A Model of Care Optimized for Marginalized Remote Population Unravels Migration Pattern in India.

BACKGROUND AND AIMS: Access to basic health needs remains a challenge for most of world's population. In this study, we developed a care model for preventive and disease-specific health care for an extremely remote and marginalized population in Arunachal Pradesh, the northeasternmost state of India. APPROACH AND RESULTS: We performed patient screenings, performed interviews, and obtained blood samples in remote villages of Arunachal Pradesh through a tablet-based data collection application, which was later synced to a cloud database for storage. Positive cases of hepatitis B virus (HBV) were confirmed and genotyped in our central laboratory. The blood tests performed included liver function tests, HBV serologies, and HBV genotyping. HBV vaccination was provided as appropriate. A total of 11,818 participants were interviewed, 11,572 samples collected, and 5,176 participants vaccinated from the 5 westernmost districts in Arunachal Pradesh. The overall hepatitis B surface antigen (HBsAg) prevalence was found to be 3.6% (n = 419). In total, 34.6% were hepatitis B e antigen positive (n = 145) and 25.5% had HBV DNA levels greater than 20,000 IU/mL (n = 107). Genotypic analysis showed that many patients were infected with HBV C/D recombinants. Certain tribes showed high seroprevalence, with rates of 9.8% and 6.3% in the Miji and Nishi tribes, respectively. The prevalence of HBsAg in individuals who reported medical injections was 3.5%, lower than the overall prevalence of HBV. CONCLUSIONS: Our unique, simplistic model of care was able to link a highly resource-limited population to screening, preventive vaccination, follow-up therapeutic care, and molecular epidemiology to define the migratory nature of the population and disease using an electronic platform. This model of care can be applied to other similar settings globally.

An economic reappraisal of hepatitis B virus testing strategy for blood donors in Taiwan.

BACKGROUND AND OBJECTIVES: Taiwan is among the few hepatitis B virus (HBV) high-endemic countries that implement universal mini-pool nucleic acid testing (MP-NAT) and hepatitis B surface antigen (HBsAg) testing together with confirmatory individual donor nucleic acid testing (ID-NAT) for its blood supply since 2013. The aim of this study was to reappraise the value of HBsAg test in Taiwan's HBV testing strategy. MATERIALS AND METHODS: A Markov model was constructed, and cost-effectiveness analysis was conducted in order to reappraise the existing HBV screening strategy in Taiwan. RESULTS: The incremental cost-effectiveness ratio (ICER) for the current testing strategy in Taiwan was estimated to be $US 443 154 per quality-adjusted life year (QALY) gained. This is almost six times the willingness-to-pay (WTP) threshold that reflects local preferences. CONCLUSION: Universal HBsAg and MP-8-NAT together with confirmatory ID-NAT testing prevents a significant amount of HBV infections from entering the Taiwan blood supply. However, this comes at a disproportionate increase in cost.

A tool to measure the economic impact of Hepatitis B elimination: A case study in Saudi Arabia.

BACKGROUND: No virologic cure exists for hepatitis B virus (HBV) infection, and existing therapies are designed to control viral replication. We aimed to estimate the national prevalence of HBsAg in 2017 and study the impact of an enhanced diagnosis rate and universal treatment administration on HBV-related outcomes in Saudi Arabia. MATERIALS AND METHODS: A dynamic transmission and disease burden model was developed to estimate the future economic burden of HBV infection. The infected population was tracked by age and gender-defined cohorts; direct costs (healthcare, screening, diagnostics and treatment) and indirect costs (disability-adjusted life years and the value of a statistical life year) were calculated. The impact of two intervention scenarios (Achieve WHO Targets: diagnose 90% of infections and treat 80% of high viral load patients by 2030; and Diagnose and Treat All: diagnose and treat all infected patients by 2022) were compared against the Base Case scenario (no policy action), with near-universal vaccination coverage rates held constant. A sensitivity analysis of future treatment cost was also conducted. RESULTS: In 2017, HBsAg prevalence was estimated at 1.7%, corresponding to 574,000 infections. The same year, there was an estimated incidence of 490 cases of decompensated cirrhosis, 1500 cases of hepatocellular carcinoma (HCC) and 1740 liver-related deaths (LRD). HBsAg prevalence was 0.1% among 5-year-olds and <0.1% among infants. Disease burden outcomes by 2030, as compared with 2015, were as follows - Base Case: LRDs and HCC incidence were projected to increase by 70%. WHO Targets: A 30-35% decline in both HCC incidence and LRDs. Diagnose and Treat All: A 50-55% decline in HCC incidence and LRDs. In all scenarios, HBsAg prevalence among infants and 5-year-olds declined to <0.1% with the Diagnose and Treat all scenario resulting in a prevalence approaching zero in this age group. Annual direct costs are projected to increase and peak by 2022 in both intervention scenarios due to expansion of treatment and diagnostics. However, these are offset by the reduction of indirect economic costs, starting immediately in the WHO Targets scenario and by 2023 in the strategy to diagnose and treat all. Achieving WHO Targets is estimated to achieve a positive return on investment (ROI) by 2021 when examining direct costs and indirect economic losses at a treatment price of $2700 USD per patient yearly. Diagnosing and treating all patients, however, would require at least a 50% reduction in the unit cost of treatment to achieve a positive ROI by 2029. CONCLUSIONS: Increased diagnosis and treatment rates of HBV would lead to substantial declines in HCC and LRD. This effect would be dramatically enhanced by administering treatment to all HBV cases regardless of viral load and estimated to be highly cost-effective if treatment prices can be substantially reduced.

Disease burden of chronic hepatitis B and complications in China from 2006 to 2050: an individual-based modeling study.

BACKGROUND: Chronic hepatitis B has become a major public health problem in China. An accurate depiction of the disease burden has not yet been thoroughly conducted. We aimed to project the disease burden of chronic hepatitis B virus (HBV) infection and related complications by modeling various scenarios. METHOD: An individual-based Markov model was used to predict disease burden from 2006 through 2050. We simulated 5 scenarios with different annual incidences, diagnoses and nucleotide analog (NA) treatment rates as well as treatment eligibility, which included a natural history without diagnosis or NA therapy, a base case, a World Health Organization (WHO)-proposed target case and two ideal cases. RESULT: The natural history scenario is projected to have the fewest HBsAg losses (27.59 million) and highest number of HBV-related deaths (27.19 million). With improved diagnosis and treatment rates of NA therapy, ideal cases have fewer HBV-related deaths (14.46-14.77 million) than do WHO-proposed cases (15.13 million) and base cases (16.89 million), but the proportion of HBsAg loss is similar among them. With a reduction in new infections, the prevalence of chronic HBV in 2050 is expected to be a minimum of 27.03-27.49 million under WHO and ideal cases. CONCLUSION: Ideal scenarios 1 and 2 contribute to the lowest disease burden of HBV and its complications in the future, in which new infection control is more effective than increasing diagnosis, treatment rate and treatment eligibility. However, considering the large existing chronic HBV infected population and the low HBsAg loss rate of NA therapy, it is still difficult to avert the increasing trend of cumulative cirrhosis, DC, HCC, LT, and HBV-related death in all scenarios. If new high-potency drugs are not developed, the disease burden of chronic HBV will remain high in the future.

Early detection of chronic hepatitis B and risk factor assessment in Turkish migrants, Middle Limburg, Belgium.

BACKGROUND: Turkey is an intermediate hepatitis B virus (HBV) endemic country. However, prevalence among Turkish migrants in Belgium is unknown, especially in those born in Belgium with a foreign-born parent, i.e. second-generation migrants (SGM). AIMS: To evaluate the prevalence of HBV infection and associated risk factors in Turkish first-generation migrants (FGM), i.e. foreign-born, and SGM. METHODS: Between September 2017 and May 2019, free outreach testing for hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (anti-HBc), and antibodies against HBsAg was offered to Turkish migrants in Middle-Limburg, Belgium. Face-to-face questionnaire assessed HBV risk factors. HBsAg positive patients were referred and followed up. Turkish SGM were stratified into birth cohort born before and after 1987, since those born after 1987 should be covered by the universal infant vaccination program. RESULTS: A total of 1,081/1,113 (97.1%) Turkish did go for HBV testing. Twenty-six (2.4%) were HBsAg positive; 11/26 were unaware of their status and 10/11 were successfully referred. HBsAg prevalence was 3.0% in FGM and 1.5% in SGM, p = .070. Only one out of seven HBsAg positive SGM was born after 1987. In the multiple generalized estimating equations model, the most important risk factors for anti-HBc positivity were male gender (p = .021), older age (p < .001), FGM (p < .001), low educational level of the mother (p = .003), HBV infected mother (p = .008), HBV infected siblings (p = .002), HBV infected other family member (p = .004), gynaecological examination in Turkey or unsafe male circumcision (p = .032) and dental treatment in Turkey (p = .049). CONCLUSION: Outreach testing was well-accepted and referral to specialist care was generally successful. National HBV screening should be implemented in the Turkish FGM population and might be considered in SGM not covered by primary prevention strategies.

Post-vaccination anti-HBs testing among healthcare workers: More economical than post-exposure management for Hepatitis B.

OBJECTIVE: to compare the direct cost, from the perspective of the Unified Health System, of assessing the post-vaccination serological status with post-exposure management for hepatitis B among health care workers exposed to biological material. METHOD: cross-sectional study and cost-related, based on accident data recorded in the System of Information on Disease Notification between 2006 and 2016, where three post-exposure and one pre-exposure management scenarios were evaluated: A) accidents among vaccinated workers with positive and negative serological status tests for hepatitis B, exposed to known and unknown source-person; B) handling unvaccinated workers exposed to a known and unknown source-person; C) managing vaccinated workers and unknown serological status for hepatitis B and D) cost of the pre-exposure post-vaccination test. Accidents were assessed and the direct cost was calculated using the decision tree model. RESULTS: scenarios where workers did not have protective titles after vaccination or were unaware of the serological status and were exposed to a positive or unknown source-person for hepatitis B. CONCLUSION: the direct cost of hepatitis B prophylaxis, including confirmation of serological status after vaccination would be more economical for the health system.

Tenofovir prophylaxis for preventing mother-to-child hepatitis B virus transmission in China: A cost-effectiveness analysis.

OBJECTIVES: This study aimed to evaluate whether tenofovir prophylaxis for mothers with high viral loads in late pregnancy is a cost-effective way to prevent mother-to-child hepatitis B virus (HBV) transmission in China. METHODS: A decision tree Markov model was constructed for a cohort of infants born to HBV surface antigen-positive mothers in China, 2016. The expected cost and effectiveness were compared between the current active-passive immunoprophylaxis strategy and the tenofovir prophylaxis strategy, and the incremental cost-effectiveness ratio was calculated. One-way and multi-way probabilistic sensitivity analyses were performed. RESULTS: For 100,000 babies born to mothers positive for hepatitis B surface antigen, tenofovir prophylaxis strategy will prevent 2213 perinatal HBV infections and will gain 931 quality-adjusted life years when compared with the current active-passive immunoprophylaxis strategy. The incremental cost-effectiveness ratio was ï¿¥59,973 ($9087) per quality-adjusted life years gained. This result was robust over a wide range of assumptions. CONCLUSIONS: Tenofovir prophylaxis for mothers with high viral loads in late pregnancy was found to be more cost-effective than the current active-passive immunoprophylaxis alone. Embedding tenofovir prophylaxis for mothers with high virus loads into the present hepatitis B prevention strategies should be considered to further prevent mother-to-child hepatitis B transmission in China.

Assessment of a poly-epitope candidate vaccine against Hepatitis B, C, and poliovirus in interaction with monocyte-derived dendritic cells: An ex-vivo study.

Design and application of epitope-based polyvalent vaccines have recently garnered attention as an efficient alternative for conventional vaccines. We previously have reported the in silico design of HHP antigen which encompasses the immune-dominant epitopes of Hepatitis B surface antigen (HBsAg), Hepatitis C core protein (HCVcp) and Poliovirus viral proteins (VPs). It has been shown that the HHP has desirable conformation to expose the epitopes, high antigenicity and other desired physicochemical and immunological properties. To confirm the accuracy of these predictions, the ex-vivo immunogenicity of the HHP was assessed. The HHP gene was chemically synthesized in pET28a and expressed in E. coli (BL21). The expressed protein was purified and its immunological potency was evaluated on dendritic cells (DCs) as antigen presenting cells (APCs). Functional analysis was assessed in co-cultivation of autologous T-cells with matured DCs (mDCs). T-cell activation, proliferation and cytokines secretion were evaluated using flowcytometry and ELISA methods. Our results indicated that the HHP could induce the DC maturation. The mDCs were able to trigger T-cell activation and proliferation. In silico design and ex-vivo confirmation of immunological potential could pave the way to introduce efficient immunogens for further analysis. The ability of HHP in DC maturation and T-cell activation makes it an amenable vaccine candidate for further in-vivo studies.

Hepatitis B-related outcomes following direct-acting antiviral therapy in Taiwanese patients with chronic HBV/HCV co-infection.

BACKGROUND & AIMS: The outcome of HBV infection, including the dynamics of HBsAg and HBV virological reactivation, among patients coinfected with HCV receiving direct-acting antivirals (DAAs) remains unclear. Thus, we aimed to analyze HBV-related outcomes in these patients. METHODS: Serial HBsAg and HBV DNA levels were measured in 79 HBV/HCV-coinfected patients receiving DAAs (13 receiving anti-HBV nucleot(s)ide analog [NUC] therapy simultaneously). The endpoints included HBsAg dynamics and seroclearance, HBV reactivation (HBV DNA >1 log increase or >100 IU/ml if undetectable at baseline) and HBV-related clinical reactivation. RESULTS: HBsAg levels declined from a median of 73.3 IU/ml at baseline to 16.2 IU/ml at the end-of-DAA treatment and increased to 94.1 IU/ml at 12 months post-treatment. During a mean 11.1-months of follow-up, 8 (10.1%) patients experienced HBsAg seroclearance and 30 (38.0%) HBV reactivation (12-month cumulative incidence, 10.3% and 40.4%, respectively). Patients with pre-treatment HBsAg ≤10 IU/ml had a significantly higher rate of HBsAg seroclearance (hazard ratio [HR] 8.52; 95% CI 1.048-69.312) and lower risk of HBV reactivation than those with pre-treatment HBsAg >10 IU/ml (HR 2.88; 95% CI 1.057-7.844) in multivariate analyses. Six patients (4 cirrhotics) not receiving NUC therapy experienced HBV-related clinical reactivation; 3 of the 4 cirrhotics developed liver failure and 2 died despite immediate NUC therapy. Compared to untreated HBV-monoinfected patients, HBV/HCV-coinfected patients without NUC prophylaxis had a similar rate of HBsAg seroclearance, but a significantly higher risk of HBV reactivation following DAA therapy (HR 6.59; 95% CI 2.488-17.432). CONCLUSIONS: DAA-treated HBV/HCV-coinfected patients had significantly higher rates of HBV seroclearance, particularly among those with low pre-treatment HBsAg titer, but were at higher risk of HBV reactivation, particularly among those with higher pre-treatment HBsAg titer. Prophylactic anti-HBV therapy is essential for cirrhotic patients, irrespective of baseline HBV DNA levels. LAY SUMMARY: We studied outcomes relating to hepatitis B virus (HBV) in patients coinfected with both hepatitis B and C. Patients receiving direct-acting antiviral treatment for hepatitis C were more likely to experience seroclearance (or functional cure of HBV), but were also more likely to experience HBV reactivation, which can lead to hepatitis, liver failure and death. In coinfected cirrhotic patients being treated for HCV, prophylactic treatment for HBV is mandatory.

Post-vaccination anti-HBs testing among healthcare workers: More economical than post-exposure management for Hepatitis B / Teste anti-HBs pós-vacinação entre trabalhadores da saúde: mais econômico que manejo pós-exposição para Hepatite B / Pruebas anti-HBs post-vacunación entre los trabajadores de la salud: más económico que el manejo post-exposición para la Hepatitis B

Objective: to compare the direct cost, from the perspective of the Unified Health System, of assessing the post-vaccination serological status with post-exposure management for hepatitis B among health care workers exposed to biological material. Method: cross-sectional study and cost-related, based on accident data recorded in the System of Information on Disease Notification between 2006 and 2016, where three post-exposure and one pre-exposure management scenarios were evaluated: A) accidents among vaccinated workers with positive and negative serological status tests for hepatitis B, exposed to known and unknown source-person; B) handling unvaccinated workers exposed to a known and unknown source-person; C) managing vaccinated workers and unknown serological status for hepatitis B and D) cost of the pre-exposure post-vaccination test. Accidents were assessed and the direct cost was calculated using the decision tree model. Results: scenarios where workers did not have protective titles after vaccination or were unaware of the serological status and were exposed to a positive or unknown source-person for hepatitis B. Conclusion: the direct cost of hepatitis B prophylaxis, including confirmation of serological status after vaccination would be more economical for the health system.

Objetivo: comparar o custo direto, sob a perspectiva do Sistema Único de Saúde, da avaliação do status sorológico pós-vacinação com o manejo pós-exposição para hepatite B entre trabalhadores da área da saúde expostos ao material biológico. Método: estudo transversal e de custo, realizado a partir dos dados de acidentes registrados no Sistema de Informação de Agravos de Notificação entre 2006 e 2016, em que foram avaliados três cenários de manejo pós-exposição e um de pré-exposição: A) acidentes entre trabalhadores vacinados com status sorológico positivo e negativo para hepatite B, expostos à pessoa-fonte conhecida e desconhecida; B) manejo dos trabalhadores não vacinados expostos à pessoa-fonte conhecida e desconhecida; C) manejo dos trabalhadores vacinados e status sorológico desconhecido para hepatite B e D) custo do teste pós vacinação pré-exposição. Os acidentes foram avaliados e o custo direto foi calculado utilizando o modelo árvore de decisão. Resultados: apresentaram maior custo os cenários em que os trabalhadores não possuíam títulos protetores após a vacinação ou desconheciam o status sorológico e foram expostos à pessoa-fonte positivo ou desconhecida para hepatite B. Conclusão: o custo direto da profilaxia para hepatite B, incluindo a confirmação do status sorológico após vacinação seria mais econômico para o sistema de saúde.

Objetivo: comparar el costo directo, desde la perspectiva del Sistema Único de Salud, de la evaluación del status serológico post-vacunación con el manejo post-exposición para la hepatitis B entre los trabajadores de la salud expuestos a material biológico. Método: estudio transversal y de costos, basado en datos de accidentes registrados en el Sistema de Información de Enfermedades Notificables entre 2006 y 2016, en el que se evaluaron tres escenarios de gestión posteriores a la exposición y uno previo a la exposición: A) accidentes entre trabajadores vacunados con status serológico positivo y negativo para hepatitis B, expuestos a una fuente de origen conocida y desconocida; B) manejo de trabajadores no vacunados expuestos a una fuente conocida y desconocida; C) manejo de trabajadores vacunados y estado serológico desconocido para hepatitis B y D) costo de la prueba de pre-exposición post-vacunación. Se evaluaron los accidentes y se calculó el costo directo utilizando el modelo de árbol de decisión. Resultados: los escenarios en los que los trabajadores no tenían títulos de protección después de la vacunación o desconocían el status serológico y estaban expuestos a una persona fuente positiva o desconocida para la hepatitis B reflejaron un costo más alto. Conclusión: el costo directo de la profilaxis para la hepatitis B, incluida la confirmación del status serológico después de la vacunación sería más económico para el sistema de salud.

HCV and HBV prevalence based on home blood self-sampling and screening history in the general population in 2016: contribution to the new French screening strategy.

BACKGROUND: The advent of effective direct-acting antivirals (DAAs), has prompted an assessment of the French Hepatitis C virus (HCV) screening strategy, which historically targeted high-risk groups. One of the options put forward is the implementation of combined (i.e., simultaneous) HCV, Hepatitis B virus (HBV) and HIV screening for all adults at least once during their lifetime ("universal combined screening"). However, recent national survey-based data are lacking to guide decision-making regarding which new strategy to implement. Accordingly, we aimed to provide updated data for both chronic hepatitis C (CHC) and B (CHB) prevalence and for HCV and HBV screening history, using data from the BaroTest and 2016 Health Barometer (2016-HB) studies, respectively. METHODS: 2016-HB was a national cross-sectional phone based health survey conducted in 2016 among 20,032 randomly selected individuals from the general population in mainland France. BaroTest was a virological sub-study nested in 2016-HB. Data collected for BaroTest were based on home blood self-sampling on dried blood spots (DBS). RESULTS: From 6945 analyzed DBS, chronic hepatitis C (CHC) and B (CHB) prevalence was estimated at 0.30% (95% Confidence Interval (CI): 0.13-0.70) and 0.30% (95% CI: 0.13-0.70), respectively. The proportion of individuals aware of their status was estimated at 80.6% (95% CI: 44.2-95.6) for CHC and 17.5% (95% CI: 4.9-46.4) for CHB. Universal combined screening would involve testing between 32.6 and 85.3% of 15-75 year olds according to whether we consider only individuals not previously tested for any of the three viruses, or also those already tested for one or two of the viruses. CONCLUSIONS: Our data are essential to guide decision-making regarding which new HCV screening recommendation to implement in France. They also highlight that efforts are still needed to achieve the WHO's targets for eliminating these diseases. Home blood self-sampling may prove to be a useful tool for screening and epidemiological studies.

Chronic hepatitis delta: A state-of-the-art review and new therapies.

Chronic delta hepatitis is the most severe form of viral hepatitis affecting nearly 65 million people worldwide. Individuals with this devastating illness are at higher risk for developing cirrhosis and hepatocellular carcinoma. Delta virus is a defective RNA virus that requires hepatitis B surface antigen for propagation in humans. Infection can occur in the form of a co-infection with hepatitis B, which can be self-limiting, vs superinfection in a patient with established hepatitis B infection, which often leads to chronicity in majority of cases. Current noninvasive tools to assess for advanced liver disease have limited utility in delta hepatitis. Guidelines recommend treatment with pegylated interferon, but this is limited to patients with compensated disease and is efficacious in about 30% of those treated. Due to limited treatment options, novel agents are being investigated and include entry, assembly and export inhibitors of viral particles in addition to stimulators of the host immune response. Future clinical trials should take into consideration the interaction of hepatitis B and hepatitis D as suppression of one virus can lead to the activation of the other. Also, surrogate markers of treatment efficacy have been proposed.

Survey of Impediments to Prevention of Mother-to-infant Transmission of Hepatitis B Virus by International Societies.

OBJECTIVE: Mother-to-infant transmission (MIT) is the leading cause of hepatitis B virus (HBV) infections globally. The aim of this international study was to assess the impediments to prevention of (MIT) of HBV. METHODS: A cross-sectional survey was developed by the Federation of the International Societies for Pediatric Gastroenterology, Hepatology and Nutrition. (FISPGHAN) The survey was sent to HBV experts of the 5-member societies of FISPGHAN, and 63 of 91 countries/regions responded. Main outcome measures include percentage of countries having vaccine programs, timing of the first dose of HBV vaccine, availability of HBV vaccine for outborn neonates, payment of HBV vaccine and hepatitis B immune globulin, screening HBV markers during pregnancy, and antivirals to highly infectious pregnant mothers. RESULTS: Among the participating countries/regions, 11% did not implement infant HBV immunization programs. The first dose of vaccine was given >24 hours in 36% of the total countries and 100% of African countries. The recommended birth dose was unavailable for outborn neonates in 45% of the total countries, including 92% of African and 50% of Latin American countries/regions. During pregnancy, 44% countries do not screen maternal viral markers, and 46% do not provide third trimester antiviral therapy for highly viremic pregnant mothers. CONCLUSIONS: Our study demonstrated multiple obstacles to achieving the goal of preventing MIT of HBV. Comprehensive public health programs to enhance vaccine coverage rate, supply HBV vaccine for out-born neonates, screening maternal HBV markers, treating highly viremic pregnant mothers are proposed to overcome these obstacles and achieve the goal of preventing MIT of HBV.

Modelling cost-effectiveness of tenofovir for prevention of mother to child transmission of hepatitis B virus (HBV) infection in South Africa.

BACKGROUND: International sustainable development goals for the elimination of viral hepatitis as a public health problem by 2030 highlight the need to optimize strategies for prevention, diagnosis and treatment of hepatitis B virus (HBV) infection. An important priority for Africa is to have affordable, accessible and sustainable prevention of mother to child transmission (PMTCT) programmes, delivering screening and treatment for antenatal women and implementing timely administration of HBV vaccine for their babies. METHODS: We developed a decision-analytic model simulating 10,000 singleton pregnancies to assess the cost-effectiveness of three possible strategies for deployment of tenofovir in pregnancy, in combination with routine infant vaccination: S1: no screening nor antiviral therapy; S2: screening and antiviral prophylaxis for all women who test HBsAg-positive; S3: screening for HBsAg, followed by HBeAg testing and antiviral prophylaxis for women who are HBsAg-positive and HBeAg-positive. Our outcome was cost per infant HBV infection avoided and the analysis followed a healthcare perspective. RESULTS: Based on 10,000 pregnancies, S1 predicts 45 infants would be HBV-infected at six months of age, compared to 21 and 28 infants in S2 and S3, respectively. Relative to S1, S2 had an incremental cost of $3940 per infection avoided. S3 led to more infections and higher costs. CONCLUSION: Given the long-term health burden for individuals and economic burden for society associated with chronic HBV infection, screening pregnant women and providing tenofovir for all who test HBsAg+ may be a cost-effective strategy for South Africa and other low/middle income settings.

Anti-HBc prevalence among Croatian blood donors in a 14-year period (2004-2017): Assessment of trends, risks and need for implementing routine testing.

OBJECTIVES: The anti-HBc prevalence over a 14-years period (2004-2017), trends, infectivity, residual risk, and need for testing in blood donors (BD) of the Croatian Institute of Transfusion Medicine were assessed. MATERIAL AND METHODS: Anti-HBc was tested in 19,969 BD serum samples collected in 2004 (N=7561), 2013 (N=7318) and 2017 (N=5090). All serums were initially screened for HBsAg, anti-HCV, HIV Ag/Ab, and anti-TP. 2013 and 2017 samples were also tested by ID-NAT. RESULTS: Over a 14-years period, the anti-HBc prevalence significantly decreased among Croatian BD (5.24% in 2004, 2.56% in 2013, and 1.32% in 2017). Similarly, the prevalence of anti-HBc-only profiles decreased from 0.62% in 2004, 0.25% in 2013, and 0.21% in 2017. The 4-time decreasing trend was observed in all age groups of BD from 2017 but mostly among repeat donors (5.90% to 1.38%). First-time donors showed no significant difference in anti-HBc prevalence probably due to their younger age (<29 years) and HBV vaccine status. However, similar anti-HBs carriage rates (80.56%, 87.57%, and 82.09%) were reported in anti-HBc positive donors over the study period. HBsAg and HBV DNA were not detected. No OBI infection was found in the study despite an OBI frequency of 1:10,900 donations previously reported in Croatia. A HBV decreasing residual risks of 68, 88, and 12 per million donations were estimated for years 2004, 2013, and 2017, respectively. CONCLUSION: Anti-HBc testing is an additional measure of preventing HBV infection by transfusion. Implementation of anti-HBc testing will result in the deferral of 1.3% BD and should be supported by cost-benefit analyses.

An Assessment of Upper Limits of Normal for ALT and the Impact on Evaluating Natural Course of Chronic Hepatitis B Virus Infection in Chinese Children.

BACKGROUND: The current upper limits of normal (ULN) for serum alanine aminotransferase (ALT) are increasingly challenged. We aimed to re-evaluate the ULN for ALT and assess the potential impact on the classification of natural course of chronic hepatitis B virus (HBV) infection in children. METHODS: Laboratory data obtained from three hospitals in China were retrospectively analysed. In total, 2054 children with chronic HBV infection and 8149 healthy children at age ≤18 years were included in the study. RESULTS: Age-specific and gender-specific ULNs for ALT, at averages of 30 U/L for boys and 24 U/L for girls, were calculated from the data of healthy children. Using the revised ULNs vs. the current ULNs (40-50 U/L), 31-60% vs. 9-17% of the 2054 HBV-infected children had an abnormal result as seen in their ALT baseline analysis, and the highest abnormality rate was seen in the infants. Data of 516 HBV-infected children were applied for the classification of clinical phase, 28.8% vs. 19.8% of the children were classified into the phases of hepatitis B e antigen (HBeAg-)positive/negative hepatitis. During a median follow-up of 62 months, 39 of 153 children underwent HBeAg seroconversion, whereas 3 of them had persistently "normal" ALT, according to the current ULN. CONCLUSIONS: The revision of ULN for ALT in children substantially impacts the classification of the natural course of chronic HBV infection. Mild ALT fluctuation is common during the stage childhood, suggesting a need to rethink the current conceptions of immune tolerance and natural course of chronic HBV infection in the children.

The Effectiveness and Cost-Effectiveness of Screening for and Vaccination Against Hepatitis B Virus among Migrants in the EU/EEA: A Systematic Review.

Migrants from hepatitis B virus (HBV) endemic countries to the European Union/European Economic Area (EU/EEA) comprise 5.1% of the total EU/EEA population but account for 25% of total chronic Hepatitis B (CHB) infection. Migrants from high HBV prevalence regions are at the highest risk for CHB morbidity. These migrants are at risk of late detection of CHB complications; mortality and onwards transmission. The aim of this systematic review is to evaluate the effectiveness and cost-effectiveness of CHB screening and vaccination programs among migrants to the EU/EEA. We found no RCTs or direct evidence evaluating the effectiveness of CHB screening on morbidity and mortality of migrants. We therefore used a systematic evidence chain approach to identify studies relevant to screening and prevention programs; testing, treatment, and vaccination. We identified four systematic reviews and five additional studies and guidelines that reported on screening and vaccination effectiveness. Studies reported that vaccination programs were highly effective at reducing the prevalence of CHB in children (RR 0.07 95% CI 0.04 to 0.13) following vaccination. Two meta-analyses of therapy for chronic HBV infection found improvement in clinical outcomes and intermediate markers of disease. We identified nine studies examining the cost-effectiveness of screening for CHB: a strategy of screening and treating CHB compared to no screening. The median acceptance of HB screening was 87.4% (range 32.3⁻100%). Multiple studies highlighted barriers to and the absence of effective strategies to ensure linkage of treatment and care for migrants with CHB. In conclusion, screening of high-risk children and adults and vaccination of susceptible children, combined with treatment of CHB infection in migrants, are promising and cost-effective interventions, but linkage to treatment requires more attention.

World hepatitis day in Burkina Faso, 2017: seroprevalence and vaccination against hepatitis B virus to achieve the 2030 elimination goal.

BACKGROUND: Burkina Faso is a high endemicity country for HBV infection. However, there are few data on vaccine coverage against HBV. The aim of this study was to contribute to the improvement of HBV vaccine coverage in Ouagadougou through HBV screening. METHODS: Awareness campaigns and voluntary hepatitis B screening were organized in the twelve districts of Ouagadougou by the "SOS Hepatitis Burkina" association. A rapid HBsAg detection test (Abon Biopharma Guangzhou, Co., Ltd. Chine) was performed on 2216 individuals, who voluntarily answered a series of questions. Vaccination against hepatitis B was proposed to HBV negative participants. RESULTS: In a sample of 2216 participants, aged 1 to 78 years (mean age 29.7 ± 14.7 years); a prevalence of 10.4% (230/2216) of HBsAg was obtained. This prevalence was high in the age groups 31 to 40 years (14.5%) and 41 to 50 years (15.0%). The prevalence of HBV was higher in the sixth district (14.3%) of Ouagadougou. At the end of the screening, 1202/1986 HBV negative participants were vaccinated, resulting in a vaccination rate of 60.5%. Vaccination coverage ranged from 44.5 to 73.7% all twelve districts. CONCLUSIONS: This study still reports a high prevalence of HBV infection among young people with a peak in the sixth district of Ouagadougou. The study achieved high vaccination coverage in all age groups and districts of Ouagadougou. TRIAL REGISTRATION: The present study has been approved by the Ethics Committee for Health Research of Burkina Faso. CERS201501006 Registered 14 January 2015.

Hepatitis B virus reactivation in patients with rheumatoid arthritis: Analysis of the National Database of Japan.

This study aimed to determine the incidence and risk factors for hepatitis B virus (HBV) reactivation in patients with rheumatoid arthritis (RA) undergoing immunosuppressive therapy. The National Database of Japan, in which insurance claim data have been comprehensively accumulated, was utilized. The subjects were 76 641 RA patients who were plausibly initiated on immunosuppressive therapy from April 2013 to March 2014. Laboratory tests of the hepatitis B surface antigen, anti-hepatitis B virus surface antibody, and anti-hepatitis B virus core antibody were performed in 28.23%, 12.52% and 14.63% of patients, respectively, when the therapy was initiated. We found that HBV reactivation and fulminant hepatitis occurred in both the patients with and without HBV DNA monitoring, indicating insufficient monitoring in Japan during the study. The cumulative incidence of HBV reactivation over 24 months was 1.57% (95% confidence interval [CI] = 1.28%-1.92%) in the monitoring group, which consisted of those with resolved HBV infection. Glucocorticoid administration was a potent risk factor for HBV reactivation (hazard ratio [HR]  = 1.70, 95% CI = 1.26-2.29, P = .001 in all subjects, and HR = 1.82, 95% CI = 1.18-2.81, P = .007 in the nonmonitoring group), although it was not statistically significant in the monitoring group (HR = 1.49, 95% CI = 0.99-2.26 and P = .057). No significant risk difference was observed between single administration of methotrexate and biological drugs.