慢性乙型肝炎功能性治愈不是梦

庄辉

doi:10.12449/JCH250101

慢性乙型肝炎功能性治愈不是梦

DOI: 10.12449/JCH250101

庄辉^, ,

北京大学医学部病原生物学系和感染病中心，北京 100191

利益冲突声明：本文不存在任何利益冲突。

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通信作者:
庄辉， zhuangbmu@126.com （ORCID： 0000-0001-9119-6325）

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出版历程
- 收稿日期: 2024-11-16
- 录用日期: 2024-11-28
- 出版日期: 2025-01-25

Functional cure of chronic hepatitis B is not a dream

Hui ZHUANG^{,
,}

Department of Microbiology and Center of Infectious Diseases，Peking University Health Science Center，Beijing 100191，China

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Corresponding author: ZHUANG Hui， zhuangbmu@126.com （ORCID： 0000-0001-9119-6325）

摘要

摘要: 慢性乙型肝炎功能性治愈的定义是在停止抗病毒治疗后至少24周，HBsAg<0.05 IU/mL，血清HBV DNA<10 IU/mL。这需要抑制HBV复制、降低病毒抗原产生，同时恢复对HBV感染的免疫应答。约30%～50%接受核苷（酸）类似物治疗并经严格选择的慢性乙型肝炎患者，加用或单用聚乙二醇干扰素α治疗，或经核苷（酸）类似物有限疗程治疗后HBsAg<100 IU/mL者，可获得功能性治愈。目前有40余种新的抗HBV药物和免疫调节剂正在进行临床试验。抑制HBV复制、降低病毒抗原，以及提高HBV感染免疫应答药物的联合应用，可能是慢性乙型肝炎功能性治愈的理想治疗策略。但确定最佳的联合、用药时间、用药顺序和治疗期限等尚需进一步研究。
- 乙型肝炎，慢性 /
- 乙型肝炎病毒 /
- 功能性治愈 /
- 完全治愈 /
- 抗病毒药
Abstract: Functional cure of chronic hepatitis B （CHB） is defined as HBsAg<0.05 IU/mL and serum HBV DNA<10 IU/mL for at least 24 weeks after discontinuation of antiviral therapy. This requires suppression of HBV replication and reduction of viral antigen production， as well as restoration of immune response to HBV infection. About 30% — 50% of highly selected CHB patients treated with nucleos（t）ide analogues can achieve functional cure after add-on therapy or monotherapy with pegylated interferon-α or a finite course of treatment with nucleos（t）ide analogues among patients with HBsAg<100 IU/mL. At present， clinical trials are being conducted for more than 40 types of novel anti-HBV drugs and immunomodulators. The combination of drugs that inhibit viral replication， reduce antigen burden， and restore immune response to HBV infection may be an ideal strategy to achieve the functional cure of CHB. However， further studies are needed to determine the optimal drug combination， the timing and sequence of medication， and the duration of treatment.
- Hepatitis B， Chronic /
- Hepatitis B Virus /
- Functional Cure /
- Complete Cure /
- Antiviral Agents

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图 1 功能性治愈示意图

Figure 1. A sketch map of functional cure

下载: 全尺寸图片幻灯片

图 2 对NAs治疗的CHB优势人群，加用或单用PEG-IFN-α的功能性治愈率

Figure 2. Functional cure rates of highly selected chronic hepatitis B patients treated with nucleos（t）ide analogues who receive an add-on or monotherapy of pegylated interferon-α

下载: 全尺寸图片幻灯片

图 3 CHB患者NAs有限疗程治疗策略

Figure 3. Finite treatment strategies of nucleos（t）ide analogues for chronic hepatitis B

下载: 全尺寸图片幻灯片

图 4 BPV Ⅱb期B-Together临床试验

Figure 4. B-Together clinical trail of Bepirovirsen in phase Ⅱb

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图 5 CHB理想的联合治疗策略

Figure 5. Ideal combination treatment strategies for functional cure of chronic hepatitis B

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表 1 进入Ⅱ期临床试验的免疫调节剂新药^［28］

Table 1. Novel immunomodulators for hepatitis B treatment in phase Ⅱ clinical trails

药物	药名	用药途径和剂量	临床试验
诱导固有免疫
Toll样受体7拮抗剂	R07020531	口服，150 mg/d	Ⅱ期
Toll样受体8拮抗剂	Selgantolimod	口服，1.5～3.0 mg/周	Ⅱ期
诱导适应性免疫
可溶性双特异性T淋巴细胞受体	IMC-1109V		Ⅰ期
检查点抑制剂	ASC22	皮下注射，0.3～2.5 mg/kg	Ⅱ期
治疗性疫苗	BRII 179 （VBI-2501）	肌内注射	Ⅱ期
	HepTcell	肌内注射	Ⅱ期
	GSK3528869A	肌内注射	Ⅰ/Ⅱ期
	VVX001	皮下注射	Ⅱ期
	VTP-300	肌内注射	Ⅱ期

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