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Hepatitis B – chronic carrier status and pregnancy outcomes: An obstetric perspective

https://doi.org/10.1016/j.bpobgyn.2020.03.006Get rights and content

Abstract

Antenatal screening for hepatitis B surface antigen (HBsAg) only identifies women with hepatitis B virus (HBV) infection for neonatal immunoprophylaxis. It does not reflect the phase of chronic infection, viral genotype and activity, hepatic inflammation, or other co-existing liver disorders. Coinfection with other viruses and micro-organisms may also be present. These factors in various combinations can impact pregnancy outcomes, and they are probably responsible for the conflicting literature on this issue. Pregnancy complications may interact with maternal HBV infection and hepatitis flares, leading to serious and lethal complications. Hepatitis flares are common especially postpartum, and they are unpredictable and unpreventable with antiviral treatment. Evidence on the association between HBsAg seropositivity with gestational diabetes mellitus, preterm birth, increased foetal growth, and reduced pregnancy hypertensive disorders is stronger than other adverse pregnancy outcomes. Baseline assessment of liver function, and viral markers and activity, can delineate the truly high-risk pregnancies for close monitoring.

Introduction

Antenatal screening for hepatitis B virus (HBV) infection by serological testing of hepatitis B surface antigen (HBsAg) is routine in many parts of the world to identify the pregnancies at risk of maternal-to-child transmission (MTCT) for timely combined neonatal immunization. In this chapter, the implications of chronic maternal HBV infection are discussed from an obstetric perspective.

Section snippets

General aspects of chronic hepatitis B virus infection

Chronic HBV infection is influenced by host factors including sex and age at infection, presence of co-morbidities, coinfections, and viral factors that include genotype and presence of specific mutations [1], so that there are no uniform interactions with or impact on pregnancy outcomes.

Maternal immune response and viral replication in pregnancy

Immune adaptation to pregnancy and modulation by chronic HBV infection can interact. Pregnancy could facilitate HBV replication, as HBV DNA has been detected in 19.6% and 30.4% in the second and third trimesters respectively in mothers without detectable HBV DNA in the first trimester [13]. Increased HBV replication could impact pregnancy outcomes, as the second-trimester HBV DNA level is associated with the risk of preterm birth (PTB) [14,15], with 18% increase for each log10 copy/mL increase

The presence and effect of coinfection

Among HIV patients, 5–10% have coinfection with HBV, whereas 0.5–1.5% of HBV patients have HIV coinfection [1,28], which adversely affect the natural history of HBV infection, and antiretroviral treatment may select resistant mutations in HBV and immune reconstitution flares on initiation of treatment [1]. Coinfection with hepatitis C virus (HCV) has been reported in 2–8% of the total chronic HBV patients [1,29], and 5% of HBV patients are coinfected with hepatitis D virus [1], with have

Liver dysfunction and liver disorders unrelated to hepatitis B virus infection

Abnormal liver enzyme levels irrespective of HBV status could impact pregnancy outcomes. Gamma glutamyltransferase (GGT) levels at the time of antenatal oral glucose tolerance test (OGTT) correlated with the 2-h glucose level, and high GGT both before [34] and in the first two trimesters of pregnancy [[35], [36], [37]] is an independent risk factor for GDM through interaction with insulin resistance [34,37]. Elevated GGT reflects hepatic fibrosis in HBV patients [38], and is also a marker of

Maternal HBsAg seropositivity and pregnancy complications

From this discussion, it is clear that HBsAg per se is limited as a marker of high-risk pregnancy, especially in countries with low endemicity and variable proportions of immigrants such as the USA [4,5,30] and Europe [49,50]. Nevertheless, being the usual available marker, the impact of maternal HBsAg seropositivity is discussed below.

Maternal HBsAg seropositivity and foetal/perinatal outcome

Increased miscarriage, SB, prematurity and LBW, and congenital malformations were first reported among 264 women with viral hepatitis, but as the proportion of these events was higher in HBsAg-seropositive than in the seronegative women (80% versus 44%) and varied according to the trimester when viral hepatitis occurred; the findings could not be related to chronic HBV infection alone [80].

Conclusions

Maternal HBsAg seropositivity has implications on maternal health and pregnancy outcomes, the latter influenced by other maternal and viral factors. Initial assessment with liver function test, HBeAg status and HBV DNA level, and hepatic ultrasound, if necessary, could segregate the truly high-risk pregnancies for close monitoring and appropriate treatment. Postpartum management by hepatologists would be beneficial to the mothers in the long term.

Summary

The obstetric implications of maternal HBsAg seropositivity found at routine antenatal screening remains uncertain. Evidence for its association with GDM, PTB, increased infant size, and reduced pregnancy hypertensive disorders is stronger than the other common pregnancy complications and adverse perinatal outcomes. Pregnancy outcomes are influenced by factors such as the effect of racial disparity in obstetric outcome; viral genotypes, prevalence, and phase of chronic infection in the

Declaration of Competing Interest

None.

Practice points

  • •

    Routine screening of liver function, and where resources are available, the additional screening of HBeAg and HBV DNA, is beneficial for pregnancies in women with HBsAg seropositivity.

  • •

    Gravidae with any abnormal screening results should be managed as high-risk.

  • •

    Additional investigation for underlying hepatic disorder or injury is indicated if liver function is abnormal, with referral to physicians for joint management where indicated.

  • •

    Watch out for hepatitis flares during and

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