Serological and vaccine evaluation for hepatitis B among Community Health Workers / Avaliação sorológica e vacinal para hepatite B entre Agentes Comunitários de Saúde / Evaluación serológica y vacuna para la hepatitis B entre Agentes Comunitarios de Salud

Abstract Objective: to identify the vaccination and serological status against hepatitis B among community health workers; to vaccinate against hepatitis B virus and to evaluate the immune response of susceptible workers. Method: phase I, cross-sectional and descriptive study, among community health workers in a capital city of the Midwest region, through a self-administered questionnaire, checking of vaccination cards, and blood collection for testing of serological markers for hepatitis B. Phase II, cohort study carried out in vaccinated non-immune workers identified in phase I. They received one dose of vaccine (challenge dose) and serological testing. Results: a total of 109 workers participated in the study. Most had vaccination record (97; 89.0%) and vaccination completeness (75; 77.3%), while the isolated anti-HBs (Antibodies against hepatitis B virus) marker was detected in 78 (71.6%) workers. The prevalence of hepatitis B virus exposure was 8.2%. Of the ten non-immune vaccinated workers, after challenge dose, one remained susceptible. Conclusion: although most workers are vaccinated and show immunological response to hepatitis B, susceptibility after challenge dose was identified. Therefore, it is necessary to have a surveillance program of the vaccination situation and serological status for this virus, to promote these workers' safety.

Resumo Objetivo: identificar a situação vacinal e sorológica contra hepatite B entre agentes comunitários de saúde; vacinar contra o vírus da hepatite B e avaliar a resposta imunológica dos agentes susceptíveis. Método: fase I, estudo transversal e descritivo, entre agentes comunitários de saúde de uma capital da região Centro-oeste, por meio de questionário autoaplicável, conferência do cartão vacinal e coleta de sangue para testagem dos marcadores sorológicos para hepatite B. Fase II, estudo de coorte realizado em trabalhadores vacinados não imunes e identificados na fase I. Estes receberam uma dose da vacina (dose desafio) e teste sorológico. Resultados: participaram do estudo 109 agentes. A maioria tinha registro de vacinação (97; 89,0%) e completude vacinal (75; 77,3%), já o marcador anti-HBs (anticorpos contra o vírus da hepatite B) isolado foi detectado em 78 (71,6%) agentes. A prevalência de exposição ao vírus da hepatite B foi de 8,2%. Dos dez agentes vacinados não imunes, após a dose desafio, um permaneceu susceptível. Conclusão: apesar da maioria dos trabalhadores estarem vacinados e apresentarem resposta imunológica para hepatite B, a suscetibilidade após a dose desafio foi identificada. Portanto, é necessário que haja um programa de vigilância da situação vacinal e estado sorológico para este vírus, para promover a segurança destes trabalhadores.

Resumen Objetivo: identificar la situación de la vacunación y serología contra la hepatitis B entre agentes comunitarios de la salud, vacunar contra el virus de la hepatitis B y evaluar la respuesta inmunológica de los agentes susceptibles. Método: fase I, estudio transversal y descriptivo, entre agentes comunitarios de la salud de una capital de la región centro oeste, por medio de cuestionario autoadministrado, verificación del carné de vacunación y extracción de sangre para comprobar los marcadores serológicos para la hepatitis B. Fase II, estudio de cohorte realizado en trabajadores vacunados no inmunes e identificados en la Fase I; estos recibieron una dosis de la vacuna (dosis de desafío) y realizaron el test serológico. Resultados: participaron del estudio 109 agentes. La mayoría tenía registro de vacunación (97; 89,0%) y de cobertura de vacunación (75; 77,3%); el marcador anti-HBs (Anticuerpos contra el virus de la hepatitis B) aislado fue detectado en 78 (71,6%) de los agentes. La prevalencia de exposición al virus de la hepatitis B fue de 8,2%. De los diez agentes vacunados no inmunes, después de la dosis desafío, uno permaneció susceptible. Conclusión: a pesar de que la mayoría de los trabajadores estaban vacunados y presentaron respuesta inmunológica para la hepatitis B, la susceptibilidad, después de la dosis desafío, fue identificada. Por tanto, es necesario que exista un programa de vigilancia de la situación de vacunación y estado serológico para este virus, para promover la seguridad de estos trabajadores.

Seroepidemiological survey of hepatitis B among children aged eight months to 14 years in Dali Bai Autonomous Prefecture, 2013-2020 / 中华传染病杂志

Objective:To analyze the hepatitis B vaccine (HepB) vaccination rate and immune level among children aged eight months to 14 years in Dali Bai Autonomous Prefecture, and to evaluate the effect of immune prevention and control.Methods:A stratified and cluster sampling was designed to survey and collect serum samples of the 17 236 cases from 12 counties (cities) in Dali Bai Autonomous Prefecture. The cases were divided into four age groups (eight to 17 months, 18 to 35 months, three to six years, seven to 14 years). Serum levels of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) were detected by enzyme linked immunosorbent assay (ELISA). Statistical analysis was conducted by Spearman rank correlation analysis and chi-square test.Results:The overall HepB vaccination rate, timely vaccination rate, and full course vaccination rate among 17 236 children were 98.78%(17 025/17 236), 84.13%(14 500/17 236) and 97.69%(16 838/17 236), respectively. The positive rates of HBsAg and anti-HBs were 0.28%(49/17 236) and 70.57%(12 164/17 236), respectively. From 2013 to 2020, the trend of the vaccination rate, timely vaccination rate, and full vaccination rate of HepB increased year by year. The timely vaccination rate (88.64%(3 989/4 500)) and the positive rate of anti-HBs (92.78%(4 175/4 500)) were the highest at the age of eight to 17 months. Age was negatively correlated with the positive rate of anti-HBs ( rs=-0.427, P<0.001). The vaccination rate, full course vaccination rate, and positive rate of HBsAg in males were higher than those in females ( χ2=4.41, 6.05 and 0.92, respectively, all P<0.05), while the vaccination rate, timely vaccination rate and full course vaccination rate in rural areas were higher than those in urban areas ( χ2=51.75, 4.81 and 33.20, respectively, all P<0.05). The vaccination rate, full course vaccination rate and the positive rate of anti-HBs in minority nationality were higher than those in Han nationality ( χ2=29.44, 11.83 and 5.04, respectively, all P<0.05). The differences were all statistically significant. The positive rates of anti-HBs in individuals with a history of immunization, timely vaccination, and full vaccination of HepB were higher than those in individuals without a history of HepB immunization, timely vaccination, and full vaccination, and the differences were all statistically significant ( χ2=64.67, 65.46 and 13.39, respectively, all P<0.001). Conclusions:The positive rate of anti-HBs in the older age group has decreased significantly. While continuing carrying out routine immunization work, monitoring, strengthening supplementary immunization should be emphasized, and HepB vaccination in older children should be explored to consolidate the immune barrier.

Biomarcadores convencionales y emergentes en hepatitis B / Conventional and emerging biomarkers in hepatitis B

A nivel mundial, 300 millones de personas están infectadas por el virus de la hepatitis B (VHB). A pesar de que existe una vacuna que previene la infección y se dispone de tratamiento antiviral que suprime la replicación del virus, no hay cura aún. El principal problema que evita la recuperación total del paciente, incluso para aquel que recibe tratamiento, es la persistencia de dos formas del genoma viral en los hepatocitos: el ADN circular covalentemente cerrado (ADNccc), el cual se encuentra en forma de episoma y tiene la capacidad de replicarse, y las secuencias lineales subge-nómicas que se integran en el genoma humano, con potencial oncogénico. Hasta el momento se dispone de unos pocos biomarcadores para monitorear o predecir la progresión de la enfermedad y la respuesta al tratamiento. Estos biomarcadores se detectan durante la infección, y son la base para la monitorización de la enfermedad y hacer un diagnóstico de la fase clínica de la infección. Recientemente han surgido nuevos biomarcadores como el antígeno relacionado con el core del virus de la hepatitis B (HBcrAg) y la detección del ARN del VHB, que parecen correlacionarse con los niveles transcripcionales del ADNccc, además, durante el tratamiento parecen ayudar a predecir la respuesta y podrían identificar aquellos a quienes se les puede suspender la terapia sin riesgo de recaída. En esta revisión, se describe la utilidad de los principales biomarcadores convencionales en hepatitis B, y se abordan los dos biomarcadores emergentes más estudiados que prometen evaluar el curso de la infección, al igual que determinar la progresión de la enfermedad y la respuesta al tratamiento.

Globally, 300 million people are infected with hepatitis B virus (HBV). Although there is a vaccine that prevents infection and antiviral treatment that suppresses the replication of the virus, there is still no cure. The main problem that prevents the total recovery of the patient, even for those who recei-ve treatment, is the persistence of two forms of the viral genome in hepatocytes: covalently close circular DNA (cccDNA), which is in the form of an episome that has the ability to replicate, and linear subgenomic sequences that are integrated into the human genome, with oncogenic potential. Few biomarkers are currently available to monitor or predict disease progression and response to treatment. These biomarkers are detected during infection and are the basis for monitoring the di-sease and making a diagnosis of the clinical phase of the infection. New biomarkers have recently emerged, such as hepatitis B core-related antigen (HBcrAg) and HBV RNA detection, which seem to correlate with cccDNA transcriptional levels while during treatment seem to help predict response, and could identify those for whom therapy can be discontinued without risk of relapse. In this review, the usefulness of the main conventional biomarkers in hepatitis B is described, and the two most studied emerging biomarkers are mentioned, which promise to evaluate the course of the infection, as well as to determine disease progression and treatment response.

Analysis of hepatitis B virus infection status in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective:To investigate the effect of systemic lupus erythematosus (SLE) on the status of hepatitis B virus (HBV) infection, and provide data for clarifying the relationship between autoimmunity and infection.Methods:SLE patients in the department of rheumatology and immunology of the First Affiliated Hospital of Xi'an Jiaotong University from January 2016 to December 2019 were screened. A retrospective case-control study was carried out. SLE patients with positive hepatitis B surface antigen (HBsAg) were gender and age matched with chronic hepatitis B (CHB) in a 1∶4 ratio. Chi-square test was used to compared the positive rates of hepatitis B e antigen (HBeAg) and Paired-Samples t test or Signed rank Wilcoxon test was used to compare the HBV DNA load and HBsAg titer. Results:The positive rate of HBsAg in SLE patients was lower than the prevalence rate of HBsAg in general population in the second Chinese National Hepatitis Seroepidemiological Survey in 2006 [2.2%(27/1 227) vs 7.2%], but the positive rate of HBcAb was not obviously different from that in general population in China [33.9%(416/1 227) vs 34.1%]. Compared with matched CHB patients, the positive rate of HBeAg [37.0%(10/27) vs 58.3%(63/108), χ2=3.94, P=0.047], the HBV DNA load [0(0, 3.7) lg U/ml vs 4.8(2.2, 3.7) lg U/ml, Z=-5.37, P<0.001] and HBsAg titer [(2.0±1.5) lg U/ml vs (3.3±1.1) lg U/ml, t=-4.26, P<0.001] in SLE patients were lower. Conclusion:The HBV infection status of SLE patients is different from that of patients with chronic hepatitis B and the HBV infection is more likely to be controlled.

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.

Clinical significance and application of quantification of hepatitis B core antibody / 临床肝胆病杂志

Hepatitis B virus (HBV) infection is a global public health problem. Hepatitis B core antibody (anti-HBc) is one of the serum immunological markers in human body after HBV infection. Previous studies have shown that the low serum level of anti-HBc in HBeAg-positive mothers are associated with immunoprophylaxis failure in infants. In addition, anti-HBc is an important biomarker associated with liver inflammatory activity and therapeutic outcome and can be used to evaluate liver inflammation and predict the efficacy of antiviral therapy and sustained response after drug withdrawal. Anti-HBc quantification provides a new direction for individualized treatment of hepatitis B patients.

Influence of dual positivity of HBsAg and anti-HBs on the development of hepatocellular carcinoma in patients with chronic hepatitis B: A Meta-analysis / 临床肝胆病杂志

ObjectiveTo investigate the influence of dual positivity of HBsAg and anti-HBs on the development of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) infection. MethodsPubMed, Embase, Cochrane Library, CNKI, and Wanfang Data were searched for articles on the influence of dual positivity of HBsAg and anti-HBs on the risk of HCC published from July 1, 1975 to March 27, 2019. RevMan5.3 and Stata11.2 were used for statistical analysis of data. A heterogeneity analysis was performed for the studies included; a random effects model was used in case of significant heterogeneity, and a fixed effects model was used in case of non-significant heterogeneity. Odds ratio (OR) and corresponding 95% confidence interval (CI) were used to investigate the association of dual positivity of HBsAg and anti-HBs with the development of HCC. Begg funnel plots were used to investigate publication bias. By removing one article each time, the sensitivity analysis was used to assess the quality and reliability of the Meta-analysis. ResultsA total of 4 articles were included, with 2 studies in the Korean population and 2 in the Chinese population, and there were 3042 patients in total. The meta-analysis showed that there was no significant association between dual positivity of HBsAg and anti-HBs and the development of HCC (OR=1.46, 95%CI: 0.76-2.80, P=0.25). A country-based subgroup analysis showed significant association between dual positivity of HBsAg and anti-HBs and the development of HCC in the Korean population (OR=2.67, 95%CI: 1.61-4.43, P=0.000 1), while no significant association was found in the Chinese population (OR=0.89, 95%CI: 0.48-1.64, P=0.70). ConclusionThere is no significant association between dual positivity of HBsAg and anti-HBs and the development of HCC, and further studies are needed in future.

Clinical value of anti-HBc quantification for chronic HBV infection / 临床肝胆病杂志

As the achivement of a major project during the 12th Five-year Plan Period in China,the technique of anti-HBc quantification has been approved for commercial use and holds promise for wide application in clinical practice.Chinese scholars have explored the clinical significance of anti-HBc in various aspects and found that it has great values in the assessment of natural course of chronic hepatitis B virus (HBV) infection and the baseline prediction of antiviral therapy.Studies have shown that anti-HBc is significantly positively correlated with alanine aminotransferase (ALT) and significantly associated with liver inflammation.In chronic HBV infection patients with a normal ALT level,anti-HBc can be used instead as an indicator,with great significance for the development of therapeutic strategy in such patients.

Anti-HBs level in 15 years after vaccination in adults and newborns / 基础医学与临床

Objective To investigate the anti-HBs level in 15 years after vaccination in adults and newborns in Beijing and provide the suggestion for the adult hepatitis B (HB) immunization plan.Methods A serological survey was conducted in 6 705 subjects aged > 1 year old by multistage randomized cluster sampling in Beijing during August 2013 to February 2014.The subjects who had received a 3-dose recombination HB vaccine when they were newborns or adults aged ≥15 years old and did not undergo revaccination were selected.Antibody to hepatitis B surface antigen (anti-HBs) titers and positive rates in 15 years after vaccination were evaluated.Results A total of 129 and 463 subjects who were vaccinated in adults and newborns were enrolled in the study.Based on the self-limited rate(30%) of HBV infection among the general population aged 15 to 59 years, anti-HBs positive rates for the subjects vaccinated in adults were estimated to be 58.6%,62.5 % and 48.4% during 0-4, 5-9 and 10-15years after vaccination respectively.The corresponding median of anti-HBs titers were 288.8, 120.6 and 62.6 mIU/mL.The anti-HBs positive rates for the subjects vaccinated in newborns during 0-4, 5-9 and 10-15 years after vaccination were 83.3%, 47.3% and 43.5%, respectively.The corresponding anti-HBs titers were 71.8, 8.9 and 6.7 mIU/mL.Conclusions The protection afforded by primary immunization with recombination vaccine in adults and newborns lasts at least 15 years.

Anti-HBs persistence after revaccination with three doses of hepatitis B vaccine among low-responder infants following primary vaccination: 4-year of follow-up / 中华预防医学杂志

Objective@#Assess the 4-year antibody against hepatitis B surface antigen (anti-HBs) persistence after revaccination with 3-dose of hepatitis B vaccine (HepB) among low-responder infants following primary vaccination.@*Methods@#According to stratified cluster sampling, a total of 4 147 infants were enrolled and primarily vaccinated with 5 μg HepB derived in Saccharomyces Cerevisiae (HepB-SC) at 0-1-6 months schedule from 75 towns of Jinan, Weifang, Yantai, Weihai prefectures, Shandong Province, China in Aug and Sep 2009. Blood samples were collected one to six months after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). 717 infants who appeared low response (10 mU/ml ≤ anti-HBs<100 mU/ml) were revaccinated with 3-dose of HepB. Blood samples were collected from a total of 315 infants one month (T0), four years (T1) after revaccination and anti-HBs, antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were detected by CMIA. Information about their birth, primary vaccination were collected. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple non-conditional logistic regression analysis and multifactor linear regression model analysis, respectively.@*Results@#Among 315 children, 165 (52.38%) were male and 150 (47.62%) were female. The positive rate was 83.81% (264/315) at T0 and it decreased to 16.51% (149/529) at T1. The corresponding GMC decreased from 473.15 mU/ml to 17.37 mU/ml. The average annual decreasing rate of positive rate and GMC was 33.38% and 56.23% from T0 to T1. Multivariable analysis showed the positive rate and GMC among those whose anti-HBs titer higher at T0 were significantly higher at T1. The positive rate at T1 among those whose anti-HBs titer 400-<600, 600-<800, 800-<1 000, ≥1 000 mU/ml at T0 were significantly higher than those whose anti-HBs titer less than 200 mU/ml. The OR (95%CI) of the positive rate was 4.29 (1.03-17.84), 4.53 (1.25-16.47), 4.19 (1.10-15.97) and 9.13 (2.91-28.63), respectively. The GMC at T1 among those whose anti-HBs titer 400-<600, 600-<800, 800-<1 000 mU/ml and those whose anti-HBs titer ≥1 000 mU/ml at T0 were higher than those whose anti-HBs titer<200 mU/ml. The b value (95% CI) of GMC was 0.84 (0.06-1.62), 1.13 (0.46-1.79), 1.33 (0.65-2.01) and 1.88 (1.33-2.44), respectively. GMC among full-term infants were significantly higher than premature infants at T1. The b value (95% CI) of GMC was 0.86 (0.04-1.68).@*Conclusion@#Anti-HBs GMC decreased rapidly 4 years after revaccination among low-responder infants, but still kept good protection. The anti-HBs persistence after revaccination was associated with anti-HBs level of titer one month after revaccination.