Real‐world study of tenofovir disoproxil fumarate to prevent hepatitis B transmission in mothers with high viral load

Abstract

SummaryBackgroundData on tenofovir disoproxil fumarate (TDF) therapy for preventing vertical transmission of hepatitis B virus (HBV) in the real‐world setting are limited.AimTo investigate TDF for preventing vertical transmission of HBV in real‐world practice.MethodsHepatitis B e‐antigen (HBeAg)‐positive mothers with HBV‐DNA >6 log10 IU/mL to receive TDF between gestational weeks 24‐33 and delivery were prospectively enrolled and followed until post‐partum week 28. All infants received immunoprophylaxis. Primary endpoints were safety of TDF use and mother‐to‐child transmission rates. Secondary outcomes were maternal HBV‐DNA level suppression (<200 000 IU/mL) at delivery and HBeAg and hepatitis B surface antigen (HBsAg) serologic changes during the study.ResultsAmong 147 mothers enrolled, 143 started TDF and 143/144 infants completed the study. At delivery, 93.7% (134/143) of the mothers achieved HBV‐DNA<200 000 IU/L. On‐treatment, alanine aminotransferase (ALT) flares were observed in 8.4% (12/143) of mothers. After TDF cessation, ALT increased in 7.7% (11/143) of the mothers and 2.8% (4/143) achieved HBeAg negativity, but none had HBsAg loss. At birth, HBsAg was detected in 13.9% (20/144) of newborns and none at post‐partum week 28. Vertical transmission rates among infants were 0.7% (1/144, intention‐to‐treat) and 0% (per‐protocol). No infants had birth defects. No serious adverse effects were reported in either mothers or infants. Breastfeeding did not increase the HBV infection rate among infants although mothers had viral rebound after TDF cessation.ConclusionsTDF for highly viraemic mothers was well tolerated and reduced vertical transmission of HBV in a real‐world setting. There were no safety concerns during the postpartum 28‐week follow‐up.Registry number: Chinese Clinical Trial Registration No. ChiCTR‐OIC‐17010869

Decreased neonatal hepatitis B virus (HBV) viremia by maternal tenofovir treatment predicts reduced chronic HBV infection in children born to highly viremic mothers

“…3,19 Clinical trials from different study groups of maternal anti-viral therapy have shown the efficient reduction of maternal viral load to below 6.0 log 10 IU/mL at delivery and reduction of children's infection rates. 14,15,19,23 In continuation with our previous work, 19 the efficacy of mater- Maternal anti-viral therapy could potentially reduce maternal HBV DNA levels during third trimester and also has chance to reduce risk of intrauterine transmission. In our study, one infant in the tenofovir group with prevention failure had detectable HBsAg and HBV DNA at birth that persist at 6 and 12 months, although the mother had optimal viral reduction after anti-viral treatment.…”

“…Our previous study has shown that high levels of maternal viral load are the major risk factor for the infection of children . Clinical trials from different study groups of maternal anti‐viral therapy have shown the efficient reduction of maternal viral load to below 6.0 log 10 IU/mL at delivery and reduction of children's infection rates …”

Letter: tenofovir disoproxil fumarate is safe for prevention of mother‐to‐child transmission of hepatitis B virus. Authors’ reply

“…The principle of meta-analysis does not allow for combining effect estimates from various study designs. 2 In the present meta-analysis the authors combined crude event rates from two randomised trials specifically designed for HCC, four randomised trials addressing different questions (analysed as cohort studies) and 17 observational studies (three prospective and 14 retrospective). The fact that this was done in the past does not make it appropriate.…”

“…Authors' reply EDITORS, Dr Fan et al commented on the safety data in our study and presented a meta-analysis involving 624 mothers on TDF. 1,2 Their positive comments are much appreciated. Although they indicated the need to further reveal the maternal and foetal safety of TDF in realworld studies, their meta-analysis data were largely extracted from three RCTs (n = 316 on TDF), [3][4][5] which may not necessarily represent patients in the real-world setting.…”

Editorial: tenofovir disoproxil fumarate and prevention of mother‐to‐child transmission of hepatitis B virus

“…TDF is preferred due to its minimal risk of viral resistance and high tolerability. However, the ideal treatment regimen has not been well determined regarding the optimal time of initiation, appropriate duration and target maternal HBV DNA level at delivery because of heterogeneous study design . In Chang's study, the infected infant in TDF group was considered to have intrauterine infection before maternal intervention initiated at 30‐32 gestational weeks.…”