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基于真实世界研究,慢性乙型肝炎患者细胞因子的变化及HBeAg与HBV RNA呈正相关。

Change of Cytokines in Chronic Hepatitis B Patients and HBeAg are Positively Correlated with HBV RNA, Based on Real-world Study.

作者信息

Zhang Qiqi, Huang Hui, Sun Aijun, Liu Chunyan, Wang Zhidong, Shi Feifan, Duan Wei, Sun Xueying, Wang Qi, Sun Ping, Pu Chunwen, Zhang Yong

机构信息

Department of Biobank, The Sixth Affiliated People's Hospital of Dalian Medical University, Dalian, Liaoning, China.

Outpatient Department of Hepatitis, The Sixth Affiliated People's Hospital of Dalian Medical University, Dalian, Liaoning, China.

出版信息

J Clin Transl Hepatol. 2022 Jun 28;10(3):390-397. doi: 10.14218/JCTH.2021.00160. Epub 2021 Sep 18.

DOI:10.14218/JCTH.2021.00160
PMID:35836760
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9240249/
Abstract

BACKGROUND AND AIMS

The natural course of chronic hepatitis B virus (HBV) infection is widely studied; however, follow-up studies of the same patients are scanty. Here, we studied the dynamic changes of serum HBV RNA and cytokines in hepatitis B virus e antigen (HBeAg)-positive patients treated with entecavir (ETV) to explore the relationship between the HBV serum viral nucleic acids and host immunity.

METHODS

Thirty-three chronic hepatitis B patients who are HBeAg-positive, with high virus load (HBV DNA >20,000 IU/mL), and received standard nucleos(t)ide analogue (NA) antiviral therapy (ETV) for more than 48 weeks were included. The serum levels of HBV nucleic acids and selected cytokines were measured at 0, 12, 24, and 48 weeks respectively.

RESULTS

Serum HBV RNA could still be detected while serum HBV DNA had fallen below the detection limit in patients treated with ETV. There was a strong positive correlation between HBV RNA and HBeAg, with a concomitant decrease in the secretion of cytokines from type 1 helper T (Th1)/type 2 helper T (Th2)/interleukin (IL)-17 producing T (Th17) cells. IL-4 and IL-10 were the main cytokines negatively associated with serum HBV RNA.

CONCLUSIONS

HBeAg can be used to reflect the load of HBV RNA indirectly, because serum HBV RNA has not been widely used in clinical practice. Meanwhile, serum IL-4 and IL-10 might be explored in combination with HBV RNA in guiding future clinical antiviral therapy.

摘要

背景与目的

慢性乙型肝炎病毒(HBV)感染的自然病程已得到广泛研究;然而,对同一患者的随访研究却很少。在此,我们研究了接受恩替卡韦(ETV)治疗的乙肝e抗原(HBeAg)阳性患者血清HBV RNA和细胞因子的动态变化,以探讨HBV血清病毒核酸与宿主免疫之间的关系。

方法

纳入33例HBeAg阳性、病毒载量高(HBV DNA>20,000 IU/mL)且接受标准核苷(酸)类似物(NA)抗病毒治疗(ETV)超过48周的慢性乙型肝炎患者。分别在0、12、24和48周时检测血清HBV核酸和选定细胞因子的水平。

结果

接受ETV治疗的患者血清HBV DNA已降至检测限以下,但仍可检测到血清HBV RNA。HBV RNA与HBeAg之间存在强正相关,同时1型辅助性T细胞(Th1)/2型辅助性T细胞(Th2)/分泌白细胞介素(IL)-17的T细胞(Th17)分泌的细胞因子减少。IL-4和IL-10是与血清HBV RNA呈负相关的主要细胞因子。

结论

由于血清HBV RNA尚未在临床实践中广泛应用,HBeAg可用于间接反映HBV RNA的负荷。同时,血清IL-4和IL-10可能与HBV RNA联合用于指导未来的临床抗病毒治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d24/9240249/3d1a51907b8f/JCTH-10-390-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d24/9240249/9f1332c32796/JCTH-10-390-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d24/9240249/cac6515244b2/JCTH-10-390-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d24/9240249/3d1a51907b8f/JCTH-10-390-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d24/9240249/9f1332c32796/JCTH-10-390-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d24/9240249/cac6515244b2/JCTH-10-390-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d24/9240249/3d1a51907b8f/JCTH-10-390-g003.jpg

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