Prevention of Vertical Hepatitis B Virus Transmission in China (2014)

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

Abstract

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, 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 continue the collaboration with Sun Yat-sen University (SYSU) by conducting a feasibility study to obtain preliminary data for the preparation of a randomized, controlled clinical trial (RCT), which will be designed to determine if tenofovir, a nucleotide analogue anti-HBV drug, given to high risk mothers in early pregnancy, in addition to active birth-dose vaccine given to the infant, can decrease rates of MTCT of HBV in China. We believe such a strategy will be successful since it has proven to be effective for prevention of MTCT of HIV. This HBIg withdrawal strategy may help overcome the many problems with HBIg and may also be more effective than HBIg. Another important aim is to continue fostering efficient collaboration with SYSU investigators and to establish a study team to compete for clinical trials in the global context.

We used the pilot grant received in 2013 effectively and developed a strong and cooperative work relationship with our SYSU colleagues. We completed the training of a SYSU fellow in epidemiology and clinical trial methodology and we prepared a survey on knowledge and attitudes of healthcare providers and pregnant women at the third affiliated hospital at SYSU. In addition, we developed the data collection instruments needed for aim 2 below. Two manuscripts have been jointly prepared.

The specific aims of the proposed study are:

1. To determine the proportion of HBsAg positive pregnant women, the distribution of HBeAg and HBV DNA levels among these women, and the factors associated with high HBV DNA.

2. Pilot intervention: to estimate the median time until HBV DNA <200 IU/ml 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.