外部验证REAL-B评分对抗病毒治疗的慢性乙型肝炎患者肝细胞癌发生风险的预测价值
DOI: 10.3969/j.issn.1001-5256.2022.08.010
Value of external validation of REAL-B score in predicting the risk of hepatocellular carcinoma in chronic hepatitis B patients treated by antiviral therapy
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摘要:
目的 探究肝细胞癌(HCC)预测模型REAL-B评分对抗病毒治疗的慢性乙型肝炎患者HCC风险的预测性能,并与mPAGE-B、aMAP、PAGE-B评分进行比较。 方法 回顾性收集2013年1月—2015年12月天津市第二人民医院1160例接受1年以上恩替卡韦(ETV)或替诺福韦(TDF)治疗的慢性乙型肝炎患者的临床资料,并记录肝癌事件的发生。通过受试者工作特征曲线下面积(AUC)评估REAL-B、mPAGE-B、aMAP、PAGE-B评分对HCC的预测性能。采用Kaplan-Meier方法评估不同时间点HCC累积发生率,并通过log-rank检验比较不同评分分组间肝癌发生的差异。符合正态分布的计量资料2组间比较采用独立样本t检验;不符合正态分布的计量资料2组间比较采用Mann-Whitney U检验;计数资料2组间比较采用χ2检验。 结果 1160例慢性乙型肝炎患者中,有108 (9.8%)例患者在中位随访5.3(5.0~6.3)年内进展为HCC。REAL-B评分预测5年内HCC发生的AUC及其95%CI为0.848 (0.816~0.880),其次为aMAP评分[0.823(0.786~0.860)]、mPAGE-B评分[0.822(0.788~0.857)]和PAGE-B评分[0.780(0.736~0.824)]。在REAL-B评分低危组(0~3分)中,5年内肝癌累积发生率为0.8%, 低于中危组(4~7分)11.8%和高危组(8~13分)35.6%(P < 0.05)。REAL-B评分低危组中,3年和5年发生HCC的阴性预测值分别为100%和99.67%。 结论 REAL-B评分准确地预测了接受抗病毒治疗的慢性乙型肝炎患者HCC风险,并在抗病毒治疗3年中的预测价值优于其他风险模型。 Abstract:Objective To investigate the value of the hepatocellular carcinoma (HCC) risk model REAL-B score in predicting the risk of HCC in chronic hepatitis B (CHB) patients receiving antiviral therapy in comparison with mPAGE-B, aMAP and PAGE-B scores. Methods A retrospective analysis was performed for the clinical data of 1160 CHB patients who received entecavir or tenofovir treatment for more than 1 year from January 2013 to December 2015 in Tianjin Second Peolple's Hospital, and the events of HCC were recorded. The area under the ROC curve (AUC) was used to evaluate the value of REAL-B, mPAGE-B, aMAP, and PAGE-B scores in predicting HCC. The Kaplan-Meier method was used to evaluate the cumulative incidence rate of HCC at different time points, and the log-rank test was used to compare the incidence rate of HCC between the groups with different scores. The independent samples t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. Results Among the 1160 CHB patients, 108 (9.8%) progressed to HCC within a median follow-up time of 5.3 (5.0-6.3) years. REAL-B score had an AUC of 0.848 (95% confidence interval [CI]: 0.816-0.880) in predicting the onset of HCC within 5 years, followed by aMAP score (AUC=0.823, 95% CI: 0.786-0.860), mPAGE-B score (AUC=0.822, 95%CI: 0.788-0.857), and PAGE-B scores (AUC=0.780, 95%CI: 0.736-0.824). The 5-year cumulative incidence rate of HCC was 0.8% in the low-risk group (with a REAL-B score of 0-3 points), which was significantly lower than the incidence rate of 11.8% in the medium-risk group (with a REAL-B score of 4-7 points) and 35.6% with the high-risk group (with a REAL-B score of 8-13 points) (P < 0.05). In the low-risk group, REAL-B score had a negative predictive value of 100% and 99.67%, respectively, in predicting HCC within 3 and 5 years. Conclusion REAL-B score accurately predicts the risk of HCC in CHB patients receiving antiviral therapy, with a better predictive value than the other risk models within 3 years of antiviral therapy. -
Key words:
- Hepatitis B, Chronic /
- Carcinoma, Hepatocellular /
- Risk Factors
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表 1 1160例慢性乙型肝炎患者基本特征
Table 1. Basic characteristics of 1160 patients with chronic hepatitis B
项目 总体(n=1160) 非HCC组(n=1052) HCC组(n=108) 统计值 P值1) 年龄(岁) 45.8±12.9 44.5±12.5 58.2±8.9 t=-11.047 <0.001 男性[例(%)] 764 (65.9) 686(65.2) 78(72.2) χ2=2.143 0.143 肝硬化[例(%)] 283(24.4) 217(20.6) 66(61.1) χ2=87.031 <0.001 糖尿病[例(%)] 302(26.0) 262(24.9) 40(37.0) χ2=7.486 0.006 高血压[例(%)] 126(10.9) 100(9.5) 26(24.1) χ2=21.470 <0.001 饮酒[例(%)] 88(8.3) 72(6.8) 16(14.8) χ2=8.876 0.003 肝癌家族史[例(%)] 122(10.5) 111(10.6) 11(10.2) χ2=0.014 0.906 HBeAg阳性[例(%)] 621(53.5) 578(54.9) 43(39.9) χ2=9.011 0.003 ALT (U/L) 36.0(22.0~72.0) 36.2(22.6~76.0) 32.3(21.8~49.8) Z=-1.939 0.052 AST(U/L) 32.2(22.0~55.7) 32(22.0~55.8) 34.3(26.0~55.7) Z=-1.740 0.082 TBil (mg/dL) 0.9(0.7~1.3) 0.9(0.7~1.3) 1.1(0.8~1.5) Z=-3.318 0.001 Alb (g/L) 42.0±6.5 42.3±6.4 39.1±6.6 t=-4.632 <0.001 PLT (×109/L) 156.0(107.0~204.0) 162.0(114.0~210.0) 99.0(69.0~153.0) Z=-7.015 <0.001 HBV DNA(log10 IU/mL) 4.5±2.3 4.6±2.3 4.7±1.8 t=1.392 0.164 AFP(ng/mL) 4.2(2.5~8.5) 3.1(2.5~7.1) 4.7(2.5~13.6) Z=-1.694 0.009 NLR 1.7(1.2~2.4) 1.6(1.2~2.3) 2.0(1.5~3.2) Z=-3.915 <0.001 随访时间(年) 5.3(5.0~6.2) 5.3(5.1~6.2) 2.9(2.0~4.9) Z=-11.386 <0.001 抗病毒治疗[例(%)] χ2=0.032 0.859 ETV 1036(89.3) 939(89.3) 97(8.4) TDF 124(10.7) 113(10.7) 11(10.2) REAL-B评分 4.3±2.3 4.0±2.1 6.9±1.6 t=-13.441 <0.001 mPAGE-B评分 10.0±3.9 9.6±3.8 14.0±2.6 t=-11.882 <0.001 aMAP评分 52.9±9.0 51.9±8.7 62.3±6.7 t=-12.058 <0.001 PAGE-B评分 13.2±5.4 12.7±5.3 18.0±4.2 t=-9.948 <0.001 注:REAL-B评分,由男性、年龄、基线时肝硬化、饮酒、糖尿病、PLT和AFP构成;PAGE-B评分,由年龄、男性、PLT构成;mPAGE-B评分,由年龄、性别、PLT、Alb构成;aMAP评分,由年龄、男性、白蛋白-胆红素、PLT构成。 表 2 HCC发生的危险因素分析
Table 2. Analysis of risk factors for HCC
变量 单因素分析 多因素分析 HR (95%CI) P值 HR (95%CI) P值 年龄>50岁 6.415(4.014~10.252) <0.001 4.392(2.685~7.183) <0.001 男性 1.362(0.894~2.075) 0.150 - - 肝硬化 5.487(3.726~8.080) <0.001 3.256(2.103~5.043) <0.001 饮酒史 1.708(1.156~2.524) 0.007 0.792(0.448~1.401) 0.423 糖尿病 2.183(1.284~3.712) 0.004 1.427(0.920~2.213) 0.112 Alb<40 g/L 2.011(1.375~2.942) <0.001 0.872(0.578~1.315) 0.513 PLT<100×109/L 3.879(2.659~5.659) <0.001 1.616(1.061~2.460) 0.025 AFP>10 ng/mL 1.847(1.224~2.787) 0.003 1.585(1.022~2.458) 0.040 TBil>2 mg/dL 1.656(0.959~2.861) 0.071 - - 表 3 各HCC风险评分AUC分析
Table 3. AUC of different HCC risk scores
时间 HCC风险评分 AUC 95%CI 3年 REAL-B 0.865 0.830~0.901 mPAGE-B1) 0.820 0.778~0.862 aMAP1) 0.819 0.772~0.866 PAGE-B1) 0.775 0.720~0.829 5年 REAL-B 0.848 0.816~0.880 mPAGE-B 0.822 0.788~0.857 aMAP 0.823 0.786~0.860 PAGE-B1) 0.780 0.736~0.824 注:与REAL-B评分比较,1)P<0.05。 表 4 各HCC风险评分低危组诊断性能
Table 4. Diagnostic accuracy of low risk groups in different HCC risk scores
组别 3年 5年 敏感度(95%CI) 阴性预测值(95%CI) 敏感度(95%CI) 阴性预测值(95%CI) REAL-B评分(0~3) 100% 100% 99.07% (97.22%~100%) 99.67% (98.97%~100%) mPAGE-B评分(8) 100% 100% 100% 100% aMAP评分(<50) 95.31%(89.06%~100%) 99.37%(98.53%~100%) 95.37%(90.74%~99.07%) 98.94%(97.88%~99.78%) PAGE-B评分(9) 98.44%(95.31%~100%) 99.67%(98.95%~100%) 98.15%(95.37%~100%) 99.52%(98.78%~100%) -
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