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AASLD 2015: Tenofovir During Pregnancy Reduces Risk of Mother-to-Child Hepatitis B Transmission

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 AASLD Liver Meeting in San Francisco. Another study showed that women with hepatitis B often experience viral load or ALT "flares" during pregnancy or post-partum.

Calvin Pan from New York University School of Medicine and colleagues from China conducted a randomized 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%-30% of infants born to women with high HBV DNA become infected. Current World Health Organization guidelines do not recommend antiviral therapy for hepatitis B during pregnancy.

This analysis included 200 pregnant women in 5 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 log 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 disease.

The women were randomly assigned (1:1) to receive either 300 mg tenofovir disoproxil fumarate starting at 30-32 weeks gestation and continuing through post-partum week 4, or else no antiviral treatment. About half delivered by cesarean section. All infants received standard immunoprophylaxis using HBIG and an HBV vaccine.

Results

• Prior to delivery HBV DNA levels decreased to <200,000 IU/mL in 68% of tenofovir-treated women and 2% of untreated women.
• 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%).
• HBV serological outcomes did not differ significantly between the 2 groups of women.
• 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 1 case each of torticollis and umbilical hernia in the tenofovir group, and 1 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 randomized, 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 2 years to analyze longer-term outcomes.

Hepatitis B Flares During Pregnancy

A related study looked at the prevalence of hepatitis B "flares" in alanine aminotransferase (ALT) liver enzymes or HBV DNA during pregnancy and the early post-partum period.

Christine Chang from Stanford University Medical Center and colleagues looked at the occurrence of flares -- characterized by steep elevation in ALT (>2 x upper limit of normal or baseline level) or rises in HBV DNA (>1 log increase) -- among women with hepatitis B during pregnancy and the first 6 months after delivery.

This retrospective analysis included 74 mothers who had 88 pregnancies at 3 California centers during 1999-2015. Most were Asian and the mean age was 32 years. Women with hepatitis A, C, delta, or HIV were excluded. The women were not on hepatitis B treatment for at least a year prior to pregnancy. 33 were classified as having low HBV DNA at baseline (<2000 IU/mL; mean 2.0 log IU/mL) while 55 had high viral load (>2000 IU/mL; mean 6.1 log IU/mL).

A total of 5 mothers (6%) had HBV DNA and ALT flares during pregnancy, and 2% did so post-partum. ALT flares alone were substantially more common post-partum (31%) than during pregnancy (16%), while viral load flares alone were slightly more common during pregnancy (12%) than post-partum (8%).

Women with high baseline viral load were less likely to have HBV DNA flares, but more likely to have ALT flares than those with low baseline levels. More than half of ALT flares exceeded 5 x upper limit of normal. About 60% of women who experienced flares during pregnancy started HBV treatment, and a third of post-partum ALT flares were associated with stopping therapy after delivery. Women who had had fewer children were more likely to experience flares.

Based on these findings the researchers concluded that HBV DNA and ALT flares are common during pregnancy and early post-partum in mothers with chronic hepatitis B, indicating that they should be closely monitored for increases in HBV DNA and ALT, especially during their first pregnancy.

11/19/15

References

CQ Pan, ZP Duan, E Dai, et al. Tenofovir Disoproxil Fumarate (TDF) Reduces Perinatal Transmission of Hepatitis B Virus in Highly Viremic Mothers: A Multi-center, Prospective, Randomized and Controlled Study. AASLD Liver Meeting 2015. San Francisco, November 13-17, 2015. Abstract 209.

CY Chang, N Aziz, HN Trinh, et al. Serum Alanine Aminotransferase (ALT) and Hepatitis B Virus (HBV) DNA Flares In Pregnant and Postpartum Women With Chronic Hepatitis B (CHB). AASLD Liver Meeting 2015. San Francisco, November 13-17, 2015. Abstract 123.