"HEPARJOC-ACTÚA": herramienta educativa creada a través de un proceso de investigación-acción participativa con colectivos inmigrantes vulnerables para mejorar la accesibilidad al diagnóstico de la hepatitis B / "HEPARJOC-ACTÚA": educational tool created through a process of participatory action research with vulnerable immigrant groups to improve accessibility to diagnosis of hepatitis B

OBJETIVO: La Organización Mundial de la Salud estima que 257 millones de personas padecen infección crónica por el virus de la hepatitis B (HB). Es habitual que el diagnóstico se retrase o que nunca se llegue a realizar. En España, los inmigrantes procedentes de áreas endémicas presentan prevalencias en torno al 8%. En el año 2015, se inició este estudio con el objetivo de mejorar la accesibilidad al diagnóstico de la hepatitis B en colectivos inmigrantes. MÉTODOS: Se realizó un estudio cualitativo descriptivo, basado en la investigación acción participativa (IAP). Se dividió en dos ciclos: en el primer ciclo, después de configurar un grupo motor (GIAP), se realizó un diagnóstico comunitario participativo (DCP) con la población, a través de un estudio cualitativo descriptivo-interpretativo (ECDI) con 3 grupos focales (n=17). Se llevó a cabo un análisis narrativo de contenido temático. En el segundo ciclo, se realizaron 2 talleres de trabajo colaborativo (coworking) para crear una herramienta educativa (HEPAJOC) y coconstruir un plan de acción (PDA). Como prueba piloto se llevó a cabo este PDA a través 8 talleres (n=56). Se utilizó un cuestionario de conocimientos para comparar la media de respuestas correctas pre y post taller utilizando el t de Student para datos apareados. RESULTADOS: Se configuró un GIAP con 8 miembros de diferentes sectores y espacios comunitarios. En el DCP se observó que existía un desconocimiento en diferentes aspectos sobre la hepatitis B. Se propusieron, como herramientas educativas, materiales visuales e interactivos, elaborando como producto final el "HEPARJOC". En la prueba piloto del PDA, la media de las respuestas correctas al cuestionario de conocimientos sobre la HB fue de 7,7 (DE=3) previamente, y de 10,6 (DE=0,2) posteriormente. La mejoría de la media fue de 2,9 puntos (IC 95% 2,2-3,6), siendo estadísticamente significativa (p < 0,001). Solicitaron el cribado 30 personas (53,6%), siendo cribadas 23 (41%). CONCLUSIONES: "HEPARJOC-ACTUA" es una estrategia que puede contribuir a transformar conocimientos y a mejorar la accesibilidad al diagnóstico de la hepatitis B en colectivos inmigrantes

OBJECTIVE: The World Health Organization estimates that 257 million people suffer from chronic infection by the hepatitis B (HB) virus. It is common for diagnosis to be delayed or never given at all. In Spain, immigrants that come from endemic areas present a prevalence of infection of around 8%. In the year 2015, this study was begun with the aiml of improving accessibility to hepatitis B diagnoses in immigrant communities. METHODS: A descriptive qualitative study was carried out, based on participatory action research (IAP). It was divided into two cycles: in the first cycle, after forming a motor group (GIAP), a participatory community assessment (DCP) was performed with the population, through a descriptive-interpretative qualitative study (ECDI) with 3 focal groups (n=17). A narrative analysis was then performed of thematic content. In the second cycle, two collaborative workshops (coworking) were held to create an educational tool (HEPARJOC) and to co-create an action plan (PDA). As a pilot test, the PDA was put into practice through eight workshops (n=56). A knowledge questionnaire was used to compare the median number of correct responses before and after the workshop, using the t of Student for paired data. RESULTS: A GIAP was formed with 8 members of different sectors and community spaces. In the DCP it was observed that there was a lack of knowledge about different aspects of hepatitis B. Visual, interactive materials were proposed as educational tools, and "HEPARJOC" was created as the final product. In the pilot test of the PDA, the median of correct responses to the knowledge questionnaire about HB was 7.7 (DE=3) before the workshop, and 10.6 (DE=0.2) afterward. The improvement of the median was 2.9 points (IC 95% 2.2-3.6), which is statistically significant (p < 0.001). 30 people sought screening (53.6% of participants), and 23 of those people were screened (41% of participants). CONCLUSIONS: "HEPARJOC-ACTUA" is a strategy that could contribute to transforming knowledge and improving accessibility to hepatitis B diagnosis in immigrant communities

The prevalence and significance of isolated hepatitis B core antibody (anti-HBc) in endemic population.

OBJECTIVE: There are three major serologic markers for hepatitis B virus (HBV) infection: hepatitis B surface antigen (HBsAg); hepatitis B surface antibody (anti-HBs); and hepatitis B core antibody (anti-HBc). HBV screening programs, however, often test only HBsAg and anti-HBs, missing those individuals who have anti-HBc as the only detectable marker. Isolated anti-HBc can represent chronic infection in which HBsAg is not detectable by serology. We, therefore, investigated the prevalence of isolated anti-HBc in an ethnic community at moderate to high risk for HBV infection. RESULTS: Of 7157 Korean American adults in New Jersey, 2736 (38.2%) lacked anti-HBs, potentially susceptible to HBV. Of these 2736 subjects, 771 subjects had anti-HBc. The prevalence of isolated anti-HBc increased with age: 0.8% (age 21-30); 2.4% (age 31-40); 6.05% (age 41-50); 11.7% (age 51-60); 18.3% (age 61-70); and 24.5% (age 71-91). Similarly, the percentage of the individuals with isolated anti-HBc in anti-HBs lacking subjects showed a striking age dependence. We conclude that serologic HBV screening should include anti-HBc to accurately assess the prevalence of HBV exposure. Serologic screening with only HBsAg and anti-HBs may overestimate the prevalence of non-immune population. It can also underestimate the prevalence of HBV and increase the risk of HBV reactivation during immunosuppression.

Risk of hepatitis B reactivation in hepatitis B surface antigen seronegative and core antibody seropositive kidney transplant recipients.

BACKGROUND: Previous contact with Hepatitis B virus (HBV) is common in patients undergoing hemodialysis. Literature has shown conflicting results on the risk of HBV reactivation in kidney transplant (KT) recipients with serologic evidence of past HBV infection. METHODS: We reviewed 631 consecutive KT recipients and selected 70 patients simultaneously HBsAg negative and anti-HBc positive before KT, regardless of hepatitis B surface antibody (anti-HBs) status. Demographic characteristics, coinfection with other viruses, the presence of a previous KT, induction and maintenance immunosuppression, length of follow up, biopsy-proven acute rejection episodes, incidence of impaired liver function, and causes of graft loss and mortality were collected. Hepatitis B virus reactivation was defined as detection of HBV DNA viral load >2000 IU/mL during follow up. Outcome data included HBV reactivation episodes, graft function, and patient survival. RESULTS: Median follow-up was 151 months; 91.4% of patients were positive to anti-HBs prior to KT. No patient received HBV prophylaxis and 11 patients (15.7%) received rituximab as part of induction therapy. Anti-HBs titers remained stable in all patients throughout the observation period but two patient showed evidence of HBV reactivation after KT. CONCLUSION: Hepatitis B virus reactivation in HBsAg-negative and anti-HBc-positive after KT is rare but possible. We suggest evaluating HBV serologies, HBV DNA viral load, and liver enzymes before KT and routinely monitoring serologic HBV markers after KT. As only two patients experienced HBV reactivation, it is neither possible to define risk factors for HBV reactivation nor to evaluate the impact of different immunosuppressants or the benefit of prophylactic regimens. Further studies regarding HBV reactivation in solid organ transplant recipients are necessary.

Generation and Characterization of a Neutralizing Human Monoclonal Antibody to Hepatitis B Virus PreS1 from a Phage-Displayed Human Synthetic Fab Library.

The hepatitis B virus (HBV) envelope contains small (S), middle (M), and large (L) proteins. PreS1 of the L protein contains a receptor-binding motif crucial for HBV infection. This motif is highly conserved among 10 HBV genotypes (A-J), making it a potential target for the prevention of HBV infection. In this study, we successfully generated a neutralizing human monoclonal antibody (mAb), 1A8 (IgG1), that recognizes the receptor-binding motif of preS1 using a phage-displayed human synthetic Fab library. Analysis of the antigen-binding activity of 1A8 for different genotypes indicated that it can specifically bind to the preS1 of major HBV genotypes (A-D). Based on Bio-Layer interferometry, the affinity (KD) of 1A8 for the preS1 of genotype C was 3.55 nM. 1A8 immunoprecipitated the hepatitis B virions of genotypes C and D. In an in vitro neutralization assay using HepG2 cells overexpressing the cellular receptor sodium taurocholate cotransporting polypeptide, 1A8 effectively neutralized HBV infection with genotype D. Taken together, the results suggest that 1A8 may neutralize the four HBV genotypes. Considering that genotypes A-D are most prevalent, 1A8 may be a neutralizing human mAb with promising potential in the prevention and treatment of HBV infection.

The prevalence of occult hepatitis B in chronic hepatitis C patients treated with interferon-based antiviral therapy.

BACKGROUND AND STUDY AIMS: Occult hepatitis B infection (OBI) is known to be mostly prevalent in chronic hepatitis C (CHC) patients and OBI reactivation might be life-threatening in patients undergoing interferon (IFN)-free direct acting antiviral (DAA) therapy. As previous studies have revealed a relationship between OBI and non-response to IFN-based antiviral therapy, the aim of the current study was to determine if there was a higher prevalence of OBI in IFN non-responders than responders. PATIENTS AND METHODS: This retrospective cross-sectional study was conducted in CHC patients who had previously received IFN-based antiviral therapy. Serum samples of 100 HBsAg negative CHC patients were tested for HBV DNA, anti-HBc IgG, anti-HBs, ALT and AST. The presence of OBI was compared between 50 IFN responders and 50 IFN non-responders. Patients with a history of previous HBV infection, patients with evidence of cirrhosis and patients who had received IFN therapy within the last one year were excluded from the study. RESULTS: Anti-HBc IgG positivity was determined in 53% of the patients. HBV DNA positivity, indicating OBI was determined in 1 (1%) patient. This patient was anti-HBc IgG positive, anti-HBs negative, ALT and AST levels were normal. The HBV DNA and anti-HBc IgG positivity rates were higher in the non-responder group than in the responder group, but the difference was not statistically significant (p = 0.31 and p = 0.07 respectively). CONCLUSION: According to the results of this study, the prevalence of OBI is lower than expected amongst CHC patients in Turkey and it may not be necessary to apply routine screening to IFN non-responders for OBI infection before DAA therapy. However, there is a need for multicentre studies with larger patient series.

Safety of hepatitis B virus core antibody-positive grafts in liver transplantation: A single-center experience in China.

BACKGROUND: Given the shortage of suitable liver grafts for liver transplantation, proper use of hepatitis B core antibody-positive livers might be a possible way to enlarge the donor pool and to save patients with end-stage liver diseases. However, the safety of hepatitis B virus core antibody positive (HBcAb+) donors has been controversial. Initial studies were mainly conducted overseas with relatively small numbers of HBcAb+ liver recipients, and there are few relevant reports in the population of mainland China. We hypothesized that the safety of HBcAb+ liver grafts is not suboptimal. AIM: To evaluate the safety of using hepatitis B virus (HBV) core antibody-positive donors for liver transplantation in Chinese patients. METHODS: We conducted a retrospective study enrolling 1071 patients who underwent liver transplantation consecutively from 2005 to 2016 at West China Hospital Liver Transplantation Center. Given the imbalance in several baseline variables, propensity score matching was used, and the outcomes of all recipients were reviewed in this study. RESULTS: In the whole population, 230 patients received HBcAb+ and 841 patients received HBcAb negative (HBcAb-) liver grafts. The 1-, 3- and 5-year survival rates in patients and grafts between the two groups were similar (patient survival: 85.8% vs 87.2%, 77.4% vs 81.1%, 72.4% vs 76.7%, log-rank test, P = 0.16; graft survival: 83.2% vs 83.6%, 73.8% vs 75.9%, 70.8% vs 74.4%, log-rank test, P = 0.19). After propensity score matching, 210 pairs of patients were generated. The corresponding 1-, 3- and 5-year patient and graft survival rates showed no significant differences. Further studies illustrated that the post-transplant major complication rates and liver function recovery after surgery were also similar. In addition, multivariate regression analysis in the original cohort and propensity score-matched Cox analysis demonstrated that receiving HBcAb+ liver grafts was not a significant risk factor for long-term survival. These findings were consistent in both HBV surface antigen-positive (HBsAg+) and HBsAg negative (HBsAg-) patients.Newly diagnosed HBV infection had a relatively higher incidence in HBsAg- patients with HBcAb+ liver grafts (13.23%), in which HBV naive recipients suffered most (31.82%), although this difference did not affect patient and graft survival (P = 0.50 and P = 0.49, respectively). Recipients with a high HBV surface antibody (anti-HBs) titer (more than 100 IU/L) before transplantation and antiviral prophylaxis with nucleos(t)ide antiviral agents post-operation, such as nucleos(t)ide antiviral agents, had lower de novo HBV infection risks. CONCLUSION: HBcAb+ liver grafts do not affect the long-term outcome of the recipients. Combined with proper postoperative antiviral prophylaxis, utilization of HBcAb+ grafts is rational and feasible.

A novel general and efficient technique for dissociating antigen in circulating immune complexes.

Circulating immune complexes (CICs) are produced during the immune response. It is more clinically important to establish a general and efficient CICs dissociation technique for the detection of antigens for CICs other than the detection of free antigens in the serum. Polyethylene glycol (PEG) two-precipitation separation and glycine-HCl as a buffer system were employed to develop a general and efficient buffer dissociation technique to separate CICs from serum and dissociate antigens from CICs. The measurement value of new PEG two-precipitation separation technique was higher than traditional PEG precipitation separation technique. There were slight differences in the dissociation conditions of HCV Core-IC, HIV P24-IC, Ins-IC and TG-IC as compared to HBsAg-IC. The detection of antigens in HBsAg-IC, HCV Core-IC, HIV P24-IC, Ins-IC and TG-IC with this technique was superior to that with HCl Dissociation, Trypsin Digestion or Immune Complex Transfer technique. PEG two-precipitation dissociation technique may reduce macromolecular protein and the adhesion of free antigens during the co-precipitation, which increases the efficiency of separation and precipitation of CICs. This technique also avoids the damage of reagents to antigens, assuring the repeatability, reliability and validity. Thus, this technique is application in samples negative or positive for free antigens.

No evidence of hepatitis B virus reactivation in patients with resolved infection treated with direct-acting antivirals for hepatitis C in a large real-world cohort.

BACKGROUND: Hepatitis B virus (HBV) reactivation has been observed following interferon (IFN)-based treatment in HBV/hepatitis C virus (HCV) co-infected patients. Recent reports suggest that reactivation may also occur in both hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative patients during HCV treatment with direct-acting antivirals (DAAs). AIM: To investigate the rate of patients with HBV reactivation during IFN-based and IFN-free HCV treatment in a large real-world cohort. METHODS: A total of 848 patients with chronic hepatitis C were treated with different combinations of DAAs. Among patients with available outcome and HBV data, there were 272 patients hepatitis B core antibody (HBcAb)-positive (HBsAg-positive, n=9; HBsAg-negative, n=263), and 536 were HBcAb-negative. All HBcAb-positive patients were tested for HBV DNA at the end of DAA therapy and alanine transaminase (ALT) levels were frequently measured during therapy and follow-up. RESULTS: Seventy-three percent (n=192/263) of HBsAg-negative/HBcAb-positive patients had elevated ALT levels at baseline, which declined to normal values in all but 18 patients, and no HBV reactivation was observed. Eight patients had detectable but not quantifiable HBV DNA (<20 IU/mL) at end of treatment, but none were associated with elevated ALT. Five of nine HBsAg-positive/HBcAb-positive patients experienced transient or permanent HBV reactivation, three of whom required nucleos(t)ide treatment during (n=1) or after (n=2) DAA therapy. CONCLUSIONS: HBV reactivation was not observed in HBsAg-negative/HBcAb-positive patients but common in HBsAg-positive/HBcAb-positive patients treated with different combinations of DAAs for HCV.

Persistence of antibodies 20 y after vaccination with a combined hepatitis A and B vaccine.

Vaccination is the most effective and well-tolerated method of conferring long-term protection against hepatitis A and B viruses (HAV; HBV). Long-term studies are required to characterize the duration of protection and need for boosters. Following primary immunization of 150 and 157 healthy adults with 3-doses of combined hepatitis A/hepatitis B vaccine (HAB; Twinrix™, GSK Vaccines, Belgium) at 0-1-6 months in 2 separate studies, we measured vaccine-induced antibody persistence against HAV and HBV annually for 20 y (Study A: NCT01000324; Study B: NCT01037114). Subjects with circulating anti-HAV antibodies < 15 mIU/mL or with anti-hepatitis B surface antigen < 10 mIU/mL were offered an additional monovalent hepatitis A and/or B vaccine dose (Havrix™/Engerix™-B, GSK Vaccines, Belgium). Applying the immunogenicity results from these studies, mathematical modeling predicted long-term persistence. After 20 y, 18 and 25 subjects in studies A and B, respectively, comprised the long-term according-to-protocol cohort for immunogenicity; 100% and 96.0% retained anti-HAV antibodies ≥ 15 mIU/mL, respectively; 94.4% and 92.0% had anti-HBs antibodies ≥ 10 mIU/mL, respectively. Between Years 16-20, 4 subjects who received a challenge dose of monovalent hepatitis A vaccine (N = 2) or hepatitis B vaccine (N = 2), all mounted a strong anamnestic response suggestive of immune memory despite low antibody levels. Mathematical modeling predicts that 40 y after vaccination ≥ 97% vaccinees will maintain anti-HAV ≥ 15 mIU/mL and ≥ 50% vaccinees will retain anti-HBs ≥ 10 mIU/mL. Immunogenicity data confirm that primary immunization with 3-doses of HAB induces persisting anti-HAV and anti-HBs specific antibodies in most adults for up to 20 y; mathematical modeling predicts even longer-term protection.

Estudio multicéntrico español PIBHE: prevalencia e inmunización de la infección crónica por el virus de la hepatitis B en pacientes en hemodiálisis en España / Spanish multicentre PIBHE study: Prevalence and immunization of chronic hepatitis B in haemodialysis patients in Spain

Introducción: El estudio PIBHE, promovido por la Asociación Española de Hígado y Riñón y el Grupo de Virus en Diálisis de la Sociedad Española de Nefrología, es el primer estudio que determina la situación de los pacientes en hemodiálisis con infección crónica por el VHB y la inmunización frente a la vacuna. Método: Estudio nacional multicéntrico, observacional, de corte transversal, entre enero de 2013 y de 2014. Se envió un cuaderno de recogida de datos a todos los servicios de nefrología y unidades extrahospitalarias de hemodiálisis de España, para que lo cumplimentaran a partir de la historia clínica del paciente, tras consentimiento informado. Los datos se incluyeron en una base central. Resultados: Participaron 215 centros (15.645 pacientes), con una prevalencia del VHB del 1,03%. El 7,2% de los pacientes VHB(+) estaba coinfectado por el VHC o VIH. La carga viral era inferior a 2.000 UI/ml en el 80%. Los niveles de GOT y GPT fueron de 19,1±10,1 y 15,9±9,6 UI/ml, respectivamente. La biopsia hepática se había realizado en el 7,1%. El 30% había recibido tratamiento antiviral, que se había suspendido en el 12,5%. El más empleado había sido entecavir (13,3%), seguido de lamivudina (10%), adefovir y tenofovir (6,7%) e interferón (3,3%). El 34,5% era candidato a trasplante renal y el 6,9% no había sido evaluado. Se encontraban en seguimiento por un digestólogo el 64,3%. No había sido vacunado el 27,2% de los pacientes VHB(−) sin inmunización. Se emplearon 14 pautas distintas de vacunación, con un 58,8% de inmunización. La media de anti-HBs se situaba en 165,7±297,8mUI/ml. El 72,7% de los pacientes había recibido un ciclo de vacunación; el 26,4%, 2 ciclos; el 1,0%, 3 ciclos y el 11,6%, una dosis de recuerdo. El 28,3% tuvo una respuesta pobre (anti-HBs 10-99mUI/ml); el 22,4%, una respuesta óptima (anti-HBs 100-999mUI/ml); y el 7,9%, una respuesta excelente (anti-HBs≥1.000mUI/ml). La edad se asoció significativamente con la respuesta a la vacunación, de manera que los pacientes que no respondieron tenían una edad media significativamente mayor que los pacientes que obtuvieron cualquier tipo de respuesta (p<0,05). La mayor probabilidad de conseguir una respuesta inmunitaria se alcanzaba con 4 dosis de 40mcg de vacuna adyuvada (OR: 7,3; IC 95%: 3,4-15,7), a igualdad de edad y número de revacunaciones y recuerdos. La edad, la vacuna adyuvada, la dosis y el esquema de vacunación influían en la respuesta inmunitaria y en el título de anti-HBs alcanzado (p<0,05). Conclusión: La prevalencia de la infección crónica por el VHB en hemodiálisis en España es baja, así como las tasas de inmunización frente a este virus. Los esquemas de vacunación empleados son muy diversos y se han correlacionado con la respuesta inmunitaria, por lo que sería necesario protocolizar la pauta más eficaz para aumentar la inmunización en estos pacientes (AU)

Introduction: The PIBHE study, promoted by the Spanish Liver and Kidney Association and the Dialysis Virus Group of the Spanish Society of Nephrology, is the first study to determine the status of haemodialysis patients with chronic HBV infection and the immunisation against the vaccine. Method: The study has a national multicentre, observational, cross-sectional design and was carried out between January 2013 and 2014. A data collection folder was sent to all the nephrology departments and outpatient haemodialysis units in Spain, to be completed based on patient medical files after informed consent. The data were recorded in a central database. Results: A total of 215 centres participated (15,645 patients), with an HBV prevalence of 1.03%. HCV or HIV was present in 7.2% of the HBV(+) patients. Viral load was below 2,000 IU/ml in 80%. GOT and GPT levels were 19.1±10.1 and 15.9±9.6 IU/ml, respectively. Liver biopsy was performed in 7.1%. Antiviral treatment was prescribed in 30% and suspended in 12.5%: entecavir (13.3%), lamivudine (10%), adefovir and tenofovir (6.7%), and interferon (3.3%). A total of 34.5% were candidates for renal transplantation and 6.9% had not been evaluated; 64.3% were followed up by a gastroenterologist; 27.2% of HBV(−) patients without immunisation had not been vaccinated. Fourteen different immunisation schedules had been used, with an immunisation rate of 58.8%. Mean anti-HBs stood at 165.7±297.8mIU/ml. A total of 72.7% of patients had received a vaccination course; 26.4%, 2 cycles; 1.0%, 3 cycles; and 11.6%, a booster dose. A total of 28.3% had a poor response (anti-HBs 10-99mIU/ml); 22.4%, an optimal response (anti-HBs 100-999mIU/ml); and 7.9%, an excellent response (anti-HBs ≥ 1,000mIU/ml). Age was significantly associated with response to vaccination; the mean age of nonresponders was significantly higher than patients who had a response of any kind (P<.05). The highest probability of an immune response was achieved with 4 doses of 40 mcg of adjuvanted vaccine (OR: 7.3; 95% CI 3.4 to 15.7), for the same age and number of cycles and boosters. Age, adjuvanted vaccine, dose and vaccination schedule influenced the immune response and the anti-HBs titres reached (P<.05). Conclusion: The prevalence of chronic HBV infection in haemodialysis in Spain is low and so are the rates of immunisation against the virus. The vaccination schedules used are very diverse and have been observed to correlate with the immune response. It would therefore be necessary to establish a protocol for the most effective vaccination schedule to increase immunisation in these patients (AU)

Vaccination Against Hepatitis B Virus (HBV) in HIV-1-Infected Patients With Isolated Anti-HBV Core Antibody: The ANRS HB EP03 CISOVAC Prospective Study.

BACKGROUND: Although an isolated anti-hepatitis B virus (HBV) core antibody (anti-HBc) serological profile is frequent in human immunodeficiency virus (HIV)-infected patients, data on HBV vaccination in these patients are scarce. METHODS: A prospective multicenter study was conducted to assess the immunogenicity of HBV vaccination in 54 patients with an isolated anti-HBc profile and undetectable HIV load. They were vaccinated with 1 dose (20 µg) of recombinant HBV vaccine. Those with an anti-HBV surface antibody (anti-HBs) level of <10 mIU/mL 4 weeks after vaccination received 3 additional double doses (40 µg) at weeks 5, 9, and 24. RESULTS: At week 4, 25 patients (46%) were responders. Only the ratio of CD4(+) T cells to CD8(+) T cells was associated with this response in multivariate analysis (odds ratio for +0.1, 1.32; 95% confidence interval, 1.07-1.63; P = .008). At week 28 and month 18, 58% of these patients (14 of 24) and 50% (10 of 20), respectively, maintained anti-HBs level of ≥10 mIU/mL.Among nonresponding patients at week 4, who received further vaccinations, 89% (24 of 27) and 81% (21 of 26) had an anti-HBs level of ≥10 mIU/mL at week 28 and month 18, respectively. The preS2-specific interferon γ T-cell response increased between week 0 and week 28 in patients who finally responded to reinforced vaccination (P = .03). CONCLUSIONS: All of the patients with an isolated anti-HBc profile who did not have an anti-HBs titer of >100 mIU/mL 4 weeks after a single recall dose of HBV vaccine should be further vaccinated with a reinforced triple double-dose scheme.

Utilization of Donors with Hepatitis B Core Antibodies in Liver Transplantation.

BACKGROUND: At present, the scarcity of organs is one of the major problems in transplantation. We present our own experience in expanding the acceptance criteria for deceased donors. We aimed to evaluate the potential impact of using hepatitis B virus (HBV) core antibody (anti-HBc)-positive donor grafts on the long-term liver transplantation results. MATERIAL AND METHODS: We retrospectively analyzed data from 324 consecutive liver transplantation procedures performed in the largest transplant center in Poland, between January 2007 and February 2012. These patients included 36 who had received a liver from anti-HBc-positive donors. RESULTS: The presence of anti-HBc antibodies in the donor did not have a significant negative impact on the overall 3-year patient or graft survival rates. Among recipients with pre-transplant HBV infection, patients who received an organ from an anti-HBc-positive donor tended to have an improved survival rate compared with patients who received liver transplants from seronegative donors (p=0.080). However, there was a statistically significant reduction in graft survival (p=0.035) in the recipients without serological markers of HBV infection who received liver transplants harvested from anti-HBc-positive donors. CONCLUSIONS: These results confirm the validity of extending the acceptance criteria to anti-HBc-positive donors, particularly for patients with a prior HBV infection. Despite the increased risk of graft loss, liver transplantation from anti-HBc-positive donors among recipients not infected with HBV may also be considered in appropriate cases.

Serologic control against hepatitis B virus among dental students of the University of Granada, Spain

BACKGROUND: To evaluate the immunological situation against hepatitis B virus (HBV) of a cohort of dentistry students, to analyze the behavior of the levels of hepatitis B surface antigen (anti-HBs) after the administration of one or three vaccine doses, and to determine the influence of age and sex on the immune response. MATERIAL AND METHODS: This retrospective cohort study included students attending the School of Dentistry of the institution where the study was performed from 2005 to 2012 who had completed the public health vaccination calendar for HBV at the age of 12-13. Data on age, sex, basal anti-HBs levels, post-vaccination anti-HBs results and final anti-HBs levels were collected. Comparisons of the basal and final levels, as well as associations regarding age and sex, were performed by means of the Student t and Chi-square tests. RESULTS: Of the 359 students, 97 (27.02%) had basal antibody concentrations

Reactivación del virus de la hepatitis B en pacientes tratados con rituximab: incidencia y factores de riesgo / Hepatitis B virus reactivation in rituximab-treated patients: incidence and risk factors

La reactivación del virus de la hepatitis B en pacientes tratados con quimioterapia es una complicación conocida. La incidencia y los factores de riesgo aún no están bien definidos. El objetivo de nuestro estudio es determinar la incidencia y los factores de riesgo de la reactivación del virus de la hepatitis B en pacientes tratados con rituximab (RTX), e investigar si la dosis acumulada de RTX es un factor de riesgo independiente para la reactivación del virus de la hepatitis B. Se revisaron de forma retrospectiva 320 pacientes tratados con RTX en nuestro hospital, de los cuales 42 (13,12%) tenían marcadores serológicos de hepatitis B. Durante el seguimiento, 9 (21%) de los 42 pacientes con marcadores serológicos del virus de la hepatitis B presentaron una reactivación. Los factores de riesgo para la reactivación del virus de la hepatitis B fueron la presencia de HBsAg positivo (p < 0,05), anti-HBc aislado (p < 0,05), el linfoma de la zona marginal y linfoma de células del manto (p < 0,05) y la mediana de la dosis de rituximab tendió a ser mayor en los pacientes que presentaron reactivación (p = 0,06)

Hepatitis B virus (HBV) reactivation after chemotherapy regimens is a well-known complication. The incidence and risk factors for HBV reactivation remain to be elucidated. We aimed to determine the incidence and risk factors for HBV reactivation in patients receiving rituximab, and the potential role of the cumulative rituximab dose in HBV reactivation. We retrospectively reviewed 320 patients receiving rituximab in our hospital. Of these, 42 (13.12%) had serological markers of hepatitis B. During follow-up, 21% (9/42) had HBV reactivation. Risk factors for reactivation were HBsAg positivity (p < 0.05), isolated anti-HBc positivity (p < 0.05), marginal zone lymphoma, and Mantle cell lymphoma (p < 0.05). The median rituximab dose tended to be higher in patients with reactivation (p = 0.06)

Virus de la hepatitis B en el embarazo y el paciente inmunosuprimido / Hepatitis B virus infection in pregnancy and the immunosuppressed patient

La hepatitis B sigue siendo un importante problema de salud pública a nivel mundial. Si bien las indicaciones de tratamiento están bien establecidas en las guías de práctica clínica, existen ciertos grupos de riesgo como las embarazadas y los pacientes inmunosuprimidos, que requieren de un manejo diferente y específico de la infección por el virus de la hepatitis B (VHB). En el caso de las mujeres gestantes, la indicación de tratamiento debe individualizarse y valorar el riego de transmisión del VHB al recién nacido, y a que a pesar de la inmunoprofilaxis activa y pasiva, todavía existen casos de transmisión vertical de la hepatitis B. Con respecto a los pacientes que reciben tratamiento inmunosupresor, la reactivación del VHB se asocia a una alta morbimortalidad incluso en pacientes con infección por el VHB pasada enfatizando la importancia tanto del despistaje como de la necesidad valoración de tratamiento profiláctico en algunos casos

Hepatitis B virus (HBV) infection continues to be a major public health problem worldwide. Although treatment indications are well established in clinical practice guidelines, there are some risk groups, such as pregnant women and immunosuppressed patients, who require different and specific management of HBV infection. In pregnant women, treatment indication should be individualized and the risk of HBV transmission to the newborn evaluated because cases of vertical transmission continue to be reported, despite active and passive immunoprophylaxis. In patients receiving immunosuppressive therapy, HBV reactivation is associated with high morbidity and mortality, even in patients with past HBV infection, highlighting the importance of screening and the need to evaluate prophylactic therapy in some cases

[Persistence of immune memory to hepatitis B vaccine among infants with normal or high antibody response to primary vaccination: a five-year following-up study].

OBJECTIVE: To examine the immune memory status to hepatitis B vaccine among infants with normal or high antibody response to primary vaccination, 5 years after the primary vaccination and the risk factors associated with the immune memory. METHODS: Titers of the antibody against hepatitis B surface antigen (anti-HBs) were detected, five years after the primary vaccination among children who appeared normal or high response to hepatitis B primary vaccination in infancy. Those whose anti-HBs titers were low than protective level (10 mIU/ml) were given a challenge dose of hepatitis B vaccine and titers of anti-HBs were detected 14 days after the challenge. Positive rate and geometric mean titer (GMT) of anti-HBs were calculated. Level of the anti-HBs titers after primary vaccination, at following-up and after the challenge periods were divided into different levels, respectively. Risk factors associated with the levels of anti-HBs titer after the challenge were examined by univariate analysis that and multivariable analysis. RESULTS: Anti-HBs waned to the level below protective standard among 37.98% of the children with normal or high antibody response to hepatitis B primary vaccination; among those children whose anti-HBs were below the protection standard. The seroconversion rate and GMT of anti-HBs after the challenge dose were 98.95% (757/765) and 2 811.69 mIU/ml [95% Confidence Interval (CI) :2 513.55-3 145.19 mIU/ml] , respectively. Titers and levels of anti-HBs after the challenge, appeared an increase with anti-HBs after primary vaccination and the anti-HBs in the following-up (F=5.46, 10.23 respectively; P<0.000 1 for both) periods. Results from the multivariable analysis showed that gender, premature birth and birth weight were factors insignificantly associated with the anti-HBs titers after the dose of challenge, while the anti-HBs levels were independently associated with the levels of anti-HBs titer after the challenge [OR = 1.001 (95%CI: 1.000-1.002) , P<0.001; OR=1.28 (95%CI: 1.81-1.39) , P<0.001]at the following-up periods. CONCLUSIONS: Strong immune memory could be found among those children with normal or high responses to hepatitis B vaccination, 5 years after the primary vaccination. The intensity of immune memory might be associated with the anti-HBs titer after primary vaccination as well as the anti-HBs titers before the challenge dose was given.

[Frequency of antibodies against surface and nuclear antigens of hepatitis B virus in population of St. Petersburg in 2013].

AIM: Determine the frequency of antibodies to surface (anti-HBs) and core (anti-HBc) antigens of hepatitis B in population of St. Petersburg of various age for evaluation of protective herd immunity against hepatitis B virus (HB). MATERIALS AND METHODS: Blood sera of 970 individuals (491 males, 479 females) of 10 age groups from 0 to 50 years and older were examined for the presence of anti-HBs and anti-HBc IgG by enzyme immunoassay using commercial diagnostic test-systems. RESULTS: In general anti-HBs at the level of 5 mIU/ml and above were detected in 603 of the examined individuals (62.2%). Anti-HBs at the level of 10 mIU/ml and above were detected in 53.9%. The frequency of anti-HBs in protective titers in males and females in general turned out to be similar (52.6% and 55.2%, respectively). Juxtaposition of age-specific parameters of seroprotection and acute HB morbidity in St. Petersburg revealed an inverse correlation of medium strength (r = - 0.54). CONCLUSION: Results of the study confirm high effectiveness of the program of HB vaccine prophylaxis in St. Petersburg and emphasize the necessity of further implementation of broad measures of population immunization against HB.

Biosensors for hepatitis B virus detection.

A biosensor is an analytical device used for the detection of analytes, which combines a biological component with a physicochemical detector. Recently, an increasing number of biosensors have been used in clinical research, for example, the blood glucose biosensor. This review focuses on the current state of biosensor research with respect to efficient, specific and rapid detection of hepatitis B virus (HBV). The biosensors developed based on different techniques, including optical methods (e.g., surface plasmon resonance), acoustic wave technologies (e.g., quartz crystal microbalance), electrochemistry (amperometry, voltammetry and impedance) and novel nanotechnology, are also discussed.

[Toxocariasis in children and adolescents with allergic and bronchopulmonary diseases, HIV infection, hepatitis B and C risk groups: results of serological screening].

Enzyme immunoassay was used to determine the presence of immunoglobulins class G to Toxocara canis antigens in the sera of children and adolescents (hereinafter referred to as children) with allergic and bronchopulmonary diseases from HIV infection and hepatitis B and C risk groups. A total of 422 dwellers of the Republic of Altai, including 144 subjects aged 1 to 17 years, were examined. Toxocara antibodies were found in 18.8 +/- 3.3% of the children and in 21.9 +/- 2.5% of the adults. The infection rate in children with bronchopulmonary and allergic diseases was 27.1 +/- 5.8 and 14.3 +/- 5.0%, respectively; that in the hepatitis B and C risk groups was 13.1 +/- 6.2%. The children (n = 6) from the HIV infection risk group were seronegative. The infection rate in the adults from the HIV infection and hepatitis risk group was 19.2 +/- 3.5 and 24.3 +/- 3.5%, respectively. Diagnostic antibody titers in the children and adults were determined in 9.0 +/- 2.3 and 8.3 +/- 1.6%, respectively. Immunological assays should be used to rule out toxocariasis in the examinees. If there are seropositive results, specific antiparasitic threatment should be performed.