Women with chronic hepatitis B and high viral
load who were treated with tenofovir (Viread)
during pregnancy were significantly less likely to transmit hepatitis B virus
(HBV) to their babies, according to study findings presented this week at the 2015 AASLD Liver Meeting in San Francisco. Another study showed that women with hepatitis B
often experience viral load or ALT 'flares' during pregnancy or postpartum.
Calvin Pan from New York University School of Medicine
and colleagues from China conducted a randomised study of the effect of
tenofovir on perinatal transmission of HBV.
Prevention of mother-to-child HBV
transmission is the most effective way to reduce the global burden of chronic
hepatitis B infection and liver cancer, Pan said. Despite immunoprophylaxis
using hepatitis B immunoglobulin (HBIG), about 10 to 30% of
infants born to women with high HBV DNA become infected. Current World Health
Organization (WHO) guidelines do not recommend antiviral therapy for hepatitis
B during pregnancy.
This analysis included 200 pregnant women in five regions
of China, with a mean age of 27 years. They were hepatitis B 'e' antigen
(HBeAg) positive and had HBV DNA > 200,000 IU/ml at baseline (mean > 8 log10
IU/ml). Women who also had hepatitis C, E, delta or HIV were excluded, as were
those with a history of kidney dysfunction, liver cancer or decompensated liver
The women were randomly assigned (1:1) to receive
either 300mg tenofovir disoproxil fumarate starting at 30-32 weeks gestation
and continuing through postpartum week 4, or else no antiviral treatment.
About half delivered by caesarean section. All infants received standard
immunoprophylaxis using HBIG and an HBV vaccine.
Prior to delivery HBV DNA levels decreased to
< 200,000 IU/ml in 68% of tenofovir-treated women and 2% of untreated women.
HBV serological outcomes did not differ significantly between the two groups.
At postpartum week 28, the mother-to-child
transmission rate was significantly lower for infants born to tenofovir-treated
women compared to untreated women, both in an intent-to-treat analysis (5.16%
vs 18.0%) and in a per-protocol analysis (0% vs 6.82%).
Treatment was generally well-tolerated. Adverse
events were uncommon and safety profiles were similar in the treated and
untreated groups. There was no significant difference in the rate of birth
defect between babies born to treated and untreated mothers (2.11% vs 1.14%);
these included one case each of torticollis and umbilical hernia in the
tenofovir group and one case of hypospadias in the untreated group.
"Our study demonstrates that [tenofovir]
treatment during late pregnancy effectively reduced mother-to-child
transmission in highly viremic mothers," the researchers concluded.
"[Tenofovir] treatment was well-tolerated and resulted in a rapid viral reduction.
There were no safety concerns for both mothers and infants."
They recommended that "[tenofovir] should
strongly be considered for mothers whose HBV DNA levels exceeded 200,000 IU/ml
and should be started at gestation week 30-32."
After the presentation, Pan was asked about the
ethics of conducting a placebo-controlled study when it is already apparent
that tenofovir can reduce the risk of perinatal HBV transmission. He replied
that prior studies were not randomised, and said that more data confirming the
safety and benefits of tenofovir are needed because many women decline to
receive treatment during pregnancy due to uncertainty about its risks.
Pan was also asked about reduced bone
density among children exposed to tenofovir during gestation, which has been
seen in studies of women who took tenofovir for HIV treatment. He said that
bone loss is difficult to determine in infants, but follow-up would continue
for two years to analyse longer-term outcomes.