中国临床药理学杂志

老年乙肝相关肝硬化患者肝细胞癌风险预测模型的临床研究

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龙春梅 ¹ , 周敏华 ² , 郑中伟 ¹ , 陈定贵 ¹ , 付子毅 ³

中国临床药理学杂志 | 临床与基础桥接研究 2026,42(7): 927-933

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中国临床药理学杂志 |临床与基础桥接研究 2026 , 42 (7) : 927 -933

老年乙肝相关肝硬化患者肝细胞癌风险预测模型的临床研究

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龙春梅¹, 周敏华², 郑中伟¹, 陈定贵¹, 付子毅³

作者信息

^1.常州市第三人民医院消化肿瘤科，江苏常州 2130002

^2.常州市第三人民医院超声科，江苏常州 213000

^3.江苏省肿瘤医院科技处，江苏南京 210008

通讯作者:

周敏华，主治医师 MP: 13775125286 E-mail: 295764125@qq.com

作者简介:

龙春梅（1978-），女，副主任医师，主要从事消化病相关的研究及工作

Study on the efficacy of risk prediction models for hepatocellular carcinoma in elderly patients with hepatitis B-related cirrhosis

Chun-mei LONG¹, Min-hua ZHOU², Zhong-wei ZHENG¹, Ding-gui CHEN¹, Zi-yi FU³

Affiliations

^1.Department of Digestive Oncology, Changzhou Third People’s Hospital, Changzhou 213002, Jiangsu Province, China

^2.Department of Ultrasound, Changzhou Third People’s Hospital, Changzhou 213000, Jiangsu Province, China

^3.Department of Science and Technology, Jiangsu Cancer Hospital, Nanjing 210008, Jiangsu Province, China

出版时间: 2026-04-17 doi: 10.13699/j.cnki.1001-6821.2026.07.005

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摘要

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目的

评估不同风险模型对接受恩替卡韦片（ETV），富马酸替诺福韦二吡呋酯片（TDF），富马酸丙酚替诺福韦片（TAF）抗病毒治疗的慢性乙型肝炎（CHB）相关肝硬化患者肝细胞癌（HCC）的预测价值，明确不同核苷（酸）类似物（NAs）制剂[恩替卡韦（ETV）、替诺福韦酯（TDF）、丙酚替诺福韦（TAF）]的药理差异对肝癌风险的影响，为临床诊疗提供参考。

方法

将本院接受NAs抗病毒治疗的无肝癌病史、未接受过抗病毒治疗的乙肝相关肝硬化患者，根据患者接受的核苷（酸）类似物抗病毒治疗方案分为ETV组、TDF组和TAF组。用Cox比例风险模型构建肝癌风险预测模型，按亚太肝病联盟（REAL-B）评分分为低危组（0~3）分、中危组（4~7）分、高危组（8~13）分，所有患者持续接受对应NAs治疗并随访至研究终点；用时间依赖性受试者工作特征曲线下面积（AUROC）比较各风险评分的预测效能，同时分析不同NAs组的肝癌发生率差异。主要观察指标包括肝癌发生率、国际标准化比（INR）、甲胎蛋白（AFP）、糖尿病患病情况、饮酒史、REAL-B评分预测效能及不同NAs制剂的药理相关预后影响。

结果

共筛选252例，最终ETV组108例，TDF组96例和TAF组48例。中位随访56.96个月，19.00%（48例/252例）患者确诊肝癌。ETV组、TDF组、TAF组1年肝癌发生率分别为4.63%（5例/108例）、5.21%（5例/96例）、4.17%（2例/48例），3年分别为12.96%（14例/108例）、13.54%（13例/96例）、12.50%（6例/48例），5年分别为17.59%（19例/108例）、18.75%（18例/96例）、16.67%（8例/48例），3组间比较，在统计学上差异均无统计学意义（均P>0.05）。多因素逐步回归分析显示，INR（HR=2.77，95% CI：1.46~5.25，P<0.01）、AFP（HR=1.00，95% CI：1.00~1.00，P<0.05）、糖尿病（HR=3.06，95% CI：1.54~6.08，P<0.01）及饮酒史（HR=2.25，95% CI：1.04~4.86，P<0.05）为肝癌发生的独立危险因素。REAL-B评分在3年（AUROC=0.74）和5年（AUROC=0.70）时的预测效能持续高于除RWS-HCC外的其他模型，1年时AUROC与其他模型相近。中危组与高危组1、3及5年肝癌发生率比较，在统计学上差异均有统计学意义（均P<0.001）。

结论

不同NAs制剂（ETV、TDF、TAF）在乙肝相关肝硬化患者肝癌风险控制中疗效相当，其药理特性差异未显著影响肝癌发生风险；REAL-B评分对接受NAs抗病毒治疗的患者具有稳定且优异的HCC风险预测能力，可作为临床预后评估的优选工具。

关键词

恩替卡韦片 / 富马酸替诺福韦二吡呋酯片 / 富马酸丙酚替诺福韦片 / 乙肝相关肝硬化 / 肝细胞癌 / 风险预测模型

Abstract

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Objective

To evaluate the predictive value of different risk models for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB)-related cirrhosis receiving antiviral therapy with entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide fumarate (TAF), and to clarify the effects of pharmacological differences among various nucleos(t)ide analogs (NAs) on HCC risk, so as to provide a reference for clinical diagnosis and treatment.

Methods

A total of 252 treatment-naive patients with CHB-related cirrhosis without a history of HCC who received NA antiviral therapy from May 2015 to May 2020 were retrospectively enrolled. They were divided into the ETV group (n=108), TDF group (n=96), and TAF group (n=48) according to the NA used. Cox proportional hazards model was used to construct an HCC risk prediction model. Patients were classified into low-risk group (0-3 points), intermediate-risk group (4-7 points), and high-risk group (8-13 points) based on the Asia-Pacific Association for the Study of the Liver (APASL) REALB score. All patients continued to receive corresponding NA therapy and were followed up until the study endpoint. The predictive performance of each risk score was compared using time-dependent area under the receiver operating characteristic curve (AUROC), and the differences in HCC incidence among different NA groups were analyzed. The main outcome measures included HCC incidence, international normalized ratio (INR), alpha-fetoprotein (AFP), diabetes mellitus, drinking history, predictive performance of the REALB score, and prognosis-related effects of different NAs.

Results

A total of 252 patients were screened, and finally 108 patients were assigned to the ETV group, 96 to the TDF group, and 48 to the TAF group. The median follow-up duration was 56.96 months, and hepatocellular carcinoma (HCC) was diagnosed in 19.00% (48 cases/252 cases) of patients. The 1year incidence rates of HCC in the ETV, TDF, and TAF groups were 4.63% (5 cases/108 cases), 5.21% (5 cases/96 cases), and 4.17% (2 cases/48 cases), respectively; the 3 year rates were 12.96% (14 cases/108 cases), 13.54% (13 cases/96 cases), and 12.50% (6 cases/48 cases), respectively; and the 5 year rates were 17.59% (19 cases/108 cases), 18.75% (18 cases/96 cases), and 16.67% (8 cases/48 cases), respectively. No statistically significant differences were observed among the three groups (all P>0.05). Multivariate stepwise regression analysis revealed that INR (HR=2.77, 95% CI: 1.46-5.25, P<0.01), AFP (HR=1.00, 95% CI: 1.00-1.00, P<0.05), diabetes mellitus (HR=3.06, 95% CI: 1.54-6.08, P<0.01), and history of alcohol consumption (HR=2.25, 95% CI: 1.04-4.86, P<0.05) were independent risk factors for HCC development. The predictive performance of the REALB score at 3 years (AUROC=0.74) and 5 years (AUROC=0.70) remained higher than that of other models except the RWSHCC model, while its 1year AUROC was similar to those of other models. Statistically significant differences in the 1, 3, and 5 year HCC incidence rates were found between the intermediaterisk group and the highrisk group (all P<0.001).

Conclusion

Different NAs (ETV, TDF, TAF) have comparable efficacy in controlling HCC risk in patients with CHB-related cirrhosis, and differences in their pharmacological properties do not significantly affect HCC risk. The REALB score shows stable and excellent predictive ability for HCC in patients receiving NA antiviral therapy and can be used as a preferred tool for clinical prognosis evaluation.

Key words

entecavir tablets / tenofovir disoproxil fumarate tablets / tenofovir alafenamide fumarate tablets / hepatocellular carcinoma / risk prediction model

引用本文

龙春梅, 周敏华, 郑中伟, 陈定贵, 付子毅. 老年乙肝相关肝硬化患者肝细胞癌风险预测模型的临床研究. 中国临床药理学杂志, 2026 , 42 (7) : 927 -933 . DOI: 10.13699/j.cnki.1001-6821.2026.07.005

Chun-mei LONG, Min-hua ZHOU, Zhong-wei ZHENG, Ding-gui CHEN, Zi-yi FU. Study on the efficacy of risk prediction models for hepatocellular carcinoma in elderly patients with hepatitis B-related cirrhosis[J]. Chinese Journal of Clinical Pharmacology, 2026 , 42 (7) : 927 -933 . DOI: 10.13699/j.cnki.1001-6821.2026.07.005

基金

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国家自然科学基金资助项目(82173327)

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2026年第42卷第7期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2026.07.005

接收时间：2025-11-24
首发时间：2026-08-06
出版时间：2026-04-17

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收稿日期：2025-11-24

基金

国家自然科学基金资助项目(82173327)

作者信息

^1.常州市第三人民医院消化肿瘤科，江苏常州 2130002

^2.常州市第三人民医院超声科，江苏常州 213000

^3.江苏省肿瘤医院科技处，江苏南京 210008

通讯作者:

周敏华，主治医师 MP: 13775125286 E-mail: 295764125@qq.com

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https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2026.07.005

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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