By Shreeya Nanda
Two studies have independently identified quantitative hepatitis B surface antigen (HBsAg) as a marker to identify pregnant women with chronic hepatitis B virus (HBV) infection whose infants are at high-risk of infection despite immunoprophylaxis.
The authors of both studies believe that use of quantitative HBsAg could be a valid alternative to HBV DNA testing to identify high-risk mothers and determine eligibility for treatment, especially in resource-limited regions as the currently available assays to quantify HBV DNA levels are expensive.
The first of these studies, conducted in a Taiwanese cohort of 568 HBsAg-positive women who did not receive antiviral therapy during pregnancy, found a strong positive correlation between quantitative maternal HBsAg titres and maternal viral load (r=0.69; p<0.001). However, the correlation was mainly driven by the subgroup of women positive for hepatitis B e antigen (HBeAg), in whom HBsAg and HBV DNA levels correlated strongly (r=0.65; p<0.001), while the correlation in HBeAg-negative participants was suboptimal (r=0.12; p=0.046), the team reports.
Multivariate analysis showed that infants of mothers with higher HBsAg levels had a significantly increased risk of infection, with an adjusted odds ratio (OR) for each log10 IU/mL rise of 15.02 (p<0.001). Higher maternal HBV DNA levels were the only other factor associated with an increased vertical transmission risk (adjusted OR for each log10 IU/mL increase=2.36; p<0.001).
Area under the receiver operating characteristic curve (AUC) analysis showed that quantitative HBsAg predicted infection in infants with 89% accuracy, which was comparable to the 87% accuracy of maternal viral load to predict infection.
And at the optimal cutoff of 4.10 log10 IU/mL, maternal quantitative HBsAg predicted infant infection with a sensitivity of 100.0% and a specificity of 71.3%, Huey-Ling Chen (National Taiwan University Hospital, Taipei) and colleagues report in Hepatology.
In the other study, a Canadian team recruited a multi-ethnic (65% Asian, 23% African, 12% Caucasian or Hispanic) cohort of 99 pregnant women with chronic HBV, of whom 13% received tenofovir disoproxil fumarate for a median of 83 days prior to delivery.
In this study, the optimal quantitative HBsAg cutoff was 4.3 log10 IU/mL to predict HBV DNA levels of 7.0 log10 IU/mL and above, known to be associated with immunoprophylaxis failure, say the researchers. At this cutoff, quantitative HBsAg was 98.7% accurate, 94.7% sensitive and 94.4% specific for high maternal viraemia.
In contrast to the Taiwanese study, Carla Coffin, from the University of Calgary in Alberta, and fellow investigators only found a moderate correlation between quantitative HBsAg and HBV DNA levels, although the correlation was significant (r=0.44; p<0.05). But similar to Chen et al, HBsAg and maternal viraemia correlated strongly and significantly in HBeAg-positive women (r=0.79; p<0.05), but not in those negative for HBeAg (r=0.17; p=0.06).
Coffin et al write in Liver International: "Given the very low risk of transmission in HBeAg-negative pregnant patients, [quantitative HBsAg] testing for predicting high maternal viraemia could be performed only in HBeAg-positive mothers, especially in resource poor regions."
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