丁型肝炎抗病毒治疗药物的研究进展

王彦; 张福杰

doi:10.3969/j.issn.1001-5256.2023.04.007

丁型肝炎抗病毒治疗药物的研究进展

DOI: 10.3969/j.issn.1001-5256.2023.04.007

王彦,
张福杰^, ,

首都医科大学附属地坛医院感染科，北京 100102

基金项目:

美国庄马尔田基金会 (2017-G14)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：王彦负责查阅和收集资料，撰写论文；张福杰负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
张福杰，treatment@chinaaids.cn (ORCID: 0000-0001-6386-9879)

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出版历程
- 收稿日期: 2022-10-08
- 录用日期: 2022-11-08
- 出版日期: 2023-04-20

Research advances in antiviral drugs for the treatment of hepatitis D

Yan WANG,
Fujie ZHANG^{,
,}

Department of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100102, China

Research funding:

John C. Martin Foundation (2017-G14)

More Information

Corresponding author: ZHANG Fujie, treatment@chinaaids.cn (ORCID: 0000-0001-6386-9879)

摘要

摘要: 丁型肝炎病毒(HDV)是一种乙型肝炎病毒(HBV)的卫星病毒，需借助HBV包膜蛋白完成自身的组装和复制，进而建立新的感染。慢性HDV感染是病毒性肝炎最严重的形式，可加速疾病进展，提高肝癌的发生风险，HDV感染者迫切需要有效的抗病毒治疗以缓解疾病进展，但能够用于抗HDV感染的治疗药物仅包括2020年7月欧洲药品管理局有条件批准的Bulevirtide以及之前推荐使用的干扰素。目前，针对病毒复制周期的几种靶向抗病毒药物正在研究中，且前期临床试验结果表现良好。这意味着HDV的抗病毒药物研发取得了重要突破，为丁型肝炎的治疗带来了希望。本文就目前丁型肝炎抗病毒药物进行简要综述，并对相关的治疗方案进行了讨论，为丁型肝炎的治疗提供参考。
- δ肝炎病毒 /
- 病毒复制 /
- 抗病毒药 /
- 药物疗法
Abstract: Hepatitis D virus (HDV) is a satellite virus of hepatitis B virus (HBV) and needs the help of HBV envelope protein to complete its own assembly and replication and then establish a new infection cycle. Chronic HDV infection is considered the most severe form of viral hepatitis, which can accelerate disease progression and increase the risk of liver cancer. Effective antiviral therapy is urgently needed to delay disease progression in patients with HDV infection, but Bulevirtide conditionally approved by European Medicines Agency in July 2020 and interferon previously recommended are the only drugs used for the treatment of HDV infection. At present, studies are being conducted for several antiviral drugs targeting viral replication cycle, and early clinical trials have obtained good results. This means that important breakthroughs have been made in the development of antiviral drugs, bringing hope for the treatment of hepatitis D. This article summarizes the current antiviral drugs for hepatitis D and discusses related treatment regimens, so as to provide a reference for the treatment of hepatitis D.
- Hepatitis Delta Virus /
- Virus Replication /
- Antiviral Agents /
- Drug Therapy

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图 1 HDV的病毒复制过程

Figure 1. HDV life cycle

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表 1 慢性HDV感染的抗病毒药物临床试验

Table 1. Summary of clinical trials of antiviral agents for HDV infection

药物靶向	药物名称	研究阶段	治疗策略	状态
免疫调节	PEG-IFNα-2a	Phase 2	PEG-IFNα 180 mg/周，治疗3年	已完成
	PEG-IFNα-2a	Phase 2	PEG-IFNα-2a单药治疗48周；PEG-IFNα-2a联合Ribavirin治疗48周	已完成
	PEG-IFNα-2a	Phase 2	PEG-IFNα-2a 180 μg/周，联合安慰剂； PEG-IFNα-2a 180 μg/周，联合Tenofovir disoproxilfumar 245 mg/d	已完成
	PEG-IFNα-2a	Phase 3	PEG-IFNα-2a单药治疗48周，随访24周	已完成
	PEG-IFNα-2a	Phase 3	PEG-IFNα-2a 180 mg/周，治疗96周； Tenofovir 245 mg/d，治疗96周；安慰剂治疗96周	已完成
	PEG-IFNα-2b	Phase 3	PEG-IFNα-2b每周1.5 mg/kg，治疗52周	已完成
	PEG-IFNλ	Phase 2	PEG-IFNλ 180 μg/周，每周1次，治疗48周；PEG-IFNλ 120 μg/周，每周1次，治疗48周	已完成
	PEG-IFNλ	Phase 3	PEG-IFNλ 180 mg/周，每周1次，治疗48周然后随访24周；不处理12周后PEG-IFNλ 180 mg/周，每周1次，治疗48周然后随访24周	进行中
	Ropeginterferon alfa-2b	Phase 1	Ropeginterferon alfa-2b，Nivolumab和Entecavir联合用药	进行中
进入抑制剂	Myrcludex B	Phase 1和2	Myrcludex B 2 mg/d，治疗24周，然后PEG-IFNα-2a每周180 μg/0.5 mL，治疗48周；Myrcludex B 2 mg/d联合PEG-IFNα-2a每周180 μg/0.5 mL治疗24周，然后PEG-IFNα-2a每周180 μg/0.5 mL治疗24周；PEG-IFNα-2a每周180 μg/0.5 mL治疗48周	已完成
	Myrcludex B	Phase 2	Myrcludex B 2 mg/d，治疗24周，然后Tenofovir治疗24周；Myrcludex B 5 mg/d，治疗24周，然后Tenofovir治疗24周；Tenofovir单药治疗48周	已完成
	Bulevirtide	Phase 2	PEG-IFNα 180 mg/周，治疗48周；Bulevirtide 2 mg/d联合PEG-IFNα 180 mg/周，治疗48周，然后Bulevirtide 2 mg/d单药治疗48周；Bulevirtide 10 mg/d联合PEG-IFNα 180 mg/周，治疗48周，然后Bulevirtide 10 mg/d单药治疗48周；Bulevirtide 10 mg/d单药治疗96周	进行中
	Bulevirtide	Phase 3	观察48周后Bulevirtide 10 mg/d治疗96周；立即采用Bulevirtide 2 mg/d治疗144周；立即采用Bulevirtide 10 mg/d治疗144周	进行中
异戊烯化(法尼基化)抑制剂	Lonafarnib	Phase 2	Lonafarnib 100 mg；Lonafarnib 200 mg；安慰剂	已完成
	Lonafarnib	Phase 2	Lonafarnib 200 mg/d，每日2次；Lonafarnib 300 mg/d，每日2次；Lonafarnib 100 mg/d，每日3次； Lonafarnib 100 mg/d，每日2次，联合PEG-IFNα 180 μg/周，每周1次；Lonafarnib 200 mg/d，每日2次，联合PEG-IFNα 180 μg/周，每周1次；Lonafarnib 300 mg/d，每日2次，联合PEG-IFNα 180 μg/周，每周1次；Lonafarnib 100 mg/d，每日2次，联合Ritonavir 100 mg/d，每日1次	已完成
	Lonafarnib	Phase 2	Lonafarnib 100 mg/d，每日2次，联合Ritonavir 100 mg/d，每日1次；Lonafarnib 150 mg/d，每日1次，联合Ritonavir 100 mg/d，每日1次；Lonafarnib 75 mg/d，每日2次，联合Ritonavir 100 mg/d，每日2次，第12周联合PEG-IFNα 180 μg/周，每周1次；Lonafarnib 50 mg/d，每日2次，联合Ritonavir 100 mg/d，每日2次，第12周联合PEG-IFNα 180 μg/周，每周1次；Lonafarnib 100 mg/d，每日2次，联合Ritonavir 50 mg/d，每日2次；Lonafarnib 100 mg/d，每日1次，联合Ritonavir 100 mg/d，每日1次；Lonafarnib 50 mg/d，每日2次，联合Ritonavir 100 mg/d，每日2次；联合PEG-IFNα 180 μg/周，每周1次；Lonafarnib 25 mg/d，每日2次，联合Ritonavir 100 mg/d，每日2次，联合PEG-IFNα 180 μg/周，每周1次；Lonafarnib 50 mg/d，每日2次，联合Ritonavir 100 mg/d，每日2次；Lonafarnib 25 mg/d，每日2次，联合Ritonavir 100 mg/d，每日2次	已完成
	Lonafarnib	Phase 2	Lonafarnib 50 mg/d，每日2次，联合Ritonavir 100 mg/d，每日2次，然后Lonafarnib 75 mg/d，每日2次，最后提高到100 mg/d，每日2次，治疗6个月，随访6个月	已完成
	Lonafarnib	Phase 2	Lonafarnib(50 mg/d)和Ritonavir(100 mg/d)治疗24周；Lonafarnib(75 mg/d)和Ritonavir(100 mg/d)治疗24周；Lonafarnib(100 mg/d)和Ritonavir(100 mg/d)治疗24周；安慰剂治疗12周，然后Lonafarnib(50 mg/d)和Ritonavir(100 mg/d)治疗12周；安慰剂治疗12周，然后Lonafarnib(75 mg/d)和Ritonavir(100 mg/d)治疗12周；安慰剂治疗12周，然后Lonafarnib(100 mg/d)和Ritonavir(100 mg/d)治疗12周	已完成
	Lonafarnib	Phase 2	Lonafarnib, Ritonavir和PEG-IFNλ联合用药	已完成
	Lonafarnib	Phase 3	Lonafarnib 50 mg/d，每日2次，联合Ritonavir 100 mg/d，每日2次；Lonafarnib 50 mg/d，每日2次，联合Ritonavir 100 mg/d，每日2次+PEG-IFNα-2a 180 μg/周；Lonafarnib安慰剂和Ritonavir安慰剂联合PEG-IFNα-2a 180 μg/周；Lonafarnib安慰剂和Ritonavir安慰剂	进行中
核酸聚合物	REP 2139-Ca	Phase 2	REP 2139-Ca 500 mg/周，治疗15周，然后REP 2139-Ca 250 mg/周联合PEG-IFNα-2a 180 μg/周，治疗15周，之后PEG-IFNα-2a 180 μg/周，治疗33周	已完成
RNA干扰	JNJ-3989	Phase 2	治疗组：JNJ-73763989每4周皮下注射1次，联合核苷酸类似物治疗144周对照组：安慰剂联合核苷酸类似物治疗52周，然后JNJ-73763989每4周皮下注射1次，联合核苷酸类似物治疗96周	进行中
注：信息收集截止于2021年11月11日。

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