Mother-to-infant transmission of hepatitis B virus infection: Significance of maternal viral load and strategies for intervention
Authors: Ka Wang Cheung, Mimi Tin Yan Seto, Chin Peng Lee
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 1PreviewImmunoprophylaxis reduces but does not completely eradicate hepatitis B virus (HBV) transmission. This prospective study aims at assessing the rate and risk factors of maternally transmitted HBV infection. Full-Text PDF Reply to: Mother-to-infant transmission of hepatitis B virus infection: Significance of maternal viral load and strategies for interventionJournal of HepatologyVol. 59Issue 2PreviewWe 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. Full-Text PDF Open Access We read with great interest the paper by Wen et al. [[1]Wen W.H. Chang M.H. Zhao L.L. Ni Y.H. Hsu H.Y. Wu J.F. et al.Mother-to-infant transmission of hepatitis B virus infection: significance of maternal viral load and strategies for intervention.J Hepatol. 2013; 59: 24-30Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar], 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]Cheung K.W. Seto M.T. Wong S.F. Towards complete eradication of hepatitis B infection from perinatal transmission: review of the mechanisms of in utero infection and the use of antiviral treatment during pregnancy.Eur J Obstet Gynecol Reprod Biol. 2013; Google Scholar]. However, we believed that further clarification of the data would be needed before change in clinical practice can be recommended. First of all, the timing of blood test on the viral load of the subjects was not clearly stated. The authors mentioned that it was checked in the third trimester or within 2 months after delivery. However, the viral load may vary throughout pregnancy and after delivery. In a retrospective study which evaluated the change of viral load in 33 HBsAg positive mothers, of whom 9 were hepatitis B e antigen (HBeAg) positive, it was found that viral load increased by a mean of 0.4 log in late pregnancy or early postpartum, of which four HBeAg negative mothers had >1 log change during pregnancy [[3]Soderstrom 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 another retrospective study, ter Borg et al. studied 38 HBsAg pregnancies of which 24 were HBeAg positive. Lamivudine was started in the third trimester to reduce the viral load in 13 pregnancies. The median viral load increased from 7.8 log10 copies/ml before, to 8.2 log10 copies/ml during pregnancy, and then decreased to 6.8 log10 copies/ml after delivery [[4]ter Borg M.J. Leemans W.F. de Man R.A. Janssen H.L. Exacerbation of chronic hepatitis B infection after delivery.J Viral Hepat. 2008; 15: 37-41PubMed Google Scholar]. We were not told the reason why a proportion of the women's blood tests were collected after delivery for viral load testing and not before delivery, in this prospective study. Assuming the postpartum viral load to be similar to the antenatal level may give rise to a wrong conclusion. Therefore, it would be important for the authors to provide the median gestational weeks when the blood test was taken, and to clarify the proportion of mothers having postpartum test. Furthermore, as the authors also pointed out, the result would be more meaningful if the viral load levels were obtained before 28 weeks of gestation. Anti-viral therapy was started from 28 weeks of gestation in most of the trials evaluating the efficacy of anti-viral treatment to decrease the risk of immunoprophylaxis failure in women with high viral load [[5]Shi Z. Yang Y. Ma L. Li X. Schreiber A. Lamivudine in late pregnancy to interrupt in utero transmission of hepatitis B virus: a systematic review and meta-analysis.Obstet Gynecol. 2010; 116: 147-159Crossref PubMed Scopus (129) Google Scholar]. Viral load quantification in the late third trimester, at delivery, or even after delivery, would be less useful clinically as intervention to alter outcome may not be possible. Caesarean delivery could not decrease the risk of immunoprophylaxis failure [[2]Cheung K.W. Seto M.T. Wong S.F. Towards complete eradication of hepatitis B infection from perinatal transmission: review of the mechanisms of in utero infection and the use of antiviral treatment during pregnancy.Eur J Obstet Gynecol Reprod Biol. 2013; Google Scholar] and late viral load quantification would not allow adequate time for anti-viral treatment to decrease viral load. Secondly, we also wondered if any subjects were receiving anti-viral therapy during the studied period. Anti-viral therapy initiated after the blood test before delivery, or vice versa, could affect the viral load level and subsequent correlation with risk of the immunoprophylaxis failure. Thirdly, horizontal transmission of hepatitis B virus was possible [[6]Komatsu H. Inui A. Sogo T. Hiejima E. Kudo N. Fujisawa T. Source of transmission in children with chronic hepatitis B infection after the implementation of a strategy for prevention in those at high risk.Hepatol Res. 2009; 39: 569-576Crossref PubMed Scopus (28) Google Scholar] in 17.5% of children who were tested for HBsAg at 1–3 years of age. The HBsAg positive status in this group could be due to horizontal infection rather than genuine immunoprophylaxis failure. Finally, we were interested in the high rate of invasive prenatal diagnostic test (amniocentesis/CVS) and first vaccine given beyond 24 hours in the ten infants who suffered from chronic hepatitis B infection. Could these be the potential factors that led to a higher rate of immunoprophylaxis failure? We hope the authors could provide more data on that. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.