瞬时弹性成像联合甲胎蛋白对肝细胞癌的早期预警价值

肝脏 ›› 2019, Vol. 24 ›› Issue (1): 20-23.

瞬时弹性成像联合甲胎蛋白对肝细胞癌的早期预警价值

陈松海, 纪冬, 胡志军, 陆荫英, 王春艳, 邵清, 陈国凤

100039 北京解放军总医院第五医学中心肝硬化诊疗二中心(陈松海,纪冬,王春艳,邵清,陈国凤),肝脏肿瘤诊疗中心(陆荫英);宝鸡市中医院脾胃肝病二科(胡志军)

收稿日期:2018-07-16 出版日期:2019-01-31 发布日期:2020-04-09
通讯作者: 陈国凤,Email:guofengchen302@163.com;纪冬,Email:jidg302@126.com
基金资助:
中国肝炎防治基金会王宝恩肝纤维化研究基金重点项目(2011xjs0408)、面上项目(CFHPC20151025);北京市自然科学基金面上项目(7122177);国家自然科学基金面上项目(81371799)

Transient elastography combined with alpha fetoprotein as an early-warning model for hepatocellular carcinoma

CHEN Song-hai¹, JI Dong¹, HU Zhi-jun³, LU Yin-ying², WANG Chun-yan¹, SHAO Qing¹, CHEN Guo-feng¹

1. The Second Liver Cirrhosis Diagnosis and Treatment Center, The fifth medical center of the Chinese PLA General Hospital, Beijing 100039, China;
2. Comprehaensive Liver Cancer Center, The fifth medical center of the Chinese PLA General Hospital, Beijing 100039, China;
3. Department Ⅱ of spleen-stomach liver disease, Baoji traditional Chinese medicine hospital, Shanxi 721000, China

Received:2018-07-16 Online:2019-01-31 Published:2020-04-09
Contact: CHEN Guofeng, E-mail:guofengchen302@163.com; JI dong, E-mail: jidg302@126.com

摘要/Abstract

摘要： 目的探讨肝细胞癌(hepatocellular carcinoma, HCC)无创早期预警模型的早期预警价值。方法筛选2008至2017年在中国人民解放军总医院第五医学中心肝硬化诊疗二中心(原解放军第三○二医院)住院的HBV相关肝硬化及HCC患者2 176例,最终纳入321例,行肝脏瞬时弹性成像检测,结果以肝脏硬度值(liver stiffness measurement, LSM)表示,ELISA检测甲胎蛋白(alpha fetoprotein, AFP)及其他血清学指标,采用增强MRI扫描诊断HCC。通过Logistic回归确定HCC无创预测因子,建立基于年龄、LSM和AFP的HCC早期无创预警模型(ALA)。利用受试者工作特征 (receiver operating characteristic, ROC) 曲线分析评价ALA对HCC的早期预警效能。结果 321例患者按照2∶1随机分为两组(建模组200例,验模组121例),两组的临床参数(年龄、性别、Child-Pugh评分、肝功能、AFP、LSM)无差异,建模组和验模组年龄分别为(51.4±10.1) 岁和(49.96±10.23) 岁, HCC患者占比分别为34%和35.5%, 肝功能Child-A级患者占比分别为65%和57%,AFP分别为12和6 ng/mL,LSM分别为25和27 kPa。多因素Logistics回归分析,年龄、LSM和AFP是HCC发生的独立危险因素,建模组ALA的AUROC为0.91 (95% CI: 0.86~0.95),使用ALA分值9.61作为截断值,验模组的准确度为84.3%。结论应用年龄、LSM及AFP建立的ALA可提高HCC早期诊断率,为HCC患者提供早期治疗干预的机会。

关键词: 肝细胞癌, 甲胎蛋白, 肝脏硬度值, 瞬时弹性成像, 无创, 早期预警模型

Abstract: Objective To establish a noninvasive early-warning model for hepatocellular carcinoma (HCC) and improve the diagnosis accuracy of high-risk individuals as early as possible.Methods Patients with hepatitis B virus related-cirrhosis or HCC, who were admitted to our hospital from 2008 to 2017, were enrolled. They were followed up at least 3 times with an interval of 3 to 6 months. Liver stiffness measurement (LSM) by transient elastography was performed on the day enrolled. Alpha-fetoprotein (AFP) and other serum parameters were detected at each visit. HCC was diagnosed using multiphase-dynamic-contrast-enhanced magnetic resonance imaging scan. The noninvasive predictors for HCC were identified using logistic regression, and an early-warning model named ALA was constructed with age, LSM and AFP. The receiver operating characteristic (ROC) curve analysis was applied to evaluate the early warning effectiveness of ALA on HCC. Results A total of 321 consecutive patients were included in the study, who were randomly divided into 2 groups at the ratio of 2∶1 (200 cases in training group and 121 cases in validation group). The clinical parameters (age, sex, Child-Pugh score, liver function, AFP, LSM) showed no differences between the 2 groups. The age, percentage of HCC patients, percentage of Child-A patients, median of AFP and median of LSM in training and validation group was 51.42±10.10 and 49.96±10.23 years old, 34% and 35.5%, 65% and 57%, 12 ng/ml and 6 ng/ml, 25 kPa and 27kPa, respectively. Multivariable logistic regression showed that age, LSM and AFP were the independent risk factors for HCC. The ALA model was calculated using 0.103×age (years) +0.116×LSM (kPa) +0.026×AFP (ng/ml). The area under ROC curve of ALA was 0.91 (95% confidence interval, 0.86-0.95) in the training group. Using ALA of 9.61 as the cut-off value, the accuracy was 84.3% in the validation group.Conclusion ALA, a noninvasive early-warning model consisting of age, LSM and AFP, is worthy of clinical application, which might improve the early diagnosis rate of HCC and provide early curative interventions for HCC patients.

Key words: Hepatocellular carcinoma, Alpha-fetoprotein, Liver stiffness measurement, Transient elastography, Noninvasive, Early warning model

陈松海, 纪冬, 胡志军, 陆荫英, 王春艳, 邵清, 陈国凤. 瞬时弹性成像联合甲胎蛋白对肝细胞癌的早期预警价值[J]. 肝脏, 2019, 24(1): 20-23.

CHEN Song-hai, JI Dong, HU Zhi-jun, LU Yin-ying, WANG Chun-yan, SHAO Qing, CHEN Guo-feng. Transient elastography combined with alpha fetoprotein as an early-warning model for hepatocellular carcinoma[J]. Chinese Hepatolgy, 2019, 24(1): 20-23.

参考文献

[1] 杨秉辉.原发性肝癌的临床诊断与分期标准. 现代实用医学, 2002, 14:324.
[2] 原发性肝癌诊疗规范(2011年版). 临床肝胆病杂志,2011,27:1141-1159.
[3] 中华医学会肝病学分会、感染病学分会. 慢性乙型肝炎防治指南. 中华传染病杂志,2005,23:421-431.
[4] 中华医学会肝病学分会、中华医学会感染病学分会. 慢性乙型肝炎防治指南(2010年版). 传染病信息,2010,23:139-143.
[5] 纪冬,邵清,韩萍,等. 瞬时弹性成像联合血清学标志物检测对肝纤维化的诊断效能分析. 解放军医学杂志,2011,36:1136-1138.
[6] 纪冬,陈国凤.肝纤维化无创诊断研究进展及其临床应用. 传染病信息,2013,26:190-194.
[7] Tatsumi A, Maekawa S, Sato M, et al. Liver stiffness measurement for risk assessment of hepatocellular carcinoma. Hepatology Research, 2015, 45:523-532.
[8] Bosch FX,Ribes J,Diaz M,et al. Primary liver cancer: worldwide incidence and trends. Gastroenterology, 2004,127:S5-S16.
[9] 李军. 血清AFP、TKI、DKKI联合检测在原发性肝癌诊断中的价值.基因组学与应用生物学,2017,36:3526-3531.
[10] 黎晓武,李金张,罗向波,等.血清GP73、HSP27联合AFP检测在HBV相关早期肝细胞癌诊断的价值.实用预防医学,2016,23:1319-1321.
[11] Park SJ, Jang JY, Jeong SW, et al. Usefulness of AFP, AFP-L3, and PIVKA-II, and their combinations in diagnosing hepatocellular carcinoma. Medicine, 2017, 96:e5811.
[12] Morikawa K, Izumi T, Sho T, et al. Risk assessment of hepatocellular carcinoma in chronic liver disease patients with a combination of liver stiffness measurement and controlled attenuation parameter by FibroScan. J Hepatol, 2018, 68:S445.
[13] Jung KS, Kim SU, Ahn SH, et al. Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using liver stiffness measurement (FibroScan). Hepatology,2011,53:885-894.
[14] Jeon MY, Lee HW, Kim SU, et al. Subcirrhotic Liver Stiffness by Fibroscan Correlates with Lower Risk of hepatocellular carcinoma in Patients with HBV-related Cirrhosis. Hepatol Int. 2017,11:268-276.
[15] Wong GL, Chan HL, Wong CK, et al. Liver stiffness-based optimization of hepatocellular carcinoma risk score in patients with chronic hepatitis B. J Hepatol, 2014, 60:339-345.