免疫耐受期HBV感染者抗病毒治疗的临床争议

胡林慧; 王艳

doi:10.12449/JCH240505

免疫耐受期HBV感染者抗病毒治疗的临床争议

DOI: 10.12449/JCH240505

胡林慧,
王艳^, ,

北京大学第一医院感染科，北京 100034

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：胡慧林负责文章撰写；王艳负责结构框架设计并最后定稿。

详细信息

通信作者:
王艳， wangyanwang@bjmu.edu.cn （ORCID： 0000-0002-8577-0527）

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出版历程
- 收稿日期: 2024-03-03
- 录用日期: 2024-04-10
- 出版日期: 2024-05-25

Clinical controversies over antiviral therapy for patients in the immune-tolerant phase of hepatitis B virus infection

Linhui HU,
Yan WANG^{,
,}

Department of Infectious Diseases，Peking University First Hospital，Beijing 100034，China

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Corresponding author: WANG Yan， wangyanwang@bjmu.edu.cn （ORCID： 0000-0002-8577-0527）

摘要

摘要: 为实现“2030年消除病毒性肝炎作为公共卫生危害”的目标，目前针对慢性HBV感染提倡更广泛筛查、更积极预防和抗病毒治疗。但“慢性HBV感染免疫耐受期患者是否启动抗病毒治疗”尚无统一观点。部分专家认为免疫耐受期患者肝脏免疫微环境稳定，疾病进展可能小，且治疗效果不佳，不建议启动抗病毒治疗；而另有多项研究提示免疫耐受期患者肝脏仍存在炎症损伤，有疾病进展风险，接受抗病毒治疗后成本效益高，因此部分专家建议对免疫耐受期患者应积极启动抗病毒治疗。本文对慢性HBV感染者免疫耐受期的定义、抗病毒治疗的利弊进行文献综述，并基于既往文献进行初步的系统分析，以增加对慢性HBV感染免疫耐受期是否抗病毒治疗的证据积累，为未来免疫耐受期患者的规范临床诊疗奠定基础。
- 乙型肝炎病毒 /
- 免疫耐受 /
- 治疗学
Abstract: To achieve the goal of “eliminating viral hepatitis as a public health hazard by 2030”， extensive screening， active prevention， and antiviral therapy are currently recommended for chronic hepatitis B virus （HBV） infection； however， no consensus has been reached on whether to initiate antiviral therapy for patients in the immune-tolerant phase of chronic HBV infection. Some experts believe that patients in the immune-tolerant phase tend to have a stable liver immune microenvironment， with a low risk of disease progression and poor response to treatment， and thus it is not recommended to initiate antiviral therapy. However， various other studies have shown that patients in the immune-tolerant phase still have inflammatory damage in the liver， with a risk of disease progression and a high level of cost effectiveness， and therefore， some experts suggest that antiviral therapy should be actively initiated for patients in the immune-tolerant phase. This article performs a literature review of the definition of patients in the immune-tolerant phase of chronic HBV infection and the advantages and disadvantages of antiviral therapy and conducts a preliminary analysis based on previous studies， in order to accumulate the evidence for whether to initiate antiviral therapy in the immune-tolerant phase of chronic HBV infection and lay a foundation for standardized clinical diagnosis and treatment of patients in the immune-tolerant phase.
- Hepatitis B virus /
- Immune Tolerance /
- Therapeutics

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表 1 不同国家指南CHB患者IT期的标准

Table 1. Diagnostic criteria of IT in different guidelines of AASLD， EASL， APASL， JSG and CMA

地区	IT期定义
地区	HBsAg	HBeAg	HBV DNA（IU/mL）	ALT（U/L）	组织病理
美国肝病学会（AASLD）^［2］	+	+	>10⁶	男性<35 女性<25	无炎症坏死或纤维化
欧洲肝病学会（EASL）^［3］	+	+	>10⁷	男女均<40	无炎症坏死或纤维化
亚太肝病学会（APASL）^［4］	+	+	>2×10⁴	男女均<40	无炎症坏死或纤维化
日本肝病学会（JSG）^［5］	+	+	≥2 000	男女均<30 排除其他因素所致ALT水平异常升高	无炎症坏死或纤维化
中国^［6］	>10⁴ IU/mL	+	>2×10⁷	ALT水平持续正常（1年内连续随访3次，每次至少间隔3个月）	无炎症坏死或纤维化

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表 2 不同国家指南对CHB患者IT期监测标准及抗病毒治疗汇总

Table 2. Summary of indications of antiviral treatment in the different guildelines of AASLD， EASL， APASL， JSG and CMA

地区	监测标准	抗病毒治疗时机
AASLD^［2］	正常的ALT（男性<30 U/L，女性<25 U/L）和高HBV DNA水平（≥20 000 IU/mL）；每6个月监测ALT和HBV DNA水平	肝活检或无创检查提示重度炎症（≥A3）或显著纤维化（≥F2），特别是年龄>40岁；ALT水平持续升高（除外其他因素），仍保持HBeAg阳性且HBV DNA水平>20 000 IU/mL
EASL^［3］	正常的ALT（<40 U/L）和高HBV DNA水平（≥2 000 IU/mL）；每3～6个月监测ALT和HBV DNA水平	年龄>30岁，或有肝硬化或者肝癌家族史或有肝外表现，或纤维化阶段使用肝活检或无创检查提示显著纤维化（≥F2）或中重度炎症（≥A2或更高），肝硬度值≥12 kPa，或ALT水平升高（除外其他因素）
APASL^［4］	正常的ALT（<40 U/L）和高HBV DNA水平（≥20 000 IU/mL）；每3个月监测ALT和HBV DNA水平	年龄>35岁，或肝穿刺显示≥显著纤维化（≥F2）或重度炎症（≥A3），或无创检查有明显肝纤维化（肝硬度值≥8 kPa），或ALT水平持续升高（除外其他因素），或有肝硬化或者肝癌家族史
JSG^［5］	HBeAg血清学转换患者，无活动性炎症［即随访3次/年以上，并满足HBeAg持续阴性、ALT水平持续正常（<30 U/L）、HBV DNA<2 000 IU/mL 3个条件］ HBeAg阳性，ALT水平异常升高但无纤维化进展和重症倾向者，建议随访1年左右再评估	ALT水平间歇性升高，或HBV DNA高，或血小板计数<15×10⁴/μL且患者年龄>40岁，则建议确定肝纤维化（通过肝活检或无创检查）
中国^［6］	每隔6～12个月监测一次	符合下列情况之一：（1）有乙型肝炎肝硬化或HCC家族史；（2）年龄>30岁；（3）无创指标或者肝组织学检查，提示肝脏存在明显炎症（G≥2）或纤维化（F≥2）；（4）HBV相关肝外表现（如 HBV相关性肾小球肾炎等）

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