血清miRNA预测HBe抗原阴性患者聚乙二醇化干扰素治疗48周后持

StephenW

Int J Mol Sci. 2018 Jul 2;19(7). pii: E1940. doi: 10.3390/ijms19071940.
Serum miRNAs Predicting Sustained HBs Antigen Reduction 48 Weeks after Pegylated Interferon Therapy in HBe Antigen-Negative Patients.
Fujita K1, Mimura S2, Iwama H3, Nakahara M4, Oura K5, Tadokoro T6, Nomura T7, Tani J8, Yoneyama H9, Morishita A10, Oryu M11, Himoto T12, Nishitsuji H13, Shimotohno K14, Omata M15, Masaki T16.
Author information

1
    Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793, Japan. [email protected].
2
    Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793, Japan. [email protected].
3
    Life Science Research Center, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793, Japan. [email protected].
4
    Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793, Japan. [email protected].
5
    Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793, Japan. [email protected].
6
    Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793, Japan. [email protected].
7
    Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793, Japan. [email protected].
8
    Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793, Japan. [email protected].
9
    Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793, Japan. [email protected].
10
    Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793, Japan. [email protected].
11
    Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793, Japan. [email protected].
12
    Department of Medical Technology, Kagawa Prefectural University of Health Sciences, 281-1 Hara, Mure, Takamatsu, Kagawa 761-0123, Japan. [email protected].
13
    Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516, Japan. [email protected].
14
    Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516, Japan. [email protected].
15
    Department of Gastroenterology, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi 400-8506, Japan. [email protected].
16
    Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa 761-0793, Japan. [email protected].

Abstract

The therapeutic goal for hepatitis B virus (HBV) infection is HBs antigen (HBsAg) seroclearance, which is achieved through 48-week pegylated interferon (Peg-IFN) therapy. This study aimed to identify predictive biomarkers for sustained HBsAg reduction by analyzing serum microRNAs. Twenty-two consecutive chronic HBV infection patients negative for HBe antigen (HBeAg) with HBV-DNA levels <5 log copies/mL, alanine aminotransferase (ALT) <100 U/L, and compensated liver functions, were enrolled. The patients were subcutaneously injected with Peg-IFNα-2a weekly for 48 weeks (treatment period), followed by the 48-week observation period. HBsAg 1-log drop relative to baseline levels recorded at the end of the observation period was considered effective. Sera were obtained at weeks 0 and 24 during the treatment period analyzed for microRNAs. The microRNA (miRNA) antiviral activity was evaluated in vitro using Huh7/sodium taurocholate cotransporting polypeptide (NTCP) cells. As a result, six patients achieved the HBsAg 1-log drop after the observation periods. Comparison of serum microRNA levels demonstrated that high miR-6126 levels at week 24 predicted HBsAg 1-log drop. Furthermore, miR-6126 reduced HBsAg in culture medium supernatants and intracellular HBV-DNA quantities in Huh7/NTCP cells. In conclusion, high serum miR-6126 levels during Peg-IFN therapy predicted the HBsAg 1-log drop 48 weeks after the completion of therapy. In vitro assays revealed that miR-6126 was able to suppress HBsAg production and HBV replication.
KEYWORDS:

hepatitis B surface antigens; hepatitis B virus; interferons; microRNAs; solute carrier proteins

PMID:
    30004437
DOI:
    10.3390/ijms19071940

StephenW

Int J Mol Sci。 2018年7月2日; 19（7）。 pii：E1940。 doi：10.3390 / ijms19071940。
血清miRNA预测HBe抗原阴性患者聚乙二醇化干扰素治疗48周后持续HBs抗原减少。
Fujita K1，Mimura S2，Iwama H3，Nakahara M4，Oura K5，Tadokoro T6，Nomura T7，Tani J8，Yoneyama H9，Morishita A10，Oryu M11，Himoto T12，Nishitsuji H13，Shimotohno K14，Omata M15，Masaki T16。
作者信息

1
    香川大学医学部消化内科和神经科，1750-1 Ikenobe，Miki，Kita，Kagawa 761-0793，Japan。 [email protected]。
2
    香川大学医学部消化内科和神经科，1750-1 Ikenobe，Miki，Kita，Kagawa 761-0793，Japan。 [email protected]。
3
    香川大学生命科学研究中心，1750-1 Ikenobe，Miki，Kita，Kagawa 761-0793，Japan。 [email protected]。
4
    香川大学医学部消化内科和神经科，1750-1 Ikenobe，Miki，Kita，Kagawa 761-0793，Japan。 [email protected]。
五
    香川大学医学部消化内科和神经科，1750-1 Ikenobe，Miki，Kita，Kagawa 761-0793，Japan。 [email protected]。
6
    香川大学医学部消化内科和神经科，1750-1 Ikenobe，Miki，Kita，Kagawa 761-0793，Japan。 [email protected]。
7
    香川大学医学部消化内科和神经科，1750-1 Ikenobe，Miki，Kita，Kagawa 761-0793，Japan。 [email protected]。
8
    香川大学医学部消化内科和神经科，1750-1 Ikenobe，Miki，Kita，Kagawa 761-0793，Japan。 [email protected]。
9
    香川大学医学部消化内科和神经科，1750-1 Ikenobe，Miki，Kita，Kagawa 761-0793，Japan。 [email protected]。
10
    香川大学医学部消化内科和神经科，1750-1 Ikenobe，Miki，Kita，Kagawa 761-0793，Japan。 [email protected]。
11
    香川大学医学部消化内科和神经科，1750-1 Ikenobe，Miki，Kita，Kagawa 761-0793，Japan。 [email protected]。
12
    香川县立卫生科学大学医疗技术系，日本香川县高松市Mure，281-1 Hara，761-0123。 [email protected]。
13
    国家全球卫生和医学中心肝炎和免疫学研究中心，日本千叶县市川市1-7-1 Kohnodai，272-8516。 [email protected]。
14
    国家全球卫生和医学中心肝炎和免疫学研究中心，日本千叶县市川市1-7-1 Kohnodai，272-8516。 [email protected]。
15
    山梨县立中央医院消化内科，日本山梨县富士见1-1-1富士见400-8506。 [email protected]。
16
    香川大学医学部消化内科和神经科，1750-1 Ikenobe，Miki，Kita，Kagawa 761-0793，Japan。 [email protected]。

抽象

乙型肝炎病毒（HBV）感染的治疗目标是HBs抗原（HBsAg）血清清除，这是通过48周聚乙二醇化干扰素（Peg-IFN）治疗实现的。本研究旨在通过分析血清microRNA来鉴定持续降低HBsAg的预测生物标志物。共纳入22例连续慢性HBV感染HBe抗原阴性的患者（HBeAg），HBV-DNA水平<5 log拷贝/ mL，丙氨酸氨基转移酶（ALT）<100 U / L，肝功能代偿。每周皮下注射Peg-IFNα-2a持续48周（治疗期），然后进行48周的观察期。相对于观察期结束时记录的基线水平的HBsAg 1-log下降被认为是有效的。在治疗期间的第0周和第24周获得血清，分析微小RNA。使用Huh7 /牛磺胆酸钠协同转运多肽（NTCP）细胞在体外评估microRNA（miRNA）抗病毒活性。结果，6名患者在观察期后达到HBsAg 1-log下降。血清microRNA水平的比较表明，第24周的高miR-6126水平预测HBsAg 1-log下降。此外，miR-6126降低培养基上清液中的HBsAg和Huh7 / NTCP细胞中的细胞内HBV-DNA量。总之，Peg-IFN治疗期间的高血清miR-6126水平预测治疗完成48周后HBsAg 1-log下降。体外测定显示miR-6126能够抑制HBsAg产生和HBV复制。
关键词：

乙型肝炎表面抗原;乙型肝炎病毒;干扰素;微RNA;溶质载体蛋白

结论：
    30004437
DOI：
    10.3390 / ijms19071940