Principais motivos de descarte de córneas para transplante na Paraíba: por que o anti-HBc merece atenção?* / Main reasons for discarding corneas for transplant in Paraíba: why does anti-HBc deserve attention?*

RESUMO Objetivo: Identificar o perfil dos doadores de tecidos oculares humanos na área de atuação do Banco de Olhos da Paraíba, destacando o impacto da sorologia positiva para hepatite B no descarte dos tecidos para transplante. Métodos: O estudo é transversal e utilizou dados do Banco de Olhos da Paraíba entre janeiro de 2013 e dezembro de 2022. Dados sobre procedência, idade, sexo, causa do óbito, tempo entre óbito e enucleação, resultados sorológicos e motivo de descarte das córneas dos doadores foram coletados. Resultados: O maior motivo de descarte foi por sorologia positiva (56,5%), sendo positivadas as sorologias positivas para hepatite B e HBsAg em 11,1% e 4,75% dos pacientes, respectivamente. Conclusão: A sorologia positiva para hepatite B como um critério de descarte absoluto é responsável por grande parcela de descartes, apesar da pouca informação sobre suas repercussões e representação de infectividade nos receptores do transplante.

ABSTRACT Objective: To identify the profile of human ocular tissue donors in the area covered by the Eye Bank of Paraíba (PB), highlighting the impact of positive serology for hepatitis B (anti-HBc) in the disposal of tissues for transplantation. Methods: This is a cross-sectional that uses data from the Eye Bank of Paraíba (PB) between January 2013 and December 2022. Data on origin, age, sex, cause of death, time between death and enucleation, serological results, and reason for discarded donor corneas were collected. Results: The main reason for discarding was due to positive serology (56.5%), with positive anti-HBc and HBsAg serology in 11.1% and 4.75% of patients, respectively. Conclusion: Anti-HBc positive serology as an absolute disposal criterion is responsible for great part of disposals, despite little information about its repercussions and representation of infectivity in transplant recipients.

Trends and spatial distribution of hepatitis B in pregnant women in Brazil / Tendência e distribuição espacial da hepatite B em gestantes no Brasil

Abstract Objectives: to analyze the trend and spatial distribution of hepatitis B in pregnant women in Brazil. Methods: ecological study based on all notified cases of hepatitis B in pregnant women through the Information System for Notifiable Diseases - Sinan between 2009 and 2018. Hepatitis B virus (HBV) detection rates were calculated in all municipalities. Spatial analysis was performed using the Global Moran Index for global data and local indicators of spatial association (Lisa) for the 5,570 municipalities. For trend analysis by State, the Prais-Winsten generalized linear regression model was used. Results: 15,253 pregnant women with HBV were reported. High detection rates were observed in the municipalities of São Miguel da Boa Vista-SC (68.96/1000 live births (LB)), Araguaiana-MT (68.18/1000 LB), Reserva do Cabaçal-MT (80, 00/1,000 LB), São Geraldo da Piedade-MG (75/1000 LB), Porto Mauá-RS (111, 11/1000 LB), in the respective bienniums. Moran (I) (I=0.056) showed a positive spatial association. In Lisa, 78 municipalities were included in the high-high cluster, 51.28% in the South region and 48 in the low-low cluster with 72.91% in the Southeast. There was an increasing trend in Maranhão (p=0.004) and Pernambuco (p=0.007) and a decrease in Mato Grosso (p=0.012), Paraná (p=0.031) and Santa Catarina (p=0.008). Conclusion: the detection of hepatitis B in pregnant women was observed in most Brazilian municipalities, with an increasing trend in two states and a decrease in three others.

Resumo Objetivos: analisar a tendência e distribuição espacial da hepatite B em gestantes no Brasil. Métodos: estudo ecológico a partir de todos os casos notificados de hepatite B em gestantes pelo Sistema de Informação de Agravos de Notificação - Sinan entre 2009 e 2018. Foram calculadas as taxas de detecção do vírus da hepatite B (HBV) em todos os municípios. A análise espacial foi realizada por meio do Índice Global de Moran para os dados globais e os indicadores locais de associação espacial (Lisa) para os 5.570 municípios. Para análise de tendências por Estado, utilizou-se o modelo de regressão linear generalizada de Prais-Winsten. Resultados: foram notificadas 15.253 gestantes com HBV. Observou-se altas taxas de detecção nos municípios de São Miguel da Boa Vista-SC (68,96/1000 Nascidos vivos (NV)), Araguaiana-MT (68,18/1000 NV), Reserva do Cabaçal-MT(80,00/1.000 NV), São Geraldo da Piedade-MG (75/1000 NV), Porto Mauá-RS (111,11/1000 NV), nos respectivos biênios. Moran (I) (I=0,056) apresentou associação espacial positiva. No Lisa observou-se 78 municípios inserido no cluster alto-alto, sendo 51,28%na região Sul e 48 no cluster baixo-baixo com 72,91% no Sudeste. Verificou-se tendência crescente no Maranhão (p=0,004) e Pernambuco (p=0,007) e diminuição no Mato Grosso (p=0,012), Paraná (p=0,031) e Santa Catarina (p=0,008). Conclusão: Observou-se a detecção de hepatite B em gestantes na maioria dos municípios brasileiros, com tendência crescente em dois estados e diminuição em outros três.

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.

Perfil bioquímico e sorológico das hepatites b e c num centro recuperação para dependentes químicos / Biochemical and serological profile of hepatitis b and c in a recovery center for chemical dependents / Perfil bioquímico y serológico de hepatitis b y c en un centro de recuperación de dependientes químicos

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)

The synergism of hepatitis B and aflatoxicosis in hepatocellular carcinoma development: A mini-review

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

Sécurité transfusionnelle infectieuse pendant la pandémie à COVID-19: Evaluation de quelques marqueurs sérologiques au centre hospitalier et universitaire de Yaoundé, Cameroun / Infectious transfusion safety during the COVID-19 pandemic: evaluation of some serological markers at the Yaoundé University Teaching Hospital, Cameroon

Objectif. Mettre à jour les données sur la prévalence des infections transmissibles par transfusion en contexte de pandémie à coronavirus est très important pour la sécurité transfusionnelle dans notre milieu. Méthodes. Une étude transversale prospective a été menée du 05 avril au 02 mai 2021 au Centre Hospitalier et Universitaire de Yaoundé. Les donneurs de sang ont été inclus consécutivement après un entretien médical et dépistés pour les infections du Virus de l'Immunodéficience Humaine, du virus de l'hépatite B, du virus de l'hépatite C et du Treponema pallidum. L'analyse statistique a été faite à l'aide du logiciel SPSS version 23.0 avec pour seuil de significativité p<0,05. Résultats. Au total, 32/232 donneurs (13,8 %) avaient au moins une infection transmissible par transfusion. Les prévalences étaient de 7,8 %, 5,6 %, 0,9 % et 0,9 % respectivement pour l'infection à Virus de l'Immunodéficience Humaine, Virus de l'hépatite B, Virus de l'hépatite C et Treponema pallidum. La régression logistique binaire concernant le Virus de l'Immunodéficience Humaine a montré que le sexe masculin et le groupe sanguin AB étaient significativement associés à cette infection. Aucune association n'a été retrouvée pour les autres infections. Conclusion. Avec le contexte difficile lié à la pandémie à coronavirus, la prévalence cumulée des infections transmissibles par transfusion est restée relativement élevée. Une bonne sélection médicale des donneurs reste la clé pour permettre la sécurité transfusionnelle.

Objective. Updating data on the prevalence of transfusion-transmissible infections in the context of the coronavirus pandemic is very important for blood safety in our environment. Method. A prospective cross-sectional study was conducted from April 05 to May 02, 2021 at the Yaoundé University Teaching Hospital. Blood donors were included consecutively after a medical interview and screened for Human Immunodeficiency Virus, Hepatitis B virus, Hepatitis C virus and Treponema pallidum infections. Statistical analysis was performed using SPSS version 23.0 software with the significance level p<0.05. Results. In total, 32/232 donors (13.8%) had at least one transfusion-transmissible infection. The prevalences were 7.8%, 5.6%, 0.9% and 0.9% respectively for infection with Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus and Treponema pallidum. Binary logistic regression for Human Immunodeficiency Virus showed that male sex and AB blood group were significantly associated with this infection. No association was found for the other infections. Conclusion. With the difficult context linked to the coronavirus pandemic, the cumulative prevalence of infections transmissible by transfusion has remained relatively high. A good medical selection of donors remains the key to allow transfusion safety.

Hepatitis B chronic infection among pregnant women attending the antenatal care in Bor State Referral Hospital, South Sudan

Introduction: Hepatitis B virus (HBV) is a major public health problem affecting 400 million people worldwide, and is a common cause of chronic liver failure (cirrhosis) and hepatocellular carcinoma. Sixty-eight percent of infected people are from the African and Pacific regions. Vertical transmission from mother to newborn baby is one of the mechanisms by which chronic hepatitis virus infection spreads, besides infections from contaminated needles and syringes and sexual contact. Hepatitis B chronic infection is endemic in many poor countries, especially in Africa. Method: A cross-sectional study was conducted between July and August 2021. Pregnant women attending the antenatal care (ANC) in Bor State referral hospital, South Sudan, were interviewed to collect information on their socio-demographic characteristics and risk factors for hepatitis B infection. The objective was to determine the seroprevalence of hepatitis B chronic infection through blood testing. Prevalence ratios for certain risk factors were calculated. Results: Two hundred pregnant women were enrolled. The Prevalence Rate for chronic infection with hepatitis B virus, diagnosed using the rapid immune-chromatographic assay for Hepatitis B surface antigen (HBsAg), was 8.5%. (95% CI; 4.7% - 12.3%). None of the suspected risk factors studied were found to be significantly associated with testing positive for HBV, except for a history of previous jaundice. Conclusion: The prevalence of HBV chronic infection among pregnant women in Bor, Jonglei State, is high hence there is a need for established public health interventions that can lead to a reduction of HBV vertical transmission. Treatment of pregnant women with HBV chronic infection using anti-viral medications during pregnancy might curb the vertical transmission rates.

Seroprevalence and associated risk factors for hepatitis B virus among pregnant women attending health facility in Osogbo, Nigeria

Background Hepatitis B virus (HBV) infection among pregnant women has a high rate of vertical transmission and consequential effects on fetal and neonatal outcomes. The aim of this study was to determine the prevalence and associated risk factors of infection among pregnant women attending antenatal care services in Osogbo, Nigeria. Methodology This hospital based cross-sectional study was conducted among pregnant women attending routine antenatal care clinic between April and June 2021. Systematic random sampling technique was used to recruit 240 pregnant women, their data were collected by face to face interview using a pretested questionnaire, while blood sample was collected aseptically to determine hepatitis B surface antigen by enzyme linked immunosorbent assay test kit. Univariate and multivariate logistic regression were used to examine the association between explanatory variables and outcome variable. Results The mean age and seroprevalence of the study population were 27.50 ± 4.4 years and 5.8% respectively. The significant risk factors for HBV infection were tattooing (aOR = 5.22; 95% CI = 0.52­8.01; p = 0.0000), history of multiple sexual partners (aOR = 2.88; 95% CI = 1.92­12.42; p = 0.0044); and past history of contact with HBV patient (aOR = 2.17; 95% CI = 1.21­15.32; p = 0.0310) were significant predictors of HBV infection. Conclusion The seroprevalence of HBV from this study was of intermediate endemicity. We therefore, advocate for continuous health education programs on the mode of HBV transmission, high-risk behaviors and methods of preventions at antenatal care clinics to raise the awareness of mothers and limit the spread of infection.

Risk factors of transfusion transmissible infections among blood donors at Karongi Regional Centre for blood transfusion in Rwanda

Background Blood transfusion saves human lives, but also it can be a route for TransfusionTransmissible Infections (TTIs) including Human Immuno-Deficiency Virus (HIV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), and syphilis. Objective This study aimed to explore the risk factors associated with TTIs among blood donors at Regional Centre for Blood Transfusion (RCBT) of Karongi, Rwanda. Methods This was a retrospective cross-sectional study design conducted among 36,708 blood donors from 2015 to 2019. Data were extracted from the system known as eProgesaused and the outcome variable were TTIs including HBV, HCV and HIV (measured using Enzyme Immuno-Assay/Chemiluminescence Immunoassay) and syphilis (determined by Rapid Reagin Plasma). Descriptive statistics was computed to describe the characteristics of the blood donors. Bivariate and multivariable logistic regression were performed to assess the risk factors associated with TTIs. P value less than 0.05 was considered statistically significant. Results The study found that the overall prevalence of TTIs was 2.1%, while the prevalences of HBV, HCV, HIV, and syphilis were 1.3%, 0.4%, 0.06%, and 0.34%, respectively. Multivariable analysis showed that the factors associated with HBV, HCV, HIV and syphilis were being male, age more than 25 years, being married, living in urban areas, first time blood donors and blood donors living in Rusizi, Rusizi, Nyamasheke and Karongi districts. Conclusion This study revealed that the most frequent TTI was HBV among blood donors and the main risk groups were males, age group of 26-35 years, married and first time donors. Hence, while developing health policies to reduce the effects of HBV infection on safe blood transfusion, these study findings should be taken into account.

Knowledge, attitude, and practice towards hepatitis B and C viruses among the population of Lubumbashi, Democratic Republic of Congo

Background Hepatitis B (HBV) and C (HCV) infection remains significant public health problem worldwide. Unfortunately, the Democratic Republic of Congo is in an area of high endemicity, and its population remains poorly informed about these viral infections. Therefore, this study aims to determine Lubumbashi's knowledge, attitudes, and practices toward HBV and HCV. Methods We conducted a cross-sectional descriptive study from March to August 2022 in Lubumbashi. A total of 704 participants were enrolled. We targeted all people of both sexes and ages. The participants' Knowledge, Attitudes, and Practices (KAP) survey was assessed using online and printed or paper questionnaires. Data were analyzed using SPSS version 22 software. Results Of the 704 participants, 70.9% had poor knowledge of viral hepatitis B and C, whereas 28.6% had terrible attitudes towards these infections and preferred to consult traditional healers instead of going to the hospital. A minority of the participants (12.2%) had good practices, those as being screened regularly to exclude any possible infection and being willing to be vaccinated depending on the availability of the HBV vaccine. Most participants (69.2%) needed to be aware of drugs that could effectively treat these infections. Conclusion Knowledge and practice about HBV and HCV in the Congolese population living in Lubumbashi have proven wrong. Similarly, the attitudes of the people towards these infections were negative. Therefore, an extensive health education program should be given to increase the awareness of this part of the Congolese population about HBV and HCV infection to provide better care.

Protection level of anti­hepatitis B vaccine and immunoglobulin in a pediatric Cameroonian population

Despite the availability for nearly twenty years of an effective vaccine, hepatitis B remains one of the most frequent viral diseases throughout the world. Mother to child transmission is one of the primary routes of transmission in children. To assess the vaccine response in children born to HBV infected mothers. HBsAg positive consenting mothers registered in the antenatal care (ANC) service database of Centre Hospitalier Dominicain St Martin de Porres, Yaounde were enrolled with their children. Socio demographic char acteristics were collected using a tested questionnaire. The 5 markers of hepatitis B were tested and the quantification of anti HBsAg antibodies was done by indirect ELISA method. The data collected was analyzed using Microsoft excel and Epi info softwares. Out of 5,996 women registered, 143 were identified as HBsAg positive (2.38% prevalence) and none was HBeAg positive. Of these 143 HBsAg positive women, 50 were enrolled in the study. Of the 50 positive mothers, 78 children were included with a mean age ± standard deviation of 2.33±2.86 years. No child was infected with HBV, but all have been exposed to the virus (HBeAb positive). Overall 64 (82.05%) received at birth both anti HBs immunoglobulin (HBIG) and a dose of vaccine, while 14 (17.95%) received only the birth dose of vaccine. 72 (92.31%) children received all three recommended doses of vaccine. Vaccine responders were 62.82% (above 10 IU/ml), while 37.18% of children were non responders; representing a higher risk group if not boosted. The coverage of the anti HBV vaccine in children in this study was 92.31%. The protection level of 62.82% is below the 95% recommended rate by WHO. The factors sustaining this suboptimal protection should be investigated

A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.

TRIM25 inhibits HBV replication by promoting HBx degradation and the RIG-I-mediated pgRNA recognition / 中华医学杂志(英文版)

BACKGROUND@#The hepatitis B virus (HBV) vaccine has been efficiently used for decades. However, hepatocellular carcinoma caused by HBV is still prevalent globally. We previously reported that interferon (IFN)-induced tripartite motif-containing 25 (TRIM25) inhibited HBV replication by increasing the IFN expression, and this study aimed to further clarify the anti-HBV mechanism of TRIM25.@*METHODS@#The TRIM25-mediated degradation of hepatitis B virus X (HBx) protein was determined by detecting the expression of HBx in TRIM25-overexpressed or knocked-out HepG2 or HepG2-NTCP cells via Western blotting. Co-immunoprecipitation was performed to confirm the interaction between TRIM25 and HBx, and colocalization of TRIM25 and HBx was identified via immunofluorescence; HBV e-antigen and HBV surface antigen were qualified by using an enzyme-linked immunosorbent assay (ELISA) kit from Kehua Biotech. TRIM25 mRNA, pregenomic RNA (pgRNA), and HBV DNA were detected by quantitative real-time polymerase chain reaction. The retinoic acid-inducible gene I (RIG-I) and pgRNA interaction was verified by RNA-binding protein immunoprecipitation assay.@*RESULTS@#We found that TRIM25 promoted HBx degradation, and confirmed that TRIM25 could enhance the K90-site ubiquitination of HBx as well as promote HBx degradation by the proteasome pathway. Interestingly, apart from the Really Interesting New Gene (RING) domain, the SPRY domain of TRIM25 was also indispensable for HBx degradation. In addition, we found that the expression of TRIM25 increased the recognition of HBV pgRNA by interacting with RIG-I, which further increased the IFN production, and SPRY, but not the RING domain is critical in this process.@*CONCLUSIONS@#The study found that TRIM25 interacted with HBx and promoted HBx-K90-site ubiquitination, which led to HBx degradation. On the other hand, TRIM25 may function as an adaptor, which enhanced the recognition of pgRNA by RIG-I, thereby further promoting IFN production. Our study can contribute to a better understanding of host-virus interaction.

Ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China: a CR-HepB-based real-world study / 中华肝脏病杂志

Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.

Recompensation of complications in patients with hepatitis B virus-related decompensated cirrhosis treated with entecavir antiviral therapy / 中华肝脏病杂志

Objective: To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods: Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results: 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion: Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.

Regulation and influence of mitochondria on macrophages during hepatitis B virus infection / 中华肝脏病杂志

Hepatitis B virus (HBV) infection is an important public health concern, as approximately 3.5% of the world's population is currently chronically infected. Chronic HBV infection is the primary cause of cirrhosis, hepatocellular carcinoma, and deaths related to liver disease globally. Studies have found that in HBV infection, viruses can directly or indirectly regulate mitochondrial energy metabolism, oxidative stress, respiratory chain metabolites, and autophagy, thereby altering macrophage activation status, differentiation types, and related cytokine secretion type and quantity regulations. Therefore, mitochondria have become an important signal source for macrophages to participate in the body's immune system during HBV infection, providing a basis for mitochondria to be considered as a potential therapeutic target for chronic hepatitis B.

Clinical value of plasma scaffold protein SEC16A in evaluating hepatitis B-related liver cirrhosis and hepatocellular carcinoma / 中华肝脏病杂志

Objective: To investigate the clinical value of plasma scaffold protein SEC16A level and related models in the diagnosis of hepatitis B virus-related liver cirrhosis (HBV-LC) and hepatocellular carcinoma (HBV-HCC). Methods: Patients with HBV-LC and HBV-HCC and a healthy control group diagnosed by clinical, laboratory examination, imaging, and liver histopathology at the Third Hospital of Hebei Medical University between June 2017 and October 2021 were selected. Plasma SEC16A level was detected using an enzyme-linked immunosorbent assay (ELISA). Serum alpha-fetoprotein (AFP) was detected using an electrochemiluminescence instrument. SPSS 26.0 and MedCalc 15.0 statistical software were used to analyze the relationship between plasma SEC16A levels and the occurrence and development of liver cirrhosis and liver cancer. A sequential logistic regression model was used to analyze relevant factors. SEC16A was established through a joint diagnostic model. Receiver operating characteristic curve was used to evaluate the clinical efficacy of the model for liver cirrhosis and hepatocellular carcinoma diagnosis. Pearson correlation analysis was used to identify the influencing factors of novel diagnostic biomarkers. Results: A total of 60 cases of healthy controls, 60 cases of HBV-LC, and 52 cases of HBV-HCC were included. The average levels of plasma SEC16A were (7.41 ± 1.66) ng/ml, (10.26 ± 1.86) ng/ml, (12.79 ± 1.49) ng /ml, respectively, with P < 0.001. The sensitivity and specificity of SEC16A in the diagnosis of liver cirrhosis and hepatocellular carcinoma were 69.44% and 71.05%, and 89.36% and 88.89%, respectively. SEC16A, age, and AFP were independent risk factors for the occurrence of HBV-LC and HCC. SAA diagnostic cut-off values, sensitivity, and specificity were 26.21 and 31.46, 77.78% and 81.58%, and 87.23% and 97.22%, respectively. The sensitivity and specificity for HBV-HCC early diagnosis were 80.95% and 97.22%, respectively. Pearson correlation analysis showed that AFP level was positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), and γ-glutamyltransferase (GGT) with P < 0.01, while the serum SEC16A level was only slightly positively correlated with ALT and AST in the liver cirrhosis group (r = 0.268 and 0.260, respectively, P < 0.05). Conclusion: Plasma SEC16A can be used as a diagnostic marker for hepatitis B-related liver cirrhosis and hepatocellular carcinoma. SEC16A, combined with age and the AFP diagnostic model with SAA, can significantly improve the rate of HBV-LC and HBV-HCC early diagnosis. Additionally, its application is helpful for the diagnosis and differential diagnosis of the progression of HBV-related diseases.

Analysis of clinical characteristics and risk factors of hepatic fibrosis in children with chronic hepatitis B combined with metabolic-related fatty liver disease / 中华肝脏病杂志

Objective: To compare the clinical and pathological features of children with chronic viral hepatitis B combined with metabolic-associated fatty liver disease (CHB-MAFLD) and chronic viral hepatitis B alone (CHB alone), and to further explore the effect of MAFLD on the progression of hepatic fibrosis in CHB. Methods: 701 initially treated CHB children confirmed by liver biopsy admitted to the Fifth Medical Center of the PLA General Hospital from January 2010 to December 2021 were collected continuously. They were divided into CHB-MAFLD and CHB-alone groups according to whether they were combined with MAFLD. A retrospective case-control study was conducted. CHB-MAFLD was used as the case group, and 1:2 propensity score matching was performed with the CHB alone group according to age and gender, including 56 cases in the CHB-MAFLD group and 112 cases in the CHB alone group. The body mass index (BMI), metabolic complications, laboratory indicators, and pathological characteristics of liver tissue were compared between the two groups. The related factors affecting liver disease progression in CHB were analyzed by a binary logistic regression model. The measurement data between groups were compared using the t-test and rank sum test. The χ (2) test was used for the comparison of categorical data between groups. Results: Alanine aminotransferase (ALT, P = 0.032) and aspartate aminotransferase (AST, P = 0.003) levels were lower in the CHB-MAFLD group than those in the CHB alone group, while BMI (P < 0.001), triglyceride (TG, P < 0.001), total cholesterol (P = 0.016) and the incidence of metabolic syndrome (P < 0.001) were higher in the CHB alone group. There were no statistically significant differences in HBsAg quantification or HBV DNA load between the two groups (P > 0.05). Histologically, the proportion of significant liver fibrosis (S2-S4) was higher in the CHB-MAFLD group than that in the CHB alone group (67.9% vs. 49.1%, χ (2) = 5.311, P = 0.021). Multivariate regression results showed that BMI (OR = 1.258, 95% CI: 1.145 ~ 1.381, P = 0.001) and TG (OR = 12.334, 95% CI: 3.973 ~ 38.286, P < 0.001) were the risk factors for hepatic steatosis occurrence in children with CHB. MAFLD (OR = 4.104, 95% CI: 1.703 ~ 9.889, P = 0.002), liver inflammation (OR = 3.557, 95% CI: 1.553 ~ 8.144, P = 0.003), and γ-glutamyl transferase (OR = 1.019, 95% CI: 1.001 to 1.038, P = 0.038) were independent risk factors for significant hepatic fibrosis in children with CH. Conclusion: MAFLD occurrence is related to metabolic factors in children with CHB. Additionally, the combination of MAFLD may promote liver fibrosis progression in CHB patients.

A conceptual framework for dynamics of cccDNA in hepatitis B virus / 中华肝脏病杂志

The resolution of the hepatitis C issue has raised expectations for a chronic hepatitis B cure, driving the industry to expand investment in research and development efforts to strengthen functional cure strategies. These strategies have a wide variety of types, and the published research findings are heterogeneous. The theoretical analysis of these strategies is of great significance for determining prioritized research orientations as well as sensibly allocating research and development resources. However, due to a paucity of necessary conceptual models, current theoretical analysis has not been able to unify various therapeutic strategies into a proper theoretical framework. In view of the fact that the decrease in the quantity of cccDNA is an inevitable core event accompanied by the process of functional cure, this paper intends to analyze several chronic hepatitis B cure strategies using cccDNA dynamics as a framework. Furthermore, there are currently few studies on the dynamics of the cccDNA field, hoping that this article can promote recognition and research in this field.

Evaluation of peripheral blood T-lymphocyte subpopulations features in patients with hepatitis B virus-related acute-on-chronic liver failure based on single-cell sequencing technology / 中华肝脏病杂志

Objective: T lymphocyte exhaustion is an important component of immune dysfunction. Therefore, exploring peripheral blood-exhausted T lymphocyte features in patients with hepatitis B virus-related acute-on-chronic liver failure may provide potential therapeutic target molecules for ACLF immune dysfunction. Methods: Six cases with HBV-ACLF and three healthy controls were selected for T-cell heterogeneity detection using the single-cell RNA sequencing method. In addition, exhausted T lymphocyte subpopulations were screened to analyze their gene expression features, and their developmental trajectories quasi-timing. An independent sample t-test was used to compare the samples between the two groups. Results: Peripheral blood T lymphocytes in HBV-ACLF patients had different differentiation trajectories with different features distinct into eight subpopulations. Among them, the CD4(+)TIGIT(+) subsets (P = 0.007) and CD8(+)LAG3(+) (P = 0.010) subsets with highly exhausted genes were significantly higher than those in healthy controls. Quasi-time analysis showed that CD4(+)TIGIT(+) and CD8(+)LAG3(+) subsets appeared in the late stage of T lymphocyte differentiation, suggesting the transition of T lymphocyte from naïve-effector-exhausted during ACLF pathogenesis. Conclusion: There is heterogeneity in peripheral blood T lymphocyte differentiation in patients with HBV-ACLF, and the number of exhausted T cells featured by CD4(+)TIGIT(+)T cell and CD8(+)LAG3(+) T cell subsets increases significantly, suggesting that T lymphocyte immune exhaustion is involved in the immune dysfunction of HBV-ACLF, thereby identifying potential effective target molecules for improving ACLF patients' immune function.