Tenofovir Disoproxil Fumarate Therapy to Prevent Hepatitis B Virus Vertical Transmission

A Review of Maternal and Infant Outcomes

Golasa Samadi Kochaksaraei; Abdel A. Shaheen; Cynthia H. Seow; Herman W. Barkema; Carla S. Coffin

Disclosures

Liver International. 2022;42(8):1712-1730. 

In This Article

Abstract and Introduction

Abstract

Hepatitis B virus (HBV) is a global health problem. Vertical transmission of HBV from HBV surface antigen (HBsAg)-positive mothers to their infants is the most common cause of HBV infection worldwide. The use of passive–active immunoprophylaxis is >90% effective in reducing the risk of vertical transmission, but immunoprophylaxis failure can occur in infants born to mothers with high viraemia. Thus, it is recommended that pregnant women with HBV-DNA level >200 000 IU/ml receive nucleos(t)ide analogue (NA) treatment [i.e. tenofovir disoproxil fumarate (TDF), lamivudine or telbivudine] during third trimester to prevent infant immunoprophylaxis failure. TDF is recommended as the first-line therapy based on available data on efficacy, safety and resistance profile. However, maternal immunological reconstitution following parturition can increase immune-mediated flares to viral antigens that is potentially exacerbated following TDF withdrawal. In this article, we review available data on the efficacy and safety of TDF administration to prevent HBV mother-to-child transmission. We also discuss changes in maternal viral markers [i.e. HBV-DNA, HBV e antigen and HBsAg] and alanine aminotransferase during follow-up post-partum in mothers received NA to prevent HBV vertical transmission.

Introduction

Hepatitis B virus (HBV) is a global public health threat. Chronic HBV (CHB) is the leading global cause of hepatocellular carcinoma (HCC),[1] and ~25% of CHB patients will develop cirrhosis and/or HCC.[2]

HBV vertical transmission from HBV surface antigen (HBsAg)-positive mothers to their infants is the most common cause of CHB worldwide.[2,3] Moreover, the age at which the HBV infection is acquired influences the risk of chronicity. The risk of developing CHB following exposure to HBV is ~90% in infants to 5% in adults.[4,5] Thus, the prevention of vertical transmission of HBV is crucial to achieving the WHO goal of viral hepatitis elimination by 2030, defined as a 90% reduction in incidence and a 65% reduction in mortality of CHB, compared to 2015. In particular, HBV elimination requires a reduction in the prevalence of CHB to <0.1% in children aged 5 years.[6]

The use of immunoprophylaxis with hepatitis B immune globulin (HBIg) and the recombinant HBV vaccine is >90% effective in reducing the risk of vertical transmission, but immunoprophylaxis failure can occur in infants born to highly viremic HBV e antigen (HBeAg)-positive mothers.[7–10] Furthermore, epidemiological data suggest that infant vaccination alone would be insufficient to achieve the 0.1% CHB prevalence goal in children by 2030 (compared with the baseline prevalence of 1.3% in 2015).[11,12] Thus, it is recommended that pregnant women with HBV-DNA >5.3 log IU/ml (200 000 IU/ml) receive nucleos(t)ide analogue (NA) treatment [i.e. tenofovir disoproxil fumarate (TDF), lamivudine (LAM) or telbivudine (LdT)] in the third trimester to reduce the risk of infant immunoprophylaxis failure (Table 1).[12–16] TDF is recommended as the first-line therapy in preventing HBV immunoprophylaxis failure on the basis of available data on its efficacy, safety and resistance profile.[17–21]

The maternal immune system undergoes unique changes such as suppressing cell-mediated immunity to tolerate fetal antigens.[22] Pregnancy-related changes in the immune system can affect the course of CHB. Immune reconstitution post-partum can increase host immune-mediated flares to viral antigens that is potentially exacerbated following TDF withdrawal.[23,24]

We conducted a literature review to summarize currently available data on the efficacy and safety of TDF administration to prevent mother-to-child transmission (MTCT) of HBV. We also discussed changes in maternal viral markers (i.e. HBV-DNA, HBeAg and HBsAg) and alanine aminotransferase (ALT) during follow-up post-partum in mothers received NA (i.e. TDF, LdT, LAM) to reduce the risk of MTCT of HBV.

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