替诺福韦富马酸替索罗非酯和聚乙二醇化干扰素-α2a联合疗

StephenW

Pilot study of tenofovir disoproxil fumarate and pegylated interferon-alpha 2a add-on therapy in Japanese patients with chronic hepatitis B
Akihiro Matsumoto  1 , Shuhei Nishiguchi  2 , Hirayuki Enomoto  2 , Yasuhito Tanaka  3 , Noboru Shinkai  3 , Chiaki Okuse  4 , Jong-Hon Kang  5 , Takeshi Matsui  5 , Shiho Miyase  6 , Hiroshi Yatsuhashi  7 , Shinya Nagaoka  7 , Tatsuo Kanda  8 , Masaru Enomoto  9 , Ryoko Yamada  10 , Naoki Hiramatsu  11 , Satoru Saito  12 , Koichi Takaguchi  13 , Kiyoaki Ito  14 , Tsutomu Masaki  15 , Daisuke Morihara  16 , Masataka Tsuge  17 , Kazuaki Chayama  17 , Fusao Ikeda  18 , Tatehiro Kagawa  19 , Yasuteru Kondo  20 , Kazumoto Murata  21 , Eiji Tanaka  22
Affiliations

    PMID: 32666202 DOI: 10.1007/s00535-020-01707-6

Abstract

Background: A prospective pilot study of tenofovir disoproxil fumarate (TDF) and pegylated interferon alpha 2a (P-IFN) add-on therapy was conducted to evaluate its efficacy in reducing viral antigen levels in Japanese patients with chronic hepatitis B (UMIN 000020179).

Methods: Patients with chronic hepatitis B receiving maintenance TDF therapy and exhibiting hepatitis B surface antigen (HBsAg) level > 800 IU/ml were divided into two arms. P-IFN was added for 48 weeks in the add-on arm (n = 32), while TDF monotherapy was maintained in the control arm (n = 51). Both groups were followed for 96 weeks after baseline measurements.

Results: Almost all patients in the control arm displayed a slow and constant reduction in HBsAg during follow-up. In contrast, roughly half of the add-on arm exhibited a sharp decline in HBsAg during P-IFN administration, which disappeared after halting P-IFN. At 96 weeks after baseline, 41% (13/32) of patients in the add-on arm had shown a rapid decrease in HBsAg, versus 2% (1/51) in the control arm (p < 0.001). Add-on therapy and increased cytotoxic T-cell response were significant factors associated with a rapid decrease in HBsAg according to multivariate analysis. In addition, higher HB core-related antigen (HBcrAg) level at baseline (p = 0.001) and add-on therapy (p = 0.036) were significant factors associated with a rapid reduction in HBcrAg.

Conclusions: TDF and P-IFN add-on therapy in Japanese patients with chronic hepatitis B facilitated rapid decreases in HBsAg and HBcrAg. Further studies are needed to improve early HBsAg clearance rate.

Keywords: Add-on therapy; Hepatitis B core-related antigen; Hepatitis B surface antigen; Pegylated interferon; Tenofovir.
Grant support

    17fk0210306h003/The Japan Agency for Medical Reserch and Developement
    JP18fk0210034/The Japan Agency for Medical Research and Development

StephenW

替诺福韦富马酸替索罗非酯和聚乙二醇化干扰素-α2a联合疗法在日本慢性乙型肝炎患者中的初步研究
松本昭弘1，西口秀平2，ray本广之郎2，田中康人3，升新海3，千秋Okuse 4，姜钟汉5，松井武5，宫保四濑6，八桥广史7，长冈伸也7，o田隆男8，江本正9，山田凉10，平松直树11，斋藤悟12，高口浩一13，伊藤清昭14，Tsu武昌树15，森原大辅16，正隆昌17，茶山一昭17，池田丰雄18，香川照宏19，近藤康20，村田和本21，田中荣次22
隶属关系

    PMID：32666202 DOI：10.1007 / s00535-020-01707-6

抽象

背景：替诺福韦富马酸替诺福韦（TDF）和聚乙二醇化干扰素α2a（P-IFN）联合治疗进行了前瞻性初步研究，以评估其在日本慢性乙型肝炎患者中降低病毒抗原水平的功效（UMIN 000020179）。

方法：将接受维持性TDF治疗且表现为> 800 IU / ml的乙型肝炎表面抗原（HBsAg）的慢性乙型肝炎患者分为两组。 P-IFN在附加组中添加了48周（n = 32），而TDF单一疗法在对照组中保持（n = 51）。基线测量后，两组均进行了96周的随访。

结果：在随访期间，对照组中几乎所有患者的HBsAg持续缓慢且持续降低。相反，在P-IFN给药期间，大约有一半的附加臂显示HBsAg急剧下降，在停止P-IFN后消失。在基线后96周，附加组中41％（13/32）的患者HBsAg迅速降低，而对照组中2％（1/51）的患者表现出（p <0.001）。根据多变量分析，附加疗法和增加的细胞毒性T细胞反应是与HBsAg快速下降有关的重要因素。此外，基线时较高的HB核心相关抗原（HBcrAg）水平（p = 0.001）和附加疗法（p = 0.036）是与HBcrAg快速降低相关的重要因素。

结论：日本慢性乙型肝炎患者的TDF和P-IFN联合治疗促进了HBsAg和HBcrAg的快速下降。需要进一步研究以提高早期HBsAg清除率。

关键字：附加疗法；乙肝核心相关抗原；乙型肝炎表面抗原；聚乙二醇干扰素；替诺福韦。
赠款支持

    17fk0210306h003 /日本医学研究与发展局
    JP18fk0210034 /日本医学研究与发展局