ALT≤40 U/L的HBeAg阴性慢性HBV感染者抗病毒治疗指征的无创指标分析

李春霞; 东冰; 周路路; 任丹丹; 张瑞芹; 郭何; 徐光华; 刘娜

doi:10.3969/j.issn.1001-5256.2021.01.011

ALT≤40 U/L的HBeAg阴性慢性HBV感染者抗病毒治疗指征的无创指标分析

DOI: 10.3969/j.issn.1001-5256.2021.01.011

延安大学附属医院感染病科，陕西延安 716000

基金项目:

延安市科技惠民计划项目 (2014HM-09)

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，特此声明。

作者贡献声明：李春霞、东冰、周路路、任丹丹、刘娜负责课题设计，资料分析，撰写论文；李春霞、张瑞芹、郭何、刘娜参与收集数据，修改论文；徐光华、刘娜负责拟定写作思路，指导撰写文章，并最后定稿。

详细信息

作者简介:
李春霞(1983—)，女，主要从事肝病及相关研究

通信作者:
刘娜，liunamei1984@163.com

中图分类号: R512.62
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出版历程
- 收稿日期: 2020-07-06
- 录用日期: 2020-09-07
- 出版日期: 2021-01-20

Noninvasive indicators of indications for antiviral therapy in HBeAg-negative chronic HBV infection patients with alanine aminotransferase ≤40 U/L

Department of Infectious Diseases, Affiliated Hospital of Yan'an University, Yan'an, Shaanxi 716000, China

摘要

摘要: 目的在肝组织病理的指导下探索ALT≤40 U/L的HBeAg阴性慢性HBV感染者抗病毒指征的无创指标。方法回顾性纳入2013年10月—2018年8月延安大学附属医院收治的已行肝活检的377例ALT≤40 U/L的HBeAg阴性慢性HBV感染者，入组患者中炎症活动度＜A2且纤维化分期＜F2归为暂不需要抗病毒治疗组(n=266)，炎症活动度≥A2，或纤维化分期≥F2归为需要抗病毒治疗组(n=111)。计数资料2组间比较采用χ²检验。满足正态分布的计量资料的2组间比较采用t检验，不满足正态分布的计量资料2组间比较采用Mann-Whitney U检验；采用二元logistic单因素分析及多因素回归分析筛选是否启用抗病毒治疗的影响因素，绘制受试者工作特征曲线(ROC曲线)，应用ROC曲线评估各指标对ALT≤40 U/L的HBeAg阴性慢性HBV感染者是否需要抗病毒治疗的诊断效能。结果 377例患者中266例(70.6%)暂不需要抗病毒治疗，111例(29.4%)伴有明显肝组织损伤，需要积极启动抗病毒治疗。多因素分析显示LSM、HBsAg、HBV DNA、Alb是启动抗病毒治疗的独立影响因素(P值均＜0.05), 其HR(95%CI)分别为2.003(1.647~2.437)、1.563(1.110~2.200)、1.519(1.173~1.966)和0.939(0.884~0.998)。ROC曲线显示，LSM、HBV DNA、HBsAg预测是否需要抗病毒治疗的ROC曲线下面积(AUC)分别是0.749(0.699~0.799)、0.642(0.586~0.699)、0.565(0.507~0.623)，LSM、HBV DNA、HBsAg联合诊断的AUC值更大，为0.779(0.732~0.827)。结论 LSM、HBV DNA、HBsAg水平对ALT≤40 U/L的HBeAg阴性慢性HBV感染者启动抗病毒治疗有参考价值。
- 乙型肝炎病毒 /
- 乙型肝炎e抗原 /
- 丙氨酸转氨酶 /
- 抗病毒治疗
Abstract: Objective To investigate the noninvasive indicators of indications for antiviral therapy in HBeAg-negative chronic hepatitis B virus (HBV) infection patients with alanine aminotransferase (ALT) ≤40 U/L under the guidance of liver pathology. Methods A retrospective analysis was performed for the clinical data of 377 HBeAg-negative chronic HBV infection patients with ALT ≤40 U/L who were hospitalized in Affiliated Hospital of Yan'an University, from October 2013 to August 2018 and underwent liver biopsy, among whom the patients with inflammatory activity < A2 and fibrosis stage < F2 were enrolled as non-antiviral therapy group(n=266), and the patients with inflammatory activity ≥A2 or fibrosis stage ≥F2 were enrolled as antiviral therapy group(n=111). The chi-square test was used for comparison of categorical data between two groups; the t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; univariate and multivariate binary logistic regression analyses were used to screen out the influencing factors for the initiation of antiviral therapy; the receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic efficiency of each indicator in determining the need for antiviral therapy in HBeAg-negative chronic HBV infection patients with ALT ≤40 U/L. Results Of all 377 patients, 266 (70.6%) did not need antiviral therapy for the time being, and 111 (29.4%) had marked liver damage and thus needed active antiviral therapy. The multivariate analysis showed that liver stiffness measurement (LSM) (odds ratio [HR]=2.003, 95% confidence interval [CI]: 1.647-2.437, P < 0.05), HBsAg (HR=1.563, 95% CI: 1.110-2.200, P < 0.05), HBV DNA (HR=1.519, 95% CI: 1.173-1.966, P < 0.05), and albumin (HR=0.939, 95% CI: 0.884-0.998, P < 0.05) were independent influencing factors for the initiation of antiviral therapy. The ROC curve analysis showed that the area under the ROC curve (AUC) was 0.749 (95% CI: 0.699-0.799) for LSM, 0.642 (95% CI: 0.586-0.699) for HBV DNA, and 0.565 (95% CI: 0.507-0.623) for HBsAg, and the combination of LSM, HBV DNA, and HBsAg had a larger AUC of 0.779 (95% CI: 0.732-0.827). Conclusion The levels of LSM, HBV DNA, and HBsAg have a reference value in determining the initiation of antiviral therapy in HBeAg-negative chronic HBV infection patients with ALT≤40 U/L.
- Hepatitis B Virus /
- Hepatitis B e Antigens /
- Alanine Transaminase /
- Antiviral Treatment

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图 1 预测ALT≤ULN的HBeAg阴性患者需要抗病毒治疗的ROC曲线分析

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表 1 入组患者的基本特征

项目	无需抗病毒治疗组(n=266)	需抗病毒治疗组(n=111)	统计值	P值
年龄(岁)	40.18±10.08	40.69±10.97	t=-0.436	0.063
男性[例(%)]	129(48.5)	54(48.6)	χ²=0.001	0.978
家族史[例(%)]	136(51.1)	60(54.1)	χ²=0.269	0.604
HBV DNA(log₁₀ IU/ml)	3.22(2.69~3.78)	2.69(3.40~4.12)	Z=-1.518	0.129
HBsAg(log₁₀ IU/ml)	3.48(2.89~3.91)	3.48(3.06~3.77)	Z=-0.135	0.892
抗-HBc(S/CO)	10.31(9.20~11.54)	10.11(9.35~11.29)	Z=-0.733	0.463
ALT(U/L)	31.80±32.66	34.52±31.95	t=-0.746	0.456
AST(U/L)	26.70±16.69	30.29±20.51	t=-1.773	0.077
TBil(μmol/L)	13.66±6.21	13.67±6.68	t=-0.011	0.991
Alb(g/L)	43.74±3.92	42.83±4.00	t=2.031	0.043
PLT(×10⁹/L)	188.0(153.5~220.0)	175.0(143.0~213.0)	Z=-2.060	0.039
LSM(kPa)	4.7(4.0~5.6)	6.1(4.8~7.5)	Z=-6.260	＜0.001

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表 2 单因素和多因素分析是否需要抗病毒治疗的影响因素

项目	单因素分析		多因素分析
项目	HR(95%CI)	P值	HR(95%CI)	P值
年龄(岁)	1.016(0.992~1.041)	0.191
男性	1.002(0.598~1.681)	0.993
家族史	0.973(0.599~1.580)	0.912
HBV DNA(log₁₀ IU/ml)	1.569(1.184~2.078)	0.002	1.519(1.173~1.966)	0.002
HBsAg(log₁₀ IU/ml)	1.672(1.171~2.387)	0.005	1.563(1.110~2.200)	0.011
抗-HBc(S/CO)	0.941(0.821~1.078)	0.381
ALT(U/L)	0.991(0.969~1.014)	0.447
AST(U/L)	1.020(0.983~1.059)	0.292
TBil(μmol/L)	1.002(0.965~1.040)	0.933
Alb(g/L)	0.944(0.887~1.005)	0.071	0.939(0.884~0.998)	0.044
PLT(×10⁹/L)	0.998(0.993~1.002)	0.318
LSM(kPa)	1.984(1.623~2.425)	＜0.001	2.003(1.647~2.437)	＜0.001

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表 3 LSM、HBV DNA、HBsAg对是否抗病毒治疗的预测价值比较

项目	LSM	HBV DNA	HBsAg
AUC (95%CI)	0.749(0.699~0.799)	0.642(0.586~0.699)	0.565(0.507~0.623)
P值	＜0.001	＜0.001	0.030
最佳界值	6.05 kPa	3.8 log₁₀ IU/ml	3.27 log₁₀ IU/ml
敏感度(%)	49.4	39.8	70.5
特异度(%)	92.0	84.6	45.8
诊断准确率(%)	70.5	62.5	58.5
Youden指数	0.414	0.244	0.163

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