关注慢性乙型肝炎特殊人群抗病毒治疗时机及治疗策略
DOI: 10.12449/JCH240502
利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:丁洋负责撰写修改文章;窦晓光负责拟定文章思路并最后定稿。
Focus on the timing and strategies of antiviral therapy for special populations with chronic hepatitis B
-
摘要: 慢性乙型肝炎(CHB)特殊人群要充分衡量肝硬化和肝癌家族史、年龄、疾病分期和抗病毒疗效等因素。CHB特殊人群选择合适抗病毒治疗时机并及时调整抗病毒策略,对于延缓疾病进展和降低肝硬化及肝细胞癌的发生起到重要的作用。本文将针对年龄≤30岁且ALT水平正常慢性HBV感染者、年龄>30岁且ALT水平正常慢性HBV感染孕妇、慢性HBV感染者儿童和HBeAg阳性低病毒血症经治CHB患者等特殊人群的抗病毒治疗时机和治疗策略进行阐述,帮助临床医生对CHB特殊人群选择更好的抗病毒治疗时机和优化治疗策略。Abstract: Several factors need to be considered for special populations with chronic hepatitis B (CHB), such as the family history of liver cirrhosis and liver cancer, age, disease stage, and antiviral response. It is necessary to select the appropriate timing of antiviral therapy and timely adjust antiviral strategies for CHB populations, which plays an important role in delaying disease progression and reducing the development of liver cirrhosis and hepatocellular carcinoma. This article elaborates on the timing and strategies for antiviral therapy in the special populations such as patients with chronic HBV infection who have an age of ≤30 years and a normal alanine aminotransferase (ALT) level, pregnant women with chronic HBV infection who have an age of >30 years and a normal ALT level, children with chronic HBV infection, and treatment-experienced HBeAg-positive CHB patients with low-level viremia, so as to help clinicians choose a better timing of antiviral therapy and optimize the strategies of antiviral therapy for special CHB populations.
-
Key words:
- Hepatitis B, Chronic /
- Therapeutics /
- Special Population
-
[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(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. [2] Infectious Disease Physicians Branch of Chinese Medical Doctor Association, National Clinical Research Center for Infectious Diseasea. Expert consensus on whole-population management of hepatitis B virus infection(2023)[J]. Chin J Clin Infect Dis, 2024, 17( 1): 1- 13. DOI: 10.3760/cma.j.issn.1674-2397.2024.01.001.中国医师协会感染科医师分会, 国家感染性疾病临床医学研究中心. 乙型病毒性肝炎全人群管理专家共识(2023)[J]. 中华临床感染病杂志, 2024, 17( 1): 1- 13. DOI: 10.3760/cma.j.issn.1674-2397.2024.01.001. [3] KUMAR M, SARIN SK, HISSAR S, et al. Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT[J]. Gastroenterology, 2008, 134( 5): 1376- 1384. DOI: 10.1053/j.gastro.2008.02.075. [4] 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. e 5. DOI: 10.1016/j.cgh.2021.01.019. [5] KIM GA, LIM YS, HAN S, et al. High risk of hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis B[J]. Gut, 2018, 67( 5): 945- 952. DOI: 10.1136/gutjnl-2017-314904. [6] LIU YN, LI MW, WANG LJ, et al. HBeAg-negative chronic HBV-infected individuals with normal alanine aminotransferase and an age of ≤30 years should be taken seriously when expanding anti-HBV treatment for chronic hepatitis B[J]. J Clin Hepatol, 2022, 38( 7): 1477- 1481. DOI: 10.3969/j.issn.1001-5256.2022.07.006.刘燕娜, 李明蔚, 王雷婕, 等. 扩大慢性乙型肝炎抗病毒治疗应重视ALT正常、年龄≤30岁的HBeAg阴性慢性HBV感染者[J]. 临床肝胆病杂志, 2022, 38( 7): 1477- 1481. DOI: 10.3969/j.issn.1001-5256.2022.07.006. [7] LI T, KONG Y, LIU YY, et al. Demographic characteristics and associated influencing factors in treated patients with chronic hepatitis B with hypoviremia: a single-center retrospective cross-sectional study[J]. Chin J Hepatol, 2023, 31( 1): 42- 48. DOI: 10.3760/cma.j.cn501113-20220121-00039.李彤, 孔银, 刘元元, 等. 经治慢性乙型肝炎低病毒血症患者人群特征及其相关影响因素: 一项单中心横断面回顾性研究[J]. 中华肝脏病杂志, 2023, 31( 1): 42- 48. DOI: 10.3760/cma.j.cn501113-20220121-00039. [8] WANG FD, ZHOU J, ZHANG DM, et al. A study of the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg-positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA[J]. Chin J Hepatol, 2022, 8( 4): 389- 394. DOI: 10.3760/cma.j.cn501113-20210705-00318.王发达, 周静, 张冬梅, 等. 核苷(酸)类似物治疗丙氨酸转氨酶正常HBeAg阳性且HBV DNA高水平慢性乙型肝炎的有效性研究[J]. 中华肝脏病杂志, 2022, 8( 4): 389- 394. DOI: 10.3760/cma.j.cn501113-20210705-00318. [9] CAO ZH, LIU YL, MA LN, et al. A potent hepatitis B surface antigen response in subjects with inactive hepatitis B surface antigen carrier treated with pegylated-interferon alpha[J]. Hepatology, 2017, 66( 4): 1058- 1066. DOI: 10.1002/hep.29213. [10] Chinese Foundation for Hepatitis Prevention and Control; Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association. Management algorithm for prevention mother-to-child transmission of hepatitis B virus(2021)[J]. J Clin Hepatol, 2021, 37( 3): 527- 531. DOI: 10.3969/j.issn.1001-5256.2021.03. 007.中国肝炎防治基金会, 中华医学会感染病学分会, 中华医学会肝病学分会. 阻断乙型肝炎病毒母婴传播临床管理流程(2021年)[J]. 临床肝胆病杂志, 2021, 37( 3): 527- 531. DOI: 10.3969/j.issn.1001-5256.2021.03. 007. [11] CUI FQ, WOODRING J, CHAN PL, et al. Considerations of antiviral treatment to interrupt mother-to-child transmission of hepatitis B virus in China[J]. Int J Epidemiol, 2018, 47( 5): 1529- 1537. DOI: 10.1093/ije/dyy077. [12] DING Y, SHENG QJ, MA L, et al. Chronic HBV infection among pregnant women and their infants in Shenyang, China[J]. Virol J, 2013, 10: 17. DOI: 10.1186/1743-422X-10-17. [13] TERRAULT NA, FELD JJ, LOK ASF. Tenofovir to prevent perinatal transmission of hepatitis B[J]. N Engl J Med, 2018, 378( 24): 2348- 2349. DOI: 10.1056/NEJMc1805396. [14] Chinese Society of Infectious Diseases, Chinese Medical Association; China Grade Center. 2019 Chinese practice guideline for the prevention and treatment of hepatitis B virus mother-to-child transmission[J]. Chin J Infect Dis, 2019, 37( 7): 388- 396. DOI: 10.3760/cma.j.issn.1000-6680.2019.07.002.中华医学会感染病学分会, GRADE中国中心. 中国乙型肝炎病毒母婴传播防治指南(2019年版)[J]. 中华传染病杂志, 2019, 37( 7): 388- 396. DOI: 10.3760/cma.j.issn.1000-6680.2019.07.002. [15] Chinese Society of Hepatology, Chinese Medical Association. Consensus on the management of hepatitis B virus infection in women of childbearing age[J]. J Clin Hepatol, 2018, 34( 6): 1176- 1180. DOI: 10.3969/j.issn.1001-5256.2018.06.008.中华医学会肝病学分会. 感染乙型肝炎病毒的育龄女性临床管理共识[J]. 临床肝胆病杂志, 2018, 34( 6): 1176- 1180. DOI: 10.3969/j.issn.1001-5256.2018.06.008. [16] DING Y, CAO LH, ZHU LY, et al. Efficacy and safety of tenofovir alafenamide fumarate for preventing mother-to-child transmission of hepatitis B virus: A national cohort study[J]. Aliment Pharmacol Ther, 2020, 52( 8): 1377- 1386. DOI: 10.1111/apt.16043. [17] FUNK AL, LU Y, YOSHIDA K, et al. Efficacy and safety of antiviral prophylaxis during pregnancy to prevent mother-to-child transmission of hepatitis B virus: A systematic review and meta-analysis[J]. Lancet Infect Dis, 2021, 21( 1): 70- 84. DOI: 10.1016/S1473-3099(20)30586-7. [18] BELOPOLSKAYA M, AVRUTIN V, KALININA O, et al. Chronic hepatitis B in pregnant women: Current trends and approaches[J]. World J Gastroenterol, 2021, 27( 23): 3279- 3289. DOI: 10.3748/wjg.v27.i23.3279. [19] ZENG QL, ZHANG HX, ZHANG JY, et al. Tenofovir alafenamide for pregnant Chinese women with active chronic hepatitis B: A multicenter prospective study[J]. Clin Gastroenterol Hepatol, 2022, 20( 12): 2826- 2837. e 9. DOI: 10.1016/j.cgh.2021.12.012. [20] CUI AX, DOU XG, DING Y. Antiviral therapy for pregnant women and children with chronic HBV infection[J]. J Clin Hepatol, 2022, 38( 11): 2448- 2451. DOI: 10.3969/j.issn.1001-5256.2022.11.003.崔傲雪, 窦晓光, 丁洋. 慢性HBV感染孕妇和儿童的抗病毒治疗药物选择及疗效评价[J]. 临床肝胆病杂志, 2022, 38( 11): 2448- 2451. DOI: 10.3969/j.issn.1001-5256.2022.11.003.. [21] CHOI GH, KIM GA, CHOI J, et al. High risk of clinical events in untreated HBeAg-negative chronic hepatitis B patients with high viral load and no significant ALT elevation[J]. Aliment Pharmacol Ther, 2019, 50( 2): 215- 226. DOI: 10.1111/apt.15311. [22] SHENG QJ, WANG N, ZHANG C, et al. HBeAg-negative patients with chronic hepatitis B virus infection and normal alanine aminotransferase: Wait or treat?[J]. J Clin Transl Hepatol, 2022, 10( 5): 972- 978. DOI: 10.14218/JCTH.2021.00443. [23] 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. [24] 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. [25] DEFRESNE F, SOKAL E. Chronic hepatitis B in children: Therapeutic challenges and perspectives[J]. J Gastroenterol Hepatol, 2017, 32( 2): 368- 371. DOI: 10.1111/jgh.13459. [26] 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. e 4. DOI: 10.1053/j.gastro.2016.07.012. [27] XU ZQ, DONG Y, WANG FC, et al. Value of transient elastography in the diagnosis of liver fibrosis in chronic hepatitis B children of different ages[J]. J Clin Hepatol, 2020, 36( 6): 1268- 1272. DOI: 10.3969/j.issn.1001-5256.2020.06.016.徐志强, 董漪, 王福川, 等. 瞬时弹性成像对不同年龄慢性乙型肝炎肝纤维化患儿的诊断价值[J]. 临床肝胆病杂志, 2020, 36( 6): 1268- 1272. DOI: 10.3969/j.issn.1001-5256.2020.06.016. [28] LIU QC, LIN SW, CAI WP, et al. Liver histological characteristics of 124 children with chronic hepatitis B[J]. Chin J Exp Clin Virol, 2015, 1( 4): 322- 325.刘启材, 林思炜, 蔡卫平, 等. 124例儿童慢性乙型肝炎肝组织病理变化特征分析[J]. 中华实验和临床病毒学杂志, 2015, 1( 4): 322- 325. [29] LI J, FAN PY, XU ZQ, et al. Functional cure of chronic hepatitis B with antiviral treatment in children having High-level viremia and normal or mildly elevated serum aminotransferase[J]. J Clin Transl Hepatol, 2023, 11( 5): 1011- 1022. DOI: 10.14218/JCTH.2023.00014. [30] WANG FS, LI J, ZHANG C. Why is the functional cure rate of young children with chronic hepatitis B receiving antiviral therapy considerably high?[J]. Hepatol Int, 2024, 18( 1): 296- 298. DOI: 10.1007/s12072-023-10597-8. [31] ZHANG YT, LIU J, PAN XB, et al. Successful treatment of infantile hepatitis B with lamivudine: A case report[J]. World J Clin Cases, 2021, 9( 14): 3442- 3448. DOI: 10.12998/wjcc.v9.i14.3442. [32] ZHU SS, ZHANG HF, DONG Y, et al. Antiviral therapy in hepatitis B virus-infected children with immune-tolerant characteristics: A pilot open-label randomized study[J]. J Hepatol, 2018, 68( 6): 1123- 1128. DOI: 10.1016/j.jhep.2018.01.037. [33] PAN J, WANG HY, YAO TT, et al. Clinical predictors of functional cure in children 1-6 years-old with chronic hepatitis B[J]. J Clin Transl Hepatol, 2022, 10( 3): 405- 411. DOI: 10.14218/JCTH.2021.00142. [34] TU T, ZEHNDER B, WETTENGEL JM, et al. Mitosis of hepatitis B virus-infected cells in vitro results in uninfected daughter cells[J]. JHEP Rep, 2022, 4( 9): 100514. DOI: 10.1016/j.jhepr.2022.100514. [35] KENNEDY PTF, SANDALOVA E, JO J, et al. Preserved T-cell function in children and young adults with immune-tolerant chronic hepatitis B[J]. Gastroenterology, 2012, 143( 3): 637- 645. DOI: 10.1053/j.gastro.2012.06.009. [36] BERTOLETTI A, BONI C. HBV antigens quantity: Duration and effect on functional cure[J]. Gut, 2022, 71( 11): 2149- 2151. DOI: 10.1136/gutjnl-2021-326258. [37] ZHANG Q, CAI DC, HU P, et al. Low-level viremia in nucleoside analog-treated chronic hepatitis B patients[J]. Chin Med J(Engl), 2021, 134( 23): 2810- 2817. DOI: 10.1097/CM9.0000000000001793. [38] 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. e 6. DOI: 10.1016/j.cgh.2020.03.001. [39] SINN DH, LEE J, GOO J, et al. Hepatocellular carcinoma risk in chronic hepatitis B virus-infected compensated cirrhosis patients with low viral load[J]. Hepatology, 2015, 62( 3): 694- 701. DOI: 10.1002/hep.27889. [40] KIM JH, SINN DH, KANG W, et al. Low-level viremia and the increased risk of hepatocellular carcinoma in patients receiving entecavir treatment[J]. Hepatology, 2017, 66( 2): 335- 343. DOI: 10.1002/hep.28916. [41] BOYD A, LACOMBE K, LAVOCAT F, et al. Decay of ccc-DNA marks persistence of intrahepatic viral DNA synthesis under tenofovir in HIV-HBV co-infected patients[J]. J Hepatol, 2016, 65( 4): 683- 691. DOI: 10.1016/j.jhep.2016.05.014. [42] LI J, DONG XQ, CAO LH, et al. Factors associated with persistent positive in HBV DNA level in patients with chronic Hepatitis B receiving entecavir treatment[J]. Front Cell Infect Microbiol, 2023, 13: 1151899. DOI: 10.3389/fcimb.2023.1151899. [43] 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. [44] 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. [45] LIU LP, WU XP, CAI TP, et al. Analysis of efficacy and factors influencing sequential combination therapy with tenofovir alafenamide fumarate after treatment with entecavir in chronic hepatitis B patients with low-level viremia[J]. Chin J Hepatol, 2023, 31( 2): 118- 125. DOI: 10.3760/cma.j.cn501113-20221019-00507.刘丽萍, 邬小萍, 蔡天盼, 等. 恩替卡韦经治后低病毒血症的慢性乙型肝炎患者序贯联合富马酸丙酚替诺福韦治疗的疗效及影响因素分析[J]. 中华肝脏病杂志, 2023, 31( 2): 118- 125. DOI: 10.3760/cma.j.cn501113-20221019-00507. [46] OGAWA E, NOMURA H, NAKAMUTA M, et al. Tenofovir alafenamide after switching from entecavir or nucleos(t)ide combination therapy for patients with chronic hepatitis B[J]. Liver Int, 2020, 40( 7): 1578- 1589. DOI: 10.1111/liv.14482. [47] 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.
本文二维码
计量
- 文章访问数: 548
- HTML全文浏览量: 172
- PDF下载量: 174
- 被引次数: 0