ALT水平正常的慢性乙型肝炎患者的血清学特征及肝组织病理学分析

刘珊珊; 陆忠华

doi:10.12449/JCH240512

ALT水平正常的慢性乙型肝炎患者的血清学特征及肝组织病理学分析

DOI: 10.12449/JCH240512

刘珊珊¹,
陆忠华^{1, 2, , ,}

1.
南京医科大学附属无锡医学中心，江苏无锡 214000
2.
无锡市第五人民医院肝病科，江苏无锡 214000

基金项目:

无锡市医学重点学科建设项目-创新团队 (CXTD2021009);

太湖人才计划 (20200803)

伦理学声明： 本研究方案于2023年7月18日经由无锡第五人民医院伦理委员会审批，批号：2023-008-1。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：刘珊珊负责数据收集，统计数据，撰写论文；陆忠华负责设计论文框架，修改文章并最后定稿。

详细信息

通信作者:
陆忠华， lu_z_h@126.com （ORCID： 0000-0002-5388-8301）

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出版历程
- 收稿日期: 2023-08-04
- 录用日期: 2023-10-07
- 出版日期: 2024-05-25

Serological features and liver histopathology of chronic hepatitis B patients with normal alanine aminotransferase

Shanshan LIU¹,
Zhonghua LU^{1, 2
, ,
,}

1.
Wuxi Clinical Medical College Affiliated to Nanjing Medical University，Wuxi，Jiangsu 214000，China
2.
Department of Hepatology，Wuxi Fifth People’s Hospital，Wuxi，Jiangsu 214000，China

Research funding:

Wuxi Medical Key Discipline Construction Project-Innovation Team (CXTD2021009);

Taihu Talent Program (20200803)

More Information

Corresponding author: LU Zhonghua， lu_z_h@126.com （ORCID： 0000-0002-5388-8301）

摘要

摘要: 目的分析ALT水平正常的慢性乙型肝炎（CHB）患者的肝组织病理学特点及与血清学指标间的关系。方法收集2018年4月—2021年6月无锡市第五人民医院137例ALT水平正常CHB患者的临床资料，分析肝组织病理与血清学指标间的差异及相关性。计数资料组间比较采用χ²检验。采用Speraman秩相关进行相关性分析。采用Logistic回归进行多因素分析。结果 ALT水平<20 U/L、20～29 U/L、30～40 U/L患者中分别有57.4%、53.4%、75%具有显著炎症坏死（≥G2），63.8%、62.1%、75%具有显著纤维化（≥S2）。HBeAg阳性/阴性、不同水平的血清HBV DNA、不同水平的血清HBV RNA在炎症活动程度分级上差异均有统计学意义（χ²值分别为10.008、6.911、7.946，P值均<0.05）；HBeAg阳性/阴性、不同水平的血清HBV RNA在纤维化分期上差异均有统计学意义（χ²值分别为7.996、10.874，P值均<0.05）。肝脏炎症程度及纤维化分期与血清HBV DNA无明显相关性（r_s=0.024，P=0.785；r_s=0.039，P=0.652），与血清HBV RNA存在显著相关性（r_s=0.222，P=0.009；r_s=0.187，P=0.029）。多因素分析提示HBeAg阳性是CHB患者肝脏发生炎症坏死（OR=-0.302，95%CI：-1.160～0.386，P=0.002）及纤维化（OR=-0.387，95%CI：-1.160～0.386，P=0.011）的独立危险因素。结论 ALT水平正常的CHB患者的肝脏组织存在不同程度的显著炎症坏死及纤维化，HBeAg阳性是这类患者肝脏组织出现显著炎症坏死及纤维化的独立危险因素。
- 乙型肝炎病毒 /
- 丙氨酸转氨酶 /
- HBV DNA /
- HBV RNA /
- 病理学
Abstract: Objective To investigate the liver histopathological features of chronic hepatitis B （CHB） patients with normal alanine aminotransferase （ALT） and their correlation with serological markers. Methods Clinical data were collected from 137 patients with normal ALT who were treated in Wuxi Fifth People’s Hospital from April 2018 to June 2021， and the differences in liver histopathology and serological markers were analyzed， as well as the correlation between liver histopathology and serological markers. The chi-square test was used for comparison of categorical data between groups， and the Kruskal-Wallis H test was used for comparison of data between multiple groups. A Spearman rank correlation test was performed， and logistic regression was used to perform the multivariate analysis. Results In the ALT ≤20 U/L， 20‍ ‍—‍ ‍29 U/L， and 30‍ ‍—‍ ‍40 U/L groups， the patients with significant inflammatory necrosis （≥G2） accounted for 57.4%， 53.4%， and 75%， respectively， and the patients with significant fibrosis （≥S2） accounted for 63.8%， 62.1%， and 75%， respectively. There was a significant difference in the degree of inflammatory necrosis between the patients with positive or negative HBeAg， the patients with different levels of serum HBV DNA， and the patients with different levels of serum HBV RNA （χ²=10.008， 6.911， and 7.946， all P<0.05）， and there was a significant difference in fibrosis stage between the patients with positive or negative HBeAg and the patients with different levels of serum HBV RNA （χ²=7.996 and 10.874， both P<0.05）. The degree of liver inflammation and fibrosis stage were not significantly correlated with serum HBV DNA （r_s =0.024， P=0.785； r_s =0.039， P=0.652）， while they were significantly correlated with serum HBV RNA （r_s =0.222， P=0.009； r_s =0.187， P=0.029）. The multivariate analysis showed that in CHB patients， positive HBeAg was an independent risk factor for inflammatory necrosis （odds ratio ［OR］=-0.302， 95% confidence interval ［CI］： -1.160 to 0.386， P=0.002） and fibrosis （OR=-0.387， 95%CI： -1.160 to 0.386， P=0.011）. Conclusion There are varying degrees of inflammatory necrosis and fibrosis in the liver of CHB patients with normal ALT， and positive HBeAg is independent risk factor for significant inflammatory necrosis and fibrosis in liver tissue of these patients.
- Hepatitis B virus /
- Alanine Transaminase /
- HBV DNA /
- HBV RNA /
- Pathology

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表 1 肝组织病理学炎症活动程度分级、纤维化分期情况

Table 1. The result of liver Liver histopathology inflammation grading， fibrosis staging

炎症活动程度分级	例（%）	纤维化分期	例（%）
G0～1	55（40.1）	S0～1	47（34.3）
G2	69（50.4）	S2	47（34.3）
G3	13（9.5）	S3	22（16.1）
G4	0（0.0）	S4	21（15.3）

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表 2 临床资料与炎症活动程度分级、纤维化分期的关系

Table 2. Relationship of clinical data to inflammation grading and fibrosis staging

因素	例数	炎症活动程度分级			χ²值	P值	肝纤维化分期			χ²值	P值
因素	例数	G0～G1	G2	G3～G4	χ²值	P值	S0～S1	S2	S3～4	χ²值	P值
年龄					1.814	0.404				0.711	0.701
<30岁	8	4	4	0			2	4	2
30～39岁	38	17	19	2			13	17	8
≥40岁	91	34	46	11			32	26	33
ALT					4.858	0.088				4.755	0.093
<20 U/L	47	20	23	4			17	22	8
20～29 U/L	58	27	27	4			22	16	20
30～40 U/L	32	8	19	5			8	9	15
血清HBeAg					10.008	0.040				7.996	0.046
阳性	28	8	12	8			10	6	12
阴性	109	47	57	5			37	41	31
血清HBV DNA					6.911	0.032				5.910	0.050
<10⁴ IU/mL	96	44	44	8			37	32	27
10⁴～<10⁷ IU/mL	22	3	16	3			2	17	3
≥10⁷ IU/mL	19	8	9	2			8	6	5
血清HBV RNA					7.946	0.019				10.874	0.012
<10⁴拷贝/mL	96	45	45	6			39	34	23
≥10⁴拷贝/mL	41	10	24	7			8	13	20

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