Comparative efficacy and safety of pharmacological interventions to prevent Mother-to-Child transmission of hepatitis B virus: A systematic review and network meta-analysis
Ha T Nguyen 1 , Montarat Thavorncharoensap 2 , Toi L Phung 3 , Thunyarat Anothaisintawee 4 , Usa Chaikledkaew 2 , Abhasnee Sobhonslidsuk 5 , Pattarawalai Talungchit 6 , Nathorn Chaiyakunapruk 7 , John Attia 8 , Gareth J McKAY 9 , Ammarin Thakkinstian 10
Affiliations
Affiliations
1
Mahidol University Health Technology Assessment (MUHTA) Graduate Program, Mahidol University, Bangkok, Thailand; School of Medicine, Vietnam National University Ho Chi Minh City, Vietnam.
2
Mahidol University Health Technology Assessment (MUHTA) Graduate Program, Mahidol University, Bangkok, Thailand; Social and Administrative Pharmacy Division, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
3
Mahidol University Health Technology Assessment (MUHTA) Graduate Program, Mahidol University, Bangkok, Thailand; Health Strategy and Policy Institute, Ministry of Health, Hanoi, Vietnam.
4
Mahidol University Health Technology Assessment (MUHTA) Graduate Program, Mahidol University, Bangkok, Thailand; Department of Family Medicine, Ramathibodi Hospital, Mahidol University, Thailand.
5
Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
6
Mahidol University Health Technology Assessment (MUHTA) Graduate Program, Mahidol University, Bangkok, Thailand; Maternal and Fetal Medicine Division, Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
7
Department of Pharmacotherapy, College of Pharmacy, The University of Utah, Salt Lake City, United States.
8
School of Medicine and Public Health, The University of Newcastle, and Hunter Medical Research Institute, Newcastle, Australia.
9
Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Northern Ireland.
10
Mahidol University Health Technology Assessment (MUHTA) Graduate Program, Mahidol University, Bangkok, Thailand; Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
PMID: 35263648 DOI: 10.1016/j.ajog.2022.02.042
Abstract
Objectives: This study investigated the efficacy and safety of pharmacological interventions to prevent vertical transmission of hepatitis B virus.
Data source: Medline, Cochrane and Scopus databases were searched up to 28th October 2020.
Study eligibility criteria: All randomized controlled trials reporting vertical hepatitis B virus transmission with pharmacological intervention were included.
Study appraisal and synthesis methods: Risk of bias was assessed using the Cochrane Risk-of-Bias tool Version 2. Treatment efficacy was estimated using stratified network meta-analysis based on maternal hepatitis B envelope antigen status.
Results: Nineteen studies were included for mothers positive for hepatitis B surface and envelope antigens. Pooling indicated a combination of hepatitis B vaccine and hepatitis B immunoglobulin in infants significantly reduced transmission risk compared to vaccine alone with a risk ratio of 0.52 (95% confidence interval 0.30, 0.91). Only the addition of maternal tenofovir disoproxil fumarate, but not telbivudine, lamivudine, or maternal hepatitis B immunoglobulin further reduced transmission risk compared to a combination of hepatitis B vaccine and hepatitis B immunoglobulin in infants, with a pooled risk ratio of 0.10 (0.03, 0.35). Twelve studies conducted in mothers with hepatitis B surface antigen positivity and mixed, unknown or negative hepatitis B envelope antigen status, provided limited evidence to suggest that maternal hepatitis B immunoglobulin combined with hepatitis B vaccine and immunoglobulin in infants was the likely best treatment, but this failed to reach statistical significance compared to a combination of hepatitis B vaccine and immunoglobulin in infants. Similarly, infant hepatitis B immunoglobulin, added to vaccination, likely provides additional benefit but again failed to reach statistical significance.
Conclusion: A combination of hepatitis B vaccine and immunoglobulin in infants is the cornerstone for prevention of vertical transmission for mothers double positive for both hepatitis B surface and envelope antigens. The addition of maternal tenofovir in this infant combination regimen was considered the likely most effective treatment. For infants of mothers with hepatitis B surface antigen positivity and mixed, unknown or negative hepatitis B envelop antigen status, no additional agents provided further benefit beyond hepatitis B vaccine alone.