慢性乙型肝炎的治疗现状

陈学福; 张东敬; 罗晓丹; 陈仁

doi:10.3969/j.issn.1001-5256.2021.05.004

慢性乙型肝炎的治疗现状

DOI: 10.3969/j.issn.1001-5256.2021.05.004

广东省人民医院(广东省医学科学院) 感染科，广州 510080

基金项目:

广东省中医药局科研项目 (20181007)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献说明；陈学福参与文章设计及撰写；张东敬参与文献检索及分析；罗晓丹参与起草文章的部分内容和文献检索；陈仁参与修改文章的关键内容。

详细信息

作者简介:
陈学福(1969—)，女，主任医师，主要从事病毒性肝炎的研究

通信作者:
陈仁，crlmczx@163.com

中图分类号: R512.62
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出版历程
- 收稿日期: 2021-03-25
- 录用日期: 2020-03-25
- 出版日期: 2021-05-20

Current status of the treatment of chronic hepatitis B

Department of Infectious Diseases, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China

摘要

摘要: HBV感染引起的慢性乙型肝炎是全球性的公共卫生问题，慢性HBV感染的抗病毒治疗是关键，抗病毒治疗的目标主要通过病毒学、血清学和生化学指标来定义。已批准上市的两大类抗病毒药物干扰素和核苷(酸)类似物均能减少肝脏炎症和纤维化以及降低肝硬化和肝细胞癌的发生率。然而，抗病毒治疗的理想目标是功能性治愈，其显著改善慢性乙型肝炎的远期结局。目前治疗方法的局限性在于抑制HBV复制，但不能清除病毒，HBeAg和HBsAg血清学清除率低。研发以功能性治愈为目标的新型药物，并评价与现有药物的协同、联合等作用是HBV治疗和发展的重要方向。
- 乙型肝炎, 慢性 /
- 核苷(酸)类药物 /
- 干扰素α /
- 治疗学
Abstract: Chronic hepatitis B caused by hepatitis B virus (HBV) infection is a global public health issue. Antiviral therapy for chronic HBV infection plays a critical role, and the goal of antiviral therapy is mainly defined by virological, serological, and biochemical parameters. As the two types of antiviral drugs approved for marketing, both interferon and nucleos(t)ide analogues can alleviate liver inflammation and liver fibrosis and reduce the incidence rates of liver cirrhosis and hepatocellular carcinoma. However, the ideal goal of antiviral therapy is functional cure, which significantly improves the long-term outcome of chronic hepatitis B. The limitation of current treatment is that it can inhibit HBV replication, but cannot clear the virus, with low serological clearance rates of HBeAg and HBsAg. Development of new drugs with the goal of functional cure and evaluation of the synergistic and combined effects of existing drugs are important directions for HBV treatment and development.
- Hepatitis B, Chronic /
- Nucleo(t)ide Analogues /
- Interferon-alpha /
- Therapeutics

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表 1 现有抗病毒药物总览

患者类型	ETV		TDF		TAF		PEG-IFNα
患者类型	48周	5年	48周	8年	48周	5年(HBeAg阳性、阴性合并分析)	治疗48周，随访24周	真实世界研究随访3年
HBeAg阳性患者
HBV DNA阴转(%)	67 (＜300拷贝/ml)	94	76.7 (＜400拷贝/ml)	98	64 (＜29 IU/ml)	93	30 (＜2000 IU/ml)	-
ALT复常(%)	68	83	68.3	-	72	76	32~41	-
HBeAg血清转化(%)	21	23	21	31	10	27	30.8~36.3	-
HBsAg阴转(%)	2	1.4	3	13	1	1	2.3~3	11
HBeAg阴性患者
HBV DNA阴转(%)	90 (＜300拷贝/ml)	-	93 (＜400拷贝/ml)	99	94 (＜29 IU/ml)	-	43 (＜2000 IU/ml)	-
ALT复常(%)	78	-	76	-	83	-	59	-
HBsAg阴转(%)	0	-	0	1.1	0	-	3	16
耐药率(%)	0	1.2	0	0	0	5年未观察到基因型耐药		-
不良反应	头痛(10%)；疲劳(6%)；ALT升高(4%~10%)		头痛(10%)；鼻咽炎(10%)；恶心(9%)；疲劳(8%)；上呼吸道感染(7%)		头痛(14%)；鼻咽炎(11%)；上呼吸道感染(7%)；疲劳(6%)		流感样症状：疲劳或乏力、发热、肌痛、头痛(30%~62%)；甲状腺功能障碍(6%)；胃肠道：恶心、腹泻、食欲下降(9%~18%)；精神疾病：抑郁症(3%~21%)、失眠(8%~15%)；脱发(14%~27%)，瘙痒(5%~14%)；中性粒细胞减少症(17%~21%)；血小板减少(13%~19%)
特殊人群
代偿期肝硬化	推荐		推荐		推荐		慎用
失代偿期肝硬化	推荐		推荐		必要时应用		禁用
儿童	≥2岁体质量≥10 kg		≥2岁体质量≥10 kg		≥12岁体质量≥35 kg		≥5岁
妊娠相关情况	不建议		建议		初步数据疗效、安全性良好，有望建议		不建议
肾损伤者	推荐根据GFR调整剂量		不建议		推荐GFR≥15 ml·min^-1·1.73 m^-2不需调整剂量		肾移植患者应避免使用
HBV相关肝衰竭	建议		建议		建议		禁用
HBV相关HCC	建议		建议		建议		无禁忌证，可以使用

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