Reply to: Mother-to-infant transmission of hepatitis B virus infection: Significance of maternal viral load and strategies for intervention
Authors: Wan-Hsin Wen, Mei-Hwei Chang, Huey-Ling Chen
Journal: Journal of Hepatology (2013)

Mother-to-infant transmission of hepatitis B virus infection: Significance of maternal viral load and strategies for interventionJournal of HepatologyVol. 59Issue 2PreviewWe read with great interest the paper by Wen et al. [1], prospectively evaluating hepatitis B viral load as a significant factor for immunoprophylaxis failure of infants born of hepatitis B surface antigen (HBsAg) positive mothers. The authors suggested that the risk of immunoprophylaxis failure increased with increasing viral load and that intervention, such as anti-viral therapy in mothers with high viral load, may be considered. We agreed with the authors that high maternal viral load correlated with an increased risk of vertical transmission, but the optimal cut-off was yet to be determined [2]. Full-Text PDF Open Access We thank Dr. Cheung et al. for their thoughtful comments on our recent article published in the Journal of Hepatology. Several important issues are raised. The first one is about the time of maternal blood sampling. In our study, the testing of maternal hepatitis B e antigen (HBeAg) and viral load after delivery might be suboptimal, but the concordance of HBeAg results with those tested at prenatal screening provided evidence that the HBeAg results, although some were tested postpartum, could represent the HBeAg status at delivery. All the 81 HBeAg-positive mothers and 98.6% (219/222) HBeAg-negative mothers in our study had concordant HBeAg results with prenatal screening. The 3 mothers with HBeAg seroconversion had HBeAg and HBV DNA tested before or on the day of delivery. The median time of maternal blood sampling was 2 days post-partum. Post-partum viral load decline was found in some hepatitis B surface antigen (HBsAg)-positive mothers because a minority of HBeAg-positive mothers may become HBeAg-negative after delivery [[1]Lin H.H. Wu W.Y. Kao J.H. Chen D.S. Hepatitis B post-partum e antigen clearance in hepatitis B carrier mothers: correlation with viral characteristics.J Gastroenterol Hepatol. 2006; 21: 605-609Crossref PubMed Scopus (55) Google Scholar]. For those mothers remaining HBeAg-positive postpartum, the viral loads tested till 1 year postpartum were similar to those tested prior to or at delivery [1Lin H.H. Wu W.Y. Kao J.H. Chen D.S. Hepatitis B post-partum e antigen clearance in hepatitis B carrier mothers: correlation with viral characteristics.J Gastroenterol Hepatol. 2006; 21: 605-609Crossref PubMed Scopus (55) Google Scholar, 2Soderstrom A. Norkrans G. Lindh M. Hepatitis B virus DNA during pregnancy and post partum: aspects on vertical transmission.Scand J Infect Dis. 2003; 35: 814-819Crossref PubMed Scopus (112) Google Scholar]. In a recent study of telbivudine to reduce maternal HBV transmission, 35 HBeAg-positive mothers with a viral load above 106 copies/ml in the control group had comparable high viral loads from pregnancy until 28 weeks postpartum [[3]Pan C.Q. Han G.R. Jiang H.X. Zhao W. Cao M.K. Wang C.M. et al.Telbivudine prevents vertical transmission from HBeAg-positive women with chronic hepatitis B.Clin Gastroenterol Hepatol. 2012; 10: 520-526Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar]. The above studies support our data that HBsAg-positive mothers have stable viral loads from delivery to several months postpartum if their HBeAg status does not change after delivery. We therefore believe that our maternal viral load data are representative of the peripartum viral load status. Dr. Cheung also mentioned that the result would be more meaningful if the viral load levels were obtained before 28 weeks of gestation because antiviral therapy was started from 28 weeks of gestation in most of the trials to decrease mother-to-infant transmission. We agree that antiviral therapy needs time to achieve significant viral suppression before delivery. However, the majority of mother-to-infant transmission is thought to occur during labor and delivery [4Stevens C.E. Beasley R.P. Tsui J. Lee W.C. Vertical transmission of hepatitis B antigen in Taiwan.N Engl J Med. 1975; 292: 771-774Crossref PubMed Scopus (856) Google Scholar, 5Beasley R.P. Rocks along the road to the control of HBV and HCC.Ann Epidemiol. 2009; 19: 231-234Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar]. We think that the viral load tested at the peripartum stage represents the viral load level at which most mother-to-infant transmissions occur. Secondly, none of our HBsAg-positive mothers received antiviral therapy during the study period. Thirdly, we agree that horizontal transmission was possible in 17.5% of children tested for HBsAg at 1–3 years of age. HBsAg-positive mothers transmit HBV to their children not only in the perinatal stage but also in the post-natal stage [[6]Beasley R.P. Hwang L.Y. Postnatal infectivity of hepatitis B surface antigen-carrier mothers.J Infect Dis. 1983; 147: 185-190Crossref PubMed Scopus (238) Google Scholar]. HBV infection acquired at 1–3 years of age could result from maternal transmission. Finally, amniocentesis has not been shown to significantly increase rates of HBV transmission [[7]Towers C.V. Asrat T. Rumney P. The presence of hepatitis B surface antigen and deoxyribonucleic acid in amniotic fluid and cord blood.Am J Obstet Gynecol. 2001; 184 (discussion 1518–1520): 1514-1518Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar]. In Taiwan, the recommended schedule for the first dose of HBV vaccine was 3–5 days after birth before 2012; and the schedule has been updated to within 24 hours of birth since 2012. The 10 HBV-infected infants and those infants without chronic HBV infection had comparable rates of amniocentesis or chorionic villus sampling (50% vs. 46.4%, p = 0.821) and received the 1st HBV vaccine dose at similar ages (5.6 ± 5.3 vs. 3.8 ± 3.2 day, p = 0.0958) in our study. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.