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肝细胞癌早期筛查和诊断的研究进展
DOI: 10.3969/j.issn.1001-5256.2023.06.033
利益冲突声明: 本文不存在任何利益冲突。
作者贡献声明: 韩家鑫负责查找文献，撰写论文初稿；宓余强负责分析文献，进行文稿审改；徐亮负责拟定写作思路，指导撰写文章并最后定稿。
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摘要: 针对高危人群，早期筛查、早期诊断是实现肝癌很好控制、减轻肝癌负担的重要措施。其中，确定肝癌的高危人群和制定适合的肝癌筛查策略是实现肝癌早期筛查和诊断的关键。肝癌风险评估模型是对肝癌的高危人群便捷和快速识别的重要手段。在肝癌风险分层评估的基础上，应用影像学技术、血清学标志物、液体活组织检查、代谢组学及糖组学等方法，实现肝癌精准早筛、早诊，从而达到早治目的。Abstract: For the high-risk population, early screening and diagnosis are important measures to achieve good control of liver cancer and reduce the burden of liver cancer, and determining the high-risk population of liver cancer and formulating appropriate liver cancer screening strategies are the key to realizing the early screening and diagnosis of liver cancer. The risk assessment model for liver cancer is an important method for rapid and convenient identification of the high-risk population of liver cancer. Based on the risk stratification of liver cancer, the methods such as imaging technology, serological markers, liquid biopsy, metabolomics, and glycomics can be used for accurate early screening and diagnosis of liver cancer, so as to achieve the goal of early treatment.
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Key words:
- Carcinoma /
- Hepatocellular /
- Early Detection of Cancer /
- Early Diagnosis
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表 1 全球各国/地区对肝癌高风险人群的定义
Table 1. Definition of population at high risk of HCC by countries/regions in the world
题目 制定机构 高风险人群定义 原发性肝癌诊疗指南(2022年版)[3] 国家卫生健康委办公厅 (1)乙型肝炎和/或丙型肝炎；
(2)过度饮酒；
(3)非酒精性脂肪性肝炎；
(4)长期食用被黄曲霉毒素污染的食物；
(5)各种原因引起的肝硬化；
(6)肝癌家族史；
(7)年龄＞40岁、男性EASL clinical practice guidelines：management of hepatocellular carcinoma[5] 欧洲肝病学会(EASL) (1)Child-Pugh A级和B级肝硬化；
(2)Child- Pugh C级等待肝移植的肝硬化患者AASLD guidelines for the treatment of hepatocellular carcinoma[6] 美国肝病学会(AASLD) 肝硬化 Management of hepatocellular carcinoma in Japan：JSH consensus statements and recommendations 2021 update[7] 日本肝病学会(JSH) (1)超高危人群：既有病毒性肝炎也有肝硬化；
(2)高危人群：肝硬化、慢性乙型肝炎和丙型肝炎Hepatocellular carcinoma：ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up[8] 欧洲肿瘤内科学会(ESMO) 肝硬化 
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表 2 肝癌风险评估的预测模型
Table 2. Prediction model for HCC risk assessment
模型 制定国家/ 地区 适用人群 变量参数 THRI模型 多伦多 肝硬化人群 年龄、性别、肝硬化病因以及血小板计数 REACH-B模型 中国台湾 HBV感染者 年龄、性别、ALT、HBeAg状态和HBV DNA水平 PAGE-B模型 高加索 抗病毒治疗后HBV感染者 年龄、性别和血小板计数 mPAGE-B模型 韩国 抗病毒治疗后HBV感染者 年龄、性别、血小板计数和白蛋白水平 aMAP模型 多中心 多病因的慢性肝病患者 年龄、性别、胆红素水平、白蛋白水平和血小板计数 APAC模型 德国 肝硬化人群 年龄、可溶性β血小板衍生生长因子受体、AFP和肌酐 PLAN-B模型 多中心 HBV感染者 年龄、性别、肝硬化病因、血小板计数、抗病毒药物(恩替卡韦或富马酸替诺福韦酯)的使用、ALT、HBV DNA水平、白蛋白水平、HBeAg状态和胆红素水平
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表 3 液体活检联合诊断技术的应用价值
Table 3. Application value of liquid biopsy combined with diagnostic techniques
检测技术 敏感度 特异度 甲基化(数字PCR) 92.5% 97.5% SWGS、片段组学 95.42% 97.83% 甲基化、基因突变 88% 93% 糖组学(蛋白) 83.61% 87.84% 甲基化、CNV ＞90% ＞90% cfDNA、cfRNA、蛋白 97.9% 97.9% 注：SWGS，低深度全基因组测序；CNV，拷贝数变异测序；cfRNA，细胞游离RNA。
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