年龄&gt;30岁、ALT水平正常HBV感染孕妇的抗病毒治疗时机

盛秋菊; 汪玉涵; 丁洋

doi:10.12449/JCH240503

年龄>30岁、ALT水平正常HBV感染孕妇的抗病毒治疗时机

DOI: 10.12449/JCH240503

中国医科大学附属盛京医院感染科，沈阳 110022

基金项目:

辽宁省科技厅应用基础研究计划 (2022JH2/101500009)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：盛秋菊负责撰写修改文章；汪玉涵负责查阅文献；丁洋负责拟定文章思路并最后定稿。

详细信息

通信作者:
丁洋， yding0903@sina.com （ORCID： 0000-0003-0836-7790）

计量
- 文章访问数: 362
- HTML全文浏览量: 132
- PDF下载量: 103
- 被引次数: 0
出版历程
- 收稿日期: 2024-02-29
- 录用日期: 2024-04-07
- 出版日期: 2024-05-25

Timing of antiviral therapy for pregnant women with HBV infection and normal alanine aminotransferase level aged >30 years

Department of Infectious Diseases，Shengjing Hospital of China Medical University，Shenyang 110022，China

Research funding:

Applied Basic Research Program of Liaoning Science and Technology Department (2022JH2/101500009)

More Information

Corresponding author: Ding Yang， yding0903@sina.com （ORCID： 0000-0003-0836-7790）

摘要

摘要: 《慢性乙型肝炎防治指南（2022版）》扩大了慢性乙型肝炎患者抗病毒治疗适应证。ALT水平正常的慢性HBV感染者，HBV DNA阳性，年龄>30岁，指南建议开始抗病毒治疗。但对于年龄>30岁的孕妇，是否立即启动抗病毒治疗尚无统一观点。有观点认为，ALT水平正常的孕妇多为免疫耐受期，抗病毒治疗效果不佳，且孕期用药可能影响母婴安全。因此，即使孕妇年龄>30岁，也不主张在孕早期开始抗病毒治疗；也有观点认为，孕期机体的免疫改变可能是HBV免疫清除的特殊时期，若年龄>30岁，即使ALT水平正常，也应该立即抗病毒治疗，孕妇可能获得更好的病毒学甚至血清学应答。本文将针对上述问题，从孕期抗病毒治疗目的、治疗时机和停药时机等方面展开论述。
- 乙型肝炎病毒 /
- 丙氨酸转氨酶 /
- 治疗学 /
- 母婴传播
Abstract: Guidelines for the prevention and treatment of chronic hepatitis B （2022 edition） expanded the indications for antiviral therapy in patients with chronic hepatitis B. The guidelines recommend to initiate antiviral therapy for patients with chronic HBV infection who have a normal alanine aminotransferase （ALT） level， positive HBV DNA， and an age of >30 years. However， for pregnant women aged >30 years， no consensus has been reached on whether to start antiviral therapy immediately. Some experts believe that pregnant women with a normal ALT level are mostly in the immune-tolerant phase， and antiviral therapy tends to have an unsatisfactory therapeutic effect； in addition， medication during pregnancy may affect the safety of mothers and fetuses. Therefore， it is not recommended to start antiviral therapy immediately in early pregnancy even if the pregnant women are aged >30 years. Other experts believe that immune changes of the body during pregnancy may be a special period for HBV immune clearance， and if the patients are aged >30 years， antiviral therapy should be initiated immediately even if the patient has a normal ALT level； pregnant women may get better virologic and even serological response. With a focus on the above issues， this article elaborates on the purpose， treatment timing， and drug withdrawal timing of antiviral therapy during pregnancy.
- Hepatitis B Virus /
- Alanine Transaminase /
- Therapeutics /
- Mother-to-Child Transmission

HTML全文

参考文献(29)

[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]	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.
[3]	DUAN MH, CHI XL, XIAO HM, et al. High-normal alanine aminotransferase is an indicator for liver histopathology in HBeAg-negative chronic hepatitis B[J]. Hepatol Int, 2021, 15( 2): 318- 327. DOI: 10.1007/s12072-021-10153-2.
[4]	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.
[5]	KOFFAS A, PETERSEN J, KENNEDY PT. Reasons to consider early treatment in chronic hepatitis B patients[J]. Antiviral Res, 2020, 177: 104783. DOI: 10.1016/j.antiviral.2020.104783.
[6]	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.
[7]	CHAYANUPATKUL M, OMINO R, MITTAL S, et al. Hepatocellular carcinoma in the absence of cirrhosis in patients with chronic hepatitis B virus infection[J]. J Hepatol, 2017, 66( 2): 355- 362. DOI: 10.1016/j.jhep.2016.09.013.
[8]	WANG F, MUBARIK S, ZHANG Y, et al. Long-term trends of liver cancer incidence and mortality in China 1990-2017: A joinpoint and age-period-cohort analysis[J]. Int J Environ Res Public Health, 2019, 16( 16): 2878. DOI: 10.3390/ijerph16162878.
[9]	KUMAR M, ABBAS Z, AZAMI M, et al. Asian Pacific association for the study of liver(APASL) guidelines: Hepatitis B virus in pregnancy[J]. Hepatol Int, 2022, 16( 2): 211- 253. DOI: 10.1007/s12072-021-10285-5.
[10]	TRAN TT, AHN J, REAU NS. ACG clinical guideline: Liver disease and pregnancy[J]. Am J Gastroenterol, 2016, 111( 2): 176- 194; quiz196. DOI: 10.1038/ajg.2015.430.
[11]	WESTBROOK RH, DUSHEIKO G, WILLIAMSON C. Pregnancy and liver disease[J]. J Hepatol, 2016, 64( 4): 933- 945. DOI: 10.1016/j.jhep.2015.11.030.
[12]	ZHI YJ. Clinical analysis of 100 patients with abnormal liver function during pregnancy[J]. J Clin Pathol Res, 2022, 42( 4): 841- 846. DOI: 10.3978/j.issn.2095-6959.2022.04.011. 支艳俊. 100例妊娠期肝功能异常患者的临床分析[J]. 临床与病理杂志, 2022, 42( 4): 841- 846. DOI: 10.3978/j.issn.2095-6959.2022.04.011.
[13]	GUARINO M, COSSIGA V, MORISCO F. The interpretation of liver function tests in pregnancy[J]. Best Pract Res Clin Gastroenterol, 2020, 44-45: 101667. DOI: 10.1016/j.bpg.2020.101667.
[14]	DING Y, SHENG QJ, DOU XG. Early-stage clinical features, diagnosis and treatment progress of pregnancy-related liver disease[J]. Chin J Hepatol, 2021, 29( 10): 923- 926. DOI: 10.3760/cma.j.cn501113-20210829-00436. 丁洋, 盛秋菊, 窦晓光. 妊娠相关肝病的临床特点和早期诊治进展[J]. 中华肝脏病杂志, 2021, 29( 10): 923- 926. DOI: 10.3760/cma.j.cn501113-20210829-00436.
[15]	YI XR, YUAN YC, LI N, et al. A mouse model with age-dependent immune response and immune-tolerance for HBV infection[J]. Vaccine, 2018, 36( 6): 794- 801. DOI: 10.1016/j.vaccine.2017.12.071.
[16]	JOSHI SS, WONG D, CASTILLO E, et al. Peripartum cytokine flares in a multiethnic cohort of chronic hepatitis B carriers does not correlate with hepatitis B virus suppression or increased risk of liver disease[J]. Am J Reprod Immunol, 2017, 78( 4): 10.1111/aji. 12707. DOI: 10.1111/aji.12707.
[17]	TAN HH, LUI HF, CHOW WC. Chronic hepatitis B virus(HBV) infection in pregnancy[J]. Hepatol Int, 2008, 2( 3): 370- 375. DOI: 10.1007/s12072-008-9063-4.
[18]	ZHANG L, JIANG TT, YANG Y, et al. Postpartum hepatitis and host immunity in pregnant women with chronic HBV infection[J]. Front Immunol, 2023, 13: 1112234. DOI: 10.3389/fimmu.2022.1112234.
[19]	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.
[20]	Chinese Foundation for Hepatitis Prevention, Control; Chinese Society of Infectious Diseases, Chinese Medical Association; Chinese Society of Hepatology, Chinese Medical Association, et al. Management algorithm for prevention of mother-to-child transmission of hepatitis B virus(2021)[J]. J Clin Hepatol, 2021, 7( 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.
[21]	LIN CL, KAO JH. Development of hepatocellular carcinoma in treated and untreated patients with chronic hepatitis B virus infection[J]. Clin Mol Hepatol, 2023, 29( 3): 605- 622. DOI: 10.3350/cmh.2022.0342.
[22]	World Health Organization. Prevention of mother-to-child transmission of hepatitis B virus: Guidelines on antiviral prophylaxis in pregnancy[R]. Geneva: World Health Organization, 2020.
[23]	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.
[24]	HAN C, DOU XG. Expanding the indications for antiviral therapy for chronic hepatitis B: Advantages and disadvantages[J]. J Clin Hepatol, 2023, 39( 1): 22- 26. DOI: 10.3969/j.issn.1001-5256.2023.01.003. 韩超, 窦晓光. 扩大慢性乙型肝炎抗病毒治疗适应证:利大于弊[J]. 临床肝胆病杂志, 2023, 39( 1): 22- 26. DOI: 10.3969/j.issn.1001-5256.2023.01.003.
[25]	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.
[26]	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.
[27]	CHANG CY, AZIZ N, POONGKUNRAN M, et al. Serum aminotransferase flares in pregnant and postpartum women with current or prior treatment for chronic hepatitis B[J]. J Clin Gastroenterol, 2018, 52( 3): 255- 261. DOI: 10.1097/MCG.0000000000000822.
[28]	NGUYEN V, TAN PK, GREENUP AJ, et al. Anti-viral therapy for prevention of perinatal HBV transmission: Extending therapy beyond birth does not protect against post-partum flare[J]. Aliment Pharmacol Ther, 2014, 39( 10): 1225- 1234. DOI: 10.1111/apt.12726.
[29]	SHENG QJ, DING Y, LI BJ, et al. Telbivudine for prevention of perinatal transmission in pregnant women infected with hepatitis B virus in immune-tolerant phase: A study of efficacy and safety of drug withdrawal[J]. Chin J Hepatol, 2016, 24( 4): 258- 264. DOI: 10.3760/cma.j.issn.1007-3418.2016.04.004. 盛秋菊, 丁洋, 李佰君, 等. HBV感染免疫耐受期孕妇应用替比夫定阻断母婴传播有效性及停药安全性的研究[J]. 中华肝脏病杂志, 2016, 24( 4): 258- 264. DOI: 10.3760/cma.j.issn.1007-3418.2016.04.004.