Pilot study of tenofovir disoproxil fumarate and pegylated interferon-alpha 2a add-on therapy in Japanese patients with chronic hepatitis B
Pilot study of tenofovir disoproxil fumarate and pegylated interferon-alpha 2a add-on therapy in Japanese patients with chronic hepatitis B
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DOI：
10.1007/s00535-020-01707-6
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发表时间：
2020-07-14
影响因子：
6.3
通讯作者：
Tanaka, Eiji
中科院分区：
文献类型：
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作者：
Matsumoto, Akihiro;Nishiguchi, Shuhei;Tanaka, Eiji
背景：进行了一项富马酸替诺福韦酯（TDF）和聚乙二醇干扰素α 2a（P-IFN）添加治疗的前瞻性初步研究，以评估其在降低日本慢性乙型肝炎B患者病毒抗原水平方面的疗效（UMIN 000020179）。方法将接受TDF维持治疗的慢性B型肝炎患者分为两组，每组10例，其中B型肝炎表面抗原（HBsAg）水平> 800 IU/ml。在添加组（n = 32）中添加P-IFN 48周，而在对照组（n = 51）中维持TDF单一疗法。两组在基线测量后随访96周。结果对照组几乎所有患者在随访期间HBsAg均缓慢而持续下降。相比之下，大约一半的添加组在P-IFN给药期间HBsAg急剧下降，停止P-IFN后消失。在基线后96周，添加组中41%（13/32）的患者显示HBsAg快速下降，而对照组为2%（1/51）（p < 0.001）。根据多变量分析，辅助治疗和细胞毒性T细胞应答增加是与HBsAg快速下降相关的重要因素。此外，基线（p = 0.001）和添加治疗（p = 0.036）时较高的HB核心相关抗原（HBcrAg）水平是与HBcrAg快速降低相关的重要因素。结论日本慢性B型肝炎患者TDF和P-IFN添加治疗可促进HBsAg和HBcrAg的快速下降。提高早期HBsAg清除率需要进一步研究。
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.