辉2,吴章强3,孙跃宗4,章义利5,龚鸣6,季峰1,*()
1. 浙江大学医学院附属第一医院消化内科, 浙江 杭州 310003
2. 浙江大学金华医院肝胆胰外科, 浙江 金华 321000
3. 浙江金华广福医院胃肠外科, 浙江 金华 321000
4. 金华市中医医院, 浙江 金华 321000
5. 浙江大学金华医院体检中心, 浙江 金华 321000
6. 金华市人民医院中医科, 浙江 金华 321000
Prediction model of mid-term fatality risk after radical resection in patients with hepatocellular carcinoma based on ALBI-grade
WANG Xiaobo1(),ZHANG Zhaohui2,WU Zhangqiang3,SUN Yuezong4,ZHANG Yili5,GONG Ming6,JI Feng1,*()
1. Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
2. Department of Hepatobiliary and Pancreatic Surgery, Jinhua Hospital of Zhejiang University, Jinhua 321000, Zhejiang Province, China
3. Gastrointestinal Surgery, Jinhua Guangfu Hospital, Jinhua 321000, Zhejiang Province, China
4. Jinhua Hospital of Traditional Chinese Medicine, Jinhua 321000, Zhejiang Province, China
5. Physical Examination Center, Jinhua Hospital of Zhejiang University, Jinhua 321000, Zhejiang Province, China
6. Department of Traditional Chinese Medicine, Jinhua People's Hospital, Jinhua 321000, Zhejiang Province, China
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摘要:

目的: 构建基于白蛋白胆红素指数(ALBI)的原发性肝细胞癌(HCC)根治性手术患者中期死亡风险的临床预测模型并验证其预测能力。方法: 采用回顾性队列研究方法,纳入2010年1月至2016年8月于浙江大学金华医院、金华市人民医院、金华市中医医院、金华市广福医院接受HCC根治性手术的533例患者,提取术后生存情况等资料。训练组纳入407例患者,验证组纳入126例患者,两组间基线资料差异无统计学意义(均P>0.05)。训练组样本采用Cox比例风险模型筛选影响HCC患者术后死亡风险的临床危险因素,建立基于ALBI分级的预测模型后在验证组进行验证;使用ROC曲线和预测模型校准图评估预测模型的价值;使用列线图展示模型,方便临床使用。结果: Cox比例风险模型结果显示,丙氨酸转氨酶80 U/L及以上、肿瘤最大径5 cm及以上、门静脉癌栓形成、ALBI分级2级为HCC根治性手术患者预后的独立危险因子。据此建立预测模型,预后指数(PI)=0.550×ALT+0.512×ALBI分级+0.872×肿瘤最大径+1.377×门静脉癌栓。利用验证组样本评价模型预测能力,该模型预测患者术后12、36、60个月死亡风险的AUC分别为0.872、0.814、0.810(均P < 0.01),预测结果的拟合优度(r2)分别为0.953、0.976、0.994。以36个月死亡风险区分能力与经典HCC分期模型比较,基于ALBI的预测模型的AUC为0.814,优于ALBI(AUC=0.683)、巴塞罗那临床肝癌分期(AUC=0.713)、意大利肝癌计划评分(AUC=0.689)、肝功能Child-Pugh分级(AUC=0.645)、肿瘤TNM分期(AUC=0.612)(P < 0.05或P < 0.01)。结论: 丙氨酸转氨酶80 U/L及以上、肿瘤最大径5 cm及以上、门静脉癌栓形成、ALBI分级2级为HCC根治性手术患者死亡风险的独立危险因子,基于ALBI分级构建的预测模型对HCC根治性手术患者中期死亡风险有较高的预测价值。

关键词: 癌, 肝细胞根治性手术存活率预测白蛋白胆红素指数分级    
Abstract:

Objective: To establish a clinical prediction model of the mid-term fatality risk after radical resection in patients with primary hepatocellular carcinoma (HCC) based on the albumin-bilirubin (ALBI) grade and to assess its prediction value. Methods: Clinical data of 533 patients who received HCC radical resection in Jinhua Hospital of Zhejiang University, Jinhua People's Hospital, Jinhua Hospital of Traditional Chinese Medicine and Jinhua Guangfu Hospital from January 2010 to August 2016 were retrospectively reviewed. In the training group (n=407), Cox model was used to screen the clinical risk factors of postoperative death, and a predictive model based on ALBI grade was established and then examined in the validation group (n=126). The value of the prediction model was assessed by ROC curve and calibration curve; the prediction results of the model were visualized by the nomogram for the convenience of clinical use. Results: Cox model showed that ALT ≥ 80 U/L, tumor maximum diameter ≥ 5 cm, portal vein tumor thrombus and ALBI grade 2 were independent risk factors for the prognosis of patients with HCC radical resection. The prognosis index (PI) was 0.550×ALT+0.512×ALBI grade+0.872×maximum tumor diameter+1.377×portal vein tumor thrombus. The AUCs for predicting the risk of death in 12, 36 and 60 months were 0.872, 0.814 and 0.810, respectively (all P < 0.01), and the goodness of fit (r2) of the established model were 0.953, 0.976 and 0.994. AUC of the established model for predicting risk of death in 36 months after resection was 0.814, which was higher than those of ALBI (AUC=0.683), BCLC (AUC=0.713), CLIP (AUC=0.689), Child-Pugh (AUC=0.645), TNM (AUC=0.612) (P < 0.05 or P < 0.01). Conclusion: ALT ≥ 80 U/L, maximum tumor diameter ≥ 5 cm, portal vein tumor thrombus and ALBI grade 2 are independent risk factors of patients after HCC resection, and ALBI grade-based prediction model is satisfactory in prediction of mid-term death risk of the patients.

Key words: Carcinoma, hepatocellular    Radical resection    Survival rate    Forecasting    Albumin-bilirubin grade
收稿日期: 2020-04-01 出版日期: 2020-07-24
CLC:  R735.7  
通讯作者: 季峰     E-mail: wxb2310@163.com;jifeng@zju.edu.cn
作者简介: 王晓波(1992—), 男, 硕士研究生, 医师, 主要从事肝脏肿瘤方向研究; E-mail:wxb2310@163.com; https://orcid.org/0000-0003-2473-9291
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引用本文:

王晓波,张兆辉,吴章强,孙跃宗,章义利,龚鸣,季峰. 基于白蛋白胆红素指数的肝细胞癌根治性手术患者中期死亡风险预测模型评估[J]. 浙江大学学报(医学版), 2020, 49(3): 375-382.

WANG Xiaobo,ZHANG Zhaohui,WU Zhangqiang,SUN Yuezong,ZHANG Yili,GONG Ming,JI Feng. Prediction model of mid-term fatality risk after radical resection in patients with hepatocellular carcinoma based on ALBI-grade. J Zhejiang Univ (Med Sci), 2020, 49(3): 375-382.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2020.06.04        http://www.zjujournals.com/med/CN/Y2020/V49/I3/375

组别n性别
(男/女)
年龄
(<45/≥45岁)
丙氨酸转氨酶
(<80/≥80 U/L)
谷氨酰转移酶
(<34.2/≥34.2 U/L)
超敏C反应蛋白
(<16/≥16 mg/L)
甲胎蛋白
(<400/≥400 μg/L)
肿瘤数目
(单个/多个)
肿瘤最大径
(<5/≥5 cm)
肿瘤包膜
(有/无)
门静脉癌栓
(有/无)
HBsAg
(阳性/阴性)
肝外转移
(是/否)
肝硬化
(有/无)
肿瘤分化程度
(低/中/高)
ALBI分级
(1级/2级)
HBsAg:乙型肝炎表面抗原;ALBI:白蛋白胆红素指数.
训练组407334/7332/375316/91228/179325/82180/227355/52243/164277/13018/389316/91108/299295/112211/134/62313/94
验证组126104/2210/11693/3371/5590/3653/73109/1776/5086/406/120101/2533/9391/3570/38/1895/31
表 1  训练组、验证组患者基本信息比较
图 1  训练组与验证组患者的生存曲线
危险因素BHR(95%CI)P
丙氨酸转氨酶0.5501.733(1.207~2.486)<0.01
肿瘤最大径0.8722.392(1.698~3.370)<0.01
门静脉癌栓形成1.3773.964(2.255~6.969)<0.01
白蛋白胆红素指数分级0.5121.669(1.164~2.392)<0.01
表 2  影响肝细胞癌根治性手术患者死亡风险的多因素分析结果
图 2  基于白蛋白胆红素指数的预测模型对于验证组患者肝细胞癌根治性手术后12、36、60个月死亡风险预测的ROC曲线
时间AUC约登指数敏感度(%)特异度(%)
术后12个月0.8720.679891.6776.32
术后36个月0.8140.607171.4389.29
术后60个月0.8100.599673.8186.15
表 3  基于白蛋白胆红素指数的预测模型对于验证组患者肝细胞癌根治性手术后12、36、60个月死亡风险预测的ROC曲线分析结果
图 3  基于白蛋白胆红素指数的预测模型对于患者肝细癌根治性手术后12、36、60个月死亡风险预测的校准图
图 4  各模型预测患者肝细胞癌根治性手术后36个月死亡风险的ROC曲线
图 5  基于ALBI预测模型的列线图
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