Front Immunol:孕期抗病毒治疗对慢性乙型肝炎孕妇自然杀伤细胞的影响

2022-06-28 从医路漫漫 MedSci原创

对于HBV DNA阳性的孕妇,在妊娠晚期进行抗病毒治疗可以进一步降低HBV的母婴传播。

背景:乙型肝炎病毒(HBV)的母婴传播是中国慢性HBV感染的主要原因。对于HBV DNA阳性的孕妇,在妊娠晚期进行抗病毒治疗可以进一步降低HBV的母婴传播。产后肝炎在患有慢性乙型肝炎(CHB)的女性中很常见。我们之前的研究认为,产后肝炎主要发生在分娩前HBV DNA > 5.01 log10 IU/ml的孕妇,而HBV感染患者的产后肝功能异常主要发生在产后3-4周和9-12周。自然杀伤(NK)细胞是抗病毒免疫中重要的效应细胞之一。在慢性HBV感染过程中,NK细胞的数量和功能下降。为了通过抗病毒治疗实现免疫恢复,恢复NK细胞的数量和功能具有重要意义。目前,抗病毒治疗对慢性乙型肝炎患者产后NK细胞免疫特性影响的研究较少。

目的:在本研究中,我们设计了一个前瞻性病例队列研究,研究对象为HBV DNA阳性的CHB孕妇。我们检测了分娩前及分娩后6、12和24周孕妇外周血中NK细胞的频率,以探讨NK细胞与HBV病毒感染孕妇抗病毒治疗的相关性。

方法:将124名女性受试者分为4组:11名健康非妊娠妇女(正常组),26名处于慢性乙型肝炎病毒(HBV)感染免疫耐受期非妊娠妇女(CHB组),41名妊娠期未接受抗病毒治疗的妊娠CHB妇女(未治疗组),46名妊娠期接受抗病毒治疗的妊娠CHB妇女(治疗组)。流式细胞仪检测外周血中NK细胞的频率。从受试者抽取抗凝全血,将3 mL PerCP鼠抗人CD3、3 mL APC鼠抗人CD56和5 mL PE抗人CD335加入100 ml抗凝全血中,涡旋混合后室温避光孵育15 min,并作同型对照,加入2 ml红细胞裂解物,涡旋混合均匀,室温避光孵育3-5 min,离心细胞,用PBS洗涤,重悬细胞,用流式细胞仪检测NK细胞。根据前向散射(FSC)和侧向散射(SSC)门控淋巴细胞群,从每个样品中获得超过10000个淋巴细胞。使用FlowJo软件进行NK细胞图像分析。

结果:健康女性NK细胞频率[15.30 (12.80,18.40)]高于HBV感染女性,但无显著统计学差异(p=0.436)。CHB组的NK细胞频率[10.60 (6.00,18.30)]高于CHB孕妇[未治疗组:6.90 (4.89,10.04),P = 0.001治疗:9.42 (6.55,14.10),P=0.047】。治疗组的NK细胞频率显著高于未治疗组(P = 0.019)。未治疗组产后12周和24周的NK细胞、CD56bright NK细胞和NKp46dim NK细胞的频率明显高于分娩前。治疗组NK细胞、cd56亮NK细胞、NKp46+ NK细胞和NKp46dim NK细胞的频率在第6周和第12周均显著高于分娩前。治疗组产后NK细胞和cd56bright NK细胞频率明显高于未治疗组。治疗组分娩后CD56dim NK细胞频率显著低于未治疗组。丙氨酸氨基转移酶和天冬氨酸氨基转移酶在分娩后明显高于分娩前。结果表明,产后ALT水平与NKp 46高频呈弱正相关(r=0.199),与NKp 46二聚体频率呈弱负相关(r= -0.199)。

表1两组孕妇分娩后NK细胞频率和功能分子表达的变化。

图1 |产后ALT水平与NK频率的相关性。结果表明,产后ALT水平与nkp 46高频呈弱正相关(r = 0.199),与nkp 46二聚体频率呈弱负相关(r = -0.199)。

结论:孕期抗病毒治疗可显著增加产后NK细胞频率。产后肝炎可能与NK细胞频率变化和HBV感染引起的免疫损伤有关。

原文出处: Wang F,  Xie S,  Ran C,et al.Effect of Antiviral Therapy During Pregnancy on Natural Killer Cells in Pregnant Women With Chronic HBV Infection.Front Immunol 2022;13 

 

 

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    2022-06-29 yahu
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病毒血症、HBeAg阴性、CHB患者中,与peg-IFN联合给药时,Vonafexor是首个治疗16周后HBsAg平均降幅达-1.0 log10的口服药物

J Hepatol:一种预测韩国和高加索慢性乙型肝炎患者肝细胞癌风险的人工智能模型:PLAN-B

本研究目的是开发和验证一个人工智能辅助的HCC风险预测模型。

新型免疫疗法HepTcel治疗慢性乙型肝炎,即将开展国际多中心研究

根据世界卫生组织的估计,慢性乙型肝炎(CHB)影响全球2.92亿人,每年有近90万人死于该疾病的并发症。CHB无法治愈,目前可用的抗病毒药物只能控制这种疾病,需要终身治疗。

指南共识|慢性乙型肝炎患者如何停药、停药后如何复查——APASL指导意见

在确定CHB患者能否停用NUC的临床标准、停药策略、预测病毒学和生化学复发的临床指标、随访策略、再治疗的标准等均需要进一步的研究,以更好地完善NUC停药指导意见。

JOH:慢乙肝NA停药后仍可获得功能性治愈,与这些因素有关!

NA停药后CHB患者HBsAg消失的概率因患者种族、HBV基因型和治疗结束时病毒抗原水平而异。