Epidemiology

High maternal viral load key to vertical transmission of hepatitis B

Last Updated: 2013-03-15 9:00:52 -0400 (Reuters Health)

By Megan Brooks

NEW YORK (Reuters Health) - High maternal viral load is the most important factor causing maternally transmitted hepatitis B virus (HBV) infection and is significantly correlated with e antigen (HBeAg) positivity, according to a prospective study from Taiwan.

"Additional interventions should be considered in these mothers," Dr. Huey-Ling Chen from the Hepatitis Research Center, Hospital and College of Medicine, National Taiwan University in Taipei and colleagues conclude in a report online now in the Journal of Hepatology.

They say their data also provide "important information for the rational design of future screening and intervention strategies to further reduce maternally transmitted HBV infection."

Despite effective immunoprophylaxis, breakthrough HBV infection does occur and may result in mother-to-infant transmission. Transmission from highly viremic mothers remains a major challenge in eradicating HBV-related diseases, the investigators say.

Some studies have suggested that antiviral therapy in highly viremic HBV-infected pregnant women can reduce maternal viral load and transmission risk. Yet the optimal cutoff level of maternal viral load for antiviral therapy in pregnancy remains a topic of debate, they note.

Dr. Chen's team designed their prospective study to assess the rate and risk factors for maternally transmitted HBV infection despite immunoprophylaxis.

Mothers who were positive for hepatitis B surface antigen (HBsAg) were invited to join the study at the time of prenatal visits or delivery. All were HIV-negative. Maternal viral load was determined by a real-time PCR-based assay. Children were tested for HBsAg between four and eight months and/or one to three years of age. The study included a total of 303 mother-infant pairs.

The researchers report that 81 mothers (26.7%) were HBeAg-positive; all of their infants as well as most infants with HBeAg-negative mothers received hepatitis B immune globulin.

HBeAg-positive mothers had significantly higher viral loads than HBeAg-negative mothers (7.4 vs 2.7 log10 copies/mL, p<0.0001).

The 10 children born to HBeAg-positive mothers with high viral load (median, 8.4 log10 copies/mL) were chronically infected.

Maternal viral load was significantly associated with risk of infection in analyses adjusted for maternal age, birth type, factors related to maternal-fetal hemorrhage, gestational age, infant gender, birth weight, timeliness of vaccination, and feeding practice. The adjusted odds ratio for each log10 copy/mL increase was 3.49 (95% CI 1.63 to 7.48; p=0.001).

High maternal viral load was "the most important factor in maternally transmitted HBV," the investigators say. The rate of neonatal infection at maternal viral load 7 log10 copies/mL was 6.6%, and jumped to 14.6% and 27.7% at 8 and 9 log10 copies/mL, respectively.

The investigators think additional strategies to further reduce mother-to-child transmission should be considered in mothers with a viral load above 7-8 log10 copies/mL.

While there is no consensus on the optimal cutoff value of maternal viral load for antiviral treatment, the investigators say their findings support antiviral therapy to reduce transmission in HBV-infected pregnant women with a viral load above 7 log10 copies/mL -- and especially in those with a viral load above 8 log10 copies/mL.

Dr. Chen and colleagues emphasize, however, that the advantages of antiviral therapy need to be balanced against the risks. "Although current reports show no significant increase in birth defects and pregnancy complications," they say, "more long-term safety data of antiviral therapy, continued epidemiological surveillance on HBsAg-positive mothers and their children, and cost-effectiveness analyses are needed to develop a safe and cost-effective preventive intervention strategy."

Dr. Chen did not respond to request for comment.

Dr. Ameeta Singh, clinical professor in the division of infectious diseases at the University of Alberta, Edmonton, who reviewed the study for Reuters Health, said the findings are "definitely significant and support previous similar reports from the published literature. They also report increasing rates of transmission at increasing levels of viral load which makes sense but it is always helpful information to both patients and providers when deciding on treatment."

Dr. Singh also noted that the exact viral load cut-off at which treatment should be offered is unclear "and varies between specialists."

"Very few places," she added, "offer routine services and recommend referral to a specialist of all HBsAg infected mothers during pregnancy - many providers are either not aware that anything other than routine immunoprophylaxis can be offered in some situations. In response to similar work that we undertook a few years ago, the province of Alberta has made some changes to provincial programming to encourage providers to refer all HBsAg infected mothers to specialists."

"I think raising awareness among clinicians - particularly primary care providers and OBGYN - that more can be done to reduce mother-to-child HBV in certain situations would be a good thing," Dr. Singh concluded.

The authors and Dr. Singh have no conflicts of interest. The study was funded by the Center for Disease Control, Department of Health, Taiwan.

SOURCE: http://bit.ly/Z28Gos

J Hepatol 2013.