儿童HBV感染： ALT水平正常患儿的抗病毒治疗

傅蕾

doi:10.12449/JCH240504

儿童HBV感染： ALT水平正常患儿的抗病毒治疗

DOI: 10.12449/JCH240504

傅蕾^, ,

中南大学湘雅医院感染病科，长沙 410008

利益冲突声明：本文不存在任何利益冲突。

详细信息

通信作者:
傅蕾， fulei92@126.com （ORCID： 0000-0001-7550-1254）

计量
- 文章访问数: 326
- HTML全文浏览量: 124
- PDF下载量: 72
- 被引次数: 0
出版历程
- 收稿日期: 2024-03-02
- 录用日期: 2024-03-24
- 出版日期: 2024-05-25

Hepatitis B virus infection in children： Antiviral therapy for children with a normal alanine aminotransferase level

Lei FU^{,
,}

Department of Infectious Diseases，Xiangya Hospital of Central South University，Changsha 410008，China

More Information

Corresponding author: FU Lei， fulei92@126.com （ORCID： 0000-0001-7550-1254）

摘要

摘要: 慢性乙型肝炎（CHB）是全球范围内的重大公共卫生问题，目前我国约有200万儿童HBV感染者。儿童感染HBV后更容易慢性化，成年后发生肝硬化以及肝癌的风险高。传统观点认为儿童HBV感染多数处于免疫耐受期，无需考虑抗病毒治疗，仅对免疫活动期和代偿期或失代偿期肝硬化的儿童CHB启动抗病毒治疗。越来越多的儿童CHB临床研究结果显示，儿童CHB抗病毒治疗（特别是以干扰素为基础的方案）应答率高，低龄儿童是临床治愈的优势人群，但对于ALT水平正常，特别是处于免疫耐受期的HBV感染的患儿是否接受抗病毒治疗仍然存在争议。本文针对儿童HBV感染的特点及ALT水平正常患儿抗病毒治疗必要性，特别是关于治疗时机等方面进行综述。
- 乙型肝炎病毒 /
- 丙氨酸转氨酶 /
- 治疗学 /
- 儿童
Abstract: Chronic hepatitis B （CHB） is a major public health issue around the world， and there are currently about 2 million children with hepatitis B virus （HBV） infection in China. HBV infection in children tends to become chronic， leading to high risks of liver cirrhosis and liver cancer in adulthood. Traditionally， it is believed that children with HBV infection are mainly in the immune-tolerant phase and do not require antiviral therapy， and antiviral therapy is only initiated for CHB children who are in the immune-active phase or suffer from compensated or decompensated liver cirrhosis. More and more clinical studies on CHB in children have shown that CHB children tend to have a high response rate to antiviral therapy， especially interferon-based regimens， and young children are at the advantage of clinical cure； however， there are still controversies over whether antiviral therapy should be initiated for children with HBV infection who have a normal alanine aminotransferase （ALT） level and are in the immune-tolerant phase. This article reviews the features of children with HBV infection and the necessity of antiviral therapy for children with a normal ALT level， with a special focus on treatment timing.
- Hepatitis B virus /
- Alanine Transaminase /
- Therapeutics /
- Child

HTML全文

参考文献(37)

[1]	ZHANG HF, YANG XJ, ZHU SS, et al. Pathological changes and clinical manifestations of 1020 children with liver diseases confirmed by biopsy[J]. Chin J Pediatr, 2002, 40( 3): 131- 134. DOI: 10.3760/j.issn:0578-1310.2002.03.002. 张鸿飞, 杨晓晋, 朱世殊, 等. 1 020例小儿肝穿刺组织病理学与临床的研究[J]. 中华儿科杂志, 2002, 40( 3): 131- 134. DOI: 10.3760/j.issn: 0578-1310.2002.03.002.
[2]	SOKAL EM, PAGANELLI M, WIRTH S, et al. Management of chronic hepatitis B in childhood: ESPGHAN clinical practice guidelines: consensus of an expert panel on behalf of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition[J]. J Hepatol, 2013, 59( 4): 814- 829. DOI: 10.1016/j.jhep.2013.05.016.
[3]	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.
[4]	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.
[5]	INDOLFI G, EASTERBROOK P, DUSHEIKO G, et al. Hepatitis B virus infection in children and adolescents[J]. Lancet Gastroenterol Hepatol, 2019, 4( 6): 466- 476. DOI: 10.1016/S2468-1253(19)30042-1.
[6]	WANG C, ZHANG SH, ZHAO J, et al. Changes and gaps of global and regional disease burden of hepatitis B infection in children younger than 5 years old between 2015 and 2019: A real-world data review[J]. J Med Virol, 2023, 95( 11): e29241. DOI: 10.1002/jmv.29241.
[7]	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.
[8]	FATTOVICH G, BORTOLOTTI F, DONATO F. Natural history of chronic hepatitis B: Special emphasis on disease progression and prognostic factors[J]. J Hepatol, 2008, 48( 2): 335- 352. DOI: 10.1016/j.jhep.2007.11.011.
[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. e 4. DOI: 10.1053/j.gastro.2016.07.012.
[10]	WEN WH, CHANG MH, HSU HY, et al. The development of hepatocellular carcinoma among prospectively followed children with chronic hepatitis B virus infection[J]. J Pediatr, 2004, 144( 3): 397- 399. DOI: 10.1016/j.jpeds.2003.11.022.
[11]	POPALIS C, YEUNG LTF, LING SC, et al. Chronic hepatitis B virus(HBV) infection in children: 25 years’ experience[J]. J Viral Hepat, 2013, 20( 4): e20- e26. DOI: 10.1111/jvh.12019.
[12]	KOMATSU H, INUI A, SOGO T, et al. Chronic hepatitis B virus infection in children and adolescents in Japan[J]. J Pediatr Gastroenterol Nutr, 2015, 60( 1): 99- 104. DOI: 10.1097/MPG.0000000000000567.
[13]	DENG PF, JIA TH. A case report of pose-hepatitis b liver oirrhosis in fetus[J]. Chin J Infect Dis, 1984, 2( 4): 281. 邓平非, 贾太和. 胎儿乙型肝炎后肝硬化一例报告[J]. 中华传染病杂志, 1984, 2( 4): 281, 封 3.
[14]	CHANG MH, YOU SL, CHEN CJ, et al. Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: A 20-year follow-up study[J]. J Natl Cancer Inst, 2009, 101( 19): 1348- 1355. DOI: 10.1093/jnci/djp288.
[15]	PAGANELLI M, STEPHENNE X, SOKAL EM. Chronic hepatitis B in children and adolescents[J]. J Hepatol, 2012, 57( 4): 885- 896. DOI: 10.1016/j.jhep.2012.03.036.
[16]	DELLA CORTE C, NOBILI V, COMPARCOLA D, et al. Management of chronic hepatitis B in children: An unresolved issue[J]. J Gastroenterol Hepatol, 2014, 29( 5): 912- 919. DOI: 10.1111/jgh.12550.
[17]	ZHANG HF, ZHU SS, YANG XJ, et al. Clinical manifestations and pathological changes of hepatitis B and C in children[J]. Infect Dis Inf, 2006, 19( 3): 130- 131, 141. DOI: 10.3969/j.issn.1007-8134.2006.03.014. 张鸿飞, 朱世殊, 杨晓晋, 等. 小儿乙、丙型肝炎临床与病理研究[J]. 传染病信息, 2006, 19( 3): 130- 131, 141. DOI: 10.3969/j.issn.1007-8134.2006.03.014.
[18]	ZHANG HF, DONG Y, WANG LW. A retrospective study on pathological and clinical characteristics of 3 932 children with liver diseases[J]. Chin J Pediatr, 2014, 52( 8): 570- 574. DOI: 10.3760/cma.j.issn.0578-1310.2014.08.004. 张鸿飞, 董漪, 王丽旻, 等. 儿童肝穿刺组织病理与临床诊断3 932例回顾性研究[J]. 中华儿科杂志, 2014, 52( 8): 570- 574. DOI: 10.3760/cma.j.issn.0578-1310.2014.08.004.
[19]	WANG J, YAN XM, ZHU L, et al. Significant histological disease of patients with chronic hepatitis B virus infection in the grey zone[J]. Aliment Pharmacol Ther, 2023, 57( 5): 464- 474. DOI: 10.1111/apt.17272.
[20]	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.
[21]	JIANG SW, LIAN X, HU AR, et al. Liver histopathological lesions is severe in patients with normal alanine transaminase and low to moderate hepatitis B virus DNA replication[J]. World J Gastroenterol, 2023, 29( 16): 2479- 2494. DOI: 10.3748/wjg.v29.i16.2479.
[22]	WIRTH S, ZHANG HF, HARDIKAR W, et al. Efficacy and safety of peginterferon alfa-2a(40KD) in children with chronic hepatitis B: The PEG-B-ACTIVE study[J]. Hepatology, 2018, 68( 5): 1681- 1694. DOI: 10.1002/hep.30050.
[23]	KOBAK GE, MACKENZIE T, SOKOL RJ, et al. Interferon treatment for chronic hepatitis B: Enhanced response in children 5 years old or younger[J]. J Pediatr, 2004, 145( 3): 340- 345. DOI: 10.1016/j.jpeds.2004.05.046.
[24]	ZHU SS, DONG Y, WANG LW, et al. A retrospective study on the liver pathological characteristics and the effect of antiviral treatment for 1 to 7 years old children with heptitis B e antigen negative chronic hepatitis B[J]. Chin J Pediatr, 2016, 54( 8): 587- 591. DOI: 10.3760/cma.j.issn.0578-1310.2016.08.006. 朱世殊, 董漪, 王丽旻, 等. 1～7岁儿童E抗原阴性慢性乙型病毒性肝炎肝脏病理特征及抗病毒治疗效果[J]. 中华儿科杂志, 2016, 54( 8): 587- 591. DOI: 10.3760/cma.j.issn.0578-1310.2016.08.006.
[25]	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.
[26]	ZHANG M, LI J, XU ZQ, et al. Functional cure is associated with younger age in children undergoing antiviral treatment for active chronic hepatitis B[J]. Hepatol Int, 2024. DOI: 10.1007/s12072-023-10631-9.[ Online ahead of print]
[27]	D’ANTIGA L, AW M, ATKINS M, et al. Combined lamivudine/interferon-alpha treatment in“immunotolerant” children perinatally infected with hepatitis B: A pilot study[J]. J Pediatr, 2006, 148( 2): 228- 233. DOI: 10.1016/j.jpeds.2005.09.020.
[28]	PODDAR U, YACHHA SK, AGARWAL J, et al. Cure for immune-tolerant hepatitis B in children: Is it an achievable target with sequential combo therapy with lamivudine and interferon?[J]. J Viral Hepat, 2013, 20( 5): 311- 316. DOI: 10.1111/jvh.12007.
[29]	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.
[30]	CAREY I, D’ANTIGA L, BANSAL S, et al. Immune and viral profile from tolerance to hepatitis B surface antigen clearance: A longitudinal study of vertically hepatitis B virus-infected children on combined therapy[J]. J Virol, 2011, 85( 5): 2416- 2428. DOI: 10.1128/JVI.01449-10.
[31]	ROSENTHAL P, LING SC, BELLE SH, et al. Combination of entecavir/peginterferon alfa-2a in children with hepatitis B e antigen-positive immune tolerant chronic hepatitis B virus infection[J]. Hepatology, 2019, 69( 6): 2326- 2337. DOI: 10.1002/hep.30312.
[32]	WONG GLH, SETO WK, WONG VWS, et al. Review article: Long-term safety of oral anti-viral treatment for chronic hepatitis B[J]. Aliment Pharmacol Ther, 2018, 47( 6): 730- 737. DOI: 10.1111/apt.14497.
[33]	JONAS MM, CHANG MH, SOKAL E, et al. Randomized, controlled trial of entecavir versus placebo in children with hepatitis B envelope antigen-positive chronic hepatitis B[J]. Hepatology, 2016, 63( 2): 377- 387. DOI: 10.1002/hep.28015.
[34]	NING L, HUANG X, XU Y, et al. Boosting of hepatitis B virus-specific T cell responses after pegylated-interferon-α-2a therapy for hepatitis B e antigen-positive pediatric patients[J]. J Interferon Cytokine Res, 2019, 39( 12): 740- 751. DOI: 10.1089/jir.2019.0042.
[35]	FAN HM, LIN LP, JIA SJ, et al. Interferon alpha treatment leads to a high rate of hepatitis B surface antigen seroconversion in Chinese children with chronic hepatitis B[J]. J Viral Hepat, 2019, 26( Suppl 1): 77- 84. DOI: 10.1111/jvh.13165.
[36]	WANG HM, ZHOU YZ, CHANG YN, et al. Clinical effect and influencing factors of pegylated interferon alfa-2a and entecavir monotherapy among children with HBeAg-positive chronic hepatitis B based on a real-world study[J]. Chin J Hepatol, 2022, 30( 10): 1056- 1062. DOI: 10.3760/cma.j.cn501113-20210225-00094. 王慧敏, 周英芝, 常宇南, 等. 基于真实世界的聚乙二醇干扰素α-2a和恩替卡韦单药治疗HBeAg阳性慢性乙型肝炎儿童的效果及其影响因素[J]. 中华肝脏病杂志, 2022, 30( 10): 1056- 1062. DOI: 10.3760/cma.j.cn501113-20210225-00094.
[37]	JIANG YJ, QING L, LI YJ, et al. Efficacy and safety analysis of peginterferon α-2a and entecavir in the treatment of chronic hepatitis B in children[J]. Chin J Infect Dis, 2022, 40( 7): 415- 419. DOI: 10.3760/cma.j.cn311365-20211126-00420. 蒋育进, 卿玲, 李彦洁, 等. 聚乙二醇干扰素α-2a与恩替卡韦治疗儿童慢性乙型肝炎的疗效和安全性分析[J]. 中华传染病杂志, 2022, 40( 7): 415- 419. DOI: 10.3760/cma.j.cn311365-20211126-00420.