母婴阻断停药后HBeAg阳性慢性HBV携带者的免疫功能变化与肝炎活动的关联

摘要/Abstract

摘要： 目的探讨母婴阻断停药后HBeAg阳性慢性HBV携带者中,肝炎活动组与非肝炎活动组的免疫功能差异,并分析免疫功能变化与肝炎活动的关联。方法选取2022年1月至2024年6月沧州市人民医院就诊的105例HBeAg阳性慢性HBV携带者作为研究对象,根据停药3个月后的肝炎活动情况分为肝炎活动组(n=32)和非肝炎活动组(n=73)。收集两组患者的临床资料,包括肝功能指标(ALT、AST)、免疫指标(CD4⁺ T细胞比例、CD4⁺/CD8⁺)、 HBV DNA载量及炎症因子(IL-6、TNF-α)的变化。Pearson相关系数确定肝功能指标与免疫功能指标的相关性,多因素logistic回归分析母婴阻断停药后HBeAg阳性慢性HBV携带者肝炎活动的影响因素。结果停药1、3、6个月后,肝炎活动组的ALT、AST显著升高, CD4⁺ T细胞比例和CD4⁺/CD8⁺下降,且在停药3个月后差异最为显著[停药3个月后,ALT:(72.09±8.10) U/L vs. (36.12±6.45) U/L,P<0.05;AST:(68.59±7.22) U/L vs. (33.55±4.22) U/L,P<0.05);CD4⁺ T细胞比例:(37.01±3.04)% vs. (39.91±3.15)%,P<0.05;CD4⁺/CD8⁺:(1.48±0.18) vs. (1.70±0.19),P<0.05]。停药1、3、6个月后,肝炎活动组的HBV DNA、IL-6、TNF-α水平也显著高于非肝炎活动组,停药3个月后IL-6、TNF-α差异最为显著[IL-6:(15.67±4.02) pg/mL vs. (11.51±2.94) pg/mL,P<0.05;TNF-α:(18.41±4.55) pg/mL vs. (14.58±3.62) pg/mL,P<0.05)],停药6个月后HBV DNA差异最为显著[(6.13±0.90) vs. (4.71±0.90) log₁₀ U/mL,P<0.05)]。Pearson相关性分析显示,CD4⁺ T细胞比例与ALT、AST均呈显著负相关[r=-0.390、-0.440,P<0.05];CD4⁺/CD8⁺与ALT、AST亦呈负相关[r=-0.483、-0.460,P<0.05]。多因素logistic回归分析表明,ALT、AST、CD4⁺、CD4⁺/CD8⁺、HBV DNA、IL-6、TNF-α均是肝炎活动的影响因素(P<0.05)。结论母婴阻断停药后,HBeAg阳性慢性HBV携带者CD4⁺ T细胞比例和CD4⁺/CD8⁺下降与肝炎活动的发生显著相关。以上免疫指标、HBV DNA载量和炎症因子的变化可作为预测肝炎活动的潜在标志物。

关键词: 母婴阻断, HBeAg阳性, 慢性HBV携带者, 免疫功能, 肝炎活动

Abstract: Objective To investigate the differences in immune function between the hepatitis activity group and the non-hepatitis activity group among HBeAg-positive chronic HBV carriers after discontinuation of maternal-infant blockade therapy and to analyze the association between immune function changes and hepatitis activity. Methods A total of 105 HBeAg-positive chronic HBV carriers who attended at Cangzhou People′s Hospital from January 2022 to June 2024 were enrolled. Based on hepatitis activity status after three months of discontinuation, patients were divided into the hepatitis activity group (n=32) and the non-hepatitis activity group (n=73). Clinical data, including liver function indicators (alanine aminotransferase (ALT), aspartate aminotransferase (AST)), immune markers (CD4⁺ T-cell ratio, CD4⁺/CD8⁺ T-cell ratio), HBV DNA load, and inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor (TNF) -α), were collected. Pearson correlation coefficient was used to determine the correlation between liver function indicators and immune function markers. Multivariate logistic regression analysis was conducted to identify factors influencing hepatitis activity in HBeAg-positive chronic HBV carriers after cessation of maternal-infant blockade therapy. Results At 1, 3, and 6 months after drug withdrawal, patients in the hepatitis activity group showed significantly elevated levels of ALT and AST, along with decreased CD4⁺ T cell percentage and CD4⁺/CD8⁺. These differences were most significant after 3 months of discontinuation [ALT at 3 months: (72.09±8.10) U/L vs. (36.12±6.45) U/L, P<0.05; AST: (68.59±7.22) U/L vs. (33.55±4.22) U/L, P<0.05; CD4⁺ T cell percentage: (37.01±3.04)% vs. (39.91±3.15)%, P<0.05; CD4⁺/CD8⁺: (1.48±0.18) vs. (1.70±0.19), P<0.05]. At 1, 3, and 6 months after drug cessation, levels of HBV DNA, IL-6, and TNF-α were also significantly higher in the hepatitis activity group than in the non-hepatitis activity group. Differences in IL-6 and TNF-α were most significant at 3 months post-withdrawal [IL-6: (15.67±4.02) pg/mL vs. (11.51±2.94) pg/mL, P<0.05; TNF-α: (18.41±4.55) pg/mL vs. (14.58±3.62) pg/mL, P<0.05], while the difference in HBV DNA was most significant at 6 months [(6.13±0.90) vs. (4.71±0.90) log₁₀ U/mL, P<0.05]. Pearson correlation analysis showed that the CD4⁺ T cell percentage had significantly negative correlation with ALT and AST (r=-0.390, -0.440; P<0.05), and the CD4⁺/CD8⁺ had also negatively correlation with ALT and AST (r=-0.483, -0.460; P<0.05). Multivariate logistic regression analysis indicated that ALT, AST, CD4⁺, CD4⁺/CD8⁺, HBV DNA, IL-6, and TNF-α were all influencing factors for hepatitis activity (P<0.05). Conclusion After cessation of maternal-infant blockade therapy, the decline in CD4⁺ T-cell ratio and CD4⁺/CD8⁺ is significantly associated with the occurrence of hepatitis activity in HBeAg-positive chronic HBV carriers. Changes in these immune indicators, HBV DNA load, and inflammatory cytokines may serve as potential biomarkers for predicting hepatitis activity.

Key words: Maternal-infant blockade, HBeAg-positive, Chronic HBV carrier, Immune function, Hepatitis activity

曹艳敏, 邢宝恒, 宗方, 高素娟. 母婴阻断停药后HBeAg阳性慢性HBV携带者的免疫功能变化与肝炎活动的关联[J]. 肝脏, 2025, 30(7): 958-962.

CAO Yan-min, XING Bao-heng, ZONG Fang, GAO Su-juan. Immune function changes and their association with hepatitis activity in HBeAg-positive chronic HBV carriers after cessation of maternal-infant blockade therapy[J]. Chinese Hepatolgy, 2025, 30(7): 958-962.

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