Optimal timing of hepatitis B virus DNA quantification and clinical predictors for higher viral load during pregnancy

Abstract

Introduction: Authorities publish recommendations on the hepatitis B virus (HBV) viral load threshold to initiate antiviral treatment but the timing of quantification during pregnancy is not well defined. HBV DNA levels in pregnancy women at 28-30 weeks predict the risk of immunoprophylaxis failure. This study compared and evaluated the correlation between HBV DNA levels before 22 and 28-30 weeks' gestation. Clinical predictive factors for HBV DNA >6, 7 and 8 log₁₀ IU/mL were studied.

Material and methods: A retrospective analysis of HBV DNA levels of women <22 and 28-30 weeks of gestation was carried out in 352 pregnant HBV carriers. HBV DNA was examined using the COBAS TaqMan HBV Monitor Test coupled with the COBAS Ampliprep extraction system (Both Roche Diagnostics, Branchburg, NJ, USA).

Results: A strong positive correlation was found between the viral loads of women <22 weeks (mean 16.7 weeks) and 28-30 weeks of gestation, which was independent of the viral load level and gestational age of quantification (r = 0.942, P < 0.001). Univariate analysis showed that positive hepatitis B e antigen (HBeAg), maternal age <35 years old and body mass index ≤21 kg/m² were associated with a higher mean viral load at 28-30 weeks of gestation (P < 0.05). These factors were also associated with a higher chance of viral load >6, 7 and 8 log₁₀ IU/mL at 28-30 weeks (P < 0.05). In multiple regression analysis, only the viral load of <22 weeks and positive HBeAg remained predictive of a higher mean viral load at 28-30 weeks of gestation (P < 0.05). The receiver operating characteristic curve showed that the HBV DNA of <22 weeks was an excellent predictor for different viral load cut-offs at 28-30 weeks. The area under curve was 0.986, 0.998 and 0.994 for viral load 6, 7 and 8 log₁₀ IU/mL, respectively.

Conclusions: HBV DNA quantification should be performed before 22 weeks of gestation. Viral load cut-offs similar to those at 28 weeks can be used to determine immunoprophylaxis failure at earlier gestation. Maternal positive HBeAg status was associated with a higher chance of viral load >6, 7 or 8 log₁₀ IU/mL.

Keywords: hepatitis B virus; immunization; infectious disease transmission, vertical; pregnancy; viral load.