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.

Research progress of biomarkers of hepatitis B virus and clinical significance / 生物医学工程学杂志

The infection of Hepatitis B virus (HBV) can result in severe consequences, including chronic hepatitis, liver fibrosis, cirrhosis, and even liver cancer. Effective antiviral treatment has the potential to slow down the progression of the disease. HBV serum biomarkers play a crucial role in the dynamic management of chronic hepatitis B (CHB) patients. However, the conventional hepatitis B virus markers, such as hepatitis B serologic testing and HBV DNA, are insufficient to meet the clinical requirements. This review provided a comprehensive overview of the current research on the quantification of HBsAg and anti-HBc, HBV RNA and HBV core-associated antigen, which summarized the crucial role these markers play in the administration of antiviral medications, predicting the efficacy of treatment and anticipating the likelihood of virologic rebound following drug cessation, as well as assessing disease progression in CHB patients.

Correlation of the CTD structural domain of hepatitis B virus core protein with the encapsulation effect of indocyanine green / 生物工程学报

Hepatitis B virus core protein (HBc) has become a hot spot in drug carrier protein research due to its natural particle self-assembly ability and ease of modification. The truncation of the C-terminal polyarginine domain (CTD, aa 151-183) of HBc does not affect the self-assembly of the particles. However, it does affect the internal and external charges of the particles, which may subsequently affect drug encapsulation. Thus, the truncated C-terminal polyarginine domain (CTD) of HBc and the inserted RGD peptide were selected to construct and express three HBc variants (RH) encapsulated with ICG (RH/ICG) with different C-terminal lengths to compare the stability and drug activity of their nanoformulations. RH160/ICG was found to have a great advantages in encapsulation efficiency and biological imaging. Compared with other HBc variants, RH160/ICG significantly improved encapsulation efficiency, up to 32.77%±1.23%. Cytotoxicity and hemolysis assays further demonstrated the good biocompatibility of RH160/ICG. Cell uptake and in vivo imaging experiments in mice showed that RH160/ICG could efficiently deliver ICG in tumor cells and tumor sites with good imaging effect. This research provides a new direction for further expanding the diagnosis and treatment application of ICG and development of HBc-based nanoparticle drug carrier platform.

Seroprevalencia de infecciones hemotransmisibles en donantes de sangre / Seroprevalence of transmissible infections in blood donors

Introducción. La seguridad transfusional es el objetivo primordial de los bancos de sangre, sin embargo, conlleva un alto riesgo de eventos adversos como son las infecciones transmisibles por transfusión (ITT). El conocimiento de la prevalencia de estas infecciones fue de particular interés en esta investigación, donde se determinó su frecuencia, coinfección y relación con el tipo de donantes admitidos. Metodología. Estudio observacional retrospectivo de 2017 y 2018, en el que se incluyeron todos los registros de donantes de sangre que contenían datos demográficos y resultados de los marcadores obligatorios en el país (Ecuador), tanto de pruebas serológicas como moleculares. Se obtuvo el permiso del custodio de la información y del subcomité de bioética de investigaciones en seres humanos. Para el análisis de los datos se utilizó estadística descriptiva e inferencial. Resultados. Se determinó una prevalencia del 3,18 % de resultados reactivos para una o más ITT, el rango de edad más prevalente fue de 29 a 40 años, el 89,8 % fueron donantes compensatorios, y de ellos el 90 % fueron reactivos para una o más ITT. El marcador serológico más prevalente fue el anti-core del virus de la hepatitis B (anti-HBc), seguido por el de sífilis y los anticuerpos contra el virus de la hepatitis C (VHC). La coinfección más prevalente fue con sífilis y hepatitis B. Se encontró una diferencia estadísticamente significativa entre los resultados obtenidos en las pruebas serológicas y las moleculares (x2=26,9; p=0,000). Conclusión. Las ITT en los bancos de sangre son un riesgo latente, por lo que es necesario conocer las variaciones epidemiológicas que existen en cada población. El conocimiento de la prevalencia de las ITT en donantes de sangre permite establecer nuevas estrategias de selección del donante, que garanticen la mejor seguridad posible en las transfusiones, además debe verificarse siempre la metodología utilizada y hacer monitoreo permanente del sistema de calidad establecido

Introduction. Transfusion safety is the primary objective of blood banks, however one of the adverse reactions to blood transfusion are the transfusion transmissible infections (TTIs). Knowledge of the prevalence of these infections was of particular interest in this study where we determined their frequency, co-infection and relationship with the type of donors admitted. Methodology. Retrospective observational study during 2017 and 2018, in which all blood donor records containing demographic data and results of the country's (Ecuador) mandatory serological markers of both serological and molecular tests were included. Permission was obtained from the data custodian and the Human Research Bioethics Subcommittee. Descriptive and inferential statistics were used for data analysis. Results. A prevalence of 3,18% of reactive results to one or more TTIs was determined, the most prevalent age range was 29 to 40 years, 89.8% were compensatory donors and 90% of them were reactive to one or more TTIs. The anti- core serological marker of the hepatitis B virus (anti-HBc) was the most prevalent, followed by syphilis and hepatitis C antibodies. Syphilis and hepatitis B were identified as the most prevalent coinfection. The correlation between the results obtained in the serological and molecular tests was determined to be different and statistically significant (x2=26.9; p=0.000). Conclusion. TTIs in blood banks are a latent risk, so it is necessary to know the epidemiological variations that exist in every population. Knowledge of the prevalence of TTIs in blood donors facilitates new donor selection strategies that guarantee the best possible safety in transfusions. In addition, the methodology used must always be verified and the established quality system must be permanently monitored

Prevalence of Hepatitis B and C Virus Infection among Pregnant Women in Sharkia Governorate, Egypt

Viral infections is the cause of liver inflammation, cirrhosis and even liver hepatocellular carcinoma (HCC). Despite the availability of HBV vaccine and antiviral treatment for HBV and HCV both remain a major health problem. The aim of this study To determine the seroprevalence of HBV and HCV infection among pregnant women in Sharkia governorate, Egypt.

Hepatitis B core-related antigen reflects viral replication and protein production in chronic hepatitis B patients / 中华医学杂志(英文版)

BACKGROUND@#Hepatitis B core-related antigen (HBcrAg) is a promising disease-monitoring marker for chronic hepatitis B (CHB). We investigated correlations between HBcrAg with antiviral efficacy and virological and histological variables.@*METHODS@#One hundred and forty-five CHB patients from the mainland of China between August 2013 and September 2016 who underwent liver biopsy received entecavir therapy and had paired liver biopsy at 78 weeks. We analyzed correlations between HBcrAg and virological and histological variables in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. We also explored the predictors of HBeAg loss after 78 weeks of antiviral therapy. Pearson correlation analysis and logistic forward stepwise regression were the main statistic methods.@*RESULTS@#HBeAg-positive patients (n = 93) had higher baseline HBcrAg (median 7.4 vs. 5.3 log10 U/mL P < 0.001) and greater HBcrAg declines (median 1.6 vs. 0.9 log10 U/mL P = 0.007) than HBeAg-negative patients after 78 weeks of therapy. At baseline, HBcrAg correlated with hepatitis B virus (HBV) DNA in both HBeAg-positive (r = 0.641, P < 0.001) and -negative patients (r = 0.616, P < 0.001), with hepatitis B surface antigen (HBsAg) in HBeAg-positive patients (r = 0.495, P < 0.001), but not with anti-hepatitis B virus core antibody (anti-HBc). Weak correlations existed between HBcrAg, histology activity index (HAI; r = 0.232, P = 0.025), and Ishak fibrosis score (r = -0.292, P = 0.005) in HBeAg-positive patients. At 78 weeks, significant correlations existed only between HBcrAg and anti-HBc in HBeAg-positive (r = -0.263, P = 0.014) and HBeAg-negative patients (r = -0.291, P = 0.045). Decreased HBcrAg significantly correlated with reduced HBV DNA (r = 0.366, P = 0.001; r = 0.626, P < 0.001) and HBsAg (r = 0.526, P = 0.001; r = 0.289, P = 0.044) in HBeAg-positive and -negative patients, respectively, and with reduced HAI in HBeAg-positive patients (r = 0.329, P = 0.001). Patients with HBeAg loss (n = 29) showed a larger reduction in HBcrAg than those without (median 2.3 vs. 1.3 log10 U/mL, P = 0.001). In multivariate analysis, decreased HBcrAg was an independent predictor of HBeAg loss (P = 0.005).@*CONCLUSIONS@#HBcrAg reflects viral replication and protein production. Decreased HBcrAg could predict HBeAg loss after antiviral therapy.@*TRIAL REGISTRATION@#Clinical Trials.gov: NCT01962155; https://www.clinicaltrials.gov/ct2/show/NCT01962155?term=NCT01962155&draw=2&rank=1.

Hepatitis B: Prevalence and occult infection in HIV-infected patients

Abstract INTRODUCTION: HBV and HIV have identical transmission routes. The aim of this study was to determine the prevalence of HBV in HIV patients and to detect the presence of occult HBV infection. METHODS: All samples were tested for serology markers and using qPCR. RESULTS: This study included 232 individuals, out of which 36.6% presented with HBV markers and 11.8% presented with HBsAg or HBV-DNA, including 3 patients that showed OBI. CONCLUSIONS: We observed a high prevalence of HBV among HIV patients. In addition, the results suggest that OBI can occur in patients with serological profiles that are indicative of past infection. Therefore, the application of molecular tests may enable the identification of infections that are not evident solely based on serology.

Preparation and characterization of HBc virus like particles with site-directed coupling function / 生物工程学报

Hepatitis B virus core protein can self-assemble into icosahedral symmetrical viral-like particles (VLPs) in vitro, and display exogenous sequences repeatedly and densely on the surface. VLPs also have strong immunogenicity and biological activity. When the nanoparticles enter the body, they quickly induce specific humoral and cellular immune responses to exogenous antigens. In this study, we designed an HBc-VLPs that can be coupled with antigens at specific sites, and developed a set of efficient methods to prepare HBc-VLPs. Through site-specific mutation technology, the 80th amino acid of peptide was changed from Ala to Cys, a specific cross-linking site was inserted into the main immunodominant region of HBc-VLPs, and the prokaryotic expression vector pET28a(+)-hbc was constructed. After expression and purification, high purity HBc(A80C) monomer protein was assembled into HBc-VLPs nanoparticles in Phosphate Buffer. The results of particle size analysis show that the average particle size of nanoparticles was 29.8 nm. Transmission electron microscopy (TEM) showed that HBc-VLPs formed spherical particles with a particle size of about 30 nm, and its morphology was similar to that of natural HBV particles. The influenza virus antigen M2e peptide as model antigen was connected to Cys residue of HBc-VLPs by Sulfo-SMCC, an amino sulfhydryl bifunctional cross-linking agent, and M2e-HBc-VLPs model vaccine was prepared. The integrity of HBc-VLPs structure and the correct cross-linking of M2e were verified by cell fluorescence tracing. Animal immune experiments showed that the vaccine can effectively stimulate the production of antigen-specific IgG antibody in mice, which verified the effectiveness of the vaccine carrier HBc-VLPs. This study lays a foundation for the research of HBc-VLPs as vaccine vector, and help to promote the development of HBc-VLPs vaccine and the application of HBc-VLPs in other fields.

Anti-hepatitis B antibody levels In immunized medical students: are they at risk?

Abstract INTRODUCTION Medical students have an occupational risk for hepatitis B (HB). This study sought to determine anti-HBs and anti-HBc IgG levels in vaccinated students, check their seroconversion, and correlate this with vaccination. METHODS One hundred and forty-three students' blood samples and their vaccination schedules were analyzed. RESULTS: 65.7% were positive for anti-HBs; however, anti-HBs was absent in 34.3%. Only two samples were positive for anti-HBc IgG. CONCLUSIONS More than 30% of students did not have minimum protective levels. Comparing HBV vaccination and anti-HBs reactivity, the majority of reactive individuals received their last dose within the past 16 years.

História natural da hepatite B aguda: uma experiência de 20 anos em ambulatório de referência / Natural history of acute hepatitis B: a 20-year experience in a referral clinic

Introdução: A hepatite B trata-se de um problema mundial que afeta cerca de 257 milhões de pessoas no mundo inteiro e é responsável por complicações como cirrose e carcinoma hepatocelular. Apesar da implementação de sua vacina no calendário brasileiro de imunização infantil em 1998 e universal desde 2016, casos de hepatite B aguda ainda são rotina no Ambulatório de Hepatites Virais (AHV) e o conhecimento de sua história natural mantém-se com lacunas a serem esclarecidas. Objetivos: Avaliar mudanças no perfil populacional-epidemiológico de casos de hepatite B aguda atendidos no AHV nos últimos 20 anos, diferenciando casos agudos de crônicos anti-HBc IgM positivos, além de caracterizar as diferentes evoluções clínicas da infecção aguda e possíveis variáveis relacionadas a elas. Metodologia: Estudo transversal obtido de coorte retrospectiva de pacientes com suspeita de hepatite B aguda e anti-HBc IgM positivo de 1997 a 2017, através da revisão de prontuários. Principais resultados: Foram 581 pacientes agudos e 19 crônicos anti-HBc IgM positivos, em que houve menor média de idade entre os agudos (38 versus 46 anos, p<0,05) e maior mediana de transaminases neste mesmo grupo (ALT/AST=1500/1015 U/L versus 204/228 U/L; p<0,05) em comparação aos crônicos. Observou-se uma queda no número de casos agudos registrados desde 2014, e a distribuição entre gêneros apresentou uma tendência ao equilíbrio nos últimos três anos. A faixa etária mais prevalente foi de 20 a 39 anos (56%), que apresentou queda progressiva associada ao aumento na faixa de 40 a 59 anos desde 2009. A faixa de 0 a 19 anos apresentou quedas contínuas mantendo-se em zero desde 2014. O genótipo detectado com maior frequência foi o A (84%)

A resolução da infecção foi observada em 88%, onde 6% levaram mais de seis meses para o desaparecimento do antígeno de superfície do vírus da hepatite B (HBsAg), chamada de resolução tardia. A média de tempo para o desaparecimento do HBsAg foi de nove meses nos tardios e quatro meses para os não tardios (p<0,05). O anti-HBs acima de 10mUI/mL foi detectado em 84% dos casos resolvidos, cujo título médio foi de 219 ± 292mU/mL. Entre aqueles que cronificaram, 66% apresentaram infecção oculta e a coinfecção por HIV mostrou-se um fator de risco (pOR 4,6; IC 95% 1,1-17; p<0,05) para esse desfecho. Conclusão: Nos últimos 20 anos, houve redução nos casos atendidos de hepatite B aguda assim como aumento da idade e tendência ao equilíbrio entre os sexos infectados, no AHV. Foram notadas diferenças de idade e transaminases entre os agudos e crônicos anti-HBc IgM positivos, justificadas por suas diferenças clínicas. Houve maior prevalência de genótipo A entre os casos agudos. A taxa de cronificação foi semelhante à literatura e os pacientes que resolveram a infecção espontaneamente apresentaram títulos de anti-HBs pós infecção natural inferiores aos valores observadas entre vacinados na literatura. A coinfecção por HIV mostrou-se como um fator para evolução para cronificação na forma oculta, sendo necessária investigação minuciosa do HBV nessa população. (AU)

Response to hepatitis B vaccination in patients with inflammatory bowel disease: a prospective observational study in Korea

BACKGROUND/AIMS: Testing for hepatitis B virus (HBV) serologic markers and appropriate vaccination are required in the management of inflammatory bowel disease (IBD) patients. We evaluated immunogenicity for HBV in IBD patients and the response to the HBV vaccination. METHODS: From May 2014 to August 2016, patients diagnosed with IBD were prospectively included and evaluated for antibody to hepatitis B surface antigen, antibody to hepatitis B core antigen, and antibody to hepatitis B surface antigen. Among the 73 patients who were confirmed with nonimmunity to HBV, 44 patients who had completed the 3-dose HBV vaccination series received a single booster vaccination, while 29 patients who had not completed the vaccinations series or were unsure of receiving the vaccination received a full vaccination series. RESULTS: An optimal response was obtained in 70.5% of the patients in the booster group, and 89.7% of the patients in the full vaccination group. Age younger than 26 years (odds ratio [OR], 6.01; 95% confidence interval [CI], 1.15–31.32; P=0.033) and a complete previous vaccination series (OR, 0.15; 95% CI, 0.03–0.80; P=0.026) were associated with optimal vaccine response. Previous complete vaccination series (OR, 0.11; 95% CI, 0.02–0.73; P=0.022) was the only predictive factor for lower compliance. CONCLUSIONS: The response to the HBV vaccination was lower in patients older than 26 years and for those patients with a complete vaccination history. Since patients with a complete vaccination history also had poor compliance, serum HBV-titers should be checked more thoroughly, and a full vaccination series should be administered in cases when there is a negative response to the booster vaccination.

Report on the External Quality Assessment Scheme of Hepatitis Viral Markers in Korea, (2016–2017)

As part of the immunoserology program of the Korean Association of External Quality Assessment Service, we organized two trials on the external quality assessment of hepatitis viral markers in 2016 and 2017. The hepatitis viral antigens and antibodies program consisted of 10 test items. We delivered two and three types of pooled sera specimens to 965 and 965 institutions for the first and second trials of external proficiency testing in 2016, respectively. The number of participating laboratories was 915 (94.8%) and 913 (95.0%) in the first and second trials in 2016, respectively. We also delivered three kinds of pooled sera specimens to 936 and 1,015 institutions for the first and second trials of external proficiency testing in 2017, respectively. The number of participating laboratories was 920 (98.3%) and 996 (98.1%) in the first and second trials in 2017, respectively. The most commonly tested items were hepatitis B surface antigen, followed by the antibodies to hepatitis B surface antigen, anti-hepatitis C virus, hepatitis B envelope antigen, antibodies to hepatitis B envelope antigen, anti-hepatitis A virus and antibodies to hepatitis B core antigen. The most frequently used methods for detecting viral markers were the chemiluminescence immunoassay and the electrochemiluminescence immunoassay, but they yielded a few-false positive results due to the matrix effect. The immunochromatographic assay yielded false-negative results for anti-hepatitis A virus due to low sensitivity. Continuous improvement in the quality of viral hepatitis testing through participation in the survey seems necessary.

Expression of Hepatocyte Hepatitis B Core Antigen and Hepatitis B Surface Antigen as a Marker in the Management of Chronic Hepatitis B Patients

BACKGROUND/AIMS: We aimed to clarify the association of hepatitis B surface antigen (HBsAg)/hepatitis B core antigen (HBcAg) with the disease status and treatment response in patients with chronic hepatitis B (CHB). METHODS: We investigated 171 biopsy-proven entecavir-treated CHB patients (109 hepatitis B e antigen [HBeAg]-positive, 62 HBeAg-negative). HBcAg expression was positive when ≥10% of hepatocytes stained, and classified into nuclear, mixed, and cytoplasmic patterns. HBsAg expressions were intracytoplasmic (diffuse, globular, and submembranous) and membranous. The histologic activity index (HAI) and fibrosis stage followed Ishak system. RESULTS: In HBeAg-positive patients, older age, increased HAI score, advanced fibrosis, and reduced viral load were observed when HBcAg expression shifted from nucleus to cytoplasm in HBcAg-positive patients, and HBsAg expression from non-submembranous to submembranous in HBcAg-negative patients (all, p<0.05). In HBeAg-negative patients, only intracytoplasmic HBsAg expression patterns had clinical relevance with decreased ALT levels and viremia. In HBeAg-positive patients without favorable predictors of virologic response, negative HBcAg and membranous HBsAg expression predicted greater virologic response (both, p<0.05). The probability of HBeAg seroclearance was higher in patients with increased HAI or lacking HBcAg expression (both, p<0.05). Higher serum HBsAg levels and hepatocyte HBcAg positivity were associated with reduced serum HBsAg during first and post-first year treatment, respectively (both, p<0.05). CONCLUSIONS: Hepatocyte HBcAg/HBsAg expression is a good marker for disease status and predicting treatment response.

A Case of Primary Biliary Cirrhosis Mimicking Acute Hepatitis B in the Clinic, Republic of Korea / 가정의학회지

Primary biliary cirrhosis (PBC) is a slowly progressive cholestatic autoimmune liver disease characterized by progressive bile duct injury. The most common symptoms of this disease include fatigue and pruritus. The diagnosis of PBC is based on cholestatic biochemical liver tests, presence of antimitochondrial antibodies, and characteristic histological biopsy findings. We report a case of a patient with PBS, who was initially suspected to be in the window period of hepatitis B by a private doctor in a local clinic based on the detection of isolated immunoglobulin M antibody against hepatitis B core antigen. The presence of this antibody is the most useful index in diagnosing acute hepatitis B (+) by immunoserological test. The final diagnosis of the patient in Good Gang-An Hospital was PBC through additional tests. The patient is receiving outpatient treatment.

Prevention of Hepatitis B reactivation in the setting of immunosuppression

Advances in the treatment of malignant and inflammatory diseases have developed over time, with increasing use of chemotherapeutic and immunosuppressive agents of a range of drug classes with varying mechanism and potency in their effects on the immune system. These advances have been met with the challenge of increased risk of hepatitis B virus (HBV) reactivation in susceptible individuals. The magnitude of risk of HBV reactivation is associated with the individual's HBV serological status and the potency and duration of immunosuppression. Individuals with chronic hepatitis B (CHB) and previously infected but serologically cleared HBV infection are both susceptible to HBV reactivation. HBV reactivation in the setting of immunosuppression is a potentially life threatening condition leading to liver failure and death in extreme cases. It is important to recognize that HBV reactivation in the setting of immunosuppression is potentially preventable. Therefore, identification of patients at risk of HBV reactivation and institution of prophylactic antiviral therapy prior to initiation of immunosuppression is essential.

Prevention of Hepatitis B reactivation in the setting of immunosuppression

Advances in the treatment of malignant and inflammatory diseases have developed over time, with increasing use of chemotherapeutic and immunosuppressive agents of a range of drug classes with varying mechanism and potency in their effects on the immune system. These advances have been met with the challenge of increased risk of hepatitis B virus (HBV) reactivation in susceptible individuals. The magnitude of risk of HBV reactivation is associated with the individual's HBV serological status and the potency and duration of immunosuppression. Individuals with chronic hepatitis B (CHB) and previously infected but serologically cleared HBV infection are both susceptible to HBV reactivation. HBV reactivation in the setting of immunosuppression is a potentially life threatening condition leading to liver failure and death in extreme cases. It is important to recognize that HBV reactivation in the setting of immunosuppression is potentially preventable. Therefore, identification of patients at risk of HBV reactivation and institution of prophylactic antiviral therapy prior to initiation of immunosuppression is essential.

Nuclear Expression of Hepatitis B Virus X Protein Is Associated with Recurrence of Early-Stage Hepatocellular Carcinomas: Role of Viral Protein in Tumor Recurrence

BACKGROUND: Hepatitis B virus (HBV) plays well-known roles in tumorigenesis of hepatocellular carcinoma (HCC) in infected patients. However, HBV-associated protein status in tumor tissues and the relevance to tumor behavior has not been reported. Our study aimed to examine the expression of HBV-associated proteins in HCC and adjacent nontumorous tissue and their clinicopathologic implication in HCC patients. METHODS: HBV surface antigen (HBsAg), HBV core antigen (HBcAg), and HBV X protein (HBx) were assessed in 328 HBV-associated HCCs and in 155 matched nontumorous tissues by immunohistochemistry staining. RESULTS: The positive rates of HBsAg and cytoplasmic HBx staining in tumor tissue were lower than those in nontumorous tissue (7.3% vs. 57.4%, p < .001; 43.4% vs. 81.3%, p < .001). Conversely, nuclear HBx was detected more frequently in tumors than in nontumorous tissue (52.1% vs. 30.3%, p < .001). HCCs expressing HBsAg, HBcAg, or cytoplasmic HBx had smaller size; lower Edmondson-Steiner (ES) nuclear grade, pT stage, and serum alpha-fetoprotein, and less angioinvasion than HCCs not expressing HBV-associated proteins. Exceptionally, nuclear HBx-positive HCCs showed higher ES nuclear grade and more frequent large-vessel invasion than did nuclear HBx-negative HCCs. In survival analysis, only nuclear HBx-positive HCCs had shorter disease-free survival than nuclear HBx-negative HCCs in pT1 and ES nuclear grade 1-2 HCC subgroup (median, 126 months vs. 35 months; p = .015). CONCLUSIONS: Our data confirmed that expression of normal HBV-associated proteins generally decreases in tumor cells in comparison to nontumorous hepatocytes, with the exception of nuclear HBx, which suggests that nuclear HBx plays a role in recurrence of well-differentiated and early-stage HCCs.

Epidemiological study of hepatitis B and C in a municipality with rural characteristics: Cássia dos Coqueiros, State of São Paulo, Brazil

Abstract: INTRODUCTION: Hepatitis B and C viral infections remain an important cause of global morbidity and mortality. Studies have been conducted in population groups of large cities, leaving gaps in the knowledge regarding the situation in small municipalities. We aimed to measure the prevalence of hepatitis B and C markers and presence of infection-associated factors. METHODS: All inhabitants of Cássia dos Coqueiros aged ≥18 years who agreed to participate in the research were included. We collected blood as well as information via a questionnaire between March 2011 and December 2013. Univariate and multivariate analyses were conducted. RESULTS: Among the 1,001 participants, 41 (4.1%) participants had a serological profile of hepatitis B viral exposure, and only one (0.1%) participant was considered a virus carrier. The frequency of isolated antibody to hepatitis B virus surface antigen (anti-HBs) markers was 17.8% for the overall population. In the multivariate analysis, hepatitis B virus (HBV) infection was associated with age, birth outside the State of São Paulo, history of hepatitis, ≥2 sexual partners in the last 6 months, and tattoos. Four (0.4%) participants had a serological profile of hepatitis C viral exposure. However, after confirmation using viral ribonucleic acid (RNA) evaluation, only one (0.1%) individual remained positive. CONCLUSIONS: The positivity rates for hepatitis B and C were low, despite greater sexual freedom and the recent emergence of illicit drugs, as observed by the health personnel working in Cássia dos Coqueiros.

Clinical and epidemiological profile of female blood donors with positive serology for viral hepatitis B

ABSTRACTINTRODUCTION:Since women are frequently the minority among blood donors worldwide, studies evaluating this population usually reflect male features. We assessed the features of female blood donors with positive serology for HBV and compared them with those of men.METHODS The study comprised consecutive blood donors referred to a specialized liver disease center to be evaluated due to HBsAg- and/or anti-HBc-positive tests.RESULTS: The study encompassed 1,273 individuals, 219 (17.2%) of whom were referred due to positive HBsAg test and 1,054 (82.8%) due to reactive anti-HBc test. Subjects' mean age was 36.8±10.9 years, and 28.7% were women. Female blood donors referred for positive HBsAg screening tests demonstrated higher prevalence of healthcare workers (9.3% vs 2.5%) and lower prevalence of sexual risk behaviors (15.1% vs 41.1%) and alcohol abuse (1.9% vs 19.8%) compared to men. Women had lower ALT (0.6 vs 0.8×ULN), AST (0.6 vs 0.8×ULN), direct bilirubin (0.2 vs 0.3mg/dL), and alkaline phosphatase (0.5 vs 0.6×ULN) levels and higher platelet count (223,380±50,293 vs 195,020±53,060/mm3). Women also had a higher prevalence of false-positive results (29.6% vs 17.0%). No differences were observed with respect to liver biopsies. Female blood donors referenced for reactive anti-HBc screening tests presented similar clinical, epidemiological, and biochemical characteristics to those reported for positive HBsAg screening tests and similarly had a higher prevalence of false-reactive results.CONCLUSIONS: Compared to men, female blood donors with positive HBsAg and/or anti-HBc screening tests demonstrated higher prevalence of professional risk and false-positive results and reduced alteration of liver chemistry.

Comparison of HBV persistent infection mice models by different serotypes of AAVs carrying HBV genomes / 生物工程学报

In recent years, Hepatitis B virus (HBV) persistent infection mouse model with recombinant adeno-associated virus 8 carrying 1.3 copies of HBV genome (rAAV8-1.3HBV) is concerned. We studied and compared the efficacy among HBV persistent infection mice models by other serotypes except AAV8. First, we prepared and purified five viruses: rAAV1-1.3HBV, rAAV2-1.3HBV, rAAV5-1.3HBV, rAAV8-1.3HBV and rAAV9-1.3HBV. Then we injected each virus into 3 C57BL/6J mice with the dose of lx 1011 vg (Viral genome, vg) per mouse. We detected HBsAg and HBeAg in sera by enzyme-linked immunosorbent assay (ELISA) at different time points post injection. We killed mice 8 weeks post injection and took blood and livers for assay. We detected copies of HBV DNA by real-time quantitative PCR in sera and livers. Meantime, we detected HBcAg in the livers of mice by immunohistochemistry and further performed pathology analysis of these livers. The five groups of mice, HBeAg and HBsAg expression sustained 8 weeks in serological detection and HBV DNA was both detected in sera and livers at the time of 8 weeks post injection. HBeAg, HBsAg, HBV DNA copies expression levels in descending order were AAV8>AAV9>AAV1>AAV5>AAV2. HBcAg expression was detected in livers as well. Varied degrees of liver damage were shown in five groups of mice. This study provides more alternative AAV vector species to establish a persistent infection with hepatitis B model.