Results of the probabilistic sensitivity analysis focusing on the influential variables (from Table 4) are presented in Table 5. Both strategies remained cost-effective compared with the current recommendation. The maximum incremental cost-effectiveness ratios were $20,796 and $29,708 per QALY saved for sequential HBeAg testing and sequential HBV load testing, respectively.
Our study demonstrated that either sequential HBeAg testing or sequential HBV load testing was cost-effective under a wide range of assumptions compared with the current recommendation. The cost-effectiveness of sequential HBeAg testing and sequential HBV load testing relies on several factors, including the cost and efficacy of maternal antiviral prophylaxis and lifetime costs associated with chronic HBV infection.
Several studies have concluded that maternal antiviral prophylaxis among HBsAg-positive women during pregnancy, in addition to active-passive immunoprophylaxis for the neonate, is cost-effective or cost-saving.1,18,27 The purpose of sequential HBeAg testing and HBV load testing is to identify HBsAg-positive women whose neonates have the highest risk for perinatal transmission. If maternal antiviral prophylaxis is cost-effective in preventing perinatal HBV infection among the general population of HBsAg-positive women, identification of the highest risk population using HBeAg testing or HBV load testing is likely to be cost-effective, because the cost of testing for HBeAg or DNA is small compared with the cost of antiviral prophylaxis during pregnancy.
Several antivirals (ie, lamivudine, tenofovir, and telbivudine) reduce HBV viral load and might reduce perinatal HBV transmission.9–11 Although lamivudine is the most studied maternal antiviral for preventing HBV perinatal transmission, tenofovir or telbivudine has been considered because they effectively reduce HBV load with lower rates of drug resistance than lamivudine.18,39,40 We do not expect the choice of antiviral agent alone to change the cost-effectiveness given the results from sensitivity analyses.
Although HBeAg testing is less expensive than HBV load testing, HBeAg testing can miss a small proportion of women with negative HBeAg but high HBV load.41 In our baseline assumption, sequential HBeAg testing dominated sequential HBV load testing using 108 copies/mL or greater as the cutoff value for high viral load (lower cost, higher QALY saved for HBeAg testing). However, results of a comparison between the two strategies depends on the cutoff for high HBV load, the costs of HBeAg and HBV load testing, the prevalence of HBeAg and high HBV load among HBsAg-positive pregnant women, and the perinatal transmission rates. Sequential HBV load testing using 106 copies/mL or greater has an incremental cost-effectiveness ratio of $31,389 per QALY saved compared with sequential HBeAg testing.
This study has several limitations. First, all limitations associated generally with models are applicable because our model is a simplification of real-world events. Second, the validity of models and the results depend largely on the availability and reliability of the data. We used parameter values that varied substantially. As a result of lack of data on the parameters of the distribution for each variable, we used a triangular distribution for all variables. Using different distributions might change the results of the probabilistic sensitivity analyses. However, it is difficult to determine the magnitude or direction of any change. We assumed that the rates of adverse events for pregnant women and children from maternal antiviral prophylaxis were similar to those without maternal antiviral prophylaxis. Had we included complications attributable to antiviral therapy, the cost-effectiveness estimates for the strategies that included antiviral therapy would be higher (less favorable). An increasing body of evidence shows that the incidences of adverse events and birth defects among pregnant women and children associated with antiviral prophylaxis are comparable to those without antiviral prophylaxis.8,10,11,39,40,42 Our results might be conservative because we did not include the potential benefit of identifying women who should be treated or monitored for liver disease during pregnancy.
Drug resistance from long-term use of lamivudine has been a concern; however, the rate of drug resistance after a 3-month course of lamivudine is reported to be no higher than no antiviral prophylaxis.1,8,18 Tenofovir and telbivudine have low rates or no documented drug resistance when used in other settings.10,11,43 Another safety concern is postpartum flare.18,44,45 Studies report mixed results regarding change in the rate of postpartum flares after maternal antiviral prophylaxis.45,46 Because evidence for the safety of antiviral prophylaxis during pregnancy is still accumulating, antiviral prophylaxis for maternal liver disease during pregnancy has generally been postponed.16,47
Despite these limitations, our results suggest that health care providers might wish to consider HBeAg or HBV load sequential testing for HBsAg-positive pregnant women to identify women whose neonates are at increased risk for perinatal HBV infection and to ensure evaluation and monitoring of the pregnant women for the complications of chronic HBV infection, including during pregnancy and in the postpartum period.
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