《慢性乙型肝炎防治指南(2022年版)》解读

谢艳迪; 封波; 饶慧瑛

doi:10.3969/j.issn.1001-5256.2023.07.007

《慢性乙型肝炎防治指南(2022年版)》解读

DOI: 10.3969/j.issn.1001-5256.2023.07.007

北京大学人民医院，北京大学肝病研究所，北京 100044

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：封波、饶慧瑛提供写作思路并修改论文；谢艳迪负责查阅文献，撰写文章；饶慧瑛负责最终定稿。

详细信息

通信作者:
饶慧瑛，rao.huiying@163.com(ORCID: 0000-0003-2431-3872)

计量
- 文章访问数: 2507
- HTML全文浏览量: 190
- PDF下载量: 744
- 被引次数: 0
出版历程
- 收稿日期: 2023-05-19
- 录用日期: 2023-06-22
- 出版日期: 2023-07-20

Interpretation of guidelines for the prevention and treatment of chronic hepatitis B (2022 edition)

Peking University People's Hospital, Peking University Hepatology Institute, Beijing 100044, China

More Information

Corresponding author: RAO Huiying, rao.huiying@163.com(ORCID: 0000-0003-2431-3872)

摘要

摘要: 《慢性乙型肝炎防治指南(2022年版)》是以国内外慢性HBV感染的研究进展为依据，在既往多版指南基础上进行更新和修订而成。本文介绍了新版指南在自然史、无创纤维化诊断、治疗等多方面的更新内容。尤其是进一步扩大了慢性HBV感染者的治疗适应证，对干扰素的优势人群选择限定更清晰，对口服核苷(酸)类似物标准进行了更严格限制，对低病毒血症患者的处理更加积极，对免疫耐受期儿童的治疗也更积极。新版指南将为我国扩大筛查HBV感染者、提高诊断率、优化治疗方案、规范临床管理提供重要依据。
- 乙型肝炎, 慢性 /
- 乙型肝炎病毒 /
- 诊疗准则
Abstract: Guidelines for the prevention and treatment of chronic hepatitis B (2022 edition) are updated and revised based on the research advances in chronic hepatitis B virus infection in China and globally and the previous editions of the guidelines. This article introduces the updates in natural history and the noninvasive diagnosis and treatment of fibrosis. In particular, the guidelines further expand the indications for patients with chronic hepatitis B virus infection, clearly defines the selection of the population benefiting from interferon therapy, and strictly limits the standard of oral nucleos(t)ide analogues. Meanwhile, the guidelines also recommend more active treatment of patients with low-level viremia and children in the immune-tolerant phase. The new edition of the guidelines will provide an important basis for expanding the screening for hepatitis B virus infection, improving diagnostic rate, optimizing treatment regimens, and standardizing clinical management in China.
- Hepatitis B, Chronic /
- Hepatitis B virus /
- Practice Guidelines

HTML全文

表 1 慢性HBV感染自然史分期^[13]

Table 1. Natural history staging of chronic HBV infection^[13]

项目	HBeAg阳性慢性HBV感染(免疫耐受期)	HBeAg阳性CHB(免疫清除期)	HBeAg阴性慢性HBV感染(免疫控制期)	HBeAg阴性CHB(再活动期)
HBsAg (IU/mL)	＞1×10⁴	+	＜1×10³	+
HBeAg	+	+	-	-(+/-)
HBV DNA (IU/mL)	＞2×10⁷	+ (＞2×10⁴)	- (＜2×10³)	+(≥2×10³)
ALT	＜正常值上限(正常)	持续或反复升高	＜正常值上限(正常)	持续或反复升高
肝脏病理学	无明显炎症坏死和纤维化	有明显炎症坏死和/或纤维化	无或仅有轻度炎症，可有不同程度的纤维化	有明显炎症坏死和/或纤维化
注：红字部分为2019年版《指南》内容。

下载: 导出CSV

参考文献(51)

[1]	Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B(version 2022)[J]. Infect Dis Info, 2023, 36(1): 1-17. DOI: 10.3969/j.issn.1007-8134.2023.01.01. 中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2022年版)[J]. 传染病信息, 2023, 36(1): 1-17. DOI: 10.3969/j.issn.1007-8134.2023.01.01.
[2]	World Health Organization. Global hepatitis report, 2017[EB/OL]. [2022-12-24]. https://www.who.int/publications/i/item/9789241565455.
[3]	Polaris Observatory Collaborators. HBV progress towards coverage targets[EB/OL]. [2022-12-24]. http://cdafound.org/polaris-countries-dashboard/.
[4]	CUI FQ, SHEN LP, LI L, et al. Prevention of chronic hepatitis B after 3 decades of escalating vaccination policy, China[J]. Emerg Infect Dis, 2017, 23(5): 765-772. DOI: 10.3201/eid2305.161477.
[5]	Global progress report on HIV, viral hepatitis and sexually transmitted infections, 2021. Accountability for the global health sector strategies 2016-2021: actions for impact[EB/OL]. [2022-12-24]. https://apps.who.int/iris/bitstream/handle/10665/342808/9789240030985-eng.pdf.
[6]	Polaris Obervatory Collaborators. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: A modelling study[J]. Lancet Gastroenterol Hepatol, 2018, 3(6): 383-403. DOI: 10.1016/S2468-1253(18)30056-6.
[7]	LI AY, LIU ZX, SONG YR, et al. Reduction of the occurrence of occult HBV infection in infants by increasing the dose of hepatitis B vaccine: A large prospective cohort study[J]. Emerg Microbes Infect, 2020, 9(1): 1881-1891. DOI: 10.1080/22221751.2020.1808533.
[8]	PÉNEAU C, IMBEAUD S, LA BELLA T, et al. Hepatitis B virus integrations promote local and distant oncogenic driver alterations in hepatocellular carcinoma[J]. Gut, 2022, 71(3): 616-626. DOI: 10.1136/gutjnl-2020-323153.
[9]	ERKEN R, LOUKACHOV V, van DORT K, et al. Quantified integrated hepatitis B virus is related to viral activity in patients with chronic hepatitis B[J]. Hepatology, 2022, 76(1): 196-206. DOI: 10.1002/hep.32352.
[10]	TONG SP, REVILL P. Overview of hepatitis B viral replication and genetic variability[J]. J Hepatol, 2016, 64(1 Suppl): S4-S16. DOI: 10.1016/j.jhep.2016.01.027.
[11]	HUANG DQ, LI XH, LE MH, et al. Natural history and hepatocellular carcinoma risk in untreated chronic hepatitis B patients with indeterminate phase[J]. Clin Gastroenterol Hepatol, 2022, 20(8): 1803-1812. e5. DOI: 10.1016/j.cgh.2021.01.019.
[12]	YAO KF, LIU JC, WANG J, et al. Distribution and clinical characteristics of patients with chronic hepatitis B virus infection in the grey zone[J]. J Viral Hepat, 2021, 28(7): 1025-1033. DOI: 10.1111/jvh.13511.
[13]	Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B (version 2019)[J]. J Clin Hepatol, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007. 中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.
[14]	SONNEVELD MJ, CHIU SM, PARK JY, et al. Probability of HBsAg loss after nucleo(s)tide analogue withdrawal depends on HBV genotype and viral antigen levels[J]. J Hepatol, 2022, 76(5): 1042-1050. DOI: 10.1016/j.jhep.2022.01.007.
[15]	LI J, MAO RC, LI XL, et al. A novel noninvasive index for the prediction of moderate to severe fibrosis in chronic hepatitis B patients[J]. Dig Liver Dis, 2018, 50(5): 482-489. DOI: 10.1016/j.dld.2017.12.028.
[16]	SONG LW, LIU PG, LIU CJ, et al. Quantitative hepatitis B core antibody levels in the natural history of hepatitis B virus infection[J]. Clin Microbiol Infect, 2015, 21(2): 197-203. DOI: 10.1016/j.cmi.2014.10.002.
[17]	FAN R, SUN J, YUAN Q, et al. Baseline quantitative hepatitis B core antibody titre alone strongly predicts HBeAg seroconversion across chronic hepatitis B patients treated with peginterferon or nucleos(t)ide analogues[J]. Gut, 2016, 65(2): 313-320. DOI: 10.1136/gutjnl-2014-308546.
[18]	CHI H, LI ZD, HANSEN BE, et al. Serum level of antibodies against hepatitis B core protein is associated with clinical relapse after discontinuation of nucleos(t)ide analogue therapy[J]. Clin Gastroenterol Hepatol, 2019, 17(1): 182-191. e1. DOI: 10.1016/j.cgh.2018.05.047.
[19]	LI J, GONG QM, XIE PL, et al. Prognostic value of anti-HBc quantification in hepatitis B virus related acute-on-chronic liver failure[J]. J Gastroenterol Hepatol, 2021, 36(5): 1291-1299. DOI: 10.1111/jgh.15310.
[20]	WAI CT, CHENG CL, WEE A, et al. Non-invasive models for predicting histology in patients with chronic hepatitis B[J]. Liver Int, 2006, 26(6): 666-672. DOI: 10.1111/j.1478-3231.2006.01287.x.
[21]	DONG XQ, WU Z, ZHAO H, et al. Evaluation and comparison of thirty noninvasive models for diagnosing liver fibrosis in Chinese hepatitis B patients[J]. J Viral Hepat, 2019, 26(2): 297-307. DOI: 10.1111/jvh.13031.
[22]	LIANG XE, CHEN YP. Clinical application of vibration controlled transient elastography in patients with chronic hepatitis B[J]. J Clin Transl Hepatol, 2017, 5(4): 368-375. DOI: 10.14218/JCTH.2017.00006.
[23]	WU SS, KONG YY, PIAO HX, et al. On-treatment changes of liver stiffness at week 26 could predict 2-year clinical outcomes in HBV-related compensated cirrhosis[J]. Liver Int, 2018, 38(6): 1045-1054. DOI: 10.1111/liv.13623.
[24]	de FRANCHIS R, BOSCH J, GARCIA-TSAO G, et al. Baveno VⅡ - Renewing consensus in portal hypertension[J]. J Hepatol, 2022, 76(4): 959-974. DOI: 10.1016/j.jhep.2021.12.022.
[25]	WANG HY, WEN B, CHANG XY, et al. Baveno VI criteria and spleen stiffness measurement rule out high-risk varices in virally suppressed HBV-related cirrhosis[J]. J Hepatol, 2021, 74(3): 584-592. DOI: 10.1016/j.jhep.2020.09.034.
[26]	Chinese Society of Hepatology, Chinese Medical Association. Chinese guidelines on the management of liver cirrhosis[J]. J Clin Hepatol, 2019, 35(11): 2408-2425. DOI: 10.3969/j.issn.1001-5256.2019.11.006. 中华医学会肝病学分会. 肝硬化诊治指南[J]. 临床肝胆病杂志, 2019, 35(11): 2408-2425. DOI: 10.3969/j.issn.1001-5256.2019.11.006.
[27]	WANG Q, ZHAO H, DENG Y, et al. Validation of Baveno VⅡ criteria for recompensation in entecavir-treated patients with hepatitis B-related decompensated cirrhosis[J]. J Hepatol, 2022, 77(6): 1564-1572. DOI: 10.1016/j.jhep.2022.07.037.
[28]	WU Z, MA AL, XIE Q, et al. Significant histological changes and satisfying antiviral efficacy in chronic hepatitis B virus infection patients with normal alanine aminotransferase. Antiviral therapy decision in chronic HBV patients with normal ALT[J]. Clin Res Hepatol Gastroenterol, 2021, 45(2): 101463. DOI: 10.1016/j.clinre.2020.05.011.
[29]	TERRAULT NA, BZOWEJ NH, CHANG KM, et al. AASLD guidelines for treatment of chronic hepatitis B[J]. Hepatology, 2016, 63(1): 261-283. DOI: 10.1002/hep.28156.
[30]	TERRAULT NA, LOK ASF, MCMAHON BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance[J]. Hepatology, 2018, 67(4): 1560-1599. DOI: 10.1002/hep.29800.
[31]	MARTIN P, NGUYEN MH, DIETERICH DT, et al. Treatment algorithm for managing chronic hepatitis B virus infection in the United States: 2021 update[J]. Clin Gastroenterol Hepatol, 2022, 20(8): 1766-1775. DOI: 10.1016/j.cgh.2021.07.036.
[32]	ALSHUWAYKH O, DAUGHERTY T, CHEUNG A, et al. Incidence of hepatocellular carcinoma in chronic hepatitis B virus infection in those not meeting criteria for antiviral therapy[J]. Hepatol Commun, 2022, 6(11): 3052-3061. DOI: 10.1002/hep4.2064.
[33]	World Health Organization. Guidelines for the prevention care and treatment of persons with chronic hepatitis B infection: Mar 15[R]. Geneva: World Health Organization, 2015.
[34]	CHOI HSJ, TONTHAT A, JANSSEN HLA, et al. Aiming for functional cure with established and novel therapies for chronic hepatitis B[J]. Hepatol Commun, 2022, 6(5): 935-949. DOI: 10.1002/hep4.1875.
[35]	HOU JL, ZHAO W, LEE C, et al. Outcomes of long-term treatment of chronic HBV infection with entecavir or other agents from a randomized trial in 24 countries[J]. Clin Gastroenterol Hepatol, 2020, 18(2): 457-467. e21. DOI: 10.1016/j.cgh.2019.07.010.
[36]	LIU Y, CORSA AC, BUTI M, et al. No detectable resistance to tenofovir disoproxil fumarate in HBeAg⁺ and HBeAg^- patients with chronic hepatitis B after 8 years of treatment[J]. J Viral Hepat, 2017, 24(1): 68-74. DOI: 10.1111/jvh.12613.
[37]	CHOI J, KIM HJ, LEE J, et al. Risk of hepatocellular carcinoma in patients treated with entecavir vs tenofovir for chronic hepatitis B: A Korean nationwide cohort study[J]. JAMA Oncol, 2019, 5(1): 30-36. DOI: 10.1001/jamaoncol.2018.4070.
[38]	YIP TCF, WONG VWS, CHAN HLY, et al. Tenofovir is associated with lower risk of hepatocellular carcinoma than entecavir in patients with chronic HBV infection in China[J]. Gastroenterology, 2020, 158(1): 215-225. e6. DOI: 10.1053/j.gastro.2019.09.025.
[39]	HSU YC, WONG GLH, CHEN CH, et al. Tenofovir versus entecavir for hepatocellular carcinoma prevention in an international consortium of chronic hepatitis B[J]. Am J Gastroenterol, 2020, 115(2): 271-280. DOI: 10.14309/ajg.0000000000000428.
[40]	SU F, BERRY K, IOANNOU GN. No difference in hepatocellular carcinoma risk between chronic hepatitis B patients treated with entecavir versus tenofovir[J]. Gut, 2021, 70(2): 370-378. DOI: 10.1136/gutjnl-2019-319867.
[41]	LI M, LV TT, WU SS, et al. Tenofovir versus entecavir in lowering the risk of hepatocellular carcinoma development in patients with chronic hepatitis B: A critical systematic review and meta-analysis[J]. Hepatol Int, 2020, 14(1): 105-114. DOI: 10.1007/s12072-019-10005-0.
[42]	CHOI WM, YIP TCF, LIM YS, et al. Methodological challenges of performing meta-analyses to compare the risk of hepatocellular carcinoma between chronic hepatitis B treatments[J]. J Hepatol, 2022, 76(1): 186-194. DOI: 10.1016/j.jhep.2021.09.017.
[43]	AGARWAL K, BRUNETTO M, SETO WK, et al. 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection[J]. J Hepatol, 2018, 68(4): 672-681. DOI: 10.1016/j.jhep.2017.11.039.
[44]	BYUN KS, CHOI J, KIM JH, et al. Tenofovir alafenamide for drug-resistant hepatitis B: A randomized trial for switching from tenofovir disoproxil fumarate[J]. Clin Gastroenterol Hepatol, 2022, 20(2): 427-437. e5. DOI: 10.1016/j.cgh.2021.04.045.
[45]	LI ZB, LI L, NIU XX, et al. Switching from entecavir to tenofovir alafenamide for chronic hepatitis B patients with low-level viraemia[J]. Liver Int, 2021, 41(6): 1254-1264. DOI: 10.1111/liv.14786.
[46]	LIU Z, JIN Q, ZHANG Y, et al. 96 week treatment of tenofovir amibufenamide and tenofovir disoproxil fumarate in chronic hepatitis B patients[J/OL]. J Clin Transl Hepatol, 2023, 11(3): 649-660. DOI: 10.14218/JCTH.2022.00058.
[47]	FAN R, PAPATHEODORIDIS G, SUN J, et al. aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis[J]. J Hepatol, 2020, 73(6): 1368-1378. DOI: 10.1016/j.jhep.2020.07.025.
[48]	SUN YM, WU XN, ZHOU JL, et al. Persistent low level of hepatitis B virus promotes fibrosis progression during therapy[J]. Clin Gastroenterol Hepatol, 2020, 18(11): 2582-2591. e6. DOI: 10.1016/j.cgh.2020.03.001.
[49]	LU Y, SONG YR, ZHAI XJ, et al. Maternal hepatitis B e antigen can be an indicator for antiviral prophylaxis of perinatal transmission of hepatitis B virus[J]. Emerg Microbes Infect, 2021, 10(1): 555-564. DOI: 10.1080/22221751.2021.1899055.
[50]	ZHU SS, DONG Y, XU ZQ, et al. A retrospective study on HBsAg clearance rate after antiviral therapy in children with HBeAg-positive chronic hepatitis B aged 1-7 years[J]. Chin J Hepatol, 2016, 24(10): 738-743. DOI: 10.3760/cma.j.issn.1007-3418.2016.10.005. 朱世殊, 董漪, 徐志强, 等. 1~7岁慢性乙型肝炎HBeAg阳性儿童经抗病毒治疗HBsAg清除率的回顾性研究[J]. 中华肝脏病杂志, 2016, 24(10): 738-743. DOI: 10.3760/cma.j.issn.1007-3418.2016.10.005.
[51]	JONAS MM, LOK ASF, MCMAHON BJ, et al. Antiviral therapy in management of chronic hepatitis B viral infection in children: A systematic review and meta-analysis[J]. Hepatology, 2016, 63(1): 307-318. DOI: 10.1002/hep.28278.