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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.
Subject(s)
Humans , Hepatitis B virus , Occupational Exposure , Occupational Health , Community Health Workers , Hepatitis B/prevention & control , Hepatitis B AntibodiesABSTRACT
ABSTRACT Objective: To compare the glucose metabolism of patients with chronic hepatitis C virus infection treated with direct-acting antivirals (DAAs) in pretreatment and sustained viral response (SVR) periods. Materials and methods: This was an intervention pre-post study of 273 patients with chronic hepatitis C virus infection treated with DAAs from March 2018 to December 2019. Glycidic metabolism was evaluated through homeostasis model assessment (HOMA) - insulin resistance (IR) and HOMA-β indices and assessments of insulinemia and HbA1c levels. These parameters were analyzed with a T test by paired comparison of the means of the variables and Wilcoxon's test paired for the median; in the variables with an abnormal distribution, the Z score was generated for the mean in both the pretreatment and SVR periods. Statistical significance was considered at p ≤ 0.05. Results: Among 273 participants, 125 (45.8%) had prediabetes, and 50 (18.3%) had diabetes. In SVR, there was a significant increase in platelets, albumin, alkaline phosphatase, cholesterol and triglycerides and a significant decrease in aspartate aminotransferase, alanine aminotransferase, gamma GT and bilirubin. The HOMA-IR and HOMA-β indices increased in SVR from 1.95 to 2.29 (p = 0.087) and 71.20 to 82.60 (p = 0.001), respectively. Insulinemia increased from 7.60 μU/mL to 8.90 μU/mL (p = 0.011). HbA1c decreased from 5.6 to 5.4 (p < 0.001). Among patients with prediabetes and those with diabetes, the reduction in HbA1c values was significant (p = 0.006 and p = 0.026, respectively). Conclusion: SVR significantly impacts and leads to improvement in glucose metabolism in patients with chronic liver disease induced by hepatitis C virus.
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Abstract Introduction: Membranoproliferative glomerulonephritis (MPGN) is a rare glomerular disease with a variable prognosis. A new classification based on the presence or absence of immunoglobulins and complement deposits in immunofluorescence microscopy (IF) of kidney biopsy has recently been proposed. The objectives of the study were to determine and compare the clinical, laboratory, and histopathological characteristics of those with primary or secondary MPGN, reclassify the primary ones based on IF findings, and evaluate kidney outcomes. Methods: This was an observational retrospective cohort study carried out in a single center (UNIFESP), based on the data collected from medical records of patients followed from 1996 to 2019. Results: Of 53 cases of MPGN, 36 (67.9%) were classified as primary and 17 (32.1%) as secondary MPGN. Most patients were hypertensive (84.9%) and had edema (88.7%) and anemia (84.9%); 33 (91.7%) patients classified as primary MPGN were reclassified as immune-complex-mediated and 3 (8.3%) as complement-mediated. The secondary MPGN group had hematuria more frequently (p <0.001) and a higher prevalence of deposits of IgG (p = 0.02) and C1q (p = 0.003). Regarding the outcome, 39% of the patients achieved partial or complete remission. Lower initial serum albumin and higher initial 24-hour proteinuria were factors associated with worst renal prognosis. Conclusions: According to the new histological classification, the vast majority of MPGN cases were classified as being mediated by immune complexes. There were few differences between primary and secondary MPGN in relation to their clinical and laboratory characteristics.
Resumo Introdução: Glomerulonefrite membranoproliferativa (GNMP) é uma doença glomerular rara com prognóstico variável. Recentemente, foi proposta uma nova classificação baseada na presença ou ausência de imunoglobulinas e depósitos de complemento na microscopia de imunofluorescência (IF) da biópsia renal. Os objetivos do estudo foram determinar e comparar as características clínicas, laboratoriais e histopatológicas daqueles com GNMP primária ou secundária, reclassificar as primárias com base em achados da IF e avaliar os desfechos renais. Métodos: Este foi um estudo de coorte observacional retrospectivo realizado em centro único (UNIFESP), com base nos dados coletados de prontuários de pacientes acompanhados de 1996 a 2019. Resultados: Dos 53 casos de GNMP, 36 (67,9%) foram classificados como GNMP primária e 17 (32,1%) como GNMP secundária. A maioria dos pacientes era hipertensa (84,9%) e apresentava edema (88,7%) e anemia (84,9%); 33 (91,7%) pacientes classificados como GNMP primária foram reclassificados como mediados por imunocomplexo e 3 (8,3%) como mediados por complemento. O grupo de GNMP secundária apresentou mais frequentemente hematúria (p <0,001) e maior prevalência de depósitos de IgG (p = 0,02) e C1q (p = 0,003). Com relação ao desfecho, 39% dos pacientes alcançaram remissão parcial ou completa. Albumina sérica inicial mais baixa e proteinúria de 24 horas inicial mais elevada foram fatores associados a pior prognóstico renal. Conclusões: De acordo com a nova classificação histológica, a grande maioria dos casos de GNMP foram classificados como sendo mediados por imunocomplexos. Houve poucas diferenças entre GNMP primária e secundária em relação às suas características clínicas e laboratoriais.
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Objetivo: A pesquisa visa determinar o perfil bioquímico e sorológico das hepatites B e C em internos de um centro de recuperação, Ananindeua, Pará, Brasil. Métodos: Estudo transversal, descritivo e quantitativo, desenvolvido entre 2015 e 2018. Os dados foram coletados com o uso de Ficha de Inquérito e entrevista. Os participantes foram submetidos à coleta de sangue para realização de testes sorológicos para as hepatites virais B e C e bioquímicos. Resultados: Participaram 125 internos, com frequência de 97,6% para o sexo masculino, prevalecendo a faixa etária de 31 a 40 anos (38,4%). Os marcadores bioquímicos que mais sofreram alterações: ácido úrico, alanina aminotransferase e lipoproteína de alta densidade. O HBsAg não foi detectado, porém houve detecção de anti-HBc total reagente isolado em 1,6% dos indivíduos. Em 20,8% pode-se observar resposta vacinal contra o vírus da hepatite B. A pesquisa detectou prevalência de 3,2% de anti-VHC reagente. Conclusão: É baixa prevalência da infecção pelos vírus das hepatites B e C, apesar dessa população ser considerada de elevado risco para a transmissão desses vírus, os examinados na sua maioria referiu utilizar apenas drogas inaláveis. A baixa cobertura vacinal encontrada entre os examinados demonstrou a vulnerabilidade em adquirir a hepatite B e a importância de estudos entre usuários de drogas no Pará. (AU)
Objective: The research aims to determine the biochemical and serological profile of hepatitis B and C in inmates of a recovery center, Ananindeua, Pará, Brazil. Methods: Cross-sectional, descriptive and quantitative study, developed between 2015 and 2018. Data were collected using an Inquiry Form and an interview. Participants underwent blood collection to perform serological tests for viral hepatitis B and C and biochemicals. Results: 125 inmates participated, with a frequency of 97.6% for males, with the age group of 31 to 40 years old prevailing (38.4%). The biochemical markers that suffered the most changes: uric acid, Alanine aminotransferase and High density lipoprotein. HBsAg was not detected, but total anti-HBc reagent isolated was detected in 1.6% of individuals. In 20.8%, a vaccine response against the hepatitis B virus can be observed. The survey found a 3.2% prevalence of anti-HCV reagent. Conclusion: The prevalence of infection by the hepatitis B and C viruses is low, although this population is considered to be at high risk for the transmission of these viruses, the majority of those examined reported using only inhalable drugs. The low vaccination coverage found among those examined demonstrated the vulnerability to acquire hepatitis B and the importance of studies among drug users in Pará. (AU)
Objetivo: La investigación tiene como objetivo determinar el perfil bioquímico y serológico de la hepatitis B y C en los reclusos de un centro de recuperación, Ananindeua, Pará, Brasil. Métodos: Estudio transversal, descriptivo y cuantitativo, desarrollado entre 2015 y 2018. Los datos se recopilaron mediante el Formulario de encuesta y la entrevista. Los participantes se sometieron a extracción de sangre para pruebas serológicas de hepatitis viral B y C y bioquímicos. Resultados: Participaron 125 reclusos, con una frecuencia del 97,6% para los hombres, prevaleciendo el grupo de edad de 31 a 40 años (38,4%). Los marcadores bioquímicos que sufrieron más cambios: ácido úrico, Alanina aminotransferasa y Lipoproteínas de alta densidad. No se detectó HBsAg, pero se detectó el reactivo anti-HBc total aislado en el 1,6% de los individuos. En 20.8%, se puede observar una respuesta de vacuna contra el virus de la hepatitis B. La encuesta encontró una prevalencia del 3.2% Del reactivo anti-VHC. Conclusiones: La prevalencia de infección por los virus de la hepatitis B y C es baja, aunque se considera que esta población tiene un alto riesgo de transmisión de estos virus, la mayoría de los examinados informaron que usaban solo medicamentos inhalables. La baja cobertura de vacunación encontrada entre los examinados demostró la vulnerabilidad a contraer hepatitis B y la importancia de los estudios entre usuarios de drogas en Pará. (AU)
Subject(s)
Drug Users , Hepatitis B virus , Hepacivirus , Vaccination CoverageABSTRACT
ABSTRACT COVID-19 is commonly associated with high serum levels of pro-inflammatory cytokines, and the post-infection status can disturb self-tolerance and trigger autoimmune responses. We are reporting a 45-year-old male who was admitted with fatigue, jaundice, elevated liver enzymes (with cholestatic pattern), and acute kidney injury two weeks after recovering from a mild SARS-CoV-2 infection. Serologies for viral hepatitis and anti-mitochondrial antibody were negative, while anti-nuclear and anti-smooth muscle antibodies were positive. There were no signs of chronic liver disease, and a magnetic resonance cholangiography showed no dilatation of biliary ducts. Histologic evaluation of the liver evidenced numerous foci of lobular necrosis without ductopenia or portal biliary reaction. Considering the autoantibody profile and histologic changes, the medical team started oral prednisone, but there was a suboptimal biochemical response in the outpatient follow-up. Two months later, a second liver biopsy was performed and revealed non-suppurative destructive chronic cholangitis, extensive areas of confluent necrosis with hepatocytes regenerating into pseudorosettes, and numerous plasma cells. According to the Paris Criteria, the patient was then diagnosed with an autoimmune hepatitis-primary biliary cholangitis overlap syndrome (AIH-PBC-OS). After adding azathioprine and ursodeoxycholic acid to the treatment, there was a satisfactory response. This is the second worldwide report of an AIH-PBC-OS triggered by COVID-19, but the first case with a negative anti-mitochondrial antibody. In this setting, histologic evaluation of the liver by an experienced pathologist is a hallmark of achieving the diagnosis and correctly treat the patient.
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The objectives were to estimate hepatitis A virus seroprevalence in subjects attending to a travel medicine and immunization clinic in Rio de Janeiro, Brazil, and to develop a prediction model for hepatitis A virus seroprevalence. This retrospective research included individuals sequentially from April 2011 to June 2019 at a travel medicine and special population immunization clinic with an anti-hepatitis A virus IgG chemiluminescence result. Participants' data were verified via electronic medical records. Data were split into development and validation set taking 2018 as the date break. A cross-validated elastic generalized linear model with binomial distribution was performed. In total, 2,944 subjects were analyzed. Hepatitis A virus overall seroprevalence was 67.8%. Health professionals, travelers, and those who had contact with immunocompromised subjects had lower seroprevalence (40%-55%), whereas subjects with chronic conditions (heart, lung, and liver) ranged from 89% to 94%. The retained predictors in the final model were sex, age, year of birth, travelers, HIV/AIDS, spleen dysfunction, transplant candidates, household communicators, cancer-related immunosuppression, health care professionals. Area under the curve was 0.836 and maximum error was 0.051. Users can make predictions with the following calculator: https://pedrobrasil.shinyapps.io/INDWELL/. The groups with lower seroprevalence should be evaluated more carefully regarding need for hepatitis A virus vaccination even when they seek immunization clinics for other purposes.
Este estudo teve como objetivo estimar a soroprevalência do vírus da hepatite A, em indivíduos atendidos em uma clínica de medicina de viagem e imunização no Rio de Janeiro, Brasil, e desenvolver um modelo de predição para a soroprevalência do vírus da hepatite A. Esta pesquisa retrospectiva incluiu indivíduos sequencialmente de abril de 2011 a junho de 2019, em uma clínica de medicina de viagem e uma clínica de vacinação de população especial, que, por qualquer motivo, tem um resultado de quimioluminescência IgG antivírus da hepatite A . Os dados dos participantes foram verificados em prontuário eletrônico. Os dados foram divididos em desenvolvimento e validação, tomando 2018 como data limite da divisão. Um modelo linear generalizado elástico com distribuição binomial submetido a validação cruzada foi aplicado. Foram analisados 2.944 indivíduos atendidos. A soroprevalência geral do vírus da hepatite A foi de 67,8%. Profissionais de saúde, viajantes e contatantes de indivíduos imunocomprometidos apresentaram menor soroprevalência, variando de 40% a 55%, enquanto indivíduos com condições crônicas (coração, pulmão e fígado) tiveram soroprevalência variando de 89% a 94%. Os preditores retidos no modelo final foram sexo, idade, ano de nascimento, viajantes, HIV/aids, asplenia funcional, candidatos a transplante, comunicante domiciliar, imunossupressão relacionada ao câncer e profissionais de saúde. A área sob a curva foi de 0,836 e o erro máximo foi de 0,051. Os usuários podem fazer previsões com uma calculadora (https://pedrobrasil.shinyapps.io/INDWELL/). Os grupos com menor soroprevalência devem ser avaliados com mais cuidado quanto à necessidade de vacinação contra o vírus da hepatite A, mesmo quando procuram clínicas de vacinação para outros fins.
Los objetivos del estudio son estimar la seroprevalencia de hepatitis A en sujetos que asisten a una clínica de medicina para viajeros e inmunización en Río de Janeiro, Brasil, y desarrollar un modelo de predicción de la seroprevalencia de hepatitis A. Esta investigación de seguimiento retrospectivo incluyó a individuos de forma secuencial desde abril de 2011 hasta junio de 2019 en una clínica de medicina para viajeros y de vacunación de poblaciones especiales que por cualquier motivo tienen un resultado de quimioluminiscencia IgG anti-hepatitis A. Los datos de los participantes se verificaron en los registros médicos electrónicos. Los datos se dividieron en conjunto de desarrollo y validación tomando 2018 como fecha de corte. Se realizó un modelo lineal generalizado validado cruzado elástico con distribución binomial. Se analizaron un total de 2.944 sujetos atendidos. La seroprevalencia global del hepatitis A fue del 67,8%. Los profesionales sanitarios, los viajeros y las personas en contacto con sujetos inmunodeprimidos presentaron una seroprevalencia más baja, que osciló entre el 40% y el 55%, mientras que los sujetos con afecciones crónicas (cardíacas, pulmonares y hepáticas) presentaron una seroprevalencia que varió entre el 89% y el 94%. Los predictores retenidos en el modelo final fueron el sexo, la edad, el año de nacimiento, los viajeros, el VIH/SIDA, la disfunción del bazo, los candidatos a trasplante, los comunicadores domésticos, la inmunosupresión relacionada con el cáncer y los profesionales sanitarios. Su área bajo la curva fue de 0,836 y el error máximo de 0,051. Los usuarios pueden hacer predicciones con una calculadora (https://pedrobrasil.shinyapps.io/INDWELL/). Los grupos con menor seroprevalencia deben ser evaluados más cuidadosamente en cuanto a la necesidad de vacunación contra hepatitis A, incluso cuando acudan a las clínicas de vacunación con otros fines.
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ABSTRACT Vaccination coverage has been dropping in Brazil and other countries. In addition, immune responses after vaccination may not be homogeneous, varying according to sociodemographic and clinical factors. Understanding the determinants of incomplete vaccination and negative antibody test results may contribute to the development of strategies to improve vaccination effectiveness. In this study, we aimed to investigate the frequency of vaccine adherence, factors associated with incomplete vaccination for measles, mumps, rubella (MMR) and hepatitis A, and factors associated with the seronegative test results for measles, mumps and hepatitis A at 2 years of age. This was a population-based cohort that addressed health conditions and mother/infant nutrition in Cruzeiro do Sul city, Brazil. Vaccination data were obtained from official certificates of immunization. The children underwent blood collection at the two-year-old follow-up visit; the samples were analyzed using commercially available kits to measure seropositivity for measles, mumps, and hepatitis A. We used modified Poisson regression models adjusted for covariates to identify factors associated with incomplete vaccination and negative serology after vaccination. Out of the 825 children included in the study, adherence to the vaccine was 90.6% for MMR, 76.7% for the MMRV (MMR + varicella), and 74.9% for the hepatitis A vaccine. For MMR, after the adjustment for covariates, factors associated with incomplete vaccination included: white-skinned mother; paid maternity leave; raising more than one child; lower number of antenatal consultations; and attending childcare. For hepatitis A, the factors included: white-skinned mother and not having a cohabiting partner. The factors with statistically significant association with a negative antibody test result included: receiving Bolsa Familia allowance for measles and mumps; incomplete vaccination for measles; and vitamin A deficiency for mumps. Strategies to improve the efficiency of vaccine programs are urgently needed. These include improvements in communication about vaccine safety and efficacy, and amplification of access to primary care facilities, prioritizing children exposed to the sociodemographic factors identified in this study. Additionally, sociodemographic factors and vitamin A deficiency may impact the immune responses to vaccines, leading to an increased risk of potentially severe and preventable diseases.
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Hepatocellular carcinoma (HCC) is the twelfth most common cancer and the fifth leading cause of worldwide cancer related death. Chronic hepatitis B infection, caused by the hepatitis B virus (HBV) and exposure to aflatoxins is fundamental in the formation of HCC in developing countries. This review of scientific publications aims to establish the detrimental effects of aflatoxin-contaminated foods and highlights the correlation between aflatoxin and hepatitis B viral-associated hepatocellular carcinoma. Research has shown a significant increase in the occurrence of HCC in HBV-infected individuals exposed to fungal toxins. HBV demonstrates the ability to integrate and bind to p53 protein in the host DNA and propagate hepatocyte vulnerability through carcinogenic aflatoxin B1 (AFB1) damage. Although there has been clear evidence about the synergistic interaction of exposure to AFB1 and HBV infection in the induction of HCC, other literature has shown otherwise, mainly because incomplete and vague findings and hypotheses were made in regions where AFB1 and HBV pose a public health risk. Vaccination against hepatitis B and measures such as robust food safety systems to avoid hepatotoxicity and hepatocellular carcinogenesis induced by AFB1 is the most effective methods in the prevention of HCC induced by HBV and AFB1
Subject(s)
Hepatitis B virus , Vaccination , Aflatoxin B1 , Carcinoma, Hepatocellular , Hepatitis B, Chronic , Aflatoxins , HepatitisABSTRACT
Objectifs : Déterminer la prévalence de l'infection par le virus de l'hépatite B (VHB) chez les enfants (sujets contact) des sujets porteurs chroniques de l'Ag HBs (sujets index) et rechercher les facteurs associés à cette infection chez ces enfants.Patients et méthodes: il s'est agi d'étude rétrospective transversale portant sur les patients positifs pour l'Ag HBs (sujets index), dont la famille (sujets contact: conjoints et enfants) a été soumise à un dépistage systématique de l'infection par le VHB. Résultats: L'âge médian de nos 44 sujets était de 43,1 ± 7,49 ans. Le nombre moyen d'enfants par sujet index était de 2,3 ± 1,1. L'âge médian des 92 enfants était de 9,3 ± 4,55 (de 1 à 15 ans) et 43 (44,8%) étaient vaccinés contre le VHB. La fréquence de l'infection par le VHB était de 24%. Les facteurs indépendants associés à l'infection par le VHB chez les enfants étaient l'ADN du VHB pour les sujets index> 2000 UI/ml (OR = 11,5; p = 0,001), l'existence du VHB chez les deux parents (OR = 7,9; p = 0,03) et l'absence de vaccination contre le VHB chez les enfants (OR = 30,9; p = 0,003). Conclusion: La couverture vaccinale des enfants des sujets index était insuffisante. Outre la transmission verticale, le risque de transmission intrafamiliale était élevé en présence d'au moins un des trois facteurs associés
Objectives: To determine the prevalence of hepatitis B virus (HBV) infection in children (contact subjects) of chronic HBsAg (index subjects) and to investigate the factors associated with this infection in these children. Patients and methods: this was a retrospective cross-sectional study of HBsAg positive patients (index subjects), whose families (contact subjects: spouses and children) were routinely screened for HBV infection. Results: The median age of our 44 subjects was 43.1 ± 7.49 years. The average number of children per index subject was 2.3 ± 1.1. The median age of the 92 children was 9.3± 4.55 (1 to 15 years) and 43 (44.8%) were vaccinated against HBV. The prevalence of HBV infection was 24%. The independent factors associated with HBV infection in children were HBV DNA for index subjects> 2000 IU/ml (OR = 11.5; p = 0.001), the existence of HBV in both parents (OR = 7.9; p = 0.03) and no HBV vaccination in children (OR = 30.9; p = 0.003). Conclusion: Immunization coverage of children of index subjects was insufficient. In addition to vertical transmission, the risk of intrafamilial transmission was high in the presence of at least one of the three associated factors.
Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Mass Screening , Risk Factors , Hepatitis B , Hepatitis B Surface Antigens , Disease Transmission, InfectiousABSTRACT
ABSTRACT Children have an increased likelihood of becoming carriers of the chronic hepatitis B virus. A total of 1,381 children and adolescents were assessed in five municipalities of Maranhao State, Brazil, for detection of anti-HBc, HBsAg and anti-HBs serologic markers and sociodemographic and behavioral features. Among those who were HBsAg negative and anti-HBc negative, the proportion of anti-HBs positives was calculated after the individuals had completed the vaccination schedule. The robust variance of the Poisson's regression model was used in order to have adjusted tables and calculate the prevalence ratio. Multivariate analysis was performed to identify the factors associated with the prevalence of anti-HBc with or without HBsAg and the vaccine response. It was observed that 163 children were anti-HBc positive and nine individuals were HBsAg positive. The factors associated with the infection were: municipality of residence (residing in Morros municipality or Humberto de Campos municipality), residence in a rural area, aged between 13 and 15 years old, and illicit drug use. The percentage of individuals who were anti-HBc negative and received all three doses of the vaccine was 48.5%. Among these, only 276 (38.9%) had antibodies at protective concentrations. In an adjusted analysis, Morros municipality presented an increased positivity of vaccine response (p < 0.001), and the age ranging between 6 and 10 years old presented a reduced frequency of response. This study reveals a high prevalence of current and past HBV infection within the targeted age group which, in addition to the low vaccination coverage and serological responses, raises concerns about the management of prevention measures, especially the quality of vaccination in these locations.
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ABSTRACT BACKGROUND: Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) in the liver of individuals with undetectable hepatitis B virus surface antigen (HBsAg) in the serum. The actual prevalence of OBI and its clinical relevance are not yet fully understood. OBJECTIVE: To evaluate the prevalence of HBV DNA in liver biopsies of HBsAg-negative patients with chronic liver disease of different etiologies in a referral center in Brazil and compare two different HBV DNA amplification protocols to detect HBV. DESIGN AND SETTING: This cross-sectional observational study was conducted at the Liver Outpatient Clinic, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil, between January 2016 and December 2019. METHODS: HBV DNA was investigated in 104 liver biopsy samples from individuals with chronic liver disease of different etiologies, in whom HBsAg was undetectable in serum by nested-polymerase chain reaction (nested-PCR), using two different protocols. RESULTS: OBI, diagnosed by detecting HBV DNA using both protocols, was detected in 6.7% of the 104 individuals investigated. Both protocols showed a good reliability. CONCLUSION: In addition to the differences in the prevalence of HBV infection in different regions, variations in the polymerase chain reaction technique used for HBV DNA amplification may be responsible for the large variations in the prevalence of OBI identified in different studies. There is a need for better standardization of the diagnostic methods used to diagnose this entity.
ABSTRACT
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.
Subject(s)
Humans , Biomarkers , Hepatitis B virus , Hepatitis , Hepatitis B , DNA, Circular , RNA , Risk , Genome , Diagnosis , AntigensABSTRACT
@#Abstract：Objective To investigate the adaptability and genetic stability of hepatitis A virus（HAV）SYX1 strain in human diploid cell MRC⁃5. Methods HAV SYX1 strain isolated from feces of patients with hepatitis A was continuously propagated in MRC⁃5 cells for 28 passages，of which the 1st ~ 26th passages were determined for antigen contents and virus titers，the 6th passage was observed for the morphology under microscope and detected for physicochemical properties，and the 13th ~ 15th passages were studied for virus proliferation dynamics to determine the peak yield of virus proliferation. Genomic RNA was extracted from the 8th，12th，18th，20th，22nd，25th，26th and 28th passages and sequenced to analyze the genetic stability. The main seed batch and working seed batch of HAV SYX1 strain were established and verified according to the requirements of Chinese Pharmacopoeia（VolumeⅢ，2020 edition）. Results The antigen content of HAV SYX1 was stable at 160 ~ 320 EU／mL and the titer was maintained at 7. 3 ~ 8. 3 lgCCID50／mL after the 8th passages in MRC 5 cells；Virus particles showed two types：hollow and solid，with a diameter of 27 ~ 32 nm，spherical，without envelope and protrusions on the surface，which tolerated low pH value and ether. The peak period of virus proliferation was 10 d with an antigen content of more than 160 EU／mL and a virus titer of more than 7. 0 lgCCID50／mL. HAV SYX1 was a subtype of HAV IB，and no mutation in the coding region of all structural proteins during passage was observed. The verification results of main seed batch and working seed batch of HAV all met the relevant requirements. Conclusion HAV SYX1 strain showed good adapt⁃ ability and genetic stability in MRC⁃5，which might be used for the development and production of inactivated hepatitis A vaccine.
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Antiviral therapy for chronic hepatitis C virus (HCV) infection has entered the era of direct antiviral agent (DAA), and up to 95% of patients could be clinically cured. Under this circumstance, HCV infection has gradually changed from relative contraindication to surgical indication for kidney transplantation. However, at present, the number of kidney transplantation from HCV-infected donors or recipients has been rarely reported in China. The short-term follow-up data of HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts in other countries have confirmed that DAA yields high cure rate and safety in the treatment of HCV infection, and recipients could obtain favorable short-term survival and allograft outcome. However, the long-term safety of HCV-infected kidney transplantation remains to be validated by clinical trials with large sample size and long-term follow-up. In this article, the virological clearance, allograft outcome and safety of DAA use in HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts under the intervention of DAA were investigated, aiming to evaluate clinical safety and efficacy of this pattern of kidney transplantation and deepen the understanding of safe use of HCV-positive organs.
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Exosomes are nano-sized phospholipid bilayer vesicles containing abundant and complex biomolecules, such as DNA, mRNAs, microRNAs (miRNAs), lipids, and proteins. Exosomes can be secreted and ingested by most types of cells to transfer information through intercellular transport. After uptake by recipient cells, exosomes release bioactive substances to regulate the biological processes of recipient cells, such as promoting tumor growth and metastasis. Changes of exosomes and their contents are associated with a variety of diseases. In recent years, the role of exosomal miRNAs in the development and progression of hepatocellular carcinoma (HCC) caused by viral hepatitis has attracted wide attention, and exosomal miRNAs from different sources play different roles in this process. This article briefly reviews the research on the role of exosomal miRNAs in the development and progression of viral hepatitis-related HCC and proposes that exosomal miRNAs may be the targets for immunotherapy for HCC microenvironment.
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Objective To investigate the long-term efficacy of transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of primary biliary cholangitis (PBC) with portal hypertension. Methods A retrospective analysis was performed for 102 patients who received TIPS in Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2015 to August 2021, and these patients were divided into PBC group with 41 patients and viral hepatitis cirrhosis group with 81 patients. Related indicators were collected, including routine blood test results, liver and renal function, coagulation function, portal vein thrombosis, hepatic encephalopathy, and etiology of TIPS treatment shortly after admission, preoperative portal venous pressure, and stents used in surgery, and Child-Pugh score was calculated. Follow-up data were collected and analyzed, including postoperative upper gastrointestinal rebleeding, stent dysfunction, hepatic encephalopathy, and the data on survival and prognosis. The independent samples t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups; the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used for survival analysis, and the log-rank test was used for survival difference analysis. Results In the PBC group and the viral hepatitis cirrhosis group, the median percentage of reduction in portal venous pressure after surgery was 33.00% and 35.00%, respectively, and there was no significant difference between the two groups ( P > 0.05). At the end of follow-up, there were no significant differences between the PBC group and the viral hepatitis cirrhosis group in stent dysfunction rate (14.63% vs 24.69%, χ 2 =1.642, P > 0.05), upper gastrointestinal rebleeding rate (17.07% vs 24.69%, χ 2 =0.917, P > 0.05), the incidence rate of overt hepatic encephalopathy (12.20% vs 7.41%, χ 2 =0.289, P > 0.05), and disease-specific death rate (14.63% vs 9.88%, χ 2 =0.229, P > 0.05). Conclusion For PBC patients with portal hypertension, TIPS can achieve the same efficacy as the treatment of portal hypertension caused by viral hepatitis cirrhosis and can also effectively reduce portal hypertension without increasing the incidence rate of complications and disease-specific death rate. Therefore, it is a safe and effective treatment method.
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Objective To investigate the effect of cyclin D1 (with CCND1 as the gene name) on HBV replication and its potential mechanism. Methods With reference to GSE84044 dataset, the Spearman's rank correlation analysis was used to investigate the correlation between the expression levels of genes in liver tissue and serum HBV DNA load in patients with HBV-related liver fibrosis. Cyclin D1 and cyclin D1 T286A mutant were transiently expressed in the HBV cell replication model, and time-resolved immunofluorescence and quantitative real-time PCR were used to measure the levels of HBsAg/HBeAg and HBV DNA in cell culture supernatant; Western blot was used to measure the level of HBV core protein in cells; reverse-transcription quantitative real-time PCR was used to measure the level of HBV RNA in cells; dual-luciferase reporter assay was used to observe the effect of cyclin D1 on the activity of HBV basic core promoter (BCP). GSE83148 dataset was used to investigate the correlation between CCND1 and HBV-related regulatory factors. The independent samples t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. Results The analysis of GSE84044 data showed that 7 cell cycle genes were significantly negatively correlated with HBV DNA load in liver tissue of the patients with HBV-related liver fibrosis (all r < -0.3, all P < 0.05), which included the CCND1 gene ( r =-0.474, P < 0.001). Exogenous expression of cyclin D1 and cyclin D1 T286A mutant reduced the levels of HBsAg, HBeAg, and HBV DNA in culture supernatant of the HBV replication cell model, as well as the levels of HBV core protein and HBV RNA in cells. Exogenous expression of cyclin D1 significantly inhibited the transcriptional activity of HBV BCP. The expression level of CCND1 in liver tissue of chronic hepatitis B patients was significantly positively correlated with the expression of APOBEC3G ( r =0.575, P < 0.001), SMC5 ( r =0.341, P < 0.001), and FOXM1 ( r =0.333, P < 0.001) which inhibited HBV replication, while it was significantly negatively correlated with the expression of the HBV entry receptor NTCP ( r =-0.511, P < 0.001) and HNF1α as the transcription factor for positive regulation of HBV replication ( r =-0.430, P < 0.001). Overexpression of cyclin D1 in HepG2 cells reduced the transcriptional levels of HNF1α and NTCP. Conclusion Cyclin D1 inhibits HBV transcription and replication possibly by downregulating the expression of HNF1α and NTCP.
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Objective To establish a new model of indocyanine green (ICG) clearance test combined with total bilirubin actual resident rate (TBARR) for predicting the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) treated with artificial liver support system (ALSS) therapy. Methods A retrospective analysis was performed for the clinical data of 136 patients with HBV-ACLF who underwent ALSS therapy in Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, from June 2017 to July 2021, and according to the prognosis at 3-month follow-up, they were divided into survival group with 92 patients and death group with 44 patients. Related indicators were measured at the time of the confirmed diagnosis of ACLF, including biochemical parameters, coagulation, indocyanine green retention rate at 15 minutes (ICGR 15 ), and effective hepatic blood flow (EHBF), and related indices were calculated, including Model for End-Stage Liver Disease (MELD) score, MELD difference (ΔMELD), Child-Turcotte-Pugh (CTP) score, total bilirubin clearance rate (TBCR), total bilirubin rebound rate (TBRR), and TBARR. The Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups; the chi-square test was used for comparison of categorical data between groups. A binary logistic regression analysis was used to establish a combined predictive model for the prognosis of HBV-ACLF after ALSS therapy. The area under the ROC curve (AUC) was used to compare the accuracy of various models in judging the short-term prognosis of patients with HBV-ACLF after ALSS therapy, and the Z test was used for comparison of AUC. Results There were significant differences between the death group and the survival group in MELD score, ΔMELD, CTP score, ICGR 15 , EHBF, TBRR, TBARR, neutrophil count, percentage of neutrophils, lymphocyte count, platelet count, alkaline phosphatase, gamma-glutamyl transpeptidase, total bilirubin, albumin, prothrombin time, international normalized ratio, prothrombin time activity, prealbumin, fibrinogen, serum sodium, age, and the incidence rate of hepatic encephalopathy (all P 80%. Conclusion The combined predictive model established by ICGR 15 and TBARR has a good value for in predicting the short-term prognosis of patients with HBV-ACLF after ALSS therapy, and the combined predictive model has a better accuracy than the single model in judging prognosis.
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Objective To investigate the independent predictive factors for functional cure after long-term nucleos(t)ide analogue (NUC) antiviral therapy followed by pegylated interferon α-2b therapy in chronic hepatitis B (CHB) patients. Methods A total of 162 CHB patients who were admitted to several hospitals in Qingdao, China, from 2018 to 2021 were enrolled as subjects, and all patients received pegylated interferon α-2b for at least 48 weeks after NUC therapy for one year or longer. According to whether HBsAg clearance was achieved at week 48 of pegylated interferon α-2b treatment, the patients were divided into functional cure group with 79 patients and non-cure group with 83 patients, and related clinical indices were compared between the two groups. The two-independent-samples t test and the Mann-Whitney U rank sum test were used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Spearman correlation analysis was performed, and the univariate and multivariate logistic regression analyses were used to investigate the independent predictive factors for functional cure. The receiver operating characteristic (ROC) curve was plotted for related variables, and the area under the ROC curve (AUC) was used to evaluate the prediction accuracy of the variables. Results Compared with the non-cure group, the functional cure group had a significantly lower HBsAg level at baseline [21.63 (3.33-157.60) IU/mL vs 794.70 (336.10-1 185.34) IU/mL, Z =-8.869, P 1000 IU/mL (0 vs 8.4%, χ 2 =5.073, P =0.024), a significantly lower level of total bilirubin at baseline [12.60 (10.12-15.93) μmol/L vs 15.50 (11.80-24.10) μmol/L, Z =-3.611, P 2×upper limit of normal (16.5% vs 4.8%, χ 2 =5.835, P =0.016). The multivariate logistic regression analysis showed that baseline HBsAg (odds ratio [ OR ]=0.996, 95% confidence interval [ CI ]: 0.995-0.997, P < 0.001), HBsAg at week 12 of pegylated interferon α-2b treatment ( OR =0.990, 95% CI : 0.986-0.994, P < 0.001), HBsAg at week 24 of pegylated interferon α-2b treatment ( OR =0.983, 95% CI : 0.975-0.991, P < 0.001), and baseline total bilirubin ( OR =0.885, 95% CI : 0.826-0.949, P =0.001) were independent predictive factors for functional cure. The ROC curve of baseline HBsAg showed an AUC of 0.904 and the optimal cut-off value of 118.24 IU/mL; the ROC curve of HBsAg at week 12 of pegylated interferon α-2b treatment showed an AUC of 0.948 and the optimal cut-off value of 73.74 IU/mL; the ROC curve of HBsAg at week 24 of pegylated interferon α-2b treatment showed an AUC of 0.975 and the optimal cut-off value of 11.01 IU/mL; the ROC curve of baseline total bilirubin showed an AUC of 0.664 and the optimal cut-off value of 19.9 μmol/L. Conclusion Baseline HBsAg, HBsAg at week 12 of pegylated interferon α-2b treatment, HBsAg at week 24 of pegylated interferon α-2b, and baseline total bilirubin are independent predictive factors for functional cure at week 48 of pegylated interferon α-2b treatment in CHB patients receiving sequential therapy with NUC and pegylated interferon α-2b.
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Liver fibrosis is the inevitable course for the progression of chronic hepatitis B to liver cirrhosis and is also the most important risk factor for hepatocarcinogenesis, and therefore, blocking and reversing liver fibrosis is an important strategy to effectively reduce the development of chronic hepatitis B cirrhosis and liver cancer. There are currently no effective drugs and measures for the treatment of liver fibrosis in Western medicine, and traditional Chinese medicine (TCM) has unique advantages in the treatment of liver fibrosis; however, due to a lack of strict and standardized clinical research, there is still no high-quality evidence for support from the aspect of evidence-based medicine (EBM). With subsidies from National Science and Technology Major Project in the 12th and 13th five-year plans, the authors conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial on compound Biejia Ruangan tablets combined with entecavir in blocking and reversing chronic hepatitis B liver fibrosis. With liver biopsy as the gold standard, 1000 patients were enrolled to confirm the efficacy of compound Biejia Ruangan tablets combined with entecavir in blocking and reversing liver fibrosis and cirrhosis, and this study has become the first clinical trial investigating the anti-liver fibrosis effect of TCM supported by high-quality EBM evidence, bringing great hope to patients with chronic liver diseases and helping TCM move towards the world. This article introduces these research findings and reviews the current status and challenges of TCM in blocking and reversing liver fibrosis.