Effect of Antiviral Therapy During Pregnancy on Natural Killer Cells in Pregnant Women With Chronic HBV Infection

Wang, Fuchuan; Xie, Si; Ran, Chongping; Hao, Hongxiao; Jiang, Tingting; Deng, Wen; Bi, Xiaoping; Lin, Yanjie; Yang, Liu; Sun, Fangfang; Zeng, Zhan; Xie, Yao; Li, Minghui; Yi, Wei

doi:10.3389/fimmu.2022.893628

Cited by 4 publications

(4 citation statements)

References 18 publications

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“…Reducing viral load is beneficial to improve NK cell function ( 31 ). In pregnant women infected with HBV, antiviral therapy can significantly increase the frequency of NK cells ( 32 ). In this study, through multiple linear regression analysis of baseline clinical indicators and NK subpopulation rows, it was found that the HBV DNA level in the initial treatment group was negatively correlated with the frequency of CD69 + CD56 dim , suggesting that viral load may inhibit the activation of NK cells.…”

Section: Discussionmentioning

confidence: 99%

Changes of natural killer cells’ phenotype in patients with chronic hepatitis B in intermittent interferon therapy

Xie

et al. 2023

Front. Immunol.

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BackgroundTo investigate the changes of natural killer (NK) cell phenotype in the interferon alpha (IFN-α) treatment of chronic hepatitis B (CHB) and its relationship with clinical indicators.MethodsThe CHB patients who did not receive any antiviral treatment were set as initial treatment group and used pegylated interferon alpha (PEG-IFN α). Peripheral blood samples were collected at baseline, 4 weeks, and 12-24 weeks. For IFN-treated patients who entered the plateau were set as plateau group, and PEG-IFN α was discontinued and resumed after an interval of 12-24 weeks. Besides, we also enrolled some patients who had received oral drug for more than 6 months as oral drug group without follow up. Peripheral blood was collected during the plateau period, which was set as baseline, and after 12-24 weeks of intermittent treatment, and after 12-24 weeks of additional treatment with PEG-IFN α. The aim of the collection was to detect hepatitis B virus (HBV) virology, serology and biochemical indicators, and the NK cell related phenotype was detected by flow cytometry.ResultsIn the plateau group, subgroup of CD69+CD56dim was higher with statistical significance when comparing with the initial treatment group and oral drug group [10.49 (5.27, 19.07) vs 5.03 (3.67, 8.58), Z = -3.11, P = 0.002; 10.49 (5.27, 19.07) vs 4.04 (1.90, 7.26), Z = -5.30, P < 0.001)]. CD57+CD56dim was significantly lower than that in initial treatment group and oral drug group respectively [68.42±10.37 vs 55.85±12.87, t = 5.84, P < 0.001; 76.38±9.49 vs 55.85±12.87, t = -9.65, P < 0.001]. The CD56brightCD16- subgroup in the plateau group was higher with statistical significance compared with initial treatment group and oral drug group respectively [11.64 (6.05, 19.61) vs 3.58 (1.94, 5.60), Z = -6.35, P < 0.001; 11.64 (6.05, 19.61) vs 2.37 (1.70, 4.30), Z = -7.74, P < 0.001)]. CD57+CD56dim in the plateau group had a significant higher percentage than that at baseline after IFN discontinuation for 12-24 weeks (55.85±12.87 vs 65.95±12.94, t = -2.78, P = 0.011).ConclusionDuring the long-term treatment of IFN, the killer subgroup of NK cells is continuously depleted, leading to the differentiation of the regulatory subgroup into the killer subgroup. In the killing subgroup, although the number is continuously depleted, the activity of the subgroup is continuously increased. In the plateau phase, after stopping IFN for a period of time, the number of NK cell subsets would gradually recover, but was still lower than that in the initial treatment group.

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Section: Discussionmentioning

confidence: 99%

Changes of natural killer cells’ phenotype in patients with chronic hepatitis B in intermittent interferon therapy

Xie

et al. 2023

Front. Immunol.

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“…The result also showed that CD8 + T cells included CD8 + effector memory T cells and effector T cells that were significantly activated after childbirth in group 1 ( 72 ). A study found that compared with the group not taking antiviral drugs, the postpartum NK cell count in the group receiving antiviral therapy during pregnancy increased significantly, and postpartum hepatitis may also be related to the change of NK cell frequency and immune damage caused by HBV infection ( 73 ). Li et al.…”

Section: T Cells and Measures Of Hbv-mtct Preventionmentioning

confidence: 99%

Effects of hepatitis B virus infection and strategies for preventing mother-to-child transmission on maternal and fetal T-cell immunity

Cao

Zhang

et al. 2023

Front. Immunol.

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One of the most common routes of chronic hepatitis B virus (HBV) infection is mother-to-child transmission (MTCT). Approximately 6.4 million children under the age of five have chronic HBV infections worldwide. HBV DNA high level, HBeAg positivity, placental barrier failure, and immaturity of the fetal immune are the possible causes of chronic HBV infection. The passive-active immune program for children, which consists of the hepatitis B vaccine and hepatitis B immunoglobulin, and antiviral therapy for pregnant women who have a high HBV DNA load (greater than 2 × 105 IU/ml), are currently two of the most important ways to prevent the transmission of HBV from mother to child. Unfortunately, some infants still have chronic HBV infections. Some studies have also found that some supplementation during pregnancy can increase cytokine levels and then affect the level of HBsAb in infants. For example, IL-4 can mediate the beneficial effect on infants’ HBsAb levels when maternal folic acid supplementation. In addition, new research has indicated that HBV infection in the mother may also be linked to unfavorable outcomes such as gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, and premature rupture of membranes. The changes in the immune environment during pregnancy and the hepatotropic nature of HBV may be the main reasons for the adverse maternal outcomes. It is interesting to note that after delivery, the women who had a chronic HBV infection may spontaneously achieve HBeAg seroconversion and HBsAg seroclearance. The maternal and fetal T-cell immunity in HBV infection is important because adaptive immune responses, especially virus-specific CD8 T-cell responses, are largely responsible for viral clearance and disease pathogenesis during HBV infection. Meanwhile, HBV humoral and T-cell responses are important for the durability of protection after fetal vaccination. This article reviews the literature on immunological characteristics of chronic HBV-infected patients during pregnancy and postpartum, blocking mother-to-child transmissions and related immune mechanisms, hoping to provide new insights for the prevention of HBV MTCT and antiviral intervention during pregnancy and postpartum.

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“…The percentage and absolute count of NK cells after delivery increased temporarily ( 9 ). It was found that the frequency of NK cells increased from 6 weeks after delivery and held plateau at 6-24 weeks ( 105 ). Postpartum neutrophils increased.…”

Section: Maternal Change On Immune System and Hormone After Deliverymentioning

confidence: 99%

Postpartum hepatitis and host immunity in pregnant women with chronic HBV infection

et al. 2023

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In order to develop immune tolerant to the fetal, maternal immune system will have some modification comparing to the time before pregnancy. Immune tolerance starts and develops at the maternal placental interface. In innate immunity, decidual natural killer (dNK) cells, macrophages and dendritic cells play a key role in immue tolerance. In adaptive immunity, a moderate increase of number and immune inhibition function of regulatory T cells (Treg) are essential for immune tolerance. The trophoblast cells and immune cells expressing indoleamine 2,3-dioxygenase (IDO), the trophoblast cells expressing HLA-G, and Th1/Th2 shifting to Th2 dominant and Th17/Treg shifting to Treg domiant are in favor of maternal fetal immune tolerance. Steroids (estrogen and progesterone) and human chorionic gonadotropin (HCG) also participate in immune tolerance by inducing Treg cells or upregulating immunosuppressive cytokines. Most of the patients with chronic HBV infection are in the “HBV immune tolerance period” before pregnancy, and the liver disease is relatively stable during pregnancy. In chronic HBV infection women, after delivery, the relative immunosuppression in vivo is reversed, and Th1 is dominant in Th1/Th2 and Th17 is dominant in Th17/Treg balance. After delivery, the number of Treg decrease and NK cells increase in quantity and cytotoxicity in peripheral blood. Liver NK cells may cause liver inflammation through a non-antigen specific mechanism. After delivery, the number of CD8+ T cells will increase and HBV specific T cell response recovers from the disfunction in pregnancy. Under the background of postpartum inflammation, the rapid decrease of cortisol after delivery, and especially the enhancement of HBV specific T cell response induced by HBV DNA and cytokines, are the main reasons for postpartum hepatitis. HBeAg positive, especially HBeAg<700 S/CO, and HBV DNA>3-5Log10IU/ml are risk factors for postpartum hepatitis. Antiviral treatment in late pregnancy can reduce the incidence of mother to child transmission (MTCT) in chronic HBV infection women. Chronic HBV infection women have hepatitis both during pregnancy and more often in 12 weeks postpartum. It is generally agreed that postpartum hepatitis is mild symptoms and self-limited. Delaying drug withdrawal to 48 weeks can increase the seroconversion rate of HBeAg in delivery women with elevated alanine aminotransferase (ALT) in pregnancy.

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Effect of Antiviral Therapy During Pregnancy on Natural Killer Cells in Pregnant Women With Chronic HBV Infection

Cited by 4 publications

References 18 publications

Changes of natural killer cells’ phenotype in patients with chronic hepatitis B in intermittent interferon therapy

Changes of natural killer cells’ phenotype in patients with chronic hepatitis B in intermittent interferon therapy

Effects of hepatitis B virus infection and strategies for preventing mother-to-child transmission on maternal and fetal T-cell immunity

Postpartum hepatitis and host immunity in pregnant women with chronic HBV infection

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