HBsAg水平对ALT正常的HBeAg阳性慢性HBV感染者肝脏炎症发生的预测价值

曾湛; 高媛娇; 毕潇月; 陈凤欣; 邓雯; 蒋婷婷; 林妍洁; 杨柳; 李明慧; 谢尧

doi:10.3969/j.issn.1001-5256.2022.05.011

HBsAg水平对ALT正常的HBeAg阳性慢性HBV感染者肝脏炎症发生的预测价值

DOI: 10.3969/j.issn.1001-5256.2022.05.011

曾湛¹,
高媛娇²,
毕潇月²,
陈凤欣²,
邓雯²,
蒋婷婷²,
林妍洁¹,
杨柳²,
李明慧^{1, 2},
谢尧^{1, 2, , ,}

1.
北京大学地坛医院教学医院肝病二科，北京 100015
2.
首都医科大学附属北京地坛医院肝病二科，北京 100015

基金项目:

北京市医管中心临床专项项目 (XMLX201706);

北京市医管中心临床专项项目 (XMLX 202127);

国家科技重大专项 (2017ZX10201201-001-006);

国家科技重大专项 (2017ZX10201201-002-006);

国家科技重大专项 (2018ZX10715-005-003-005);

首都卫生发展专项公共卫生项目 (2021-1G-4061);

首都卫生发展专项公共卫生项目 (2022-1-2172);

北京市医管中心消化协同中心资助项目 (XXZ0302);

北京市医管中心消化协同中心资助项目 (XXT28);

北京市科委课题 (D161100002716002);

首都临床特色专项资助项目 (Z151100004015122)

伦理学声明：本研究方案于2018年1月25日经由首都医科大学北京地坛医院伦理委员会批准，批号：201800201。

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：谢尧、李明慧对研究思路和研究设计有关键贡献；陈凤欣、邓雯、蒋婷婷、林妍洁、杨柳收集和分析数据；高媛娇、毕潇月参与研究统计学方法的选择和文章的修改；曾湛负责撰写成文。

详细信息

通信作者:
谢尧，xieyao00120184@sina.com

曾湛、高媛娇与毕潇月对本文贡献等同, 同为第一作者

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出版历程
- 收稿日期: 2022-02-03
- 录用日期: 2022-03-14
- 出版日期: 2022-05-20

Value of HBsAg level in predicting liver inflammation in patients with HBeAg-positive chronic hepatitis B virus infection and normal alanine aminotransferase

1.
Second Department of Hepatology, Peking University Ditan Teaching Hospital, Beijing 100015, China
2.
Second Department of Hepatology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China

Research funding:

Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support (XMLX201706);

Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support (XMLX 202127);

National Science and Technology Major Project of China (2017ZX10201201-001-006);

National Science and Technology Major Project of China (2017ZX10201201-002-006);

National Science and Technology Major Project of China (2018ZX10715-005-003-005);

Special Public Health Project for Health Development in Capital (2021-1G-4061);

Special Public Health Project for Health Development in Capital (2022-1-2172);

The Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (XXZ0302);

The Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (XXT28);

Beijing Science and Technology Commission (D161100002716002);

Beijing Municipal Science & Technology Commission (Z151100004015122)

More Information

Corresponding author: XIE Yao, xieyao00120184@sina.com(ORCID: 0000-0003-4108-737)

摘要

摘要: 目的探讨ALT正常且高病毒载量的HBeAg阳性慢性HBV感染者人群的肝炎发生情况及预测因素。方法本研究临床注册号为NCT04032275。回顾性选取2008年10月—2015年5月ALT正常、高病毒载量、HBeAg阳性的慢性HBV感染者183例，根据其肝穿刺活检结果分为肝炎组和无肝炎组。计量资料两组间比较采用t检验或Mann-Whitney U检验。计数资料两组间比较采用χ²检验。使用单因素二元logistics回归分析预测因素，使用逐步后退法进行多因素二元logistics回归，使用受试者工作特征曲线(ROC)和约登指数分析截断值。结果肝炎组37例(20.2%)，无肝炎组146例(79.8%)，肝炎组的男性比例低于无肝炎组(45.9% vs 68.5%, χ²=6.508, P=0.011)、AST高于无肝炎组[24(21.25~35.55) U/L vs 21.2(18.08~24.65) U/L, Z=-3.344, P=0.001]、HBsAg log值低于无肝炎组[4.4(4.28~4.49) vs 4.46(4.4~4.74), Z=-2.184，P=0.029]。HBsAg log值是肝炎发生的预测因素(OR=0.077, P=0.017)。HBsAg的截断值为33 884.4 IU/mL。结论 ALT正常、高病毒载量的HBeAg阳性患者中有20.2%肝脏存在炎症，HBsAg或许是肝脏炎症发生的预测因素。
- 乙型肝炎病毒 /
- 乙型肝炎表面抗原 /
- 乙型肝炎e抗原 /
- 免疫耐受 /
- 炎症
Abstract: Objective To investigate the onset of liver inflammation and related predictive factors in patients with HBeAg-positive chronic hepatitis B virus (HBV) infection who have normal alanine aminotransferase (ALT) and a high viral load. Methods A retrospective analysis was performed for the clinical data of 183 patients with HBeAg-positive chronic HBV infection who had normal ALT and a high viral load and were treated from October 2008 to May 2015, and according to the results of liver biopsy, they were divided into hepatitis group and non- hepatitis group. The t-test or Mann-Whitney U testwas used for comparison of normally distributed continuous data between groups, the chi-square test was used for comparison of categorical data. The predictive factors were analyzed by univariate binary logistic regression, the multivariate binary logistic regression was carried out by stepback method, and the cut-off values were analyzed by receiver operating characteristic curve (ROC) and Jordan index. Results There were 37 patients (20.2%) in the hepatitis group and 146 patients (79.8%) in the non-hepatitis group. Compared with the non-hepatitis group, the hepatitis group had a significantly lower proportion of male patients (45.9% vs 68.5%, χ²=6.508, P=0.011), a significantly higher level of aspartate aminotransferase [24 (21.25~35.55) U/L vs 21.2 (18.08~ 24.65) U/L, Z=-3.344, P=0.001], and a significantly lower log(HBsAg) value [4.4(4.28~4.49) vs 4.46(4.4~4.74), Z=-2.184, P=0.029]. Log(HBsAg) value was a predictive factor for hepatitis (odds ratio=0.077, P=0.017), and the cutoff value of HBsAg was 33884.4I U/mL. Conclusion Among the patients with HBeAg-positive chronic HBV infection who have normal ALT and a high viral load, 20.2% have liver inflammation, and HBsAg may be a predictive factor for liver inflammation.
- Hepatitis B virus /
- Hepatitis B Surface Antigens /
- Hepatitis B e Antigens /
- Immune Tolerance /
- Inflammation

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图 1 HBsAg定量log值的ROC曲线

Figure 1. ROC curve of log(HBsAg)

下载: 全尺寸图片幻灯片

图 2 AST的ROC曲线图

Figure 2. ROC curve of AST

下载: 全尺寸图片幻灯片

表 1 肝炎组与无肝炎组基线情况对比

Table 1. Comparisons of baseline between hepatitis group and non-hepatitis group

指标	总体(n=183)	无肝炎组(n=146)	肝炎组(n=37)	统计值	P值
年龄(岁)	31.99±9.08	31.30±8.53	34.73±10.72	t=-1.806	0.077
男性[例(%)]	117(63.9)	100(68.5)	17(45.9)	χ²=6.508	0.011
ALT(U/L)	28.20(22.00~33.70)	28.20(21.50~33.05)	28.30(23.10~35.10)	Z=-0.836	0.403
ALT分层比较[例(%)]
＜20 U/L	25(13.7)	21(14.4)	4(10.8)	χ²=-0.185	0.853
20~29.9 U/L	82(44.8)	65(44.5)	17(46.0)	χ²=-0.498	0.619
30~40 U/L	76(41.5)	60(41.1)	16(43.2)	χ²=-1.230	0.219
AST(U/L)	22.10(18.80~25.50)	21.20(18.08~24.65)	24.00(21.25~35.55)	Z=-3.344	0.001
TBil(μmol/L)	12.85(9.50~17.43)	12.60(9.40~17.75)	13.20(9.55~16.25)	Z=-0.142	0.887
Alb(g/L)	46.40(44.18~48.90)	46.40(44.30~48.85)	46.40(43.70~49.10)	Z=-0.122	0.903
WBC(×10⁹/L)	5.91±1.34	5.94±1.28	5.76±1.58	t=0.698	0.486
PLT(×10⁹/L)	212.15±50.41	212.81±51.53	209.38±46.07	t=0.346	0.730
PTA(%)	88.08±9.29	88.47±9.85	86.54±6.58	t=0.929	0.355
HBV DNA(logIU/mL)	7.72(7.52~7.99)	7.72(7.5~8.01)	7.73(7.59~7.99)	Z=-0.608	0.543
HBsAg(logU/mL)	4.43(4.40~4.71)	4.46(4.40~4.74)	4.40(4.28~4.49)	Z=-2.184	0.029
HBeAg(S/CO)	1400.56(1246.11~1550.96)	1411.00(1269.70~1553.30)	1323.60(995.70~1519.30)	Z=-1.899	0.058

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表 2 单因素logistic回归分析肝炎危险因素

Table 2. Single factor logistic regression analysis of risk factors for hepatitis

项目	B值	Wald	P值	OR	95%CI
性别(男性)	-0.939	6.273	0.012	0.391	0.188~0.815
年龄(岁)	0.040	4.111	0.043	1.041	1.001~1.082
AST(U/L)	0.047	7.140	0.008	1.048	1.013~1.085
HBsAg(logU/mL)	-2.566	5.716	0.017	0.077	0.009~0.630
HBeAg(S/CO)	-0.002	7.349	0.007	0.998	0.997~1.000

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