Significación de los marcadores infecciosos para identificar portadores de hepatitis B en donantes de sangre / Significance of hepatitis B surface antigen, IgM/IgG core antibody and hepatitis B virus DNA in blood donors

Resumen Introducción: La identificación de portadores del virus de la hepatitis B en donantes de sangre es imperativo para evitar la transmisión de la enfermedad a través de transfusiones sanguíneas. Objetivo: Determinar si los donantes de sangre con resultados positivos de los marcadores serológicos HbsAg y anti-HBc eran portadores de ADN del virus de la hepatitis B. Métodos: Se recolectaron 12 745 muestras de seis bancos de sangre ecuatorianos, las cuales fueron analizadas con pruebas serológicas para identificar los marcadores infecciosos HBsAg, anti-HBc, anti-HBs mediante prueba ELISA automatizada. Todas las muestras positivas para uno, dos o los tres marcadores fueron analizadas con técnica molecular para determinar la presencia de ADN viral. Resultados: Se identificó que 27.5 % de las muestras reactivas solo a anti-HBc y 100 % de las muestras con resultados positivos de HBsAg/anti-HBc-IgM/IgG presentaron ADN del virus de la hepatitis B (p = 0.001). Conclusiones: La elección de los marcadores de infección y los métodos de detección definen los resultados. Es importante la realización de dos pruebas serológicas y una molecular para identificar a los portadores del virus de la hepatitis B y evitar su transmisión.

Abstract Introduction: Identification of hepatitis B virus carriers in blood donors is imperative in order to avoid transmission of the disease via blood transfusion. Objective: To determine if blood donors with positive results for serological markers HBsAg and anti-HBc were hepatitis B virus DNA carriers. Methods: 12,745 samples were collected from six Ecuadorian blood banks and analyzed for HBsAg, anti-HBc and anti-HBs infectious markers by automated ELISA. All samples that tested positive for one, two or all three markers were analyzed with molecular techniques to determine the presence of viral DNA. Results: 27.5 % of the samples that were reactive for anti-HBc alone and 100 % of those with positive results for HbsAg and IgM/IgG anti-HBc were identified to contain hepatitis B virus DNA (p = 0.001). Conclusions: The selection of infection markers, as well as the detection methods define the results. Performing two serological and one molecular test is important in order to identify hepatitis B virus carriers and prevent its transmission.

Risk factors for losing hepatitis B virus surface antibody in patients with HBV surface antigen negative/surface antibody positive serostatus receiving biologic disease-modifying anti-rheumatic drugs: a nested case-control study

Abstract Background: Hepatitis B virus (HBV) reactivation consequent to immunosuppressive therapy is an increasingly prevalent problem with serious clinical implications. Treatment with biologic agents conduces to the loss of protective antibody to HBV surface antigen (anti-HBs), which significantly increases the risk of HBV reactivation. Hence, we investigated the risk factors for losing anti-HBs in patients with rheumatic diseases and HBV surface antigen negative/anti-HBs positive (HBsAg-/anti-HBs+) serostatus during treatment with biologic disease-modifying anti-rheumatic drugs (DMARDs). Methods: Using a nested case-control design, we prospectively enrolled patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis/psoriasis, or juvenile idiopathic arthritis, who were treated with biologic DMARDs at Changhua Christian Hospital, Taiwan, from January 2013 to June 2019 and had HBsAg-/anti-HBs+ serostatus; the analytic sample excluded all patients with HBsAg+ or anti-HBs- serostatus. Anti-HBs titers were monitored 6-monthly and cases were defined as anti-HBs < 10 mIU/ml during follow-up. Cases were matched one- to-all with controls with anti-HBs ≥ 10 mIU/ml on the same ascertainment date and equivalent durations of biologic DMARDs treatment (control patients could be resampled and could also become cases during follow-up). Between-group characteristics were compared and risk factors for anti-HBs loss were investigated by conditional logistic regression analyses. Results: Among 294 eligible patients, 23 cases were matched with 311 controls. The incidence of anti-HBs loss was ∼ 2.7%/person-year during biologic DMARDs treatment. Besides lower baseline anti-HBs titer (risk ratio 0.93, 95% CI 0.89-0.97), cases were significantly more likely than controls to have diabetes mellitus (risk ratio 4.76, 95% CI 1.48-15.30) and chronic kidney disease (risk ratio 14.00, 95% CI 2.22-88.23) in univariate analysis. Risk factors remaining significantly associated with anti-HBs loss in multivariate analysis were lower baseline anti-HBs titer (adjusted risk ratio 0.93, 95% CI 0.88-0.97) and chronic kidney disease (adjusted risk ratio 45.68, 95% CI 2.39-871.5). Conclusions: Besides lower baseline anti-HBs titer, chronic kidney disease also strongly predicts future anti-HBs negativity in patients with HBsAg-/anti-HBs+ serostatus who receive biologic DMARDs to treat rheumatic diseases. Patients with low anti-HBs titer (≤ 100 mIU/ml) and/or chronic kidney disease should be monitored during biologic DMARDs therapy, to enable timely prophylaxis to preempt potential HBV reactivation.

Reducción en la infección por VHB y VHD en dos poblaciones indígenas de la Amazonia peruana después de la vacunación contra la hepatitis B / Reduction of HBV and HDV infection in two indigenous peoples of Peruvian Amazon after the vaccination against hepatitis B

Resumen: Objetivo: Conocer el resultado de la vacunación contra la hepatitis B en las comunidades hiperendémicas Kandozi y Chapra de la Amazonia Peruana a partir de la prevalencia de infecciones por los virus de la hepatitis B (VHB) y Delta (VHD), ocho años después de iniciada la vacunación. Material y métodos: Se realizó un estudio transversal en 2 944 pobladores de 67 comunidades indígenas Kandozi y Chapra en abril de 2010. El tamizaje serológico para el antígeno de superficie del VHB (HBsAg), anticuerpos anti-HBc IgM e IgG, anticuerpos anti-HBs y anti-VHD se determinaron mediante pruebas de ELISA. Resultados: Las tasas de prevalencia del HBsAg, anti-HBc IgG, anti-HBs ≥10 mlUI/ml y anti-VHD fueron 2.3, 39.13, 50.95 y 2.11%, respectivamente. La prevalencia del HBsAg en niños <11 años fue cero. Entre los portadores del HBsAg, las tasas de prevalencia de sobreinfeccion por el VHD e infección aguda por el VHB fueron 2.11% (todos fueron >14 años) y 11.94%, respectivamente. Conclusiones: Estos hallazgos muestran la eliminación de portadores de VHB en niños <11 años, ocho años después de iniciada la vacunación contra el VHB.

Abstract: Objective: To determine the outcome of the vaccination against hepatitis, we determined the prevalence of hepatitis B virus (HBV) and hepatitis D virus (HDV) infections, eight years after introduction of the vaccination. Materials and methods: A cross-sectional study was performed in 2 944 participants of 67 Kandozi and Chapra indigenous peoples in April 2010. Serological screening for hepatitis B surface antigen (HBsAg), antibody anti-HBc IgM and IgG, antibody anti-HBs and anti-HDV were determined by ELISA tests. Results: The prevalence rates of HBsAg, anti-HBc total, anti-HBs ≥10 mlUI/ml and anti-HDV were 2.3, 39.13, 50.95 and 2.11%, respectively. The prevalence rate of HBsAg in children <11 years was 0%. Among carriers of HBsAg, the prevalence rates of HDV and acute HBV infections were 2.11% (all were >14 years) and 11.94%, respectively. HBsAg and anti-HBc total were associated with individuals ≥10 years (p<0.001). Conclusions: These findings show the elimination of HBV carriers in children <11 years, eight years following introduction of the vaccination against HBV.

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.

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.

Búsqueda de infección por Hepatitis B en familiares de portadores crónicos de la provincia de Huanta, Ayacucho -Perú / Search of Hepatitis-B infection in relatives of chronic carriers in the province of Huanta, Ayacucho, Peru

RESUMEN Un plan de eliminación del virus de hepatitis B (HBV) es factible porque la inmunización ha tenido buen impacto, tal como ha sucedido en la provincia de Huanta en Perú. El objetivo de nuestro estudio fue determinar la frecuencia de la infección por HBV en familiares de portadores del antígeno de superficie del virus de la hepatitis B (HBsAg). Este estudio transversal incluyó a 39 familiares de portadores crónicos, identificados en el Hospital de Apoyo de Huanta. Se recolectaron datos sociodemográficos y muestras de sangre. La frecuencia total de infección por HBV fue de 10,3 % y la mayoría correspondía a infección crónica (7,7 %). Una tercera parte tenía antecedentes de infección por HBV. Los miembros de la familia con infección por HBV fueron mayormente adultos alcohólicos y no vacunados. En conclusión, encontramos una alta frecuencia de HBV en familiares de portadores de HBsAg, esta estrategia ayudaría a identificar portadores crónicos que pueden ser tratados y contribuir a un plan de eliminación de HBV.

ABSTRACTS A plan of elimination of the virus of B hepatitis (HBV) is feasible because the immunization has had good impact, as it has been documented in the province of Huanta in Peru. The objective of our study was to determine the frequency of the infection by HBV in relatives of carriers of the surface antigen of the virus of hepatitis B (HBsAg). This cross-sectional study included 39 relatives of chronic carriers, identified at Hospital de Apoyo de Huanta. Sociodemographic data and blood samples were collected. The total frequency of infection by HBV was 10.3%, and the majority corresponded to chronic infection (7.7%). One third had a history of infection by HBV. The family members with HBV infection were mainly adult alcoholics who had not been vaccinated. In conclusion, we found a high frequency of HBV in relatives of carriers of HBsAg. This strategy would help identify chronic carriers that can be treated and to contribute to a plan for the elimination of HBV.

HBV epidemiology and genetic diversity in an area of high prevalence of hepatitis B in southern Brazil

ABSTRACT Background Hepatitis B virus (HBV) infection is a major public health problem in Brazil. HBV endemicity is usually moderate to low according to geographic regions, and high prevalence of this virus has been reported in people of some specific Brazilian counties, including those with a strong influence of Italian colonization in southern Brazil. Analysis of HBV diversity and identification of the main risk factors to HBV infection are necessary to understand hepatitis B epidemiology in these high prevalence regions in southern Brazil. Objective To investigate epidemiological characteristics and HBV genotypes and subgenotypes circulating in a specific city with high HBV prevalence. Methods A cross-sectional study was performed with 102 HBV chronically infected individuals, recruited in reference outpatient clinics for viral hepatitis in a city of high HBV prevalence (Bento Gonçalves) in Rio Grande do Sul state, Brazil between July and December 2010. Socio-demographic, clinical and behavior-related variables were collected in a structured questionnaire. HBV serological markers (HBsAg, anti-HBc), viral load, genotypes/subgenotypes and drug resistance were evaluated and comparatively analyzed among all patients. Results The HBV infected subjects had a mean age of 44.9 (±12.2) years, with 86 patients (84.3%) reporting to have a family history of HBV infection, 51 (50.0%) to share personal objects, and were predominantly of Italian descendants (61; 64.9%). There was a predominance of genotype D (49/54; 90.7%), but genotype A was also detected (5/54; 9.3%). Subgenotypes D1 (1; 4.7%), D2 (3; 14.3%), and D3 (17; 81.0%) were identified. LAM-resistant mutation (rtM204I) and ADV-resistant mutations (rtA181V) were detected in only one patient each. Conclusions These results demonstrate a pivotal role of intrafamilial transmission for HBV spreading in this population. Furthermore, there is a high prevalence of HBV genotype D in this region.

Hepatitis B status in hemodialysis patients / Situação da hepatite B em pacientes em hemodiálise

ABSTRACT BACKGROUND: Patients on chronic dialysis present a high prevalence of hepatitis B virus infection. Despite infection-control practices, surveillance of serological markers, and hepatitis B vaccination, there are still outbreaks of the disease in dialysis centers. OBJECTIVE: This study aims to assess the serologic and vaccination status for hepatitis B in hemodialysis patients. METHODS: This cross-sectional study assessed serologic markers and hepatitis B vaccination status of chronic kidney disease patients on regular dialysis program in São Carlos, SP, Brazil. Patients without information about hepatitis B status (anti-HBc, HBsAg and anti-HBs) were referred for testing. Individuals with uncertain or incomplete immunization status and without serological conversion (anti-HBs <10mIU/mL) were referred to vaccination, with adverse effects monitored. RESULTS: The study included 130 from a total of 181 dialysis patients. The majority were male (63.8%), mean age 53.9 years. All patients were already screened and negative for HBsAg, and 73.8% were vaccinated against hepatitis B (59.2% complete and 14.6% incomplete schedule), with a seroconversion rate of 75.3%. Only 11 (8.5%) patients had prior dosage of anti-HBc (negative). Among the 47 patients referred for anti-HBc testing, four were anti-HBc positive and one indeterminate. Of the total of patients referred to immunization, 34 have actually received HBV vaccine; among them five had mild adverse effects. CONCLUSION: Despite the benefit of dosing of anti-HBc and anti-HBs before admission to dialysis, economic constraints have reduced the screening to only HBsAg. Since occult HBV infection has already been demonstrated in hemodialysis patients, the measure of anti-HBc should be encouraged.

RESUMO CONTEXTO: Pacientes cronicamente em diálise apresentam alta prevalência de infecção por vírus da hepatite B. Apesar de práticas de controle de infecção, vigilância de marcadores sorológicos e vacinação contra a hepatite B, ainda há surtos da doença em centros de diálise. OBJETIVO: Este estudo tem como objetivo avaliar o estado sorológico e a vacinação contra hepatite B em pacientes em hemodiálise. MÉTODOS: Estudo transversal avaliando marcadores sorológicos e vacinação contra a hepatite B em pacientes com doença renal crônica em programa regular de hemodiálise em São Carlos, SP, Brasil. Pacientes sem marcadores sorológicos para hepatite B disponíveis (anti-HBc, HBsAg e anti-HBs) foram encaminhados para testagem. Em caso de situação vacinal desconhecida, incompleta ou sem resposta vacinal (anti-HBs <10mIU/mL), os pacientes foram encaminhados para vacinação, sendo os efeitos adversos monitorados. RESULTADOS: O estudo incluiu 130 de um total de 181 pacientes em diálise. A maioria era do sexo masculino (63,8%), com idade média de 53,9 anos. Todos os pacientes já haviam sido rastreados e eram negativos para HBsAg, e 73,8% foram vacinados contra a hepatite B (59,2% esquema completo e 14,6% esquema incompleto), com uma taxa de soroconversão de 75,3%. Apenas 11 (8,5%) pacientes dispunham de dosagem prévia de anti-HBc (negativo). Entre os 47 pacientes encaminhados para testagem anti-HBc, quatro eram anti-HBc reagentes e um indeterminado. Do total de pacientes encaminhados à imunização, 34 receberam efetivamente a vacina contra o HBV; entre eles, cinco tiveram efeitos adversos leves. CONCLUSÃO: Apesar do benefício da dosagem de anti-HBc e anti-HBs antes da admissão à diálise, restrições econômicas reduziram o rastreio apenas à dosagem de HBsAg. Como a infecção oculta por HBV já foi demonstrada em pacientes em hemodiálise, a dosagem de anti-HBc deve ser incentivada.

Prevalencia de hepatitis B y C en el banco de sangre de un hospital en Callao, Perú / Hepatitis B and C prevalence in a blood bank at general hospital in Callao, Peru

Objetivo: El objetivo del presente estudio fue determinar la prevalencia de seropositividad para HBsAg, Anti-HBcAg y Anti- HVC del Banco de Sangre del Hospital Nacional Daniel Alcides Carrión (HNDAC) durante el periodo 2010 al 2012. Materiales y métodos: Estudio transversal retrospectivo. Se incluyó a los potenciales donadores. Se recolectaron las características tales como edad, sexo y conductas de riesgo. Se realizó el análisis descriptivo con el programa STATA 14. Resultados: Se incluyó 13 887 potenciales donantes del HNDAC entre enero 2010 y diciembre 2012. Se identificaron 897 potenciales donantes positivos. La prevalencia de HBsAg fue 0,55%; Anti-HBcAg, 5,15%; y Anti-HVC, 1,25%. De ellos se encontró edad promedio de 37,4 años para los pacientes infectados por virus de hepatitis B y de 36,9 para los pacientes infectados por virus de hepatitis C, 31,2% fueron mujeres del total de infectados. Conclusión: La prevalencia de serología positiva para virus de hepatitis B fue similar a reportes anteriores, por otro lado la serología positiva para virus de hepatitis C fue mayor a lo reportado en nuestro país

ABSTRACT Objective: The aim of the present study was to determine the prevalence of sero positivity for HBsAg, Anti-HBcAg and Anti- HVC in the blood bank of Hospital Daniel Carrion during the period 2010 - 2012. Materials and methods: Retrospective cross-sectional study. Potential donors who met the inclusion criteria were included. Sociodemographic factors, risk behaviors were gathered. A descriptive analysis was performed with STATA 14. Results: 13,887 potential blood donors of the HNDAC between January 2010 and December 2012 were identified. The population's mean was 37 years, 32% were women. 897 potential positive blood donors were identified. The prevalence of HBsAg was 0.55%; Anti-HBcAg, 5.15%; and Anti-HVC, 1.25%. Conclusion: The prevalence of positive serology for HBsAg was similar to the previous reports and Anti-HVC was higher than the prevalence reported in our country

Marcadores de infección para hepatitis viral en donantes de sangre de un hospital nacional de lima metropolitana / Viral Hepatitis Infection Markers Among Blood Donor in a National Hospital of Metropolitan Lima

RESUMEN El objetivo del estudio fue determinar la frecuencia de marcadores de infección para hepatitis B, hepatitis C y conocer los factores asociados en los donantes de sangre. El estudio se realizó con datos del registro de donantes de un hospital público de Lima. De 28 263 sujetos analizados entre 2012 y 2015, el 0,6% (n=156) fue reactivo para HBsAg; 5,2% (n=1465) para anti-HBc, y 0,8% (n=232) para Anti-HVC. Los resultados positivos para HBsAg (p=0,319) y anti-HVC (p=0,037) fueron en mayor proporción en los donantes voluntarios. Los resultados positivos para HBsAg y anti-HBc fueron en mayor proporción en las personas de 50 a más años de edad. Los donantes voluntarios fueron en mayor proporción en los sujetos menores de 20 años (p<0,001). En conclusión, la reactividad a los marcadores de infección para hepatitis está asociado a la donación voluntaria y al grupo de edad de los donantes.

ABSTRACT The aim of the study was to determine the frequency of infection markers for hepatitis B and hepatitis C and to identify associated factors in blood donors. The study was carried out using data obtained from blood donor medical records collected in a public hospital in Lima. Of 28,263 individuals analyzed between 2012 and 2015, 0.6% (n=156) were reactive for HBsAg; 5.2% (n=1,465), for anti-HBc; and 0.8% (n=232), for anti-HVC. Positive results for HBsAg (p=0.319) and anti-HVC (p=0.037) were more common in voluntary donors. For HBsAg and anti-HBc, positive results were more common in individuals aged 50 years or older. The number of voluntary donors was higher among individuals younger than 20 years (p<0.001). The study indicates that reactivity to hepatitis infection markers is associated with voluntary donation and the age group of blood donors.

Risk factors for hepatitis B transmission in South Brazil

BACKGROUND Hepatitis B virus (HBV) infection is a major public health problem in Brazil. Several risk factors are involved in HBV infection and their identification by a rational and essential approach is required to prevent the transmission of this infection in Brazil. OBJECTIVES To evaluate risk factors associated with HBV infection in South Brazil. METHODS A total of 260 patients with HBV and 260 controls from Caxias do Sul (state of Rio Grande do Sul, Brazil) participated in this study. All participants were given a standard questionnaire to yield the sociodemographic information and to identify HBV risk factors. HBV infection was detected by HBsAg test in all participants. FINDINGS HBV infection in these cases was strongly associated with history of a family member HBV-infected, mainly mother [odds ratio (OR) = 4.86; 95% confidence intervals (CI): 1.69-13.91], father (OR = 5.28; 95% CI: 1.58-17.71), and/or siblings (OR = 22.16; 95% CI: 9.39-52.25); sharing personal objects (OR = 1.40; 95% CI: 1.37-2.38); and having history of blood transfusion (OR = 2.05; 95% CI: 1.10-2.84). CONCLUSIONS HBV infection was strongly associated with having a family member infected with hepatitis B, sharing personal objects, and having history of blood transfusion.

Risk Factors for Prognosis of Hepatocellular Carcinoma After Curative Resection In Patients with Low Hepatitis B Viral Load

ABSTRACT Background. A retrospective cohort study was conducted to investigate the effect of hepatitis B surface antigen (HBsAg) level on prognosis in low viral load (< 2000 lU/mL) patients with hepatitis B-related hepatocellular carcinoma (HCC) after curative resection. Material and methods. A total of 192 patients with low viral load who had received curative resection of pathologically confirmed HCC were analyzed to determine the factors affecting prognosis. The risk factors for survival, early and late recurrence (2 years as a cut-off) were studied. Results. The median follow-up time was 38.5 months. The overall survival rates at 1-, 3-, and 5-year after curative resection were 94.2%, 64.0%, and 45.2%, respectively. The cumulative recurrence rates at 1-, 3-, and 5-year after curative resection were 22.4%, 46.5%, and 67.0%, respectively. Patients with high serum HBsAg levels (> 250 lU/mL) had significantly lower survival rates than those with low HBsAg levels (HR: 1.517,95% Cl: 1.005-2.292, P = 0.047). Stratified analysis showed that patients with high HBsAg levels had a significantly higher late recurrence incidence than those with low HBsAg levels (HR: 2.155, 95% Cl: 1.094-4.248, P = 0.026), but did not have a significantly higher risk of early recurrence postoperatively (HR: 1.320,95% Cl: 0. 837-2.082, P = 0.233). Multivariate analysis revealed that HBsAg > 250 lU/mL was an independent risk factor associated with late recurrence (HR: 2.109, 95% Cl: 1.068-4.165, P = 0.032). Conclusions. HBsAg > 250 lU/mL at the time of tumor resection was an independent risk factor for late recurrence in low viral load HCC patients.

Poor sensitivity of rapid tests for the detection of antibodies to the hepatitis B virus: implications for field studies

Rapid tests (RTs) can be used as an alternative method for the conventional diagnosis of hepatitis B virus (HBV). This study aims to evaluate antibodies to HBsAg (anti-HBs) and antibodies to HBeAg (anti-HBe) RTs under different Brazilian settings. The following three groups were included: GI: viral hepatitis outpatient services; GII: low resource areas; and GIII: crack users and beauticians. Imuno-rápido anti-HBsAg™ and Imuno-rápido anti-HBeAg™ RTs were evaluated and showed specificities greater than 95% in all groups. The sensitivity values to anti-HBs were 50.38%, 51.05% and 46.73% and the sensitivity values to anti-HBe were 76.99%, 10.34% and 11.76% in the GI, GII and GIII groups, respectively. The assays had a low sensitivity and high specificity, which indicated their use for screening in regions endemic for HBV.

Effects of Interleukin-4 and Interleukin-12b Gene Polymorphisms on Hepatitis B Virus Vaccination

Abstract: Approximately 10% of individuals do not respond to hepatitis B virus (HBV) vaccination, i.e. non-responders (NRs). We aimed to investigate the association of interleukin (IL)-4 and IL-12B gene polymorphisms with responsiveness to the HBV vaccine in Korean infants. Among 300 healthy infants (9-12 month), SNPs for the IL-4 gene (rs2243250, rs2070874, and rs2227284) and for the IL-12B gene (rs3213094 and rs17860508) were compared between subgroups in terms of the response to HBV vaccination. The percentages of NRs (< 10 mIU/mL), low-titer responders (LRs, 10-100 mIU/mL), and high-titer responders (HRs, ≥ 100 mIU/mL) were 20.3%, 37.7% and 42.0%, respectively. No SNPs differed in frequency between NRs and responders or between LRs and HRs. We divided the subjects into two groups according to the time interval from the 3rd dose of HBV vaccination to Ab quantification: > 6 months from the 3rd dose (n = 87) and ≤ 6 months from the 3rd dose (n = 213). In the ≤ 6 month subjects, rs2243250C and rs2227284G were significantly frequent in the lower-titer individuals (NRs + LR) than HRs (40.1 vs. 25.9%, p = 0.014 and 45.1 vs. 33.0%, p = 0.018, respectively), and the rs2243250C and rs2227284G frequencies were significantly different among the three subgroups (13.2 vs. 26.9 vs. 25.9%, p = 0.040 and 15.5 vs. 29.6 vs. 33.0%, p = 0.038, respectively). In conclusion, those results suggest that IL-4 gene polymorphisms may play a role in the response to the HBV vaccine in Korean infants.

Evolution of hepatitis B serological markers in HIV coinfected patients: a case study

ABSTRACT OBJECTIVE To describe the evolution of serological markers among HIV and hepatitis B coinfected patients, with emphasis on evaluating the reactivation or seroreversion of these markers. METHODS The study population consisted of patients met in an AIDS Outpatient Clinic in São Paulo State, Brazil. We included in the analysis all HIV-infected and who underwent at least two positive hepatitis B surface antigen serological testing during clinical follow up, with tests taken six months apart. Patients were tested with commercial kits available for hepatitis B serological markers by microparticle enzyme immunoassay. Clinical variables were collected: age, sex, CD4+ T-cell count, HIV viral load, alanine aminotransferase level, exposure to antiretroviral drugs including lamivudine and/or tenofovir. RESULTS Among 2,242 HIV positive patients, we identified 105 (4.7%) patients with chronic hepatitis B. Follow up time for these patients varied from six months to 20.5 years. All patients underwent antiretroviral therapy during follow-up. Among patients with chronic hepatitis B, 58% were hepatitis B “e” antigen positive at the first assessment. Clearance of hepatitis B surface antigen occurred in 15% (16/105) of patients with chronic hepatitis B, and 50% (8/16) of these patients presented subsequent reactivation or seroreversion of hepatitis B surface antigen. Among hepatitis B “e” antigen positive patients, 57% (35/61) presented clearance of this serologic marker. During clinical follow up, 28.5% (10/35) of those who initially cleared hepatitis B “e” antigen presented seroreversion or reactivation of this marker. CONCLUSIONS Among HIV coinfected patients under antiretroviral therapy, changes of HBV serological markers were frequently observed. These results suggest that frequent monitoring of these serum markers should be recommended.

Prevalence of occult hepatitis b infection in iranian cancer patients before chemotherapy treatment / Prevalência de infecção oculta da hepatite B em pacientes iranianos com câncer antes do tratamento de quimioterapia

ABSTRACT Background Occult hepatitis B infection is characterized by negative hepatitis B surface antigen (HBsAg) and also detectable hepatitis B virus (HBV) -DNA, with or without hepatitis B core antibody (anti-HBc). HBV reactivation in individuals under immunosuppressive therapy is critical, occurring in occult HBV. Objective In this study, we aimed to determine the prevalence of occult HBV infection among hepatitis B surface antigen negative in cancer patients before receiving chemotherapy. Methods Sera from 204 cancer patients who were negative for HBsAg, were tested for anti-HBc antibodies. The samples that were negative for HBsAg but positive for anti-HBc also examined for HBV-DNA by polymerase chain reaction (PCR). Results Of the 204 HBsAg negative blood samples, 11 (5.4%) samples were positive for anti-HBc antibodies. HBV-DNA was detected in 9/11 (81%) of anti-HBc positive samples. Occult HBV infection in hematological cancers was more than solid cancers, 4.8% and 4.3% respectively. There was no significant difference in HBc antibody positivity based on vaccination, previous blood transfusions, history of familial hepatitis or biochemical parameters (ALT, AST, total and direct bilirubin levels) (P>0.05). Conclusion Screening of occult HBV infection by HBsAg, HBV DNA and anti HB core antibody should be suggested as a routine investigation in cancer patients before receiving chemotherapy.

RESUMO Contexto A infecção oculta da hepatite B caracteriza-se por antígeno de superfície da hepatite B (AgHBs) negativo com vírus detectável da hepatite B (HBV) -DNA, com ou sem anticorpo de núcleo da hepatite B (anti-HBc). A reativação do HBV em indivíduos sob terapia imunossupressora é crítica, originando a infecção oculta pelo VHB. Objetivo Este estudo teve como objetivo determinar a prevalência de infecção oculta pelo VHB entre em pacientes com câncer e com antígeno de superfície da hepatite B negativo antes de receber quimioterapia. Métodos Soro de 204 pacientes com câncer que foram negativos para AgHBs, foram testados para anticorpos anti-HBc. As amostras que foram negativos para AgHBs, mas positivo para anti-HBc foram também examinadas para HBV-DNA, por reação em cadeia da polimerase. Resultados Entre 204 amostras de sangue AgHBs negativas, 11 (5,4%) foram positivos para anticorpos anti-HBc. HBV-DNA foi detectado em 9/11 (81%) das amostras positivas de anti-HBc. Infecção oculta de VHB em câncer hematológico foi maior que em cânceres sólidos, 4,8% e 4,3% respectivamente. Não houve diferença significativa na positividade anti-HBc, com base na vacinação, transfusões de sangue anteriores, história de hepatite familiar ou parâmetros bioquímicos (ALT, AST, total e níveis de bilirrubina total) (P & gt; 0,05). Conclusão A triagem de infecção oculta por AgHBs, HBV-DNA e anti-anticorpo de núcleo HB deve ser sugerida como uma investigação de rotina em pacientes com câncer antes de receber a quimioterapia.

Mutations in the S gene and in the overlapping reverse transcriptase region in chronic hepatitis B Chinese patients with coexistence of HBsAg and anti-HBs

Abstract Background The mechanism underlying the coexistence of hepatitis B surface antigen and antibodies to HBsAg in chronic hepatitis B patients remains unknown. Aims This research aimed to determine the clinical and virological features of the rare pattern. Methods A total of 32 chronic hepatitis B patients infected by HBV genotype C were included: 15 carrying both HBsAg and anti-HBs (group I) and 17 solely positive for HBsAg (group II). S gene and reverse transcriptase region sequences were amplified, sequenced and compared with the reference sequences. Results The amino acid variability within major hydrophilic region, especially the “a” determinant region, and within reverse transcriptase for regions overlapping the major hydrophilic region in group I is significantly higher than those in group II. Mutation sI126S/T within the “a” determinant was the most frequent change, and only patients from group I had the sQ129R, sG130N, sF134I, sG145R amino acid changes, which are known to alter immunogenicity. Conclusions In chronic patients, the concurrent HBsAg/anti-HBs serological profile is associated with an increased aa variability in several key areas of HBV genome. Additional research on these genetic mutants are needed to clarify their biological significance for viral persistence.

New perspectives of biomarkers for the management of chronic hepatitis B

With recent advances in molecular and genomic investigations, the impact of hepatitis B viral and host factors on the progression of chronic HBV infection has been explored. For viral factors, hepatitis B viral load is a strong predictor for liver disease progression. Hepatitis B viral kinetics appear to be important for successful anti-viral therapy. Serum HBsAg level serves as a complementary marker to viral load for the prediction of HBV-related adverse outcomes in patients with low viral load. In those with low viral load, high serum HBsAg level is associated with higher risks of cirrhosis and HCC. Hepatitis B core-related antigen (HBcrAg) induces host immune responses, and the reduction of the HBcrAg level as well as the increment of total anti-HBc level are significantly associated with favorable outcomes. HBV genotypes (genotype C/D) and mutants (basal core promoter and deletion mutation in pre-S genes) are well known viral genetic markers to predict disease progression. For host factors, serum inflammatory biomarkers have been developed to evaluate the HBV-associated hepatic necroinflammation and fibrosis. Host single nucleotide polymorphism on sodium taurocholate cotransporting polypeptide (NTCP, an HBV entry receptor) may be associated with a decreased risk for cirrhosis and HCC. In conclusion, patients with chronic hepatitis B should be evaluated with relevant viral and host markers to identify those who are at a higher risk of liver disease progression and then receive timely antiviral therapy.

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.