Precise estimation of national HBV prevalence: the importance of double hepatitis B surface antigen and hepatitis B core antibody testing in low endemic countries

Abstract

Background and aims: In light of the WHO viral hepatitis elimination targets set for 2030, robust and repetitive age-specific HBV prevalence studies are needed. Previous HBV prevalence studies reported a hepatitis B surface antigen (HBsAg) prevalence of 0.7% (1993/1994) and 0.66% (2003) in Belgium. However, automated HBsAg assays are typically designed to be oversensitive and might result in an overestimation of the HBV prevalence. Here, we examine the Belgian HBV seroprevalence in adults and investigate the difference in HBV seroprevalence estimates using either HBsAg positivity alone or hepatitis B core antibodies (anti-HBc) HBsAg double positivity as criterium for HBV infection. Method: 3840 residual serum samples were collected from adult ambulatory patients in 10 private diagnostic laboratories-geographically representing the whole country-during Q2/Q3 2020 (outside the COVID-19 lockdown). The number of samples in each laboratory was stratified per region, age group (10-year age bands) and sex. HBsAg and anti-HBc were analyzed on automated analyzers (Abbott Alinity I). For HBsAg positive anti-HBc negative samples, anti-HBc confirmatory assays were performed by an independent laboratory. The samples were weighted by comparing the sample and population frequencies by sex, 10-year age band and province. Results: HBsAg was detected in 27/3840 samples, resulting in a weighted HBsAg seroprevalence of 0.69% (95% CI 0.43%-1.04%). However, 15/27 HBsAg positive samples were anti-HBc negative and thus serodiscordant. Independent hepatitis B core antigen neutral-ization assays revealed that all 15 serodiscordant samples were truly anti-HBc negative, thereby confirming a significant HBsAg false positivity rate for HBV infections of 55.6%. Therefore, a weighted national HBV seroprevalence, based on HBsAg and anti-HBc double positivity, of 0.27% (95% CI 0.13%-0.49%) was obtained. The weighted age-specific seroprevalence ranged from 0.20% (95% CI 0.01%-0.87%) in the 40-49 age group to 0.91% (95% CI 0.32%-1.97%) in the 60-69 age group. There were no double positive samples in the age groups 20-29, 30-39, 80-89 and >90. Although, 8/12 (66.7%) of the double positive samples originated from males, there was no statistically significant difference between sexes (p = 0.07). Since 164/3840 (4.27%) samples were anti-HBc positive, we estimate that 4.37% (95% CI 3.65%-5.18%) of the Belgian population had a past HBV exposure. Conclusion: This population-based nationwide study estimates a Belgian HBV seroprevalence, based on HBsAg and anti-HBc double positivity, of 0.27% (95% CI 0.13%-0.49%) in 2020. Our results illustrate that HBV prevalence based on HBsAg positivity alone overestimates the number of infections due to a high false positivity of automated HBsAg assays. In low-endemic countries, confirmatory anti-HBc testing is therefore advocated to correctly assess the HBV prevalence. Background and aims: Micro-elimination strategies for hepatitis C, targeting high-risk populations such as people who are homeless, aim to efficiently prevent and treat the disease, contributing to national elimination goals by addressing specific risk factors and barriers to medical care. Implementation of point-of-care HCV RNA testing is key to testing and treatment programs, evaluating cures, and monitoring hepatitis C reinfection. The objective of this study was to estimate the prevalence, associated risk factors, and temporal trend of HCV active infection among the homeless population in Madrid, Spain. Method: A retrospective study was conducted in Madrid, Spain, spanning from 2019 to 2023 and involving 2, 709 homeless individuals. Participants were recruited through a mobile screening unit with consecutive enrollment based on the order of appearance. The inclusion of homeless people was carried out on the street or in homeless shelters. Screening involved a rapid HCV antibody test followed by HCV RNA testing using Xpert HCV VL Fingerstick. Data were analyzed using logistic regression, and p values were adjusted for multiple testing using the false discovery rate (q-values). Results: The prevalence of HCV active infection during the study period was 6.3% (from 7.2% in 2019 to 3.4% in 2023; p value = 0.039). The main risk factors for active HCV infection included being an injecting drug user (IDU), encompassing both non-active IDU (adjusted odds ratio (aOR) = 13.1; q-value<0.001) and active IDU in the last year (aOR = 31; q-value<0.001), having no economic income (aOR = 1.8; q-value = 0.015), and alcohol consumption (aOR = 1.8; q-value = 0.004). From 2019 to 2023, there was a significant decrease in the prevalence of HCV active infection across the entire population (from 7.2% to 3.4%, p value = 0.039), among IDU (from 25.3% to 9.4%, p value = 0.040), alcohol consumers (from 12.2% to 6.4%, p value<0.001), and those with no economic income (from 7.0% to 4.4%, p value = 0.033). Conclusion: Among homeless individuals, IDU was highlighted as the primary risk factor for active HCV infection, followed by other significant factors such as lack of economic income and alcohol consumption. The significant decline in HCV infection rates across the entire population and among major risk groups during the study period suggests the effectiveness of preventive policies in reducing the prevalence of HCV among the homeless population.