Mindin蛋白在经聚乙二醇干扰素α-2b治疗的慢性乙型肝炎中的动态变化及意义

王怡恺; 吴凤萍; 刘晨瑞; 郝苗; 吕莎莎; 张苗苗; 党双锁; 张欣

doi:10.12449/JCH240110

Mindin蛋白在经聚乙二醇干扰素α-2b治疗的慢性乙型肝炎中的动态变化及意义

DOI: 10.12449/JCH240110

西安交通大学第二附属医院感染科，西安 710004

基金项目:

陕西省自然科学基金 (2022JCYB-770)

伦理学声明：本研究方案由西安交通大学第二附属医院伦理委员会审批，批号为2018033。所有研究对象入组前均签署了书面知情同意书。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：王怡恺、张欣负责课题设计，资料汇总分析，撰写论文；吴凤萍、刘晨瑞、郝苗参与收集数据，修改论文；吕莎莎、张苗苗负责数据分析和整理；党双锁、张欣负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
张欣， zn661@163.com （ORCID： 0000-0002-5966-0471）

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出版历程
- 收稿日期: 2023-03-18
- 录用日期: 2023-05-31
- 出版日期: 2024-01-23

Dynamic change and significance of Mindin protein in chronic hepatitis B treated with PEG-IFNα-2b

Department of Infectious Diseases，The Second Affiliated Hospital of Xi’an Jiaotong University，Xi’an 710004，China

Research funding:

Natural Science Foundation of Shaanxi Province (2022JCYB-770)

More Information

Corresponding author: ZHANG Xin， zn661@163.com （ORCID： 0000-0002-5966-0471）

摘要

摘要: 目的分析聚乙二醇干扰素α-2b（PEG-IFNα-2b）治疗慢性乙型肝炎（CHB）过程中Mindin蛋白的变化以及作用。方法选取2018年1月—2019年12月于西安交通大学第二附属医院行PEG-IFNα-2b治疗的CHB患者29例，按照临床结局分为治愈组（n=17）与未治愈组（n=12）。分别采集治愈组和未治愈组基线、12周和24周的外周血样本，测量血常规、肝功能、乙型肝炎标志物定量和Mindin蛋白含量。分析比较各时间点HBsAg、ALT、AST及Minidn蛋白水平的组间差异。符合正态分布的计量资料两组间比较采用成组t检验；非正态分布的计量资料两组间比较采用Mann-Whitney U检验。采用Spearman相关性分析法对Mindin蛋白与HBsAg、ALT、AST的相关性进行分析。多元线性回归分析探讨HBsAg、ALT水平对Mindin蛋白的影响。结果基线资料分析发现，未治愈组和治愈组HBsAg、抗-HBe、Alb和白/球比值（A/G）水平两组间比较差异均有统计学意义（P值均<0.05）。治愈组Mindin蛋白水平呈现持续上升的趋势，24周时Mindin蛋白水平显著高于基线（P<0.05）。24周时治愈组Mindin蛋白水平显著高于未治愈组（P=0.019）。治愈组HBsAg水平均显著低于未治愈组，且组内各时间点与基线比较差异均具有统计学意义（P值均<0.05）。此外，治愈组ALT和AST的变化均呈现先升高后降低的趋势，12周的表达水平均显著高于基线（P值均<0.05）。未治愈组24周ALT和AST水平均显著高治愈组（P值均<0.05）。未治愈组12周时Mindin蛋白水平与ALT呈现出较强的直线相关性（r=0.760 8，P<0.05），进一步的多元线性回归分析同样证明两者间存在线性关系（偏回归系数为1.571，P=0.019）。结论 PEG-IFNα-2b抗病毒治疗24周时的Mindin蛋白水平在治愈组和未治愈组间存在明显差异。提示通过检测Mindin蛋白的动态变化可以更好地预测慢性乙型肝炎的治疗结局，为临床提供参考。
- 乙型肝炎，慢性 /
- Mindin蛋白 /
- 干扰素α
Abstract: Objective To investigate the change and potential role of Mindin protein in the treatment of chronic hepatitis B （CHB） with PEG-IFNα-2b. Methods A total of 29 CHB patients who received the treatment with PEG-IFNα-2b in The Second Affiliated Hospital of Xi’an Jiaotong University from January 2018 to December 2019 were enrolled， and according to their clinical outcome， they were divided into cured group with 17 patients and uncured group with 12 patients. Peripheral blood samples were collected from both groups at baseline， 12 weeks， and 24 weeks to measure blood routine indices， liver function parameters， hepatitis B markers， and Mindin protein. HBsAg， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Mindin protein at different time points were compared between the two groups. The independent-samples 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； a Spearman correlation analysis was used to investigate correlation； a multiple linear regression analysis was used to investigate the influence of HBsAg and ALT on the content of Mindin protein. Results The analysis of baseline data showed that there were significant differences in the levels of HBsAg， HBeAb， albumin， and albumin/globulin ratio between the cured group and the uncured group （all P<0.05）. The cured group tended to have a gradual increase in the level of Mindin， and the level of Mindin at 24 weeks was significantly higher than that at baseline （P<0.05）. The cured group had a significantly higher level of Mindin protein than the uncured group at 24 weeks （P=0.019）. The cured group had a significantly lower level of HBsAg than the uncured group （P<0.05）， with a significant change from baseline to each time point within the cured group （P<0.05）. In addition， the levels of ALT and AST in the cured group tended to first increase and then decrease， and the expression levels at 12 weeks were significantly higher than those at baseline （P<0.05）. At 12 weeks， there was a strong linear correlation between Mindin protein levels and ALT in the untreated group （r=0.760 8， P<0.05）， and further multiple linear regression analysis also demonstrated a linear relationship between the two （b=1.571， P=0.019）. Conclusion There is a significant difference in the level of Mindin protein between the cured group and the non-cured group after 24 weeks of PEG-IFNα-2b antiviral treatment， and therefore， detecting the dynamic changes of Mindin protein can better predict the treatment outcome of CHB， which provides a reference for clinical practice.
- Hepatitis B， Chronic /
- Mindin Protein /
- Interferon-alpha

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图 1 三组间基线Mindin水平比较

Figure 1. Comparison of baseline Mindin levels among cured， uncured， and healthy controls

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图 2 HBsAg、转氨酶和Mindin的动态变化

Figure 2. Dynamic changes in HBsAg， transaminase， and Mindin

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表 1 患者基线和人口统计学资料

Table 1. Baseline and demographic data of the patients

基线特征	未治愈组（n=17）	治愈组（n=12）	统计值	P值
男性	60%	40%	χ ²=4.441	0.060
年龄（岁）	41.1±9.9	35.2±9.4	t=1.632	0.114
HBsAg（log₁₀IU/mL）	2.6±0.7	1.9±1.1	t=-1.996	0.046
抗-HBs（mIU/mL）	0.3（0.0～2.2）	0.1（0.0～1.8）	Z=-0.142	0.887
HBeAg（s/co）	0.4（0.3～0.7）	0.4（0.3～0.6）	Z=-0.349	0.727
抗-HBe（s/co）	0.28（0.03～1.05）	0.01（0.01～1.10）	Z=-2.108	0.035
抗-HBc（s/co）	8.25±0.54	8.04±1.75	t=-0.279	0.781
TBil（μmol/L）	11.9±4.5	14.2±6.6	t=-1.043	0.307
DBil（μmol/L）	2.7（2.2～4.3）	3.3（2.0～4.7）	Z=-0.171	0.864
ALT（U/L）	25.3±16.3	19.8±12.0	t=-1.209	0.227
AST（U/L）	25.1±10.1	20.4±5.1	t=-1.285	0.199
总蛋白（g/L）	71.5±6.7	69.5±5.9	t=0.798	0.432
Alb（g/L）	45.9±3.5	41.7±4.0	t=-2.135	0.033
Glo（g/L）	25.6±4.1	27.9±3.7	t=-1.493	0.149
白蛋白/球蛋白比值	1.8±0.3	1.5±0.2	t=-2.572	0.010
GGT（U/L）	15.5（12.5～22.8）	17.0（11.0～38.8）	Z=-0.258	0.797
ALP（U/L）	74.5±24.8	63.1±34.0	t=-0.875	0.382
总胆汁酸（μmol/L）	6.2（2.8～9.2）	3.2（1.8～7.2）	Z=-0.978	0.328
a-L-岩藻糖苷酶（U/L）	26.0±5.1	26.5±7.9	t=-0.542	0.588
前白蛋白（mg/L）	225.8±31.9	212.1±46.3	t=0.863	0.397
胆碱酯酶（U/L）	8 097.8±1 593.0	7 247.1±1 738.3	t=-1.543	0.131

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表 2 HBsAg、转氨酶和Mindin基线、12周和24周的动态变化

Table 2. Dynamic changes in HBsAg， transaminase， and Mindin at baseline， 12 weeks， and 24 weeks

指标	未治愈组（n=17）	治愈组（n=12）	统计值	P值
HBsAg（log₁₀ IU/mL）
基线	2.6±0.7	1.9±1.1	t=-1.996	0.046
12周	2.7（1.9～3.1）	0.6（0.3～1.5）	Z=-3.504	<0.001
24周	1.7（1.1～2.7）	0.3（0.0～1.3）	Z=5.436	<0.001
ALT（U/L）
基线	25.3±16.3	19.8±12.0	t=-1.209	0.227
12周	27.0（18.0～57.0）	40.0（19.0～106.0）	Z=-1.059	0.289
24周	58.8±35.4	30.8±18.3	t=2.702	0.012
AST（U/L）
基线	25.1±10.1	20.4±5.1	t=-1.285	0.199
12周	55.0（41.0～60.0）	68.0（46.0～111.0）	Z=-1.082	0.279
24周	60.9±25.6	37.1±15.4	t=3.018	0.006
Mindin蛋白（pg/mL）
基线	222.4±66.5	223.7±68.8	t=-0.051	0.959
12周	260.1±65.0	259.5±71.9	t=0.024	0.981
24周	251.5±38.4	317.3±51.2	t=-2.673	0.019

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表 3 多元线性回归分析

Table 3. Multiple linear regression analysis

指标	偏回归系数	95%CI	P值
常量	154.681	52.698～256.664	0.009
HBsAg	24.129	-17.199～65.456	0.210
ALT	1.571	0.354～2.788	0.019
AST	-0.263	-1.230～0.704	0.540

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