Impact and cost-effectiveness of hepatitis B virus prophylaxis in pregnancy: a dynamic simulation modelling study

Background: In 2020, WHO recommended the addition of peripartum antiviral prophylaxis (PAP) to hepatitis B birth dose vaccination (HepB-BD) and hepatitis B infant vaccination (HepB3) to reduce mother-to-child transmission of hepatitis B virus (HBV) infection in pregnant women who have a marker of high infectivity (ie, HBV DNA ≥200 000 international units per mL or HBeAg-positive). We aimed to evaluate the impact and cost-effectiveness of this recommendation and of a theoretical simplified strategy whereby PAP is given to all pregnant women who are HBsAg-positive without risk stratification. Methods: This modelling study used a dynamic simulation model of the HBV epidemic in 110 countries in all WHO regions, structured by age, sex, and country. We assessed three strategies of scaling up PAP for pregnant women: PAP for those with high viral load (PAP-VL); PAP for those who are HBeAg-positive (PAP-HBeAg); and PAP for all pregnant women who are HBsAg-positive (PAP-universal), in comparison with neonatal vaccination alone (HepB-BD). We investigated how different diagnostic and antiviral drug costs affected the cost-effectiveness of the strategies evaluated. Using a health-care provider perspective, we calculated incremental cost-effectiveness ratios in cost (US$) per disability-adjusted life-year (DALY) averted in each country's population and compared these with country-specific cost-effectiveness thresholds. We also calculated new neonatal infections averted for each of the strategies. Findings: Adding PAP-VL to HepB-BD could avert around 1·1 million (95% uncertainty interval 1·0 million–1·2 million) new neonatal infections by 2030 and around 3·2 million (95% uncertainty interval 3·0 million–3·4 million) new neonatal infections and approximately 8·8 million (7·8 million–9·7 million) DALYs by 2100 across all the countries modelled. This strategy would probably be cost-effective up to 2100 in 28 (26%) of 106 countries analysed (which included some of the countries that have the greatest HBV burden) if costs are as currently expected to be, and in 74 (70%) countries if diagnostic and monitoring costs were lowered (by about 60–75%). The relative cost-effectiveness of PAP-VL and PAP-HBeAg was finely balanced and depended on the respective diagnostic and monitoring costs. The PAP-universal strategy could be more cost-effective than either of these strategies in most countries, but the use of antiviral treatment could be five times as high than with PAP-VL. Interpretation: PAP can provide substantial health benefits, and, although the current approach might already be cost-effective in some high-burden settings, decreased diagnostic costs would probably be needed for PAP to be cost-effective in most countries. Therefore, careful consideration needs to be given about how such a strategy is implemented, and securing reduced costs for diagnostics should be a priority. The theoretical strategy of offering PAP to all women who are HBsAg-positive (eg, if diagnostic tests to identify mothers at risk of transmission are not available) could be a cost-effective alternative, depending on prevailing costs of diagnostics and antiviral therapy. Funding: UK Medical Research Council, UK National Institute for Health and Care Research, and the Vaccine Impact Modelling Consortium.