血清AFP、AFP-L3、HSP90α对乙肝肝硬化和乙肝相关性肝癌的鉴别价值及其与HBV-DNA载量的关系

doi:10.3969/j.issn.1004-583X.2026.06.004

摘要/Abstract

摘要：

目的探讨血清甲胎蛋白(alpha fetoprotein,AFP)、甲胎蛋白异质体3(alpha-fetoprotein-L3, AFP-L3)及血浆热休克蛋白90α (plasma heat shock protein90α, HSP90α)在乙型肝炎肝硬化(乙肝肝硬化)与乙型肝炎病毒相关性肝细胞癌(HBV-associated hepatocellular carcinoma, HBV-HCC)鉴别诊断中的价值,并分析上述指标水平与乙肝病毒脱氧核糖核酸(hepatitis B virus deoxyribonucleic acid, HBV-DNA)载量的相关性。方法选取2022年8月-2025年8月安阳钢铁集团有限责任公司职工总医院收治的HBV-HCC患者(HBV-HCC组)102例、乙肝肝硬化患者(乙肝肝硬化组)74例和同期体检健康者(健康组)80例。检测和比较3组AFP、AFP-L3、HSP90α等血清指标水平和HBV-DNA载量。通过绘制受试者工作特征曲线,评估上述血清指标对乙肝肝硬化及HBV-HCC的诊断价值,并探究乙肝肝硬化及HBV-HCC患者AFP、AFP-L3、HSP90α与HBV-DNA载量的相关性。结果 HBV-HCC组AFP、AFP-L3、HSP90α水平均高于乙肝肝硬化组和健康组,且乙肝肝硬化组高于健康组(均P<0.05);HBV-HCC组HBV-DNA高于乙肝肝硬化组(P<0.05),而健康组未检出。血清AFP、AFP-L3及HSP90α3项指标联合检测对乙肝肝硬化(AUC=0.930,95%CI:0.891~0.969)和HBV-HCC(AUC=0.904,95%CI:0.861~0.947)的鉴别诊断效能均优于任一单项指标,其敏感度(93.24%、88.24%)与特异度(90.00%、83.78%)均较高(P<0.05)。Pearson相关分析表明在乙肝肝硬化患者中,血清AFP、AFP-L3及HSP90α水平均与HBV-DNA载量呈正相关(r=0.721、0.655、0.784,P<0.05);且在HBV-HCC患者中,三者与HBV-DNA载量仍呈正相关(r=0.769、0.587、0.658,P<0.05)。结论血清AFP、AFP-L3、HSP90α对乙肝肝硬化及HBV-HCC具有较好的鉴别价值,且3项指标水平与HBV-DNA载量具有明显的相关性。

关键词: 肝硬化, 肝肿瘤, 乙型肝炎病毒, 甲胎蛋白, 热休克蛋白90α, 甲胎蛋白异质体3, 病毒载量

Abstract:

Objective To investigate the value of serum alpha-fetoprotein (AFP), alpha-fetoprotein-L3 (AFP-L3), and plasma heat shock protein 90 alpha (HSP90α) in the differential diagnosis of hepatitis B cirrhosis and hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC), and to analyze the correlation between these markers and hepatitis B virus deoxyribonucleic acid (HBV-DNA) load. Methods A total of 102 patients with HBV-HCC (HBV-HCC group), 74 patients with hepatitis B cirrhosis (hepatitis B cirrhosis group), and 80 healthy individuals undergoing physical examination during the same period (healthy group) were enrolled from August 2022 to August 2025 at the General Hospital of Anyang Iron and Steel Group Co., LTD. from August 2022 to August 2025, together with 80 healthy individuals (healthy control group), were enrolled in the study. Serum AFP, AFP-L3, and HSP90α, as well as HBV-DNA load, were measured and compared among the three groups. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic value of the above serum markers for hepatitis B cirrhosis and HBV-HCC. The correlations between AFP, AFP-L3, HSP90α, and HBV-DNA load were also examined in patients with hepatitis B cirrhosis and HBV-HCC. Results The levels of AFP, AFP-L3, and HSP90α were higher in the HBV-HCC group than in the hepatitis B cirrhosis group and the healthy group, and were higher in the hepatitis B cirrhosis group than in the healthy group (all P<0.05). The HBV-DNA load was higher in the HBV-HCC group than in the hepatitis B cirrhosis group (P<0.05), while no HBV-DNA was detected in the healthy group. Combined detection of serum AFP, AFP-L3, and HSP90α showed better diagnostic performance for both hepatitis B cirrhosis (area under the curve [AUC]=0.930, 95%CI: 0.891-0.969) and HBV-HCC (AUC=0.904, 95%CI: 0.861-0.947) than any single marker, with high sensitivity (93.24%, 88.24%) and specificity (90.00%, 83.78%) (P<0.05). Pearson correlation analysis showed that in patients with hepatitis B cirrhosis, serum AFP, AFP-L3, and HSP90α levels were positively correlated with HBV-DNA load (r=0.721, 0.655, 0.784, P<0.05). The same positive correlations were also observed in patients with HBV-HCC (r=0.769, 0.587, 0.658, P<0.05). Conclusion Serum AFP, AFP-L3, and HSP90α have good diagnostic value in differentiating hepatitis B cirrhosis from HBV-HCC, and the levels of these three markers are significantly correlated with HBV-DNA load.

Key words: liver cirrhosis, liver neoplasms, hepatitis B virus, alpha-fetoprotein, heat shock protein 90 alpha, alpha-fetoprotein heterogeneity 3, viral load

中图分类号:

冯利菲, 王天慧, 吕慧. 血清AFP、AFP-L3、HSP90α对乙肝肝硬化和乙肝相关性肝癌的鉴别价值及其与HBV-DNA载量的关系[J]. 临床荟萃, 2026, 41(6): 505-510.

Feng Lifei, Wang Tianhui, Lv Hui. Diagnostic value of serum AFP, AFP-L3, and HSP90α in differentiating hepatitis B cirrhosis from HBV-associated hepatocellular carcinoma and their relationship with HBV-DNA load[J]. Clinical Focus, 2026, 41(6): 505-510.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://www.lchc.cn/CN/10.3969/j.issn.1004-583X.2026.06.004

https://www.lchc.cn/CN/Y2026/V41/I6/505

图/表 7

参考文献 22

[1]	European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatitis B virus infection[J]. J Hepatol, 2025, 83(2):502-583. doi:10.1016/j.jhep.2025.03.018.
[2]	Chen CL, Yang WS, Yang HI, et al. Plasma adiponectin levels in relation to chronic hepatitis B infection progression to liver cancer milestones: A prospective study[J]. Liver Cancer, 2024, 14(1):19-35. doi:10.1159/000539909.
[3]	林豪, 沈宝岩, 王贵明. 乙肝相关性原发性肝癌患者血清AFP, TSGF, AFU, GGT及CEA联合诊断研究[J]. 临床消化病杂志, 2023, 35(4):268-271. doi:10.3870/lcxh.j.issn.1005-541X.2023.04.04.
[4]	《原发性肝癌诊疗指南(2024年版)》编写专家委员会, 周俭. 原发性肝癌诊疗指南(2024年版)[J]. 中国临床医学, 2024, 31(2):277-334. doi:10.12025/j.issn.1008-6358.2024.20240065.
[5]	Han Y, Zhang Y, Cui L, et al. Plasma heat shock protein 90alpha as a biomarker for the diagnosis of liver cancer: In patients with different clinicopathologic characteristics[J]. World J Surg Oncol, 2021, 19(1):228. doi:10.1186/s12957-021-02269-4. pmid: 34348726
[6]	徐静, 张凤岐, 王聪, 等. 血清miR-223、HMGB1与乙肝患者HBV-DNA载量和肝功能的关系研究[J]. 国际病毒学杂志, 2021, 28(4):332-335. doi:10.3760/cma.j.issn.1673-4092.2021.04.017.
[7]	中华人民共和国国家卫生健康委员会. 原发性肝癌诊疗指南(2022年版)[J]. 肿瘤防治研究, 2022, 49(3):251-276. doi:10.3760/cma.j.cn501113-20220413-00193.
[8]	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(2022年版)[J]. 中华肝脏病杂志, 2022, 30(12):1309-1331. doi:10.3760/cma.j.cn501113-20221204-00607.
[9]	许娟, 杜粉静, 闫涛涛, 等. 多种预测抗病毒治疗HBV感染患者进展为肝细胞癌的模型验证[J]. 胃肠病学和肝病学杂志, 2024, 33(2):136-140. doi:10.3969/j.issn.1006-5709.2024.02.004.
[10]	张家鸣, 赵素贤, 刘领弟, 等. 异常凝血酶原在乙型肝炎相关肝细胞癌诊断中的价值研究[J]. 中华肝脏病杂志, 2025, 33(4):340-347. doi:10.3760/cma.j.cn501113-20250314-00095.
[11]	陈丽, 陆圣威, 向田丹, 等. 肝硬化背景下小肝癌的诊断和鉴别诊断[J]. 中华肝脏病杂志, 2025, 33(4):323-328. doi:10.3760/cma.j.cn501113-20250325-00109.
[12]	孙海青, 刘宁, 娄金丽, 等. STIP1和AFP-L3联合检测在肝细胞肝癌诊断中的价值[J]. 检验医学, 2025, 40(4):324-330. doi:10.3969/j.issn.1673-8640.2025.04.003.
[13]	赵可馨, 徐光文, 李楠, 等. 乙型肝炎病毒阳性肝硬化患者进展为肝细胞肝癌预测模型的建立及验证[J]. 中华检验医学杂志, 2022, 45(5):516-521. doi:10.3760/cma.j.cn114452-20210719-00442.
[14]	万仁均, 罗文强, 刘鑫. 血清HSP90α、GPC3、AFP-L3水平对早期原发性肝细胞癌的诊断价值[J]. 陕西医学杂志, 2025, 54(9):1248-1252.doi:10.3969/j.issn.1000-7377.2025.09.017.
[15]	孙伟, 李肖. 血浆热休克蛋白90α预测肝细胞肝癌介入治疗预后的临床价值[J]. 中华肿瘤杂志, 2024, 46(2):118-126. doi:10.3760/cma.j.cn112152-20231026-00262.
[16]	Su K, Liu X, Wang X, et al. Artificial intelligence-based personalized treatment strategies for unresectable hepatocellular carcinoma: Integrating HSP90α for prognosis and survival prediction[J]. NPJ Digit Med, 2025, 9(1):94. doi:10.1038/s41746-025-02281-y.
[17]	兰剑锋, 张应泉, 曾丽娇. 乙肝相关性肝癌患者血清异常凝血酶原、甲胎蛋白和甲胎蛋白异质体表达水平及临床意义[J]. 海南医学, 2021, 32(14):1793-1796. doi:10.3969/j.issn.1003-6350.2021.14.007.
[18]	何平, 王玉, 陈伟, 等. 血清AFP, AFP-L3, GP73及DCP在慢性乙肝和肝癌诊治中的价值分析[J]. 浙江医学, 2024, 46(15):1591-1594, 1606. doi:10.12056/j.issn.1006-2785.2024.46.15.2024-726.
[19]	陈策, 刘家琦, 丁体龙, 等. 血清AFP、AFP-L3、GP73对乙肝病毒感染相关肝癌的诊断价值及其与HBV-DNA载量的相关性[J]. 热带医学杂志, 2025, 25(7):951-954, F0004. doi:10.3969/j.issn.1672-3619.2025.07.016.
[20]	欧阳伟庆, 余广超, 隋洪, 等. GALAD模型及其类模型对早期乙型肝炎病毒相关肝细胞癌的诊断价值分析[J]. 临床肿瘤学杂志, 2025, 30(4):353-359. doi:10.3969/j.issn.1009-0460.2025.04.007.
[21]	李娟, 董先芳, 李玲, 等. 慢性乙型肝炎患者HBV-DNA载量与肝功能、肝纤维化程度及T淋巴细胞亚群的关系[J]. 中华医院感染学杂志, 2025, 35(4):490-494. doi:10.11816/cn.ni.2025-240802.
[22]	谢露, 刘光伟, 郭会军. HBV DNA载量水平与乙型肝炎相关肝癌指标的相关性分析及其对预后的影响[J]. 中西医结合肝病杂志, 2023, 33(10):925-929. doi:10.3969/j.issn.1005-0264.2023.010.014.

组别	例数	AFP(ng/ml)	AFP-L3(ng/ml)	HSP90α(ng/ml)	HBV-DNA(lgIU/ml)
HBV-HCC组	102	339.45±46.34^*#	415.48±50.79^*#	79.59±16.44^*#	5.39±0.14^*
乙肝肝硬化组	74	68.08±12.54^#	65.46±13.69^#	35.27±8.58^#	4.06±0.09
健康组	80	9.74±1.14	5.72±0.66	16.36±4.11	-
t/F值		3164.355	4172.741	720.257	71.654
P值		<0.01	<0.01	<0.01	<0.01

组别	例数	AFP(ng/ml)	AFP-L3(ng/ml)	HSP90α(ng/ml)	HBV-DNA(lgIU/ml)
HBV-HCC组	102	339.45±46.34^*#	415.48±50.79^*#	79.59±16.44^*#	5.39±0.14^*
乙肝肝硬化组	74	68.08±12.54^#	65.46±13.69^#	35.27±8.58^#	4.06±0.09
健康组	80	9.74±1.14	5.72±0.66	16.36±4.11	-
t/F值		3164.355	4172.741	720.257	71.654
P值		<0.01	<0.01	<0.01	<0.01

血清指标	AUC	标准误	P值	95%CI	截断值(ng/ml)	敏感度(%)	特异度(%)
AFP	0.904	0.022	<0.01	0.871~0.957	20.83	89.19	86.25
AFP-L3	0.818	0.036	<0.01	0.727~0.869	30.28	75.68	76.25
HSP90α	0.875	0.026	<0.01	0.834~0.936	25.17	85.14	81.25
联合	0.930	0.020	<0.01	0.891~0.969	-	93.24	90.00

血清指标	AUC	标准误	P值	95%CI	截断值(ng/ml)	敏感度(%)	特异度(%)
AFP	0.904	0.022	<0.01	0.871~0.957	20.83	89.19	86.25
AFP-L3	0.818	0.036	<0.01	0.727~0.869	30.28	75.68	76.25
HSP90α	0.875	0.026	<0.01	0.834~0.936	25.17	85.14	81.25
联合	0.930	0.020	<0.01	0.891~0.969	-	93.24	90.00

血清指标	AUC	标准误	P值	95%CI	截断值	敏感度(%)	特异度(%)
AFP	0.876	0.024	<0.01	0.828~0.924	150.28 ng/ml	84.31	86.49
AFP-L3	0.893	0.022	<0.01	0.849~0.937	200.75 ng/ml	87.25	85.14
HSP90α	0.842	0.028	<0.01	0.788~0.896	48.55 ng/ml	78.43	82.43
联合	0.904	0.022	<0.01	0.861~0.947	-	88.24	83.78