Nature Reviews Gastroenterology & Hepatology | 2021
Reply to ‘Evidence against in utero transmission of hepatitis B virus’
Abstract
We would like to thank Zhou for their corres\xad pondence on our Review (Terrault, N. A. et al. Viral hepatitis and pregnancy. Nat. Rev. Gastroenterol. Hepatol. 18, 117–130 (2021))1 and for an opportunity to expand on in utero transmission of hepatitis B virus (HBV) (Zhou, Y.\xad H. Evidence against in utero transmis sion of hepatitis B virus. Nat. Rev. Gastroenterol. Hepatol. https://doi.org/ 10.1038/s41575\xad021\xad00455\xadz (2021))2. Although the estimate of 10% incidence might be high, we believe there is ample evidence to support in utero HBV infection. In utero infection via germline is possible. HBV DNA could be detected in ova of women with HBV infection3 and in embryos of hepatitis B surface antigen (HBsAg)\xad discordant couples4. Placental infection is another mechanism of in utero infection, with HBV (detected by in situ hybridization) found in a gradient of infected placental cell layers from the maternal to the fetal side and presence of placental HBV DNA, particularly in endothelial cells, associated with fetal infection in newborns5. Fetal contamination by maternal blood during invasive prenatal tests could also be a cause of in utero infection, with maternal HBV DNA levels greater than 6\xad log IU/mL or presence of hepatitis B e antigen (HBeAg) defining a higher risk of in utero infection6. Clinical studies also support the plausi bility of intrauterine infection. In a large, rando\xad mized trial of tenofovir disoproxil fumarate (TDF) versus placebo, two of three infants who acquired HBV infection, all in the placebo arm, had a very high HBV DNA load on the day of birth. This observation is difficult to explain unless there was established infection prior to birth7. Similarly, another study found that believe consideration of earlier antiviral treatment during pregnancy in certain high\xad risk women is warranted. Thus, while the predominant risk of MTCT of HBV occurs peripartum, there is strong evidence for the existence of in utero infection and the continued efforts to improve prophylactic measures, including consideration of maternal antiviral therapy earlier than the third trimester, might reduce MTCT to zero.