《慢性乙型肝炎防治指南(2022年版)》修订过程中关于慢性HBV感染自然史的讨论
DOI: 10.3969/j.issn.1001-5256.2023.06.006
Debates on the natural history of chronic hepatitis B virus infection during the update of Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Version)
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摘要: 本文介绍了《慢性乙型肝炎防治指南(2022年版)》修订过程中关于慢性HBV感染自然史的讨论,包括命名和定义;HBV感染;免疫耐受期患者的HBV DNA阈值;不确定期与自然史;临床诊断与自然史;非活动期患者的HBV DNA阈值。Abstract: This article introduces the debates on the natural history of chronic hepatitis B virus (HBV) infection during the update of Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Version), including nomenclature and definition, HBV infection, HBV DNA threshold for patients in the immune-tolerant phase, indeterminate phase and natural history, clinical diagnosis and natural history, and HBV DNA threshold for patients in the inactive phase.
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Key words:
- Hepatitis B, Chronic /
- Hepatitis B virus /
- Infections /
- Natural History /
- Indeterminate Phase
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项目 免疫耐受期
(慢性HBV携带状态)免疫清除期
(HBeAg阳性CHB)免疫控制期(非活动性
HBsAg携带状态)再活动期
(HBeAg阴性CHB)HBV血清学标志物 HBsAg(IU/mL) >1×104 + <1×103 + 抗-HBs - - - - HBeAg + + - +/- 抗-HBe - - + +/- 抗-HBc + + + + HBV DNA(IU/mL) >2×107 >2×104 <2×103 ≥2×103 ALT 正常 持续或反复升高 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 表 2 各国指南界定的“免疫耐受期”HBV DNA水平
Table 2. HBV DNA threshols for the immune tolerant phase recommended by international guidelines
指南 HBV DNA水平 美国临床胃肠病肝病学会2015 高水平(>20 000 IU/mL) 美国肝病学会2018 很高(典型>106 IU/mL) 欧洲肝病学会2017 >107 IU/mL 亚太肝病学会2015 2×107 IU/mL 瑞典抗病毒治疗专家组2020 高水平(>107 IU/mL) 印度肝病学会2018 >107 IU/mL 中国台湾肝病学会2019 无数据 沙特肝病和移植学会2021 高水平(>107 IU/mL) 韩国肝病学会2022 一般≥107 IU/mL 表 3 各国指南建议HBeAg阴性慢性HBV感染(非活动期、免疫控制期) 的HBV DNA水平
Table 3. HBV DNA thresholds for the HBeAg negative chronic HBV infection (inactive or immune control phase) recommended by international guidelines
指南 HBV DNA水平 亚太肝病学会2015 <2 000 IU/mL 欧洲肝病学会2017 <2 000 IU/mL 美国肝病学会2018 <2 000 IU/mL 印度肝病学会2018 <2 000 IU/mL 瑞典肝病学会2020 <2 000 IU/mL 沙特肝病和移植学会2020 <2 000 IU/mL 美国临床胃肠病肝病学会2021 <2 000 IU/mL 韩国肝病学会2022 <2 000 IU/mL Dusheiko G 2023 <2 000 IU/mL -
[1] 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. [2] European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection[J]. J Hepatol, 2017, 67(2): 370-398. DOI: 10.1016/j.jhep.2017.03.021. [3] ABAALKHAIL FA, AL-HAMOUDI WK, KHATHLAN A, et al. SASLT practice guidelines for the management of Hepatitis B virus - An update[J]. Saudi J Gastroenterol, 2021, 27(3): 115-126. DOI: 10.4103/sjg.sjg_539_20. [4] 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. [5] HOWELL J, HELLARD M. Making child's play of tolerance: Defining the immune-viral interplay during combination entecavir and pegylated interferon therapy for immune-tolerant hepatitis B infection[J]. Hepatology, 2022, 76(3): 554-557. DOI: 10.1002/hep.32450. [6] DUSHEIKO G, AGARWAL K, MAINI MK. New Approaches to chronic hepatitis B[J]. N Engl J Med, 2023, 388(1): 55-69. DOI: 10.1056/NEJMra2211764. [7] JENG WJ, PAPATHEODORIDIS GV, LOK A. Hepatitis B[J]. Lancet, 2023, 401(10381): 1039-1052. DOI: 10.1016/S0140-6736(22)01468-4. [8] BERTOLETTI A, KENNEDY PT. The immune tolerant phase of chronic HBV infection: new perspectives on an old concept[J]. Cell Mol Immunol, 2015, 12(3): 258-263. DOI: 10.1038/cmi.2014.79. [9] MASON WS, GILL US, LITWIN S, et al. HBV DNA integration and clonal hepatocyte expansion in chronic hepatitis B patients considered immune tolerant[J]. Gastroenterology, 2016, 151(5): 986-998. DOI: 10.1053/j.gastro.2016.07.012. [10] RUAN P, DAI X, SUN J, et al. Different types of viral-host junction found in HBV integration breakpoints in HBV-infected patients[J]. Mol Med Rep, 2019, 19(2): 1410-1416. DOI: 10.3892/mmr.2018.9709. [11] KOFFAS A, KUMAR M, GILL US, et al. Chronic hepatitis B: the demise of the 'inactive carrier' phase[J]. Hepatol Int, 2021, 15(2): 290-300. DOI: 10.1007/s12072-021-10137-2. [12] NGUYEN MH, GARCIA RT, TRINH HN, et al. Histological disease in Asian-Americans with chronic hepatitis B, high hepatitis B virus DNA, and normal alanine aminotransferase levels[J]. Am J Gastroenterol, 2009, 104(9): 2206-2213. DOI: 10.1038/ajg.2009.248. [13] GONG X, YANG J, TANG J, et al. A mechanistic assessment of the discordance between normal serum alanine aminotransferase levels and altered liver histology in chronic hepatitis B[J]. PLoS One, 2015, 10(7): e0134532. DOI: 10.1371/journal.pone.0134532. [14] National Health Commission of the People's Republic of China. Diagnosis for HIV/AIDS[S]. 2019-01-02.中华人民共和国国家卫生健康委员会. 艾滋病和艾滋病毒感染诊断[S]. 2019-01-02. [15] CASTRO KG, WARD JW, SLUTSKER L, et al. 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults[J]. MMWR Recomm Rep, 1992, 41(RR-17): 1-19. [16] HUI CK, LEUNG N, YUEN ST, et al. Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase[J]. Hepatology, 2007, 46(2): 395-401. DOI: 10.1002/hep.21724. [17] MARTIN P, LAU DT, NGUYEN MH, et al. A Treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2015 Update[J]. Clin Gastroenterol Hepatol, 2015, 13(12): 2071-2087. e16. DOI: 10.1016/j.cgh.2015.07.007. [18] TERRAULT NA, LOK A, 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. [19] SARIN SK, KUMAR M, LAU GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update[J]. Hepatol Int, 2016, 10(1): 1-98. DOI: 10.1007/s12072-015-9675-4. [20] WESTIN J, ALEMAN S, CASTEDAL M, et al. Management of hepatitis B virus infection, updated Swedish guidelines[J]. Infect Dis (Lond), 2020, 52(1): 1-22. DOI: 10.1080/23744235.2019.1675903. [21] ARORA A, SINGH SP, KUMAR A, et al. INASL position statements on prevention, diagnosis and management of hepatitis B virus infection in India: The Andaman Statements[J]. J Clin Exp Hepatol, 2018, 8(1): 58-80. DOI: 10.1016/j.jceh.2017.12.001. [22] CHIEN RN, KAO JH, PENG CY, et al. Taiwan consensus statement on the management of chronic hepatitis B[J]. J Formos Med Assoc, 2019, 118(1 Pt 1): 7-38. DOI: 10.1016/j.jfma.2018.11.008. [23] Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines for management of chronic hepatitis B[J]. Clin Mol Hepatol, 2022, 28(2): 276-331. DOI: 10.3350/cmh.2021.0178. [24] HUANG DQ, LI X, 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. [25] YAO K, LIU J, 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. [26] ZHUANG H. Should chronic hepatitis B in the indeterminate phase be treated?[J]. J Clin Hepatol, 2021, 37(9): 2033-2036. DOI: 10.3969/j.issn.1001-5256.2021.09.007.庄辉. 不确定期慢性乙型肝炎应否治疗?[J] 临床肝胆病杂志, 2021, 37(9): 2033-2036. DOI: 10.3969/j.issn.1001-5256.2021.09.007. [27] SPRADLING PR, XING J, RUPP LB, et al. Distribution of disease phase, treatment prescription and severe liver disease among 1598 patients with chronic hepatitis B in the Chronic Hepatitis Cohort Study, 2006-2013[J]. Aliment Pharmacol Ther, 2016, 44(10): 1080-1089. DOI: 10.1111/apt.13802. [28] 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 (2022 version)[J]. Chin J Infect Dis, 2023, 41(1): 3-28. DOI: 10.3760/cma.j.cn311365-20230220-00050.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]. 中华传染病杂志, 2023, 41(1): 3-28. DOI: 10.3760/cma.j.cn311365-20230220-00050.
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