Daily treatment with the antiviral drug tenofovir during the third trimester of pregnancy reduced the mother-to-child transmission rate of hepatitis B (HBV) from 18 percent to 5 percent, according to the findings of a clinical trial led by researchers from NYU Langone Medical Center and published on June 16 in the New England Journal of Medicine.
The study focused on the most common way that children become infected with hepatitis B, an incurable viral infection that causes liver disease and cancer, which is through infection during the perinatal period. Without intervention, 80 to 90 percent of infants who are born to mothers infected with hepatitis B develop a chronic infection. The current standard of care is to provide vaccine and immune globulin to reduce transmission rates.
“Preventing mother-to-child transmission is the most effective way to reduce the global burden of chronic hepatitis B infection and liver cancer,” says Calvin Pan, MD, lead author of the study and a clinical professor of medicine at NYU Langone. “We believe that these findings will not only save many lives, but could also help to eradicate hepatitis B nationally and abroad.”
The study was conducted in five locations in China, where HBV infection is endemic. Pan and colleagues enrolled 200 pregnant women with a high “viral load,” defined as one million copies of the virus per milliliter in a blood sample. Participants were randomly assigned to either a control group that received no antiviral therapy, or to a second group that received a daily dose of 300 milligrams of tenofovir in pill form, beginning at 30 or 32 weeks of pregnancy and continuing until 4 weeks after delivery.
Treatment effectively reduced the viral load of the pregnant women, says Pan. Before delivery, 68 percent of tenofovir-treated mothers had HBV loads below 1 million copies per milliliter, compared to 2 percent of nontreated mothers.
In terms of safety, researchers found that tenofovir was well tolerated; only one participant treated with tenofovir voluntarily withdrew from the study due to nausea. Among the children born during the study, Pan and his colleagues found no significant differences between the tenofovir-treated group and the control group with regard to fetal development and infant growth.
“This study provides strong evidence on how best to care for women infected with hepatitis B during pregnancy and reduce the rate of disease transmission,” says Mark Pochapin, MD, the Sholtz/Leeds Professor of Gastroenterology and director of the Division of Gastroenterology and Hepatology at NYU Langone.
Based on the findings, the investigators recommend that women be tested for HBV viral load at week 28 of pregnancy. Those with a high viral load should receive tenofovir treatment starting at gestational week 30 until delivery to reduce the risk of transmission to their infants. In addition, infants should receive hepatitis B vaccine and immune globulin. Moving forward, longer term, observational studies are needed to confirm the safety of fetal exposure to tenofovir treatment, says Pan.
This research was supported by Gilead Sciences.
Dr. Pan’s co-authors were Zhong Ping Duan at Beijing Youan Hospital, Capital Medical University, in Beijing; Er Hei Dai and Bao Shen Zhu at Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang; Shu Qing Zhang and Wen Jing Zhao at Hepatobiliary Disease Hospital of Ji Lin Province, Changchun; Guo-Rong Han and Hong-Xiu Jiang at Second Affiliated Hospital of Southeast University, Nanjing; Yuming Wang at Institute for Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing; Huai Bin Zou at Youan Hospital, Capital Medical University, Beijing; and Huai Hong Zhang at Nanyang Center Hospital, Nanyang, Henan, all for the China Study Group for the Mother-to-Child Transmission of Hepatitis B.