Optimal Management in Preventing Mother-to-Infant Transmission of Hepatitis B: More Requires to Be Done

Abstract

Dr Hou and colleagues1Hou J. et al.Clin Gastroenterol Hepatol. 2019; 17: 1929-1936Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar proposed the management algorithm to interrupt mother-to-infant transmission of hepatitis B virus (HBV) in a recent issue of Clinical Gastroenterology and Hepatology. Although the article provides valuable information in preventing mother-to-infant transmission of HBV, I have some concerns about this article. First, to block mother-to-infant transmission of HBV, Hou et al1Hou J. et al.Clin Gastroenterol Hepatol. 2019; 17: 1929-1936Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar recommend that the antiviral therapy in mothers with HBV DNA level >2 × 106 IU/mL be started from gestational weeks 24–28. However, studies demonstrated that antiviral therapy started from gestation weeks 28–32, together with neonatal passive (hepatitis B immunoglobulin [HBIG]) and active (hepatitis B vaccine) immunoprophylaxis, can almost completely prevent mother-to-infant transmission of HBV,2Pan C.Q. et al.N Engl J Med. 2016; 374: 2324-2334Crossref PubMed Scopus (306) Google Scholar, 3Jourdain G. et al.N Engl J Med. 2018; 378: 911-923Crossref PubMed Scopus (155) Google Scholar, 4Hu Y. et al.J Viral Hepat. 2018; 25: 429-437Crossref PubMed Scopus (42) Google Scholar indicating that use of antivirals before gestation week 28 is not required. Compared with antiviral therapy initiated in the third trimester, therapy started in the second trimester did not increase the protective efficacy in blocking mother-to-infant transmission of HBV.5Pan C.Q. et al.J Viral Hepat. 2017; 24: 246-252Crossref PubMed Scopus (23) Google Scholar The findings that none of the infants born to mothers with high viral load who had received antiviral from gestation weeks 30–32 was infected with HBV2Pan C.Q. et al.N Engl J Med. 2016; 374: 2324-2334Crossref PubMed Scopus (306) Google Scholar indicate that antiviral therapy can start from gestation week 32 rather than before gestation week 30. Under the premise of no HBV transmission, from the viewpoint of fetal safety and economics, antivirals should be used as short duration as possible in pregnant women. Second, Hou et al1Hou J. et al.Clin Gastroenterol Hepatol. 2019; 17: 1929-1936Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar propose HBV DNA level >2 × 106 IU/mL as a threshold for antiviral therapy to prevent mother-to-infant transmission of HBV. However, studies from China showed that maternal HBV DNA levels >2 × 105 IU/mL (106 copies/mL) are a risk factor for infant infection.6Zou H. et al.J Viral Hepat. 2012; 19: e18-e25Crossref PubMed Scopus (235) Google Scholar The American Association for the Study of Liver Diseases and the European Association for the Study of the Liver guidelines both recommend HBV DNA levels >2 × 105 IU/mL (106 copies/mL) as the threshold for antiviral therapy. Therefore, the proposed HBV DNA level >2 × 106 IU/mL as a therapy threshold may require rethinking. Third, the proposal that infants who are negative for hepatitis B surface antigen (HBsAg) and have antibody against HBsAg <10 mIU/mL in post-vaccination serologic testing should undergo HBV DNA testing to rule out the possibility of occult HBV infection (negative HBsAg yet detectable HBV DNA in serum or liver) before revaccination lacks convincing evidence. Occult HBV infection usually follows the resolution of an overt HBV infection (positive HBsAg), but replication-competent HBV DNA may persist because of the long-lasting HBV covalently closed circular DNA in hepatocytes. Infants have extremely low chance to have occult HBV infection after neonatal immunoprophylaxis.7Liu Y. et al.PLoS One. 2014; 9: e112803Crossref PubMed Scopus (13) Google Scholar The reported occult infection in infants of HBV-infected mothers was very likely caused by imperceptible, or occult, contaminations.8Zhou Y.H. J Viral Hepat. 2016; 23: 830Crossref PubMed Scopus (6) Google Scholar Moreover, if infants with antibody against HBsAg <10 mIU/mL are considered to be susceptible to HBV infection, they require revaccination as soon as possible because they are in close contact with their HBV-infected mothers. Quantitative measurement of HBV DNA needs a couple of days or even more time to get the results and can delay revaccination. In addition, quantitative HBV DNA measurement in these infants is not cost-effective, because the cost of the quantification test is higher than that of 3 doses of hepatitis B vaccine in China, and hepatitis B vaccination in an infant with a real occult infection cannot cause additional adverse events. Therefore, HBsAg-negative infants with antibody against HBsAg <10 mIU/mL in the post-vaccination serologic testing do not need HBV DNA testing but should be revaccinated as soon as possible. Finally, although the article provides the standard immunoprophylaxis protocol in neonates (100 IU HBIG and 1 dose hepatitis B vaccine within 12 hours after birth),1Hou J. et al.Clin Gastroenterol Hepatol. 2019; 17: 1929-1936Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar I consider that it needs to emphasize that this protocol is highly efficient in preventing perinatal infection of HBV, and that it is not necessary to use 200 IU HBIG as the birth dose and usually not necessary to add an additional dose of HBIG at 2–4 weeks of age in neonates. These practices cannot increase the protective effect but can waste limited medical resources. In summary, the optimal management in preventing mother-to-infant transmission of HBV requires further investigation to determine the optimal time to start antiviral therapy in pregnant women. The threshold for antiviral therapy also requires more investigation. Management Algorithm for Interrupting Mother-to-Child Transmission of Hepatitis B VirusClinical Gastroenterology and HepatologyVol. 17Issue 10PreviewIn areas where hepatitis B virus (HBV) is endemic, mother-to-child transmission (MTCT) is the major route of infection of children. Blocking MTCT of HBV therefore would reduce its prevalence. The China Foundation of Hepatitis Prevention and Control organized a team of specialists in infectious diseases, hepatology, immunology, obstetrics, and public health to develop an algorithm for interrupting MTCT of HBV, based on the most recent hepatitis B guidelines and latest evidence. This algorithm comprises 10 steps and has been adopted in clinical practice in China. Full-Text PDF Open AccessReplyClinical Gastroenterology and HepatologyVol. 18Issue 3PreviewWe appreciate the comments by Zhou on the management algorithm for interrupting mother-to-child transmission (MTCT) of hepatitis B virus (HBV). Full-Text PDF