Prevention of Vertical Hepatitis B Virus Transmission in China (2013)

Stephan Ehrhardt, MD, MPH; Nan Guo, PhD, MHS; Kenrad Nelson, MD; Chloe Thio, MD


Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is its major mode of transmission in China and many other high and intermediate HBV endemic areas. Without any interventions, 70-90% of infants born to mothers positive for both hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) will acquire HBV perinatally, and 85-95% of perinatally-infected infants will become chronic HBV carriers. Hepatitis B vaccine administration is recommended at birth regardless of the maternal HBV status. With proper vaccination, 75-80% of MTCT HBV cases may be prevented. Hepatitis B immunoglobulin (HBIg) is suggested in addition to hepatitis B vaccine in newborns of HBsAg-positive mothers, but it is not formally recommended because HBIg is often not available in low-resource settings due to high cost, storage requiring a functioning cold chain, and its complex production. Even with the optimal adherence, the joint prophylaxis fails to prevent chronic hepatitis B in at least 5-15% of children. The largest risk factor for failure is high levels of HBV DNA in the mother. Based on studies of HIV-infected women showing that lower HIV RNA levels reduce MTCT, we hypothesize that use of anti-HBV agents that lead to undetectable levels of HBV DNA prior to delivery will be effective in preventing MTCT of HBV without the use of HBIg. We propose to conduct a feasibility study to obtain preliminary data for the preparation of a randomized, controlled clinical trial (RCT) to determine if tenofovir, a nucleotide analogue anti-HBV drug, given to high risk mothers in late pregnancy in addition to active vaccine given to the infant, can decrease rates of MTCT of HBV in China. This HBIg withdrawal strategy may help overcome the inherent problems with and may be more effective than HBIg. Another important aim is to foster efficient collaboration with SYSU investigators and to establish a study team to compete for clinical trials in the global context.

The specific aims of the proposed feasibility study are:

1. To determine the proportion of pregnant women who are HBsAg positive and the distribution of HBeAg and HBV DNA levels among the HBsAg positive women.

2. Pilot intervention: to estimate the median time until HBV DNA clearance in 30-50 women with initial HBV DNA ≥ 2×107 IU/ml who are given tenofovir starting in the second trimester through delivery. HBV vaccine and HBIg will be given to the newborn.

3. To determine knowledge, attitudes, and resources with respect to hepatitis B, its prevention, and its treatment among pregnant women and healthcare providers using a specifically designed questionnaire.

4. Mentor a SYSU Research Scholar on HBV laboratory testing, clinical trials design, and data analysis.