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NIHR Signal Tenofovir reduces mother-to-child hepatitis B transmission

Published on 25 July 2017

doi: 10.3310/signal-000455

Giving pregnant women with hepatitis B the drug tenofovir reduced the likelihood of passing the infection on to their baby by about 80% and did not have any adverse impact on mother or child.

Hepatitis B often doesn't cause any obvious symptoms in adults and typically passes in a few months without treatment, but in children it often persists for years and may cause progressive liver damage with cirrhosis and increased risk of liver cancer. Babies can get the infection from their mother during birth.

The findings of this systematic review support current NICE recommendations that pregnant women with active hepatitis B infection are treated in the third trimester using the drug tenofovir and at risk babies immunised after birth.

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Why was this study needed?

Hepatitis B is a blood-borne viral infection. It is rarer in the UK than many other parts of the world with around 0.1% to 0.5% of the population infected at any time. In adults it may cause few symptoms with clearance of the virus in a few months. It only becomes chronic in about 5% of adults. Mothers with hepatitis B often pass the infections to their babies during pregnancy and hepatitis B in the newborn is a particular concern as 90% will develop a chronic infection. 

In the UK all pregnant women are offered a blood test for hepatitis B as part of their antenatal care. Babies who are at risk of hepatitis B, because of maternal infection, can be immunised. Completing the course protects about 90-95% of children from developing a chronic infection.

This review investigated the effects of tenofovir treatment on outcomes for the mother and child.

What did this study do?

This systematic review included 10 studies; one randomised controlled trial, four non-randomised controlled trials and five case series. The results of the five controlled (randomised and non-randomised) trials were pooled. The studies were conducted in Australia, Canada, China, Taiwan and Turkey.

Pregnant women with hepatitis B viral DNA load of more than 2 x 105 IU/ml were either given tenofovir in the second or third trimester or a control. All babies were given hepatitis B immunisation at birth.

The studies were all generally assessed as having a low risk of bias except for one which used different inclusion criteria for each group and had short follow-up. To test their findings, the researchers re-ran their analysis without that study and it did not significantly change the results.

What did it find?

  • Tenofovir reduced the viral load in mothers, with a suppression rate between 62% and 98%. However, studies varied greatly in what they defined as “suppression”.
  • Using tenofovir reduced the risk of the baby having hepatitis B virus DNA in the blood, an indicator of an “active infection”, 24 hours after birth. It was present in 4.3% of the tenofovir group compared to 20.5% of the controls, a reduction in risk of 84% (odds ratio [OR] 0.16, 95% confidence interval [CI] 0.07 to 0.39).
  • Tenofovir reduced the risk of chronic hepatitis B infection at six to 12 months. Hepatitis B surface antigens were present in 3.1% of the tenofovir group compared to 14.7% of the controls, a reduction in risk of 80% (OR 0.20, 95% CI 0.09 to 0.46).
  • There were no significant differences in safety outcomes for either mother or baby, such as hepatitis flare-ups in the mother, caesarean rates, pre-term birth, congenital malformations or foetal death.

What does current guidance say on this issue?

All pregnant women in the UK are screened for hepatitis B as part of their routine antenatal care using a blood test to measure hepatitis B surface antigen. NICE 2013 guidelines recommend offering women with high hepatitis B DNA levels (>107 IU/ml) tenofovir in the last three months of pregnancy to reduce the risk of passing the infection to their baby. Hepatitis B immunisation is recommended for at risk babies within 24 hours of birth, with boosters at one, two and 12 months.

What are the implications?

This review provides support for current recommendations and includes studies that were published more recently than those used to form the NICE guidelines.

Some studies used a lower threshold for treatment than is currently recommended by NICE, and gave women tenofovir from the second rather than third trimester, but this does not imply that guidance needs to change.

The acquisition cost of tenofovir was £255 for 30 tablets in 2009. Tenofovir is licensed for use in adults over 18 years, but currently does not have a UK marketing authorisation for use in pregnancy.

Citation and Funding

Hyun MH, Lee YS, Kim JH, 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):1493-1505.

Bibliography

British Liver Trust. Hepatitis B. Bournemouth: British Liver Trust; 2012.

HSE. Hepatitis B virus (HBV). London: Health and Safety Executive. 

NHS Choices. Infections in pregnancy that may affect your baby. London: Department of Health; 2015.

NHS Choices. Hepatitis B. London: Department of Health; 2016.

NHS Choices. Hepatitis B vaccine. London: Department of Health; 2015.

NICE. Hepatitis B and C testing: people at risk of infection. PH43. London: National Institute for Health and Care Excellence; 2013.

NICE. Hepatitis B (chronic): diagnosis and management. CG165. London: National Institute for Health and Care Excellence; 2013.

NICE. Tenofovir disoproxil for the treatment of chronic hepatitis B. TA173. London: National Institute for Health and Care Excellence; 2009.

Why was this study needed?

Hepatitis B is a blood-borne viral infection. It is rarer in the UK than many other parts of the world with around 0.1% to 0.5% of the population infected at any time. In adults it may cause few symptoms with clearance of the virus in a few months. It only becomes chronic in about 5% of adults. Mothers with hepatitis B often pass the infections to their babies during pregnancy and hepatitis B in the newborn is a particular concern as 90% will develop a chronic infection. 

In the UK all pregnant women are offered a blood test for hepatitis B as part of their antenatal care. Babies who are at risk of hepatitis B, because of maternal infection, can be immunised. Completing the course protects about 90-95% of children from developing a chronic infection.

This review investigated the effects of tenofovir treatment on outcomes for the mother and child.

What did this study do?

This systematic review included 10 studies; one randomised controlled trial, four non-randomised controlled trials and five case series. The results of the five controlled (randomised and non-randomised) trials were pooled. The studies were conducted in Australia, Canada, China, Taiwan and Turkey.

Pregnant women with hepatitis B viral DNA load of more than 2 x 105 IU/ml were either given tenofovir in the second or third trimester or a control. All babies were given hepatitis B immunisation at birth.

The studies were all generally assessed as having a low risk of bias except for one which used different inclusion criteria for each group and had short follow-up. To test their findings, the researchers re-ran their analysis without that study and it did not significantly change the results.

What did it find?

  • Tenofovir reduced the viral load in mothers, with a suppression rate between 62% and 98%. However, studies varied greatly in what they defined as “suppression”.
  • Using tenofovir reduced the risk of the baby having hepatitis B virus DNA in the blood, an indicator of an “active infection”, 24 hours after birth. It was present in 4.3% of the tenofovir group compared to 20.5% of the controls, a reduction in risk of 84% (odds ratio [OR] 0.16, 95% confidence interval [CI] 0.07 to 0.39).
  • Tenofovir reduced the risk of chronic hepatitis B infection at six to 12 months. Hepatitis B surface antigens were present in 3.1% of the tenofovir group compared to 14.7% of the controls, a reduction in risk of 80% (OR 0.20, 95% CI 0.09 to 0.46).
  • There were no significant differences in safety outcomes for either mother or baby, such as hepatitis flare-ups in the mother, caesarean rates, pre-term birth, congenital malformations or foetal death.

What does current guidance say on this issue?

All pregnant women in the UK are screened for hepatitis B as part of their routine antenatal care using a blood test to measure hepatitis B surface antigen. NICE 2013 guidelines recommend offering women with high hepatitis B DNA levels (>107 IU/ml) tenofovir in the last three months of pregnancy to reduce the risk of passing the infection to their baby. Hepatitis B immunisation is recommended for at risk babies within 24 hours of birth, with boosters at one, two and 12 months.

What are the implications?

This review provides support for current recommendations and includes studies that were published more recently than those used to form the NICE guidelines.

Some studies used a lower threshold for treatment than is currently recommended by NICE, and gave women tenofovir from the second rather than third trimester, but this does not imply that guidance needs to change.

The acquisition cost of tenofovir was £255 for 30 tablets in 2009. Tenofovir is licensed for use in adults over 18 years, but currently does not have a UK marketing authorisation for use in pregnancy.

Citation and Funding

Hyun MH, Lee YS, Kim JH, 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):1493-1505.

Bibliography

British Liver Trust. Hepatitis B. Bournemouth: British Liver Trust; 2012.

HSE. Hepatitis B virus (HBV). London: Health and Safety Executive. 

NHS Choices. Infections in pregnancy that may affect your baby. London: Department of Health; 2015.

NHS Choices. Hepatitis B. London: Department of Health; 2016.

NHS Choices. Hepatitis B vaccine. London: Department of Health; 2015.

NICE. Hepatitis B and C testing: people at risk of infection. PH43. London: National Institute for Health and Care Excellence; 2013.

NICE. Hepatitis B (chronic): diagnosis and management. CG165. London: National Institute for Health and Care Excellence; 2013.

NICE. Tenofovir disoproxil for the treatment of chronic hepatitis B. TA173. London: National Institute for Health and Care Excellence; 2009.

Systematic review with meta-analysis: the efficacy and safety of tenofovir to prevent mother-to-child transmission of hepatitis B virus

Published on 25 April 2017

Hyun, M. H.,Lee, Y. S.,Kim, J. H.,Je, J. H.,Yoo, Y. J.,Yeon, J. E.,Byun, K. S.

Aliment Pharmacol Ther , 2017

BACKGROUND: Preventing mother to child transmission of chronic hepatitis B infection in the setting of a high maternal viral load is challenging. The idea has emerged from antepartum tenofovir treatment with combination immunoprophylaxis. AIMS: To demonstrate the efficacy and safety of tenofovir to prevent mother to child transmission of hepatitis B virus. METHODS: PubMed, EMBASE, and Cochrane databases were searched through August 16, 2016. Comparative trials of second or third trimester tenofovir administration vs. controls for patients with chronic hepatitis B infection and non-comparative case series assessing mother to child transmission rates and evaluating maternal and foetal safety outcomes were included. RESULTS: Ten studies (one randomised controlled trial, four non-randomised controlled trials and five case series) that enrolled 733 women were included. The pooled results from comparative trials (599 pregnancies) showed that tenofovir significantly reduced the risk of infant hepatitis B surface antigen seropositivity by 77% (odds ratio=0.23, 95% confidence intervals=0.10-0.52, P=.0004) without heterogeneity (I2 =0%). In the case series analysis (134 pregnancies), only two cases (1.5%) of mother to child transmission with extremely high maternal viral load and non-compliance to treatment were identified. Maternal and foetal safety parameters including congenital malformation and foetal death were re-assuring. CONCLUSIONS: For pregnant women with high hepatitis B virus DNA levels, tenofovir administration in the second or third trimester can prevent mother to child transmission when combined with hepatitis B immunoglobulin and the hepatitis B vaccine. Tenofovir is safe and tolerable for both the mother and foetus.

Expert commentary

Chronic hepatitis B is typically acquired at birth or in early childhood and mother to child transmission accounts for the majority of infections in highly endemic areas. Efforts to reduce vertical transmission in high hepatitis B virus DNA mothers are critical in the quest to tackle this global healthcare challenge, which accounts for 600,000 deaths per year.

In this systematic review the safety, efficacy and tolerability of tenofovir in the second or third trimester of pregnancy is demonstrated. The take home message is the importance of tenofovir combined with hepatitis B immunoprophylaxis to prevent perinatal hepatitis B transmission if mothers have high hepatitis B virus DNA.

Dr Patrick Kennedy, Consultant Hepatologist, Barts Health NHS Trust