抗乙型肝炎病毒药物在乙肝母婴阻断的治疗进展

许 智淇, 庄  鹏*
中山大学附属第八医院感染科

摘要


乙型肝炎病毒(hepatitis B virus,HBV)的母婴传播是造成慢性HBV感染的主要原因,对于HBV母婴传播
的阻断一直是降低疾病负荷的重要措施。目前可用于HBV母婴阻断的抗病毒药物有替比夫定、拉米夫定、富马酸替
诺福韦二吡呋酯,近年来,随着更多高质量证据的支持,富马酸丙酚替诺福韦亦开始用于HBV的母婴阻断。本文就
上述抗病毒药物在阻断HBV母婴传播中的用药指征、有效性、安全性、药物选择、用药时机、停药时机进行总结,
以期对临床实践中HBV母婴阻断抗病毒药物的合理应用提供帮助。

关键词


乙型肝炎病毒;母婴阻断;抗乙型肝炎病毒药物;有效性;安全性;进展

全文:

PDF


参考


[1]Yeo YH, Nguyen MH: Review article: current gaps

and opportunities in HBV prevention, testing and linkage to

care in the United States-a call for action. Aliment Pharmacol

Ther 2021, 53(1):63-78.

[2]尤红,王福生,李太生,孙亚朦,徐小元,贾继

东,南月敏,王贵强,侯金林,魏来et al:慢性乙型肝

炎防治指南(2022年版).实用肝脏病杂志,2023,26

(03):457-478.

[3]Liu J, Liang W, Jing W, Liu M: Countdown to 2030:

eliminating hepatitis B disease, China. Bull World Health

Organ 2019, 97(3):230-238.

[4]Global prevalence, treatment, and prevention of

hepatitis B virus infection in 2016: a modelling study. Lancet

Gastroenterol Hepatol 2018, 3(6):383-403.

[5]Zhang H, Pan CQ, Pang Q, Tian R, Yan M, Liu X:

Telbivudine or lamivudine use in late pregnancy safely reduces

perinatal transmission of hepatitis B virus in real-life practice.

Hepatology 2014, 60(2):468-476.

[6]Pan CQ, Duan Z, Dai E, Zhang S, Han G, Wang

Y, Zhang H, Zou H, Zhu B, Zhao W et al: Tenofovir to

Prevent Hepatitis B Transmission in Mothers with High Viral

Load. N Engl J Med 2016, 374(24):2324-2334.

[7]阻断乙型肝炎病毒母婴传播临床管理流程(2021

年).临床肝胆病杂志,2021,37(03):527-531.

[8]EASL 2017 Clinical Practice Guidelines on the

management of hepatitis B virus infection. J Hepatol 2017,

67(2):370-398.

[9]Terrault NA, Lok ASF, McMahon BJ, Chang KM,

Hwang JP, Jonas MM, Brown RS, Jr., Bzowej NH, Wong

JB: Update on prevention, diagnosis, and treatment of chronic

hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology

2018, 67(4):1560-1599.

[10]Kumar M, Abbas Z, Azami M, Belopolskaya M,

Dokmeci AK, Ghazinyan H, Jia J, Jindal A, Lee HC, Lei W

et al: Asian Pacific association for the study of liver (APASL)

guidelines: hepatitis B virus in pregnancy. Hepatol Int 2022,

16(2):211-253.

[11]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).中华

传染病杂志,2019,37(7):388-396.

[12]周乙华,杨慧霞,胡娅莉,刘兴会:乙型肝炎

病毒母婴传播预防临床指南(2020).临床肝胆病杂志,

2020,36(07):1474-1481.

[13]WHO Guidelines Approved by the Guidelines

Review Committee. In: Prevention of Mother-toChild Transmission of Hepatitis B Virus: Guidelines on

Antiviral Prophylaxis in Pregnancy. Geneva: World Health

Organization

[14]Funk AL, Lu Y, Yoshida K, Zhao T, Boucheron P,

van Holten J, Chou R, Bulterys M, Shimakawa Y: Efficacy

and safety of antiviral prophylaxis during pregnancy to

prevent mother-to-child transmission of hepatitis B virus: a

systematic review and meta-analysis. Lancet Infect Dis 2021,

21(1):70-84.

[15]李冀宏:拉米夫定和乙型肝炎疫苗及免疫球蛋

白三者联合阻断乙型肝炎母婴传播的临床研究.中国全科

医学,2017,20(S1):128-130.

[16]He T, Bai Y, Cai H, Ou X, Liu M, Yi W, Jia J:

Safety and efficacy of lamivudine or telbivudine started in

early pregnancy for mothers with active chronic hepatitis B.

Hepatol Int 2018, 12(2):118-125.

[17]Han GR, Cao MK, Zhao W, Jiang HX, Wang CM,

Bai SF, Yue X, Wang GJ, Tang X, Fang ZX: A prospective

and open-label study for the efficacy and safety of telbivudine

in pregnancy for the prevention of perinatal transmission of

hepatitis B virus infection. J Hepatol 2011, 55(6):1215-1221.

[18]Wang M, Bian Q, Zhu Y, Pang Q, Chang L,

Li R, Tiongson BC, Zhang H, Pan CQ: Real-world

study of tenofovir disoproxil fumarate to prevent hepatitis

B transmission in mothers with high viral load. Aliment

Pharmacol Ther 2019, 49(2):211-217.

[19]Lin Y, Liu Y, Ding G, Touqui L, Wang W, Xu N,

Liu K, Zhang L, Chen D, Wu Y et al: Efficacy of tenofovir

in preventing perinatal transmission of HBV infection in

pregnant women with high viral loads. Sci Rep 2018,

8(1):15514.

[20]Lim YS, Lee YS, Gwak GY, Byun KS, Kim YJ,

Choi J, An J, Lee HC, Yoo BC, Kwon SY: Monotherapy

with tenofovir disoproxil fumarate for multiple drugresistant chronic hepatitis B: 3-year trial. Hepatology 2017,

66(3):772-783.

[21]Marcellin P, Wong DK, Sievert W, Buggisch P,

Petersen J, Flisiak R, Manns M, Kaita K, Krastev Z, Lee SS

et al: Ten-year efficacy and safety of tenofovir disoproxil

fumarate treatment for chronic hepatitis B virus infection.

Liver Int 2019, 39(10):1868-1875.

[22]Chan HL, Fung S, Seto WK, Chuang WL, Chen

CY, Kim HJ, Hui AJ, Janssen HL, Chowdhury A, Tsang

TY et al: Tenofovir alafenamide versus tenofovir disoproxil

fumarate for the treatment of HBeAg-positive chronic

hepatitis B virus infection: a randomised, double-blind, phase

3, non-inferiority trial. Lancet Gastroenterol Hepatol 2016,

1(3):185-195.

[23]Kayes T, Crane H, Symonds A, Dumond J, Cottrell

M, Di Girolamo J, Manandhar S, Lim TH, Gane E, Kashuba

A et al: Plasma and breast milk pharmacokinetics of tenofovir

alafenamide in mothers with chronic hepatitis B infection.

Aliment Pharmacol Ther 2022, 56(3):510-518.

[24]Abdul Basit S, Dawood A, Ryan J, Gish R: Tenofovir

alafenamide for the treatment of chronic hepatitis B virus

infection. Expert Rev Clin Pharmacol 2017, 10(7):707-716.

[25]Li B, Liu Z, Liu X, Liu D, Duan M, Gu Y, Liu

Q, Ma Q, Wei Y, Wang Y: Efficacy and safety of tenofovir

disoproxil fumarate and tenofovir alafenamide fumarate in

preventing HBV vertical transmission of high maternal viral

load. Hepatol Int 2021, 15(5):1103-1108.

[26]Pan CQ, Yi W, Liu M, Wan G, Hu YH, Zhou MF:

Lamivudine therapy during the second vs the third trimester

for preventing transmission of chronic hepatitis B. J Viral

Hepat 2017, 24(3):246-252.

[27]Li Z, Duan X, Hu Y, Zhou M, Liu M, Kang K, Cai

H, Yi W, Fu D, Gao X: Efficacy and Safety of Lamivudine or

Telbivudine in Preventing Mother-to-Child Transmission

of Hepatitis B Virus: A Real-World Study. Biomed Res Int

2020, 2020:1374276.

[28]Jiang H, Ye X, Chen C, Zhou G, Han G: Efficacy

and Long-term Safety of Telbivudine Usage During Second

or Third Trimester in Hepatitis B Surface Antigen Positive

Mothers With High Viral Load: A 10-year Prospective Study.

J Clin Gastroenterol 2023, 57(4):423-428.

[29]Yi W, Cao X, Zeng Z, Cao W, Zhang Y, Sun F,

Wang Y, Wan G, Li M, Xie Y: Developmental consequences

of children born from mothers with telbivudine treatment

during late pregnancy: A prospective study with 3-year

follow-up. Virulence 2021, 12(1):1527-1537.

[30]Salvadori N, Fan B, Teeyasoontranon W, NgoGiang-Huong N, Phanomcheong S, Luvira A, Puangsombat

A, Suwannarat A, Srirompotong U, Putiyanun C et al:

Maternal and Infant Bone Mineral Density 1 Year After

Delivery in a Randomized, Controlled Trial of Maternal

Tenofovir Disoproxil Fumarate to Prevent Mother-tochild Transmission of Hepatitis B Virus. Clin Infect Dis 2019,

69(1):144-146.

[31]田文悦,盛秋菊,张翀,窦晓光,丁洋:乙型

肝炎病毒感染免疫耐受期孕妇应用富马酸丙酚替诺福韦

的疗效和安全性研究.中国实用内科杂志,2020,40(06):

466-470.

[32]Kourtis AP, Wiener J, Wang L, Fan B, Shepherd

JA, Chen L, Liu W, Shepard C, Wang L, Wang A et al:

Tenofovir Disoproxil Fumarate Use during Pregnancy and

Infant Bone Health: the Tenofovir in Pregnancy Pilot Study.

Pediatr Infect Dis J 2018, 37(11):e264-e268.

[33]Lampertico P, Buti M, Fung S, Ahn SH, Chuang

WL, Tak WY, Ramji A, Chen CY, Tam E, Bae H et al:

Switching from tenofovir disoproxil fumarate to tenofovir

alafenamide in virologically suppressed patients with chronic

hepatitis B: a randomised, double-blind, phase 3, multicentre

non-inferiority study. Lancet Gastroenterol Hepatol 2020,

5(5):441-453.

[34]Chan HLY, Buti M, Lim YS, Agarwal K, Marcellin

P, Brunetto M, Chuang WL, Janssen HLA, Fung S, Izumi N

et al: Long-Term Treatment With Tenofovir Alafenamide

for Chronic Hepatitis B Results in High Rates of Viral

Suppression and Favorable Renal and Bone Safety. Am J

Gastroenterol 2024, 119(3):486-496.

[35]Zeng QL, Zhang HX, Zhang JY, Huang S, Li WZ,

Li GM, Pan YJ, Feng YH, Li ZQ, Zhang GF et al: Tenofovir

Alafenamide for Pregnant Chinese Women With Active

Chronic Hepatitis B: A Multicenter Prospective Study. Clin

Gastroenterol Hepatol 2022, 20(12):2826-2837.e2829.

[36]Shen Y, Jia Y, Zhou J, Ji J, Xun P: Bayesian Network

Meta-Analysis for Assessing Adverse Effects of Anti-hepatitis B

Drugs. Clin Drug Investig 2019, 39(9):835-846.

[37]Wu Y, Liu J, Feng Y, Fu S, Ji F, Ge L, Yao N, Luo X,

Zhao Y, Chen Y et al: Efficacy and safety of antiviral therapy

for HBV in different trimesters of pregnancy: systematic

review and network meta-analysis. Hepatol Int 2020,

14(2):180-189.

[38]Liu J, Wang J, Jin D, Qi C, Yan T, Cao F, Jin L,

Tian Z, Guo D, Yuan N et al: Hepatic flare after telbivudine

withdrawal and efficacy of postpartum antiviral therapy for

pregnancies with chronic hepatitis B virus. J Gastroenterol

Hepatol 2017, 32(1):177-183.

[39]Wedemeyer H, Schöneweis K, Bogomolov P,

Blank A, Voronkova N, Stepanova T, Sagalova O, Chulanov

V, Osipenko M, Morozov V et al: Safety and efficacy of

bulevirtide in combination with tenofovir disoproxil fumarate

in patients with hepatitis B virus and hepatitis D virus

coinfection (MYR202): a multicentre, randomised, parallelgroup, open-label, phase 2 trial. Lancet Infect Dis 2023,

23(1):117-129.

[40]Asselah T, Loureiro D, Boyer N, Mansouri A:

Targets and future direct-acting antiviral approaches to

achieve hepatitis B virus cure. Lancet Gastroenterol Hepatol

2019, 4(11):883-892.

[41]Yuen MF, Schiefke I, Yoon JH, Ahn SH, Heo J,

Kim JH, Lik Yuen Chan H, Yoon KT, Klinker H, Manns M

et al: RNA Interference Therapy With ARC-520 Results in

Prolonged Hepatitis B Surface Antigen Response in Patients

With Chronic Hepatitis B Infection. Hepatology 2020,

72(1):19-31.

[42]Lee HW, Park JY, Hong T, Park MS, Ahn

SH: Efficacy of Lenvervimab, a Recombinant Human

Immunoglobulin, in Treatment of Chronic Hepatitis B Virus

Infection. Clin Gastroenterol Hepatol 2020, 18(13):3043-

3045.e3041.


Refbacks

  • 当前没有refback。