Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
Current Hepatology Reports
Published in: Current Hepatology Reports 3/2019

Open Access 01-09-2019 | Hepatitis B | Hepatitis B (JK Lim, Section Editor)

Strategies for Global Elimination of Chronic HBV Infection: 2019 Update

Authors: Shevanthi Nayagam, Mark Thursz

Published in: Current Hepatology Reports | Issue 3/2019

Login to get access

Abstract

Purpose of Review

With just over a decade to go before the WHO 2030 hepatitis elimination targets, this review takes a global perspective at the major challenges standing in the way of hepatitis B virus (HBV) elimination and discusses potential innovative solutions on the horizon for use in high burden settings.

Recent Findings

Universal HBV infant vaccination has been an incredible success. However, in order to reach the elimination targets, efforts now need to urgently focus on scaling up HBV prevention of mother-to-child (PMTCT) interventions, particularly in sub-Saharan Africa and increasing population level testing and treatment.

Summary

Innovative outreach strategies, simplified diagnostics and novel biomarkers and integration of systems are promising solutions to allow HBV elimination to be reached in an effective and affordable way. This should go alongside careful financing, policy planning and establishment of strong surveillance systems.
Literature
1.
•• Razavi-Shearer D, Gamkrelidze I, Nguyen MH, Chen D-S, Van Damme P, Abbas Z, et al. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol. 2018;3(6):383–403. An global modelling study estimating the prevalence of HBsAg and the coverage of interventions. CrossRef
2.
•• Nayagam S, Thursz M, Sicuri E, Conteh L, Wiktor S, Low-Beer D, et al. Requirements for global elimination of hepatitis B: a modelling study. Lancet Infect Dis. 2016;16(12):1399–408. A modelling study evaluating what impact could be achieved by scale-up of key prevention and treatment interventions against HBV, on a global level. CrossRef
3.
Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, et al. Epidemiological serosurvey of hepatitis B in China--declining HBV prevalence due to hepatitis B vaccination. Vaccine. 2009;27(47):6550–7.CrossRef
4.
Whittle HC, Maine N, Pilkington J, Mendy M, Fortuin M, Bunn J, et al. Long-term efficacy of continuing hepatitis B vaccination in infancy in two Gambian villages. Lancet. 1995;345(8957):1089–92.
5.
Ng KP, Saw TL, Baki A, Rozainah K, Pang KW, Ramanathan M. Impact of the expanded program of immunization against hepatitis B infection in school children in Malaysia. Med Microbiol Immunol. 2005;194(3):163–8.CrossRef
6.
Chang MH, You SL, Chen CJ, Liu CJ, Lee CM, Lin SM, et al. Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: a 20-year follow-up study. J Natl Cancer Inst. 2009;101(19):1348–55.CrossRef
7.
Chang M-H, Chen C-J, Lai M-S, Hsu H-M, Wu T-C, Kong M-S, et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. N Engl J Med. 1997;336(26):1855–9.CrossRef
8.
McMahon BJ, Bulkow LR, Singleton RJ, Williams J, Snowball M, Homan C, et al. Elimination of hepatocellular carcinoma and acute hepatitis B in children 25 years after a hepatitis B newborn and catch-up immunization program. Hepatology. 2011;54(3):801–7.CrossRef
9.
Chang CH, Lin JW, Tu YK. Secular trends were considered in the evaluation of universal hepatitis B vaccination in Taiwan. J Clin Epidemiol. 2015;68(4):405–11.CrossRef
10.
11.
Beutels P. Economic evaluations of hepatitis B immunization: a global review of recent studies (1994-2000). Health Econ. 2001;10(8):751–74.CrossRef
12.
Damme PV, Leuridan E, Hendrickx G, Vorsters A, Theeten H, Leino T, et al. Should Europe have a universal hepatitis B vaccination programme? BMJ. 2013;347.
13.
Siddiqui MR, Gay N, Edmunds WJ, Ramsay M. Economic evaluation of infant and adolescent hepatitis B vaccination in the UK. Vaccine. 2011;29(3):466–75.CrossRef
14.
Mandal S. Introduction of universal infant hepatitis B immunisation in the UK- paving the way to elimination. Hum Vaccin Immunother. 2019;15(2):440–3.CrossRef
15.
Li X, Wiesen E, Diorditsa S, Toda K, Duong TH, Nguyen LH, et al. Impact of adverse events following immunization in Viet Nam in 2013 on chronic hepatitis B infection. Vaccine. 2016;34(6):869–73.CrossRef
16.
Yu W, Liu D, Zheng J, Liu Y, An Z, Rodewald L, et al. Loss of confidence in vaccines following media reports of infant deaths after hepatitis B vaccination in China. Int J Epidemiol. 2016;45(2):441–9.CrossRef
17.
Edmunds WJ, Medley GF, Nokes DJ, Hall AJ, Whittle HC. The influence of age on the development of the hepatitis B carrier state. Proc Biol Sci. 1993;253(1337):197–201.CrossRef
18.
•• Keane E, Funk AL, Shimakawa Y. Systematic review with meta-analysis: the risk of mother-to-child transmission of hepatitis B virus infection in sub-Saharan Africa. Aliment Pharmacol Ther. 2016;44(10):1005–17. Important systematic review looking at mother-to-child transmission studies in Africa. CrossRef
19.
Shimakawa Y, Lemoine M, Bottomley C, Njai HF, Ndow G, Jatta A, et al. Birth order and risk of hepatocellular carcinoma in chronic carriers of hepatitis B virus: a case–control study in The Gambia. Liver Int. 2015;35:2318–26.CrossRef
20.
Shimakawa Y, Lemoine M, Njai HF, Bottomley C, Ndow G, Goldin RD, et al. Natural history of chronic HBV infection in West Africa: a longitudinal population-based study from The Gambia. Gut. 2016;65(12):2007–16.
21.
Shimakawa Y, Yan HJ, Tsuchiya N, Bottomley C, Hall AJ. Association of early age at establishment of chronic hepatitis B infection with persistent viral replication, liver cirrhosis and hepatocellular carcinoma: a systematic review. PLoS One. 2013;8(7):e69430.CrossRef
22.
•• Pan CQ, Duan Z, Dai E, Zhang S, Han G, Wang Y, et al. Tenofovir to prevent hepatitis B transmission in mothers with high viral load. N Engl J Med. 2016;374(24):2324–34. Important trial comparing addition of Tenofovir to standard immunoprophylaxis on mother-to-child transmission rates in China. CrossRef
23.
Hyun MH, Lee YS, Kim JH, Je JH, Yoo YJ, Yeon JE, et al. Systematic review with meta-analysis: the efficacy and safety of tenofovir to prevent mother-to-child transmission of hepatitis B virus. Aliment Pharmacol Ther. 2017;45(12):1493–505.CrossRef
24.
•• Cui F, Shen L, Li L, Wang H, Wang F, Bi S, et al. Prevention of chronic hepatitis B after 3 decades of escalating vaccination policy, China. Emerg Infect Dis. 2017;23(5):765–72. This article presents the results of the 2014 national HBV serosurvey in China and provides a good summary of the remarkable achievement that the scale-up of HBV immunisation programmes has had on reducing HBsAg prevalence in China. CrossRef
25.
Chen HL, Lin LH, Hu FC, Lee JT, Lin WT, Yang YJ, et al. Effects of maternal screening and universal immunization to prevent mother-to-infant transmission of HBV. Gastroenterology. 2012;142(4):773–81. e2.CrossRef
26.
Marion SA, Tomm Pastore M, Pi DW, Mathias RG. Long-term follow-up of hepatitis B vaccine in infants of carrier mothers. Am J Epidemiol. 1994;140(8):734–46.CrossRef
27.
Lin C-L, Kao J-H. The clinical implications of hepatitis B virus genotype: recent advances. J Gastroenterol Hepatol. 2011;26:123–30.CrossRef
28.
Hepatitis B vaccines: WHO position paper - July 2017. Wkly Epidemiol Rec. 2017;92(27):369–92.
29.
Wen W-H, Chang M-H, Zhao L-L, Ni Y-H, Hsu H-Y, Wu J-F, et al. Mother-to-infant transmission of hepatitis B virus infection: significance of maternal viral load and strategies for intervention. J Hepatol. 2013;59(1):24–30.CrossRef
30.
Brown RS, McMahon BJ, Lok ASF, Wong JB, Ahmed AT, Mouchli MA, et al. Antiviral therapy in chronic hepatitis B viral infection during pregnancy: a systematic review and meta-analysis. Hepatology. 2016;63(1):319–33.CrossRef
31.
Pan CQ, Duan Z, Dai E, Zhang S, Han G, Wang Y, et al. Tenofovir to prevent hepatitis B transmission in mothers with high viral load. N Engl J Med. 2016;374(24):2324–34.CrossRef
32.
Jourdain G, Ngo-Giang-Huong N, Harrison L, Decker L, Khamduang W, Tierney C, et al. Tenofovir versus placebo to prevent perinatal transmission of hepatitis B. N Engl J Med. 2018;378(10):911–23.CrossRef
33.
Terrault NA, Feld JJ, Lok ASF. Tenofovir to prevent perinatal transmission of hepatitis B. N Engl J Med. 2018;378(24):2348–9.CrossRef
34.
Cui F, Woodring J, Chan P, Xu F. Considerations of antiviral treatment to interrupt mother-to-child transmission of hepatitis B virus in China. Int J Epidemiol. 2018;47(5):1529–37.CrossRef
35.
Fan L, Owusu-Edusei K Jr, Schillie SF, Murphy TV. Cost-effectiveness of active-passive prophylaxis and antiviral prophylaxis during pregnancy to prevent perinatal hepatitis B virus infection. Hepatology. 2016;63(5):1471–80.CrossRef
36.
•• EASL. 2017 Clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370–98. Latest European guidelines on management of hepatitis B infection. CrossRef
37.
Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63(1):261–83.CrossRef
38.
•• WHO Guidelines Approved by the Guidelines Review Committee. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection. Geneva: World Health Organization; 2015. Copyright (c) World Health Organization 2015. First guidelines developed by the World Health Organization providing evidence-based guidance for the management of hepatitis B.
39.
Allison RD, Patel MK, Tohme RA. Hepatitis B vaccine birth dose coverage correlates worldwide with rates of institutional deliveries and skilled attendance at birth. Vaccine. 2017;35(33):4094–8.CrossRef
40.
41.
Moturi E, Tevi-Benissan C, Hagan JE, Shendale S, Mayenga D, Murokora D, et al. Implementing a birth dose of hepatitis B vaccine in Africa: findings from assessments in 5 countries. J Immunol Sci. 2018;Suppl(5):31–40.CrossRef
42.
Petit D, Tevi-Benissan C, Woodring J, Hennessey K, Kahn A-L. Countries’ interest in a hepatitis B vaccine licensed for the controlled temperature chain; survey results from African and Western Pacific regions. Vaccine. 2017;35(49, Part B):6866–71.CrossRef
43.
44.
Cui F, Li L, Hadler SC, Wang F, Zheng H, Chen Y, et al. Factors associated with effectiveness of the first dose of hepatitis B vaccine in China: 1992–2005. Vaccine. 2010;28(37):5973–8.CrossRef
45.
WHO. A systematic review of monovalent hepatitis B vaccine thermostability. Geneva: World Health Organization; 2017.
46.
Scott N, Palmer A, Morgan C, Lesi O, Spearman CW, Sonderup M, et al. Cost-effectiveness of the controlled temperature chain for the hepatitis B virus birth dose vaccine in various global settings: a modelling study. Lancet Glob Health. 2018;6(6):e659–e67.CrossRef
47.
Sutanto A, Suarnawa IM, Nelson CM, Stewart T, Soewarso TI. Home delivery of heat-stable vaccines in Indonesia: outreach immunization with a prefilled, single-use injection device. Bull World Health Organ. 1999;77(2):119–26.PubMedPubMedCentral
48.
Levin CE, Nelson CM, Widjaya A, Moniaga V, Anwar C. The costs of home delivery of a birth dose of hepatitis B vaccine in a prefilled syringe in Indonesia. Bull World Health Organ. 2005;83(6):456–61.PubMedPubMedCentral
49.
Diop A, Daff B, Sow M, Blum J, Diagne M, Sloan NL, et al. Oxytocin via Uniject (a prefilled single-use injection) versus oral misoprostol for prevention of postpartum haemorrhage at the community level: a cluster-randomised controlled trial. Lancet Glob Health. 2016;4(1):e37–44.CrossRef
50.
Guillermet E, Dicko HM, Mai LTP, N’Diaye M, Hane F, Ba SO, et al. Acceptability and feasibility of delivering pentavalent vaccines in a compact, prefilled, autodisable device in Vietnam and Senegal. PLoS One. 2015;10(7):e0132292.CrossRef
51.
•• WHO Guidelines Approved by the Guidelines Review Committee. WHO Guidelines on Hepatitis B and C Testing. Geneva: World Health Organization. Copyright (c) World Health Organization; 2017. Guidelines developed by WHO on testing strategies for increasing diagnosis for viral hepatitis.
52.
Njai HF, Shimakawa Y, Sanneh B, Ferguson L, Ndow G, Mendy M, et al. Validation of rapid point-of-care (POC) tests for detection of hepatitis B surface antigen in field and laboratory settings in the Gambia. West Afr J Clin Microbiol. 2015;53(4):1156–63.CrossRef
53.
Liaw Y-F, Sung J, Chow W, Farrell G, Lee C-Z, Yuen H, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351(15):1521–31.CrossRef
54.
Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. Jama. 2006;295(1):65–73.CrossRef
55.
Papatheodoridis GV, Manolakopoulos S, Touloumi G, Vourli G, Raptopoulou-Gigi M, Vafiadis-Zoumbouli I, et al. Virological suppression does not prevent the development of hepatocellular carcinoma in HBeAg-negative chronic hepatitis B patients with cirrhosis receiving oral antiviral(s) starting with lamivudine monotherapy: results of the nationwide HEPNET. Greece cohort study. Gut. 2011;60(8):1109–16.CrossRef
56.
Wong GL, Chan HL, Mak CW, Lee SK, Ip ZM, Lam AT, et al. Entecavir treatment reduces hepatic events and deaths in chronic hepatitis B patients with liver cirrhosis. Hepatology. 2013;58(5):1537–47.CrossRef
57.
Buti M, Tsai N, Petersen J, Flisiak R, Gurel S, Krastev Z, et al. Seven-year efficacy and safety of treatment with Tenofovir Disoproxil fumarate for chronic hepatitis B virus infection. Dig Dis Sci. 2015;60(5):1457–64.CrossRef
58.
Ford N, Scourse R, Lemoine M, Hutin Y, Bulterys M, Shubber Z, et al. Adherence to Nucleos(t)ide analogue therapies for chronic hepatitis B infection: a systematic review and meta-analysis. Hepatol Commun. 2018;2(10):1160–7.CrossRef
59.
Hutin Y, Nasrullah M, Easterbrook P, Nguimfack BD, Burrone E, Averhoff F, et al. Access to treatment for hepatitis B virus infection - worldwide, 2016. MMWR Morb Mortal Wkly Rep. 2018;67(28):773–7.CrossRef
60.
Nayagam S, Conteh L, Sicuri E, Shimakawa Y, Suso P, Tamba S, et al. Cost-effectiveness of community-based screening and treatment for chronic hepatitis B in The Gambia: an economic modelling analysis. Lancet Glob Health. 2016;4(8):e568–e78.CrossRef
61.
Dan Y, Wong J, Hamid S, Han K-H, Jia J, Liu C-J, et al. Consensus cost-effectiveness model for treatment of chronic hepatitis B in Asia Pacific countries. Hepatol Int. 2014;8(3):382–94.CrossRef
62.
Nayagam S, Chan P, Zhao K, Sicuri E, Wang X, Jia J, et al. Investment case for a comprehensive package of interventions against hepatitis B in China. J Hepatol. 2016;64(2):S469.CrossRef
63.
Chevaliez S, Pawlotsky J-M. New virological tools for screening, diagnosis and monitoring of hepatitis B and C in resource-limited settings. J Hepatol. 2018;69(4):916–26.CrossRef
64.
Bradshaw D, Rae C, Rayment M, Turner N, Turner R, Pickard G, et al. HIV/HCV/HBV testing in the emergency department: a feasibility and seroprevalence study. HIV Med. 2018;19(Suppl 1):52–7.CrossRef
65.
Williams J, Vickerman P, Douthwaite S, Nebbia G, Hunter L, Wong T, et al. THU-435-a threshold analysis for the cost-effectiveness of hepatitis B and hepatitis C testing in emergency departments in the UK. J Hepatol. 2019;70(1):e348–e9.CrossRef
66.
Suthar AB, Ford N, Bachanas PJ, Wong VJ, Rajan JS, Saltzman AK, et al. Towards universal voluntary HIV testing and counselling: a systematic review and meta-analysis of community-based approaches. PLoS Med. 2013;10(8):e1001496.CrossRef
67.
•• Lemoine M, Shimakawa Y, Njie R, Taal M, Ndow G, Chemin I, et al. Acceptability and feasibility of a screen-and-treat programme for hepatitis B virus infection in The Gambia: the prevention of liver fibrosis and Cancer in Africa (PROLIFICA) study. Lancet Glob Health. 2016;4(8):e559–67. Important research study evaluating an outreach community method of screening and treatment for hepatitis B in a high endemic country in sub-Saharan Africa.CrossRef
68.
Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10(1):1–98.CrossRef
69.
Jaquet A, Nouaman M, Tine J, Tanon A, Anoma C, Inwoley A, et al. Hepatitis B treatment eligibility in West Africa: uncertainties and need for prospective cohort studies. Liver Int. 2017;37(8):1116–21.CrossRef
70.
•• Aberra H, Desalegn H, Berhe N, Mekasha B, Medhin G, Gundersen SG, et al. The WHO guidelines for chronic hepatitis B fail to detect half of the patients in need of treatment in Ethiopia. J Hepatol. 2019;70(6):1065–71. An important study comparing European and WHO treatment guidelines in selecting patients for antiviral therapy in a hepatitis B cohort in Ethiopia. CrossRef
71.
Post G, Shalev N, Baumgarten A, Shimakawa Y, Lemoine M, Krznaric I, et al. Indication for treatment and severity of disease in treatment-naive patients with chronic hepatitis B virus infection. Eur J Gastroenterol Hepatol. 2019;31(6):723–8.CrossRef
72.
Lemoine M, Shimakawa Y, Nayagam S, Khalil M, Suso P, Lloyd J, et al. The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa. Gut. 2016;65(8):1369–76.
73.
•• Shimakawa Y, Njie R, Ndow G, Vray M, Mbaye PS, Bonnard P, et al. Development of a simple score based on HBeAg and ALT for selecting patients for HBV treatment in Africa. J Hepatol. 2018;69(4):776–84. A study looking at the performance of a simple HBV DNA free algorithm for selecting patients in need of antiviral therapy. CrossRef
74.
Yoshida K, Post G, Shimakawa Y, Thursz M, Brown A, Ingiliz P, et al. Clinical utility of TREAT-B score in African and non-African HBV-infected patients living in Europe. J Hepatol. 2019;70(6):1295–7.CrossRef
75.
•• Honer Zu Siederdissen C, Maasoumy B, Cornberg M. New viral biomarkers for Hepatitis B: are we able to change practice? J Viral Hepat. 2018;25(11):1226–35. Important review on the use of novel biomarkers for hepatitis B infection including HBcore-related antigen and HBV RNA. CrossRef
76.
Mak LY, Wong DK, Cheung KS, Seto WK, Lai CL, Yuen MF. Review article: hepatitis B core-related antigen (HBcrAg): an emerging marker for chronic hepatitis B virus infection. Aliment Pharmacol Ther. 2018;47(1):43–54.CrossRef
77.
78.
Seck A, Ndiaye F, Maylin S, Ndiaye B, Simon F, Funk AL, et al. Poor sensitivity of commercial rapid diagnostic tests for hepatitis B e antigen in Senegal, West Africa. Am J Trop Med Hyg. 2018;99(2):428–34.CrossRef
79.
• Hecht R, Hiebert L, Spearman WC, Sonderup MW, Guthrie T, Hallett TB, et al. The investment case for hepatitis B and C in South Africa: adaptation and innovation in policy analysis for disease program scale-up. Health Policy Plan. 2018;33(4):528–38. Article on an investment case to support the development of the South African national hepatitis action plan. CrossRef
80.
Hiebert L, Hecht R, Soe-Lin S, Mohamed R, Shabaruddin FH, Syed Mansor SM, et al. A stepwise approach to a National Hepatitis C Screening Strategy in Malaysia to meet the WHO 2030 targets: proposed strategy, coverage, and costs. Value Health Reg Issues. 2019;18:112–20.CrossRef
81.
Metadata
Title
Strategies for Global Elimination of Chronic HBV Infection: 2019 Update
Authors
Shevanthi Nayagam
Mark Thursz
Publication date
01-09-2019
Publisher
Springer US
Published in
Current Hepatology Reports / Issue 3/2019
Electronic ISSN: 2195-9595
DOI
https://doi.org/10.1007/s11901-019-00478-w

Other articles of this Issue 3/2019

Current Hepatology Reports 3/2019 Go to the issue

Hepatitis B (JK Lim, Section Editor)

Community-Based Strategies to Improve Screening, Diagnosis and Linkage to Care for Patients with Chronic Hepatitis B

Hepatitis B (JK Lim, Section Editor)

Role of HBsAg Testing in the Management of Patients with Chronic HBV

Hepatitis B (JK Lim, Section Editor)

Management of Virologic Failure in Patients with Chronic Hepatitis B Treated with Nucleos(t)ide Analogues

Hepatitis B (JK Lim, Section Editor)

Chronic Hepatitis B in US Veterans

Drug-Induced Liver Injury (P Hayashi, Section Editor)

The Role of Liver Biopsy in Drug-Induced Liver Injury

Drug-Induced Liver Injury (P Hayashi, Section Editor)

Bile Duct Injury Due to Drug-Induced Liver Injury

ACC 2024 Congress Coverage

Cardiology Video

Highlights from the ACC 2024 Congress

Watch now

Watch official videos from the ACC congress summarizing key highlights from the last year in heart failure, cardiomyopathies, valvular disease, pulmonary vascular disease, and pediatric cardiology.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits