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Background & Aims: In 2020, the World Health Organization (WHO) recommended peripartum antiviral prophylaxis (PAP) for pregnant women infected with hepatitis B virus (HBV) with high viremia (≥200,000 IU/ml). Hepatitis B e antigen (HBeAg) was also recommended as an alternative when HBV DNA is unavailable. To inform policymaking and guide the implementation of prevention of mother-to-child transmission strategies, we conducted a systematic review and meta-analysis to estimate the proportion of HBV-infected pregnant women eligible for PAP at global and regional levels. Methods: We searched PubMed, EMBASE, Scopus, and CENTRAL for studies involving HBV-infected pregnant women. We extracted proportions of women with high viremia (≥200,000 IU/ml), proportions of women with positive HBeAg, proportions of women cross-stratified based on HBV DNA and HBeAg, and the risk of child infection in these maternal groups. Proportions were pooled using random-effects meta-analysis. Results: Of 6,999 articles, 131 studies involving 71,712 HBV-infected pregnant women were included. The number of studies per WHO region was 66 (Western Pacific), 21 (Europe), 17 (Africa), 11 (Americas), nine (Eastern Mediterranean), and seven (South-East Asia). The overall pooled proportion of high viremia was 21.27% (95% CI 17.77-25.26%), with significant regional variation: Western Pacific (31.56%), Americas (23.06%), Southeast Asia (15.62%), Africa (12.45%), Europe (9.98%), and Eastern Mediterranean (7.81%). HBeAg positivity showed similar regional variation. After cross-stratification, the proportions of high viremia and positive HBeAg, high viremia and negative HBeAg, low viremia and positive HBeAg, and low viremia and negative HBeAg were 15.24% (95% CI 11.12-20.53%), 2.70% (95% CI 1.88-3.86%), 3.69% (95% CI 2.86-4.75%), and 75.59% (95% CI 69.15-81.05%), respectively. The corresponding risks of child infection following birth dose vaccination without immune globulin and PAP were 14.86% (95% CI 8.43-24.88%), 6.94% (95% CI 2.92-15.62%), 7.14% (95% CI 1.00-37.03%), and 0.14% (95% CI 0.02-1.00%). Conclusions: Approximately 20% of HBV-infected pregnant women are eligible for PAP. Given significant regional variations, each country should tailor strategies for HBsAg screening, risk stratification, and PAP in routine antenatal care. Impact and implications: In 2020, the WHO recommended that pregnant women who test positive for the hepatitis B surface antigen (HBsAg) undergo HBV DNA testing or HBeAg and those with high viremia (≥200,000 IU/ml) or positive HBeAg receive PAP. To effectively implement new HBV PMTCT interventions and integrate HBV screening, risk stratification, and antiviral prophylaxis into routine antenatal care services, estimating the proportion of HBV-infected pregnant women eligible for PAP is critical. In this systematic review and meta-analysis, we found that approximately one-fifth of HBV-infected pregnant women are eligible for PAP based on HBV DNA testing, and a similar proportion is eligible based on HBeAg testing. Owing to substantial regional variations in eligibility proportions and the availability and costs of different tests, it is vital for each country to optimize strategies that integrate HBV screening, risk stratification, and PAP into routine antenatal care services. Systematic review registration: This study was registered with PROSPERO (Protocol No: CRD42021266545).
ABSTRACT
BACKGROUND: As nucleos/tide analogue (NA) therapy (e.g. entecavir and tenofovir) for chronic Hepatitis B virus (HBV) infection becomes more widely indicated and available, understanding drug resistance is essential. A systematic review to quantify resistance to these agents has not previously been undertaken. METHODS: We performed a systematic review and random-effects meta-analysis to estimate the risk of HBV resistance to entecavir and tenofovir. We searched nine databases up to 29-Aug-23. We included studies of HBV infection featuring >10 individuals, written in English, reporting treatment ≥48 weeks, with assessment of HBV resistance based on viral sequence data. Data were analysed according to prior exposure history to NA, and choice of NA agent. Analyses were performed in R. FINDINGS: 62 studies involving a total of 12,358 participants were included. For entecavir, in treatment-naive individuals (22 studies; 4326 individuals), resistance increased over time to 0.9 % at ≥5 years (95 %CI 0.1-2.3 %), and resistance was increased in NA-experienced individuals (18 studies; 1112 individuals), to 20.1 % (95 %CI 1.6-50.1 %) at ≥5 years. For tenofovir, pooled resistance risk was 0.0 % at all time points, whether previously NA naive (11 studies; 3778 individuals) or experienced (19 studies; 2059 individuals). There was a lack of consistent definitions, poor global representation and insufficient metadata to support subgroup analysis. INTERPRETATION: We have generated the first pooled estimates of HBV entecavir and tenofovir resistance over time. HBV resistance to entecavir in treatment-experienced groups in particular may represent a clinical and public health challenge. To date, tenofovir appears to have an excellent resistance profile, but due to data gaps, we caution that existing studies under-estimate the true real-world risk of resistance. Robust prospective data collection is crucial to reduce health inequities and reduce blind-spots in surveillance as treatment is rolled out more widely.
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BACKGROUND: While airport screening measures for COVID-19 infected passengers at international airports worldwide have been greatly relaxed, observational studies evaluating fever screening alone at airports remain scarce. The purpose of this study is to retrospectively assess the effectiveness of fever screening at airports in preventing the influx of COVID-19 infected persons. METHODS: We conducted a retrospective epidemiological analysis of fever screening implemented at 9 airports in Okinawa Prefecture from May 2020 to March 2022. The number of passengers covered during the same period was 9,003,616 arriving at 9 airports in Okinawa Prefecture and 5,712,983 departing passengers at Naha Airport. The capture rate was defined as the proportion of reported COVID-19 cases who would have passed through airport screening to the number of suspected cases through fever screening at the airport, and this calculation used passengers arriving at Naha Airport and surveillance data collected by Okinawa Prefecture between May 2020 and March 2021. RESULTS: From May 2020 to March 2021, 4.09 million people were reported to pass through airports in Okinawa. During the same period, at least 122 people with COVID-19 infection arrived at the airports in Okinawa, but only a 10 suspected cases were detected; therefore, the capture rate is estimated to be up to 8.2% (95% CI: 4.00-14.56%). Our result of a fever screening rate is 0.0002% (95%CI: 0.0003-0.0006%) (10 suspected cases /2,971,198 arriving passengers). The refusal rate of passengers detected by thermography who did not respond to temperature measurements was 0.70% (95% CI: 0.19-1.78%) (4 passengers/572 passengers). CONCLUSIONS: This study revealed that airport screening based on thermography alone missed over 90% of COVID-19 infected cases, indicating that thermography screening may be ineffective as a border control measure. The fact that only 10 febrile cases were detected after screening approximately 3 million passengers suggests the need to introduce measures targeting asymptomatic infections, especially with long incubation periods. Therefore, other countermeasures, e.g. preboarding RT-PCR testing, are highly recommended during an epidemic satisfying World Health Organization (WHO) Public Health Emergency of International Concern (PHEIC) criteria with pathogen characteristics similar or exceeding SARS-CoV-2, especially when traveling to rural cities with limited medical resources.
Subject(s)
Airports , COVID-19 , Fever , Mass Screening , SARS-CoV-2 , Humans , COVID-19/diagnosis , COVID-19/epidemiology , Japan/epidemiology , Fever/diagnosis , Fever/epidemiology , Fever/virology , Retrospective Studies , Mass Screening/methods , SARS-CoV-2/isolation & purification , Travel , Male , Adult , FemaleABSTRACT
OBJECTIVE: Economic feasibility of eliminating mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in highly endemic African countries remains uncertain. Prevention of MTCT (PMTCT) involves screening pregnant women for hepatitis B surface antigen (HBsAg), identifying those with high viral loads or hepatitis B e antigen (HBeAg), and administering tenofovir prophylaxis to high-risk women. We estimated the costs of integrating PMTCT services into antenatal care in Burkina Faso, based on four different strategies to select women for tenofovir prophylaxis: (1) HBV DNA (≥200 000 IU/mL), (2) HBeAg, (3) hepatitis B core-related antigen rapid diagnostic test (HBcrAg-RDT) and (4) all HBsAg-positive women. METHODS: Using a micro-costing approach, we estimated the incremental economic cost of integrating each strategy into routine antenatal care in 2024, compared to neonatal vaccination alone. Sensitivity analyses explored variations in prevalence, service coverage, test and tenofovir prices. RESULTS: HBcrAg-RDT strategy was the least expensive, with a total economic cost of US$3959689, compared to HBV DNA (US$6128875), HBeAg (US$4135233), and treat-all (US$4141206). The cost per pregnant woman receiving tenofovir prophylaxis varied from US$61.88 (Treat-all) to US$1071.05 (HBV DNA). The Treat-All strategy had the lowest marginal cost due to a higher number of women on tenofovir (66928) compared to HBV DNA (5722), HBeAg (10020), and HBcrAg-RDT (7234). In sensitivity analyses, the treat-all strategy became less expensive when the tenofovir price decreased. CONCLUSION: HBcrAg-RDT minimizes resource use and costs, representing 0.61% of Burkina Faso's 2022 health budget. This study highlights the potential economic feasibility of these strategies and provides valuable resources for conducting cost-effectiveness analyses.
Subject(s)
Antiviral Agents , Hepatitis B , Infectious Disease Transmission, Vertical , Pregnancy Complications, Infectious , Prenatal Care , Tenofovir , Humans , Female , Burkina Faso , Pregnancy , Prenatal Care/economics , Prenatal Care/methods , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/prevention & control , Tenofovir/therapeutic use , Tenofovir/economics , Tenofovir/administration & dosage , Hepatitis B/prevention & control , Hepatitis B/drug therapy , Infectious Disease Transmission, Vertical/prevention & control , Antiviral Agents/therapeutic use , Antiviral Agents/economics , Antiviral Agents/administration & dosage , Mass Screening/economics , Mass Screening/methods , Hepatitis B e Antigens/blood , Cost-Benefit Analysis , Hepatitis B Surface Antigens/blood , Adult , DNA, Viral , Hepatitis B virus , Viral LoadABSTRACT
Pregnant women identified to carry hepatitis B surface antigen (HBsAg) should be linked to care for the determination of the need for long-term antiviral therapy (LTT). We assessed the performance of simplified criteria, free from HBV DNA quantification, to select women eligible for LTT using different international guidelines as a reference. A retrospective analysis of HBV-infected pregnant women enrolled in the phase 4 ANRS TA-PROHM study was conducted in Cambodia. Sensitivity, specificity, and AUROC were computed to compare three simplified criteria (TREAT-B, HBcrAg/ALT, and TA-PROHM) with the American (AASLD) and European (EASL) guidelines as a reference. An additional assessment was performed at 6 months postpartum. Of 651 HBsAg-positive women, 209 (32%) received peripartum antiviral prophylaxis using tenofovir disoproxil fumarate (TDF). During pregnancy, 9% and 12% of women were eligible for LTT according to AASLD and EASL guidelines, respectively; 21% and 24% of women were eligible for prophylactic TDF and 2% and 5% in those ineligible (p < 0.001). Using the AASLD guidelines, the AUROC of TREAT-B, HBcrAg/ALT, and TA-PROHM scores were 0.88 (95%CI, 0.85-0.90), 0.90 (95%CI, 0.87-0.92), and 0.76 (95%CI, 0.73-0.80), respectively. Using the EASL guidelines, the AUROCs were lower: 0.73 (95%CI, 0.69-0.76), 0.76 (95%CI, 0.73-0.80), and 0.71 (95%CI, 0.67-0.74), respectively. Among those ineligible for prophylactic TDF, only 2% to 6% present an indication for LTT at 24 weeks postpartum. Few pregnant women are eligible for LTT, and the use of simplified criteria could represent an efficient triage option in decentralized areas to identify those negative for whom there is no urgent indication for LTT and focus on those positive for whom other exams must be conducted to confirm LTT indication.
Subject(s)
Hepatitis B, Chronic , Pregnancy Complications, Infectious , Humans , Female , Pregnancy , Pregnant Women , Hepatitis B Surface Antigens , Cambodia/epidemiology , Retrospective Studies , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/prevention & control , Hepatitis B e Antigens , DNA, Viral/analysis , Tenofovir/therapeutic use , Antiviral Agents/therapeutic use , Hepatitis B virus/genetics , Infectious Disease Transmission, Vertical/prevention & controlABSTRACT
BACKGROUND: Hepatitis B virus (HBV) elimination requires expanding and decentralising HBV care services. However, peripheral health facilities lack access to diagnostic tools to assess eligibility for antiviral therapy. Through the Hepatitis B in Africa Collaborative Network (HEPSANET), we aimed to develop and evaluate a score using tests generally available at lower-level facilities, to simplify the evaluation of antiviral therapy eligibility in people living with HBV. METHODS: We surveyed the availability of clinical and laboratory parameters across different health-care levels in sub-Saharan Africa. We used data from the HEPSANET dataset, the largest cross-sectional dataset of treatment-naive people living with HBV in sub-Saharan Africa, to derive and validate the score. Participants from this dataset were included in the analysis if they were aged 18 years or older and had liver fibrosis stages determined by a liver stiffness measurement or liver histopathology. Participants with co-infections or metabolic disorders were excluded. We allocated participants to the derivation and validation sets by geographical site. In the derivation set, we used stepwise logistic regression to identify the best performing parameters for identifying participants that met the 2017 European Association for the Study of the Liver (EASL) criteria. Regression coefficients were converted into integer points to construct simplified algorithms for different health-care levels. In the validation set, we estimated the area under the receiver operating characteristic, sensitivity, and specificity of the simplified algorithm for identifying antiviral therapy eligibility defined by the 2017 EASL criteria. FINDINGS: At 11 sites from eight countries that returned surveys, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count were generally available at district hospital levels, and hepatitis B e antigen and point-of-care HBV DNA tests were available only at regional and provincial hospital levels or above. Among 2895 participants included from the HEPSANET database (1740 [60·1%] male, 1155 [39·9%] female), 409 (14·1%) met EASL antiviral therapy eligibility criteria. In the derivation set, the optimal district-level hospital score was: ALT (IU/L), less than 40 (0 points), 40-79 (+1), 80 or greater (+2); AST (IU/L), less than 40 (0), 40-79 (+1), 80 or greater (+2); and platelet counts (109/L), less than 100 (+2), 100-149 (+1), 150 or greater (0). When combined with family history and clinical data for decompensated cirrhosis that do not require any biological tests, a cut-off of 2 points or more had a sensitivity and specificity of 82% (95% CI 76-86) and 95% (93-96) to identify treatment-eligible individuals in the derivation set, and 78% (71-85) and 87% (86-89) in the validation set, respectively. INTERPRETATION: Using a score incorporating platelet counts, AST, and ALT, the majority of people living with HBV requiring antiviral therapy can be identified. Our findings suggest that clinical staging can be decentralised down to district hospital level in sub-Saharan Africa. FUNDING: European Association for the Study of the Liver Foundation, John C Martin Foundation. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.
Subject(s)
Hepatitis B, Chronic , Hepatitis B , Humans , Male , Female , Cross-Sectional Studies , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/drug therapy , Hepatitis B/diagnosis , Hepatitis B/drug therapy , Hepatitis B/epidemiology , Hepatitis B virus/genetics , Africa , Antiviral Agents/therapeutic useABSTRACT
BACKGROUND: Global elimination of hepatitis B virus (HBV) requires expanded uptake of antiviral therapy, potentially by simplifying testing algorithms, especially in resource-limited countries. We evaluated the effectiveness, cost-effectiveness, and budget impact of three strategies that determine eligibility for anti-HBV treatment, as compared with the WHO 2015 treatment eligibility criteria, in The Gambia. METHODS: We developed a microsimulation model of natural history using data from the Prevention of Liver Fibrosis and Cancer in Africa programme (known as PROLIFICA) in The Gambia, for an HBV-infected cohort of individuals aged 20 years. The algorithms included in the model were a conventional strategy using the European Association for the Study of the Liver (EASL) 2017 criteria, a simplified algorithm using hepatitis B e antigen and alanine aminotransferase (the Treatment Eligibility in Africa for the Hepatitis B Virus [TREAT-B] score), a Treat All approach for all HBV-infected individuals, and the WHO 2015 criteria. Outcomes to measure effectiveness were disability-adjusted life years (DALYs) and years of life saved (YLS), which were used to calculate incremental cost-effectiveness ratios (ICERs) with the WHO 2015 criteria as the base-case scenario. Costs were assessed from a modified social perspective. A budget impact analysis was also done. We tested the robustness of results with a range of sensitiviy analyses including probabilistic sensitivity analysis. FINDINGS: Compared with the WHO criteria, TREAT-B resulted in 4877 DALYs averted and Treat All resulted in 9352 DALYs averted, whereas the EASL criteria led to an excess of 795 DALYs. TREAT-B was cost-saving, whereas the ICER for Treat All (US$2149 per DALY averted) was higher than the cost-effectiveness threshold for The Gambia (0·5 times the country's gross domestic product per capita: $352). These patterns did not change when YLS was the outcome. In a modelled cohort of 5000 adults (aged 20 years) with chronic HBV infection from The Gambia, the 5-year budget impact was $1·14 million for Treat All, $0·66 million for TREAT-B, $1·03 million for the WHO criteria, and $1·16 million for the EASL criteria. Probabilistic sensitivity analysis indicated that among the Treat All, EASL, and TREAT-B algorithms, Treat All would become the most preferred strategy only with a willingness-to-pay threshold exceeding approximately $72â000 per DALY averted or $110â000 per YLS. INTERPRETATION: Although the Treat All strategy might be the most effective, it is unlikely to be cost-effective in The Gambia. A simplified strategy such as TREAT-B might be a cost-saving alternative. FUNDING: UK Research and Innovation (Medical Research Council). TRANSLATION: For the French translation of the abstract see Supplementary Materials section.
Subject(s)
Cost-Effectiveness Analysis , Hepatitis B virus , Adult , Humans , Gambia , Cost-Benefit Analysis , Africa, Western , Antiviral Agents/therapeutic useABSTRACT
BACKGROUND: Elimination of mother-to-child transmission of hepatitis B virus (HBV) requires infant immunoprophylaxis and antiviral prophylaxis for pregnant women with high viral loads. Since real-time polymerase chain reaction (RT-PCR), a gold standard for assessing antiviral eligibility, is neither accessible nor affordable for women living in low-income and middle-income countries (LMICs), rapid diagnostic tests (RDTs) detecting alternative HBV markers may be needed. To inform future development of the target product profile (TPP) for RDTs to identify highly viremic women, we used a discrete choice experiment (DCE) and elicited preference and trade-off of healthcare workers (HCW) in Africa between the following four attributes of fictional RDTs: price, time-to-result, diagnostic sensitivity, and specificity. METHODS: Through an online questionnaire survey, we asked participants to indicate their preferred test from a set of two RDTs in seven choice tasks with varying levels of the four attributes. We used mixed multinomial logit models to quantify the utility gain or loss generated by each attribute. We attempted to define minimal and optimal criteria for test attributes that can satisfy ≥ 70% and ≥ 90% of HCWs, respectively, as an alternative to RT-PCR. RESULTS: A total of 555 HCWs from 41 African countries participated. Increases in sensitivity and specificity generated significant utility and increases in cost and time-to-result generated significant disutility. The size of the coefficients for the highest attribute levels relative to the reference levels were in the following order: sensitivity (ß = 3.749), cost (ß = -2.550), specificity (ß = 1.134), and time-to-result (ß = -0.284). Doctors cared most about test sensitivity, while public health practitioners cared about cost and midwives about time-to-result. For an RDT with 95% specificity, costing 1 US$, and yielding results in 20 min, the minimally acceptable test sensitivity would be 82.5% and the optimally acceptable sensitivity would be 87.5%. CONCLUSIONS: African HCWs would prefer an RDT with the following order of priority: higher sensitivity, lower cost, higher specificity, and shorter time-to-result. The development and optimization of RDTs that can meet the criteria are urgently needed to scale up the prevention of HBV mother-to-child transmission in LMICs.
Subject(s)
Hepatitis B virus , Pregnant Women , Infant , Female , Pregnancy , Humans , Hepatitis B virus/genetics , Viral Load , Infectious Disease Transmission, Vertical/prevention & control , Sensitivity and Specificity , Antiviral Agents , Health PersonnelABSTRACT
BACKGROUND: Chronic liver disease is a major cause of premature death in sub-Saharan Africa. Efficacy of antiviral therapy among patients with hepatitis B virus (HBV)-related cirrhosis is not well established in Africa. We described the clinical characteristics and outcomes of patients with cirrhosis and hepatocellular carcinoma in The Gambia and assessed the impact of tenofovir disoproxil fumarate (TDF) on survival of HBV-infected patients with cirrhosis. METHODS: In this prospective cohort study, we followed up adults who were consecutively diagnosed with cirrhosis or hepatocellular carcinoma between 2012 and 2015 in The Gambia, west Africa. Patients with chronic HBV infection and cirrhosis, without hepatocellular carcinoma, were offered TDF. Primary outcome was overall survival. To determine the effect of TDF on survival, we performed a Cox proportional hazard regression model with inverse probability of treatment weighting (IPTW) based on propensity score. FINDINGS: Of 529 patients enrolled in this study, 336 patients (252 with hepatocellular carcinoma and 84 with cirrhosis) were analysed. Patients were predominantly male (253 [75%] men and 83 [25%] women), with a median age of 42 years (IQR 33-55). 276 (84%) of 327 of patients with data were positive for HBV biomarkers, 31 (10%) of 311 were positive for hepatitis C virus antibodies, and 22 (10%) of 223 were positive for hepatitis D virus antibodies. 64% of patients with hepatocellular carcinoma had multifocal tumour, with a median size of 7·5 cm (IQR 5·4-10·8). 173 patients with hepatocellular carcinoma and 70 patients with cirrhosis were included in the survival analysis. Median survival was 1·5 months (95% CI 1·1-2·0) in patients with hepatocellular carcinoma and 17·1 months (11·2-24·0) in patients with cirrhosis (log-rank p<0·0001). In patients with hepatocellular carcinoma, ascites (hazard ratio [HR] 1·78, 95% CI 1·21-2·60), partial or complete portal thrombosis (HR 2·61, 1·58-4·30), and platelet count (HR 1·80, 1·19-2·70) were independent predictive factors of mortality at baseline. In HBV-infected patients with cirrhosis, median turnaround time between cirrhosis diagnosis and TDF initiation was 4·9 months (IQR 3·2-7·3). In IPTW analysis, TDF treatment was associated with improved survival in patients with HBV-related cirrhosis (adjusted HR 0·14, 0·06-0·34; p<0·0001). INTERPRETATION: These results highlight poor survival of patients with cirrhosis or hepatocellular carcinoma as well as the effectiveness of TDF in reducing the premature mortality of patients with cirrhosis and HBV infection. Interventions for early diagnosis and treatment of cirrhosis as well as screening programmes for hepatocellular carcinoma are urgently required in Africa. FUNDING: European Commission and Medical Research Council UK. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Adult , Humans , Male , Female , Middle Aged , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/etiology , Antiviral Agents/therapeutic use , Liver Neoplasms/epidemiology , Liver Neoplasms/drug therapy , Liver Neoplasms/etiology , Prospective Studies , Gambia/epidemiology , Tenofovir/therapeutic use , Liver Cirrhosis/complications , Hepatitis B virus , Africa, Western/epidemiology , Treatment Outcome , Retrospective StudiesABSTRACT
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.
Subject(s)
Hepatitis B virus , Hepatitis B , Infant , Infant, Newborn , Female , Pregnancy , Humans , Hepatitis B Surface Antigens , Hepatitis B e Antigens , Cost-Benefit Analysis , Hepatitis B Vaccines/therapeutic use , Infectious Disease Transmission, Vertical/prevention & control , Hepatitis B/epidemiology , Hepatitis B/prevention & control , Hepatitis B/drug therapy , Antiviral Agents/therapeutic useABSTRACT
Approximately 80 million people live with chronic hepatitis B virus (HBV) infection in the WHO Africa Region. The natural history of HBV infection in this population is poorly characterised, and may differ from patterns observed elsewhere due to differences in prevailing genotypes, environmental exposures, co-infections, and host genetics. Existing research is largely drawn from small, single-centre cohorts, with limited follow-up time. The Hepatitis B in Africa Collaborative Network (HEPSANET) was established in 2022 to harmonise the process of ongoing data collection, analysis, and dissemination from 13 collaborating HBV cohorts in eight African countries. Research priorities for the next 5 years were agreed upon through a modified Delphi survey prior to baseline data analysis being conducted. Baseline data on 4,173 participants with chronic HBV mono-infection were collected, of whom 38.3% were women and the median age was 34 years (interquartile range 28-42). In total, 81.3% of cases were identified through testing of asymptomatic individuals. HBeAg-positivity was seen in 9.6% of participants. Follow-up of HEPSANET participants will generate evidence to improve the diagnosis and management of HBV in this region.
Subject(s)
Hepatitis B, Chronic , Hepatitis B , Humans , Female , Adult , Male , Hepatitis B, Chronic/epidemiology , Hepatitis B/epidemiology , Hepatitis B virus/genetics , Africa/epidemiology , Hepatitis B e AntigensABSTRACT
BACKGROUND: Sub-Saharan Africa is highly endemic for hepatitis B virus (HBV); historically, most people were exposed during childhood through vertical or horizontal transmission. Although all African countries now provide a three-dose infant hepatitis B vaccination starting at age 6-8 weeks, only a third of African countries have introduced birth dose (HepB-BD) vaccine. Adding HepB-BD is fundamental to prevent vertical transmission, but its effectiveness in preventing horizontal transmission, compared with the three-dose infant vaccination alone, is unknown. We aimed to estimate the risk of early horizontal transmission in children of hepatitis B surface antigen (HBsAg)-negative mothers in sub-Saharan Africa stratified according to the vaccination schedule. METHODS: In this systematic review and meta-analysis we searched MEDLINE, Global Health, Embase, African Index Medicus and African Journals Online from their inception to Oct 24, 2022, for studies reporting HBsAg or HBV DNA, or both, in children (aged 0-5 years) of HBsAg-negative mothers. We excluded studies if children were only tested at birth. Two reviewers independently screened the titles and abstracts of all articles and data were extracted using a standardised pre-piloted data extraction sheet, and authors were contacted if any important information was missing. The primary outcome was the risk of HBV infection in children of HBsAg-negative mothers, stratified by vaccination schedule (no vaccination, first dose at 6-8 weeks, or first dose at birth). We pooled the child risks of HBsAg or HBV DNA-positivity from the age of 0 years to 5 years via a random-effect meta-analysis using a generalised linear mixed model. The study was registered on PROSPERO, CRD42021236203. FINDINGS: Of 8856 articles identified, 27 studies evaluating 10â003 children of HBsAg-negative mothers were included. The pooled risks of infection were 6·16% (95% CI 3·05-12·04; 155/1407) in the no vaccination group, 0·21% (0·04-1·15; 10/3425) in children who received their first dose at 6-8 weeks, and 0·05% (0·00-1·32; 3/2902) in children who received their first dose at birth. The difference was not statistically significant in children who received their first dose at 6-8 weeks and children who received their first dose at birth after adjusting for the study period, region, and maternal HIV status (test of moderators p=0·37). INTERPRETATION: In children of HBsAg-negative mothers, the risk of infection might be minimal even with the vaccination starting at 6-8 weeks, without clear additional benefit from HepB-BD. When births take place at home and timely administration of HepB-BD is challenging, antenatal HBsAg screening and selective HepB-BD might allow efficient allocation of resources to mother and child pairs at high risk compared with universal HepB-BD. FUNDING: None. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.
Subject(s)
Hepatitis B virus , Hepatitis B , Infant , Infant, Newborn , Child , Female , Humans , Pregnancy , Mothers , Hepatitis B Surface Antigens , DNA, Viral , Hepatitis B/epidemiology , Hepatitis B/prevention & control , Hepatitis B Vaccines , Infectious Disease Transmission, Vertical/prevention & control , Africa South of the Sahara/epidemiologyABSTRACT
Background: Clinical management of chronic hepatitis B virus (HBV) infection is complex and access to antiviral treatment remains limited in sub-Saharan Africa. International guidelines recommend monitoring at least annually for disease progression among HBV-infected people not meeting treatment criteria at initial diagnosis. This study aimed to assess the impact and cost-effectiveness of alternative strategies for monitoring. Methods: We used a mathematical model of HBV transmission and natural history, calibrated to all available West African data, to project the population-level health impact, costs and cost-effectiveness of different monitoring strategies for HBV-infected individuals not initially eligible for antiviral treatment. We assumed that these patients were found in the year 2020 in a hypothetical community-based screening programme in The Gambia. Monitoring frequencies were varied between every 5 and every 1 year and targeted different age groups. Results: The currently recommended annual monitoring frequency was likely to be not cost-effective in comparison with other strategies in this setting. 5-yearly monitoring in 15-45-year olds, at US$338 per disability-adjusted life year averted, had the highest probability of being the most effective cost-effective monitoring strategy. Conclusions: Monitoring less frequently than once a year is a cost-effective strategy in a community-based HBV screening and treatment programme in The Gambia, with the optimal strategy depending on the cost-effectiveness threshold. Efficiencies may be gained by prioritising the 15-45-year age group for more intensive monitoring.
Subject(s)
Hepatitis B, Chronic , Hepatitis B , Humans , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/drug therapy , Cost-Benefit Analysis , Gambia , Hepatitis B/diagnosis , Hepatitis B/drug therapy , Antiviral Agents/therapeutic useABSTRACT
In sub-Saharan Africa, simple biomarkers of liver fibrosis are needed to scale-up hepatitis B treatment. We conducted an individual participant data meta-analysis of 3,548 chronic hepatitis B patients living in eight sub-Saharan African countries to assess the World Health Organization-recommended aspartate aminotransferase-to-platelet ratio index and two other fibrosis biomarkers using a Bayesian bivariate model. Transient elastography was used as a reference test with liver stiffness measurement thresholds at 7.9 and 12.2kPa indicating significant fibrosis and cirrhosis, respectively. At the World Health Organization-recommended cirrhosis threshold (>2.0), aspartate aminotransferase-to-platelet ratio index had sensitivity (95% credible interval) of only 16.5% (12.5-20.5). We identified an optimised aspartate aminotransferase-to-platelet ratio index rule-in threshold (>0.65) for liver stiffness measurement >12.2kPa with sensitivity and specificity of 56.2% (50.5-62.2) and 90.0% (89.0-91.0), and an optimised rule-out threshold (<0.36) with sensitivity and specificity of 80.6% (76.1-85.1) and 64.3% (62.8-65.8). Here we show that the World Health Organization-recommended aspartate aminotransferase-to-platelet ratio index threshold is inappropriately high in sub-Saharan Africa; improved rule-in and rule-out thresholds can optimise treatment recommendations in this setting.