术前抗病毒治疗对HBV相关肝癌肝切除术后肝衰竭影响

doi:10.3877/cma.j.issn.2095-3232.2025.05.007

目的

探讨术前HBV-DNA定量水平及抗病毒治疗对HBV相关肝细胞癌（HBV-HCC）患者肝切除术后肝衰竭（PHLF）的影响。

方法

研究对象为2014年1月至2021年12月在中山大学附属第一医院接受肝部分切除术的853例HBV-HCC患者。本研究为回顾性研究且豁免知情同意，符合医学伦理学规定。其中男756例，女97例；年龄18~84岁，中位年龄53岁。采用Logistic单因素和多因素回归分析PHLF的影响因素，并基于PHLF的独立危险因素构建PHLF预测模型。通过采用ROC曲线下面积（AUC）、校准曲线、临床决策曲线分析（DCA）评估预测模型效能。两组肝功能指标比较采用Mann-Whitney U检验，发生率比较采用χ²检验或Fisher确切概率法。

结果

HBV-HCC患者PHLF发生率23.9%（204/853）。Logistic多因素回归分析显示，HBV-DNA≥2 000 IU/ml、年龄、大范围肝切除、术中出血量、前白蛋白（PA）、胆汁酸（TBA）、Plt、PT为PHLF独立影响因素（OR=1.489 3，1.020 2，3.331 6，1.000 2，0.993 7，1.014 9，0.995 1，2.240 3；P<0.05）。基于以上8个独立危险因素构建PHLF的列线图预测模型，该模型预测PHLF的AUC为0.816；校准曲线显示，该模型预测PHLF风险与实际观察到的PHLF发生率具有较好的一致性，C-index为0.809 8；DCA也显示出该预测模型具有较大的临床获益。术前规律抗病毒治疗患者PHLF发生率为19.1%（47/246），明显低于未规律抗病毒治疗患者25.9%（157/607）（χ²=4.032，P=0.044）。

结论

对于HBV-HCC肝切除患者，术前HBV-DNA≥2 000 IU/ml是PHLF的独立危险因素，术前规律抗病毒治疗能有效降低PHLF的发生率。

关键词: 肝细胞癌, 乙型肝炎病毒, 乙肝病毒脱氧核糖核酸, 抗病毒治疗, 肝切除术后肝衰竭, 预测模型

Objective

To investigate the effect of preoperative HBV-DNA quantification levels and antiviral therapy on post-hepatectomy liver failure (PHLF) in patients with HBV-associated hepatocellular carcinoma (HBV-HCC).

Methods

A total of 853 patients with HBV-HCC who underwent partial hepatectomy at the First Affiliated Hospital of Sun Yat-sen University from January 2014 to December 2021 were enrolled. The local ethical committee approval was received and the requirement for written informed consent was waived due to the retrospective nature of the study. Among them, 756 patients were male and 97 female, aged from 18 to 84 years, with a median age of 53 years. Univariate and multivariate Logistic regression analyses were used to analyze the risk factors of PHLF. A prediction model for PHLF was constructed based on the independent risk factors of PHLF. The area under the ROC curve (AUC), calibration curve and decision curve analysis (DCA) were adopted to analyze the efficiency of the prediction model. Mann-Whitney U test was employed to compare the liver function parameters between two groups. The incidence rates were compared by Chi-square test or Fisher's exact test.

Results

The incidence of PHLF in HBV-HCC patients was 23.9% (204/853). Multivariate Logistic regression analysis identified HBV-DNA≥2 000 IU/ml, age, major hepatectomy, intraoperative blood loss, prealbumin (PA), total bile acid (TBA), Plt and PT as independent risk factors for PHLF (OR=1.489 3, 1.020 2, 3.331 6, 1.000 2, 0.993 7, 1.014 9, 0.995 1, 2.240 3; all P<0.05). Based on the above 8 independent risk factors, a nomogram prediction model for PHLF was constructed. The AUC of this prediction model for PHLF was 0.816. The calibration curve showed high consistency between the risk of PHLF predicted by the model and the actual incidence of PHLF, with a C-index of 0.809 8. DCA also demonstrated that the prediction model yielded more clinical benefits. The incidence of PHLF in patients receiving regular antiviral therapy before surgery was 19.1%(47/246), significantly lower than 25.9%(157/607) in those without regular antiviral therapy (χ²=4.032, P=0.044).

Conclusions

For patients with HBV-HCC undergoing hepatectomy, preoperative HBV-DNA ≥2 000 IU/ml is an independent risk factor for PHLF. Regular antiviral therapy before surgery can effectively reduce the incidence of PHLF.

Key words: Hepatocellular carcinoma(HCC), Hepatitis B virus(HBV), Hepatitis B virus deoxyribonucleic acid (HBV-DNA), Antiviral therapy, Post-hepatectomy liver failure (PHLF), Prediction model

表1 HBV-HCC患者行肝切除PHLF影响因素的Logistic回归分析

变量	单因素分析		多因素分析
变量	OR(95%CI)	P 值	OR(95%CI)	P 值
年龄	1.014 9(1.001 2~1.028 8)	0.033	1.020 2 (1.004 0~1.036 9)	0.015
HBV-DNA≥2 000 IU/ml	1.860 5(1.353 9~2.556 7)	<0.001	1.489 3 (1.030 5~2.155 6)	0.034
大范围肝切除	2.188 3(1.581 6~3.027 8)	<0.001	3.331 6 (2.235 8~5.032 0)	<0.001
术中出血量	1.000 3(1.000 1~1.000 4)	<0.001	1.000 2 (1.000 1~1.000 4)	<0.001
PA	0.985 5(0.982 2~0.988 8)	<0.001	0.993 7 (0.989 7~0.997 7)	0.002
TBA	1.025 3(1.013 9~1.036 8)	<0.001	1.014 9 (1.004 6~1.027 1)	0.004
Plt	0.997 3(0.995 2~0.999 3)	0.008	0.995 1 (0.992 8~0.997 4)	<0.001
PT	2.471 4(2.066 3~2.956 0)	<0.001	2.240 3 (1.810 5~2.777 4)	<0.001

表1 HBV-HCC患者行肝切除PHLF影响因素的Logistic回归分析

变量	单因素分析		多因素分析
变量	OR(95%CI)	P 值	OR(95%CI)	P 值
年龄	1.014 9(1.001 2~1.028 8)	0.033	1.020 2 (1.004 0~1.036 9)	0.015
HBV-DNA≥2 000 IU/ml	1.860 5(1.353 9~2.556 7)	<0.001	1.489 3 (1.030 5~2.155 6)	0.034
大范围肝切除	2.188 3(1.581 6~3.027 8)	<0.001	3.331 6 (2.235 8~5.032 0)	<0.001
术中出血量	1.000 3(1.000 1~1.000 4)	<0.001	1.000 2 (1.000 1~1.000 4)	<0.001
PA	0.985 5(0.982 2~0.988 8)	<0.001	0.993 7 (0.989 7~0.997 7)	0.002
TBA	1.025 3(1.013 9~1.036 8)	<0.001	1.014 9 (1.004 6~1.027 1)	0.004
Plt	0.997 3(0.995 2~0.999 3)	0.008	0.995 1 (0.992 8~0.997 4)	<0.001
PT	2.471 4(2.066 3~2.956 0)	<0.001	2.240 3 (1.810 5~2.777 4)	<0.001

图1 HBV-HCC患者行肝切除PHLF列线图预测模型构建和效能评估注：a为预测PHLF发生风险的列线图模型，b为列线图模型预测PHLF的ROC曲线，c为列线图预测PHLF发生风险的校准曲线，d为预测PHLF发生风险的列线图决策曲线；PHLF为肝切除术后肝衰竭，HBV-HCC为HBV相关肝细胞癌

表2 术前规律抗病毒治疗对HBV-HCC行肝切除患者影响

变量	抗病毒治疗	未抗病毒治疗	统计值	P值
ALT [U/L, M(Q₁, Q₃)]	28(19, 40)	35(25, 53)	Z=5.221	<0.001
AST [(U/L, M(Q₁, Q₃)]	32(24, 45)	40(30, 62)	Z=6.059	<0.001
ALB [(g/L, M(Q₁, Q₃)]	39(36, 41)	38(35, 40)	Z=-2.818	0.005
PA [g/L, M(Q₁, Q₃)]	201(173, 235)	185(149, 221)	Z=-4.382	<0.001
TB [μmol/L, M(Q₁, Q₃)]	14(11, 19)	15(11, 18)	Z=-0.006	0.995
TBA [μmol/L, M(Q₁, Q₃)]	7(4, 13)	7(4, 13)	Z=-0.472	0.637
Plt [×10⁹/L, M(Q₁, Q₃)]	150(112, 196)	194(145, 238)	Z=6.906	<0.001
PT [s, M(Q₁, Q₃)]	12(11, 13)	12(12, 13)	Z=2.458	0.014
AFP≥400 μg/L[例(%)]	62(25.2)	226(37.2)	χ²=10.795	0.001
Child-Pugh分级A级[例(%)]	235(95.5)	555(91.4)	χ²=3.714	0.043
HBV-DNA≥2 000 IU/ml[例(%)]	47(19.1)	334(55.0)	χ²=89.933	<0.001
PHLF发生率[例(%)]	47(19.1)	157(25.9)	χ²=4.032	0.044
ICU治疗[例(%)]	10(4.1)	31(5.1)	χ²=0.219	0.599
术后主要并发症 [例(%)]	59(24.0)	151(24.9)	χ²=0.035	0.852
围手术期死亡 [例(%)]	1(0.4)	8(1.3)	χ²=0.657	0.174
PHLF相关死亡[例(%)]	1(0.4)	4(0.7)	χ²=0.190	1.000

表2 术前规律抗病毒治疗对HBV-HCC行肝切除患者影响

变量	抗病毒治疗	未抗病毒治疗	统计值	P值
ALT [U/L, M(Q₁, Q₃)]	28(19, 40)	35(25, 53)	Z=5.221	<0.001
AST [(U/L, M(Q₁, Q₃)]	32(24, 45)	40(30, 62)	Z=6.059	<0.001
ALB [(g/L, M(Q₁, Q₃)]	39(36, 41)	38(35, 40)	Z=-2.818	0.005
PA [g/L, M(Q₁, Q₃)]	201(173, 235)	185(149, 221)	Z=-4.382	<0.001
TB [μmol/L, M(Q₁, Q₃)]	14(11, 19)	15(11, 18)	Z=-0.006	0.995
TBA [μmol/L, M(Q₁, Q₃)]	7(4, 13)	7(4, 13)	Z=-0.472	0.637
Plt [×10⁹/L, M(Q₁, Q₃)]	150(112, 196)	194(145, 238)	Z=6.906	<0.001
PT [s, M(Q₁, Q₃)]	12(11, 13)	12(12, 13)	Z=2.458	0.014
AFP≥400 μg/L[例(%)]	62(25.2)	226(37.2)	χ²=10.795	0.001
Child-Pugh分级A级[例(%)]	235(95.5)	555(91.4)	χ²=3.714	0.043
HBV-DNA≥2 000 IU/ml[例(%)]	47(19.1)	334(55.0)	χ²=89.933	<0.001
PHLF发生率[例(%)]	47(19.1)	157(25.9)	χ²=4.032	0.044
ICU治疗[例(%)]	10(4.1)	31(5.1)	χ²=0.219	0.599
术后主要并发症 [例(%)]	59(24.0)	151(24.9)	χ²=0.035	0.852
围手术期死亡 [例(%)]	1(0.4)	8(1.3)	χ²=0.657	0.174
PHLF相关死亡[例(%)]	1(0.4)	4(0.7)	χ²=0.190	1.000

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Effect of preoperative antiviral therapy on post-hepatectomy liver failure for HBV-associated hepatocellular carcinoma

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Effect of preoperative antiviral therapy on post-hepatectomy liver failure for HBV-associated hepatocellular carcinoma