Risk of hepatic decompensation from hepatitis B virus reactivation in hematological malignancy treatments.

In this editorial, we discussed the apparent discrepancy between the findings described by Colapietro et al, in their case report and data found in the literature. Colapietro et al reported a case of hepatitis B virus (HBV)-related hepatic decompensation in a patient with chronic myeloid leukemia and a previously resolved HBV infection who was receiving Bruton's tyrosine kinase (BTK) inhibitor therapy. First of all, we recapitulated the main aspects of the immune system involved in the response to HBV infection in order to underline the role of the innate and adaptive response, focusing our attention on the protective role of anti-HBs. We then carefully analyzed literature data on the risk of HBV reactivation (HBVr) in patients with previous HBV infection who were treated with either tyrosine kinase inhibitors or BTK inhibitors for their hematologic malignancies. Based on literature data, we suggested that several factors may contribute to the different risks of HBVr: The type of hematologic malignancy; the type of therapy (BTK inhibitors, especially second-generation, seem to be at a higher risk of HBVr than those with tyrosine kinase inhibitors); previous exposure to an anti-CD20 as first-line therapy; and ethnicity and HBV genotype. Therefore, the warning regarding HBVr in the specific setting of patients with hematologic malignancies requires further investigation.

Impact of Hepatitis B Surface and Core Antibody Levels on Hepatitis B Virus Reactivation.

Hepatitis B virus reactivation (HBV-R) is a serious complication that can occur in patients with resolved HBV infection during cancer chemotherapy. We examined the levels of HBV surface antibody (HBsAb) and HBV core antibody (HBcAb) to assess the incidence of HBV-R in cancer patients including hematopoietic stem cell transplantation (HSCT) and rituximab administration. This retrospective cohort study included 590 patients with resolved HBV infection. The incidence of HBV-R was evaluated 761.5 (range, 90-3898) days after the inititiation of chemotherapy. Of the patients, 13 (2.2%) developed HBV-R after the start of chemotherapy. All 13 patients exhibited lower HBsAb (<100 mIU/mL) levels at baseline. A higher level of HBcAb (≥100 cut off index (C.O.I.)) was a possible risk factor for HBV-R as well as HSCT and rituximab administration. The simultaneous presence of HBsAb <100 mIU/mL and HBcAb ≥100 C.O.I. increased the risk of HBV-R by 18.5%. Patients treated with rituximab were at a higher risk of HBV-R (18.4%) despite having HBcAb <100 C.O.I. Our results suggest that assessment of HBsAb and HBcAb levels prior to the chemotherapy is important for identifying patients at high risk of HBV-R, especially in solid cancers without HSCT and rituximab administration.

The lack of HBsAg secretion does neither facilitate induction of antiviral T cell responses nor Hepatitis B Virus clearance in mice.

Immune tolerance to the hepatitis B virus (HBV) is crucial for developing chronic hepatitis B, and the HBV surface antigen (HBsAg) produced and secreted in high amounts is regarded as a key contributor. HBsAg is expressed in HBV-infected hepatocytes and those carrying an HBV integration. Whether either HBsAg secretion or the high antigen amount expressed in the liver determines its immunomodulatory properties, however, remains unclear. We, therefore, developed a novel HBV animal model that allowed us to study the role of secreted HBsAg. We introduced a previously described HBs mutation, C65S, abolishing HBsAg secretion into a replication-competent 1.3-overlength HBV genome and used adeno-associated virus vectors to deliver it to the mouse liver. The AAV-HBV established a carrier state of wildtype and C65S mutant HBV, respectively. We investigated antiviral B- and T-cell immunity in the HBV-carrier mice after therapeutic vaccination. Moreover, we compared the effect of a lacking HBsAg secretion with that of an antiviral siRNA. While missing HBsAg secretion allowed for higher levels of detectable anti-HBs antibodies after therapeutic vaccination, it did neither affect antiviral T-cell responses nor intrahepatic HBV gene expression, irrespective of the starting level. A treatment with HBV siRNA restricting viral antigen expression within hepatocytes, however, improved the antiviral efficacy of therapeutic vaccination, irrespective of the ability of HBV to secrete HBsAg. Our data indicate that clearing HBsAg from blood cannot significantly impact HBV persistence or T-cell immunity. This indicates that a restriction of hepatic viral antigen expression will be required to break HBV immunotolerance.

Occult HBV Infection in Patients Infected by HIV or HCV: Comparison between HBV-DNA and Two Assays for HBsAg.

We investigated the frequency and serological correlates of occult hepatitis B virus infection (OBI) and the potential impact of a highly sensitive assay for HBsAg in subjects infected by human immunodeficiency virus (HIV) or hepatitis C virus (HCV), who are also at risk for hepatitis B virus (HBV) infection, often in an occult form. Samples from 499 patients with HIV, all HBsAg negative and anti-HBc positive, and 137 patients with HCV were tested for HBV-DNA, anti-HBc, anti-HBs, and HBsAg by a conventional and highly sensitive assay. HBV biomarkers were detected in 71.5% of HCV-RNA-positive, with a higher prevalence of cases positive only for anti-HBc in patients with HCV than in those with HIV. HBV-DNA was detectable in 0.6% of HIV-positive and 7.3% of HCV-RNA-positive patients. Among patients with HCV, four were positive for HBsAg and negative for HBV-DNA, bringing the rate of HBV-active infection in this group to 10.2%. Active HBV infection was not related to gender or specific patterns of HBV biomarkers but was higher in HCV patients coinfected by HIV compared to those infected only by HCV. Monitoring patients at high risk for HBV infection and reactivation may require testing for both HBV-DNA and HBsAg.

Prevalence of hepatitis B virus infection among general population of Armenia in 2021 and factors associated with it: a cross-sectional study.

OBJECTIVES: This study sought to determine the prevalence and associated factors of hepatitis B virus (HBV) infection ever in life and chronic HBV infection in Armenia. DESIGN: A population-based cross-sectional seroprevalence study combined with a phone survey of tested individuals. SETTING: All administrative units of Armenia including 10 provinces and capital city Yerevan. PARTICIPANTS: The study frame was the general adult population of Armenia aged ≥18 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The participants were tested for anti-HBV core antibodies (anti-HBc) and HBV surface antigen (HBsAg) using third-generation enzyme immunoassays. In case of HBsAg positivity, HBV DNA and hepatitis D virus (HDV) RNA PCR tests were performed. Risk factors of HBV infection ever in life (anti-HBc positivity) and chronic HBV infection (HBsAg positivity) were identified through fitting logistic regression models. RESULTS: The seroprevalence study included 3838 individuals 18 years and older. Of them, 90.7% (3476 individuals) responded to the phone survey. The prevalence of anti-HBc positivity was 14.1% (95% CI 13.1% to 15.2%) and HBsAg positivity 0.8% (95% CI 0.5% to 1.1%). The viral load was over 10 000 IU/mL for 7.9% of HBsAg-positive individuals. None of the participants was positive for HDV. Risk factors for HBsAg positivity included less than secondary education (aOR=6.44; 95% CI 2.2 to 19.1), current smoking (aOR=2.56; 95% CI 1.2 to 5.6), and chronic liver disease (aOR=8.44; 95% CI 3.0 to 23.7). In addition to these, risk factors for anti-HBc positivity included age (aOR=1.04; 95% CI 1.04 to 1.05), imprisonment ever in life (aOR=2.53; 95% CI 1.41 to 4.56), and poor knowledge on infectious diseases (aOR=1.32; 95% CI 1.05 to 1.67), while living in Yerevan (vs provinces) was protective (aOR=0.74; 95% CI 0.59 to 0.93). CONCLUSION: This study provided robust estimates of HBV markers among general population of Armenia. Its findings delineated the need to revise HBV testing and treatment strategies considering higher risk population groups, and improve population knowledge on HBV prevention.

Prevalence of Hepatitis B Virus Markers among the Women with Breast Cancer.

INTRODUCTION: Breast cancer represents a formidable peril to the female populace on a worldwide level. The association between breast cancer and various factors, including viral infections, has been extensively investigated. Recently, the link between HBV infection and breast cancer patients has garnered attention. The present research aims to assess the prevalence of HBV markers among women diagnosed with breast cancer in Ahvaz city, Iran. MATERIALS AND METHODS: Serum specimens were procured from 90 patients who had been clinically diagnosed with breast cancer. The age of the patients ranged from 29 to 80 years, with a mean age of 49.42±10.7. Histological examination of biopsy specimens revealed that 75 (83.33%) were ductal, 11 (8.88%) lobular, 2 (2.22%) mucinous, 1 (1.11%) medullary, and 1 (1.11%) was metastatic. The serum samples were subjected to initial HBsAg and anti-HBc testing via ELISA. Samples that tested seropositive (HBsAg + anti-HBc) were subsequently analyzed for the S region of HBV through nested PCR and DNA sequencing. Finally, a phylogenetic tree was constructed for positive HBV DNA tests. RESULTS: Among the 5/90 (5.55%) cancer patients, it was found that 3 (3.33%) cases of ductal carcinoma and one (1.11%) lobular carcinoma displayed positivity for HBV markers (HBsAg, anti-HBc, HBV PCR). Notably, one (1.11%) patient with ductal carcinoma solely demonstrated anti-HBc positivity. The phylogenetic tree analysis of the S region revealed that all HBV strains identified were categorized as genotype D. CONCLUSION: The statistical analysis did not reveal any significant findings (p= 0.315) in the distribution of cancer types across different age groups. Among patients diagnosed with breast cancer, a notable prevalence of 5.5% was observed in HBV markers. The dominant HBV genotype among breast cancer patients was identified as genotype D.

Outcomes of Cessation of Nucleos(t)ide Analog Administration on Hepatitis B Virus Reactivation after Allogeneic Hematopoietic Stem Cell Transplantation: A Nationwide Retrospective Study.

Monitoring of hepatitis B virus (HBV)-DNA and HBV-DNA-guided preemptive therapy using nucleos(t)ide analogs (NAs) are recommended to prevent the development of hepatitis due to HBV reactivation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in recipients with resolved HBV infection. However, little is known about the appropriate duration of NA treatment and the effect of NA cessation on the recurrence of HBV reactivation. This study aimed to clarify the consequences of NA cessation in allo-HSCT recipients with resolved HBV infection who experienced HBV reactivation following transplantation. We retrospectively reviewed the clinical records of recipients with resolved HBV infection (hepatitis B surface antigen [HBsAg]-negative, anti-HBc-positive) before allo-HSCT who had been diagnosed with HBV reactivation (HBsAg-positive and/or HBV-DNA detectable) after allo-HSCT between January 2010 and December 2020. A total of 72 patients from 16 institutions were registered (median age, 60 years; age range, 27 to 73 years; 42 males and 30 females). The day of initial HBV reactivation ranged from day 10 to day 3034 after allo-HSCT (median, 513 days). Anti-HBs were lost in >80% of the patients at the time of HBV reactivation. All 72 patients received preemptive NAs, and no fatal HBV reactivation-related hepatitis was observed. HBV-DNA without hepatitis was continuously detected in 5 patients during the follow-up period. Administration of NAs was discontinued in 24 of 72 patients (33%) by physician decision. Second HBV reactivation occurred in 11 of the 24 patients (46%) in whom administration of NAs was discontinued. The duration of NA treatment did not differ significantly between patients with or without second HBV reactivation. The frequency of further HBV reactivation tended to be lower in patients with an anti-HBs titer of >10 mIU/mL at the time of NA cessation. Multiple reactivations of HBV after NA cessation was common in patients with HBV reactivation who underwent allo-HSCT despite the long duration of NAs. Careful monitoring of HBV-DNA is important even after the discontinuation of NAs in the case with HBV reactivation after allo-HSCT, because multiple reactivations could occur. Active immunization by HB vaccine might be effective for suppressing further HBV reactivation after cessation of NAs.

Global prevalence of occult HBV infection in children and adolescents: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Occult HBV infection (OBI) is a specific form of hepatitis B virus (HBV) infection and has the possibility of developing into hepatocellular carcinoma (HCC) in adults. This study aimed to estimate the global prevalence of occult HBV infection in children and adolescents. MATERIALS AND METHODS: We systematically searched PubMed, Embase, Web of Science, and Cochrane databases for relevant studies on the prevalence of OBI in children and adolescents. Meta-analysis was performed using STATA 16 software. RESULTS: Fifty studies were included. The overall prevalence of OBI in children and adolescents was 7.5% (95% CI: 0.050-0.103). In different risk populations, OBI prevalence was remarkably high in the HIV-infected population (24.2%, 95% CI: 0.000-0.788). The OBI prevalence was 0.8% (95% CI:0.000-0.029) in the healthy population, 3.8% (95% CI:0.012-0.074) in the general population, and 6.4% (95% CI: 0.021-0.124) in children born to HBsAg-positive mothers. Based on different serological profiles, the prevalence of OBI in HBsAg-negative and anti-HBc-positive patients was 6.6% (95% CI: 0.016-0.136), 3.0% (95% CI: 0.009-0.059) in HBsAg-negative and anti-HBc-negative patients, 4.6% (95% CI: 0.015-0.088) in HBsAg-negative and anti-HBs-positive patients, and 3.7% (95% CI: 0.001-0.102) in HBsAg-negative and anti-HBs-negative patients. CONCLUSIONS: Despite HBV vaccination and hepatitis B immunoglobulin (HBIG), OBI is common in children and adolescents in high-risk groups.

Effect of previous infection with hepatitis B virus on the incidence of hepatocellular carcinoma after sustained virologic response in patients with chronic hepatitis C virus infection.

Previous infection with hepatitis B virus (HBV), which is assessed by HBV core antibody (HBcAb) or surface antibody (HBsAb) titres, has reportedly been associated with an increased risk of developing hepatocellular carcinoma (HCC). We investigated the influence of previous HBV infection on the incidence of HCC in patients with hepatitis C virus (HCV) infection who achieved eradication of HCV, that is sustained virologic response (SVR). Both HBcAb and HBsAb were measured in a total of 1214 patients with HCV infection who had not been coinfected with HBV, as determined by both negative HBs antigen and HBV DNA, and in whom SVR was confirmed. Patients were followed up for a median of 5.7 years, and the incidence of post-SVR HCC was compared based on HBcAb and/or HBsAb. In both univariate and multivariate analyses, the incidence of post-SVR HCC did not differ based on the presence of HBcAb or HBsAb. In conclusion, previous HBV infection has no impact on the incidence of HCC in patients with HCV after SVR.

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.

Hepatitis B vaccination associated with low response in patients with rheumatic diseases treated with biologics.

BACKGROUND: Hepatitis B virus (HBV) vaccination is recommended for non-immunised patients with rheumatic diseases starting biological disease-modifying antirheumatic drugs (bDMARDs). There is some evidence that HBV vaccination is effective in patients under conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), but it is currently unclear whether this also applies to bDMARDs. OBJECTIVES: To assess the efficacy and safety of HBV vaccination in patients with inflammatory arthritides treated with bDMARDs. METHODS: A prospective cohort with inflammatory arthritides treated with bDMARDs, negative for anti-HBs and anti-HBc and never vaccinated for HBV was recruited. Engerix B was administered at 0, 1 and 6 months and anti-HBs was reassessed ≥1 month after last dose. Response was defined as anti-HBs≥10 IU/L and compared against vaccinated healthy controls. Disease flare, serious adverse events and immune-related disorders not previously present were recorded. RESULTS: 62 patients, most treated with TNF inhibitors (TNFi), and 38 controls were recruited. Most patients were taking csDMARDs (67.7%) and were in remission/low disease activity (59.4%). Only 20/62 patients (32.3%) had a positive response to vaccination, in comparison to 36/38 age-matched controls (94.7%, p<0.001). Response was seen in 19/51 patients treated with TNFi (37.3%) and in 1/11 (9.1%) patients treated with non-TNFi (p=0.07), including 1/6 treated with tocilizumab (16.7%). Among TNFi, response rates ranged from 4/22 (18.2%) for infliximab to 8/14 (57.1%) for etanercept. No relevant safety issues were identified. CONCLUSIONS: HBV vaccination response in patients with rheumatic diseases treated with bDMARDs was poorer than expected. Our data reinforce the recommendation for vaccination prior to starting bDMARDs.

Serological and vaccine evaluation for hepatitis B among Community Health Workers / Avaliação sorológica e vacinal para hepatite B entre Agentes Comunitários de Saúde / Evaluación serológica y vacuna para la hepatitis B entre Agentes Comunitarios de Salud

Abstract Objective: to identify the vaccination and serological status against hepatitis B among community health workers; to vaccinate against hepatitis B virus and to evaluate the immune response of susceptible workers. Method: phase I, cross-sectional and descriptive study, among community health workers in a capital city of the Midwest region, through a self-administered questionnaire, checking of vaccination cards, and blood collection for testing of serological markers for hepatitis B. Phase II, cohort study carried out in vaccinated non-immune workers identified in phase I. They received one dose of vaccine (challenge dose) and serological testing. Results: a total of 109 workers participated in the study. Most had vaccination record (97; 89.0%) and vaccination completeness (75; 77.3%), while the isolated anti-HBs (Antibodies against hepatitis B virus) marker was detected in 78 (71.6%) workers. The prevalence of hepatitis B virus exposure was 8.2%. Of the ten non-immune vaccinated workers, after challenge dose, one remained susceptible. Conclusion: although most workers are vaccinated and show immunological response to hepatitis B, susceptibility after challenge dose was identified. Therefore, it is necessary to have a surveillance program of the vaccination situation and serological status for this virus, to promote these workers' safety.

Resumo Objetivo: identificar a situação vacinal e sorológica contra hepatite B entre agentes comunitários de saúde; vacinar contra o vírus da hepatite B e avaliar a resposta imunológica dos agentes susceptíveis. Método: fase I, estudo transversal e descritivo, entre agentes comunitários de saúde de uma capital da região Centro-oeste, por meio de questionário autoaplicável, conferência do cartão vacinal e coleta de sangue para testagem dos marcadores sorológicos para hepatite B. Fase II, estudo de coorte realizado em trabalhadores vacinados não imunes e identificados na fase I. Estes receberam uma dose da vacina (dose desafio) e teste sorológico. Resultados: participaram do estudo 109 agentes. A maioria tinha registro de vacinação (97; 89,0%) e completude vacinal (75; 77,3%), já o marcador anti-HBs (anticorpos contra o vírus da hepatite B) isolado foi detectado em 78 (71,6%) agentes. A prevalência de exposição ao vírus da hepatite B foi de 8,2%. Dos dez agentes vacinados não imunes, após a dose desafio, um permaneceu susceptível. Conclusão: apesar da maioria dos trabalhadores estarem vacinados e apresentarem resposta imunológica para hepatite B, a suscetibilidade após a dose desafio foi identificada. Portanto, é necessário que haja um programa de vigilância da situação vacinal e estado sorológico para este vírus, para promover a segurança destes trabalhadores.

Resumen Objetivo: identificar la situación de la vacunación y serología contra la hepatitis B entre agentes comunitarios de la salud, vacunar contra el virus de la hepatitis B y evaluar la respuesta inmunológica de los agentes susceptibles. Método: fase I, estudio transversal y descriptivo, entre agentes comunitarios de la salud de una capital de la región centro oeste, por medio de cuestionario autoadministrado, verificación del carné de vacunación y extracción de sangre para comprobar los marcadores serológicos para la hepatitis B. Fase II, estudio de cohorte realizado en trabajadores vacunados no inmunes e identificados en la Fase I; estos recibieron una dosis de la vacuna (dosis de desafío) y realizaron el test serológico. Resultados: participaron del estudio 109 agentes. La mayoría tenía registro de vacunación (97; 89,0%) y de cobertura de vacunación (75; 77,3%); el marcador anti-HBs (Anticuerpos contra el virus de la hepatitis B) aislado fue detectado en 78 (71,6%) de los agentes. La prevalencia de exposición al virus de la hepatitis B fue de 8,2%. De los diez agentes vacunados no inmunes, después de la dosis desafío, uno permaneció susceptible. Conclusión: a pesar de que la mayoría de los trabajadores estaban vacunados y presentaron respuesta inmunológica para la hepatitis B, la susceptibilidad, después de la dosis desafío, fue identificada. Por tanto, es necesario que exista un programa de vigilancia de la situación de vacunación y estado serológico para este virus, para promover la seguridad de estos trabajadores.

Predictive value of hepatitis B serological indicators for mortality among cancer survivors and validation in a gastric cancer cohort.

Hepatitis B virus (HBV) infection has gradually been considered to associate with cancer development and progression. This study aimed to explore the associations of serological indicators of HBV infection with mortality risk among cancer survivors and further validated using a gastric cancer (GC) cohort from China, where HBV infection is endemic. National Center for Health Statistics' National Health and Nutrition Examination Survey (NHANES) data were used in this study. Individuals with positive results of hepatitis B core antigen (anti-HBc) were considered to have current or past HBV infection. Serological indicators were positive only for hepatitis B surface antibodies (anti-HBs), indicating vaccine-induced immunity, whereas negativity for all serologic indicators was considered to indicate the absence of HBV infection and immunity to HBV. The GC cohort included patients from the First Hospital of Jilin University, China. The median follow-up time of the NHANES was 10 years; during the follow-up, 1505 deaths occurred. The results revealed that anti-HBs-positive cancer survivors had a 39% reduced risk of mortality (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.44-0.85). Men and individuals aged <65 years old with past exposure to HBV had higher mortality risk (HR 1.52, 95% CI 1.09-2.13; HR 2.07, 95% CI 1.13-3.83). In this GC cohort, individuals who were only anti-HBs-positive showed a reduced risk of mortality (HR 0.77, 95% CI 0.62-0.95). Thus, anti-HBs positivity was a significant factor of decreased mortality among cancer survivors. More rigorous surveillance is necessary for cancer survivors with anti-HBc positivity, particularly men, and younger individuals.

Seroprotection With Three Dose vs Four Dose Schedule for Hepatitis B Vaccination in Children Living With Human Immunodeficiency Virus: Follow-up Data at 36-42 Months From a Randomized Controlled Trial.

OBJECTIVE: To compare the long-term seroprotection (anti-HBs ≥10 IU/L) in children living with HIV (CLHIV) receiving a 3- or 4-dose double-strength (20 µg) recombinant Hepatitis B virus (rHBV) vaccination. METHODS: We present anti-retroviral therapy (ART) clinic based follow-up data collected from January, 2021 to August, 2022, from CLHIV who had received either 3-dose or 4-dose double-strength (20 µg) rHBV vaccination, after 36-42 months and assessed for anti-HBs titres, naïve and memory T-helper lymphocytes, CD4 counts and HIV viral load. Children found unprotected after primary immunization, were administered a single double-strength rHBV vaccine booster dose (20 µg) and seroprotection was reassessed after 4 and 12 weeks. RESULTS: Out of 50 children initially vaccinated, 45 were followed up 36-42 months after primary immunization; median (IQR) anti-HBs titres (IU/L) were 230 (80.5 - 305.7) in the 3-dose group (n=23) and 263.5 (47.1-332.9) in the 4-dose group (n=22) (P=0.33). 19 and 20 children in the 3-dose and 4-dose group, respectively, were seroprotected (P=0.24). Anti-HBs titres at 36-42 months correlated with CD4 counts at baseline, anti-HBs titres at 1 and 6 months after completion of primary immunization and percentage of memory T-helper lymphocytes. All the five children (3-dose group: 4; 4-dose group: 1) who received rHBV vaccine booster dose attained seroprotection one-month later. CONCLUSION: Three-dose double strength rHBV vaccination schedule offers comparable seroprotection to a 4-dose double strength rHBV vaccination schedule in CLHIV receiving ART.

Size Matters! Anti-HBs Titer and HBV Reactivation During Anti-TNF Therapy.

BACKGROUND AND AIMS: We and others have previously described that hepatitis B surface antibody (anti-HBs) seems to protect against clinically significant HBV reactivation in cohort studies of patients undergoing anti-tumor necrosis factor (TNF) therapy. However, there were too few cases of HBV reactivation within cohort studies to assess the role of anti-HBs titer on reactivation. The purpose of this study was to systematically review the correlation between anti-HBs titer and the degree of clinically relevant HBV reactivation in patients undergoing anti-TNF therapy. METHODS AND RESULTS: We systemically reviewed all studies discussing anti-TNF therapy in patients with resolved HBV infection, defined as hepatitis surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) positive. We identified a total of 48 cases of reactivation from 5 cohort studies and 10 case reports or case series; 21 were anti-HBs negative, 7 were only reported as anti-HBs positive, 16 were anti-HBs positive with titer below 100, and 4 were anti-HBs positive with titer above 100. HBsAg sero-reversion was dominantly seen in patients with negative, low and/or declining anti-HBs titers. There was a significant trend toward less clinically relevant form of reactivation with increase in baseline anti-HBs titer (p = 0.022). CONCLUSION: Anti-HBs titers greater than 100 iU/L protect against clinically relevant HBV reactivation, while patients with low anti-HBs titers or negative anti-HBs had more clinically relevant HBV reactivation and higher rates of HBsAg sero-reversion. This suggests the importance of baseline quantitative anti-HBs prior to starting anti-TNF therapy and consideration vaccination for boosting anti-HBs titers prior to and/or during therapy.

Antenatal hepatitis B virus sero-prevalence, risk factors, pregnancy outcomes and vertical transmission rate within 24 months after birth in a high HIV prevalence setting.

BACKGROUND: Despite the availability of an effective vaccine, chronic hepatitis B virus (HBV) infections remain a major cause of liver cirrhosis and hepatocellular carcinoma. HBV burden in pregnancy, risk factors and the timing of mother to child transmission remain poorly described especially during this era of lifelong use of Tenofovir/Lamivudine/Efavirenz as firstline for HIV treatment. We aimed to determine the burden of HBV in pregnancy and infants receiving their first dose of HBV vaccine 6 weeks after birth in a high HIV-prevalence setting. METHODS: Pregnant women ≥ 20 weeks' gestational age were enrolled and followed up as mother-infant dyads from delivery, 6, 24 and 96 weeks after birth. HBV surface antigen (HBsAg) was tested (fresh plasma, immunochromatography) in pregnancy. Women testing HBsAg-seropositive were further evaluated for other four HBV-biomarkers. Maternally HBV exposed babies were tested for HBsAg from birth and HBs-antibodies from 6 months of age. Maternal-infant factors were tested in univariable and multivariable analyses for predictors of HBsAg-seropositivity. RESULTS: Six hundred HIV-uninfected and 608 HIV-infected women on Tenofovir/Lamivudine/Efavirenz-regimen with median (interquartile range) 350: (87-1477) days of therapy use were enrolled. The overall HBsAg-seroprevalence was 32/1208: 2.65%, 95% confidence interval (CI) [1.74, 3.55]; being 7/600: 1.17%, 95% CI [0.37, 1.97] and 25/608: 4.11%, 95% CI [2.52, 5.68] in HBsAg-monoinfected and HBsAg/HIV-coinfected respectively, disproportionately detected in 31/32: 96.9%, 95% CI [90.8, 100] women presumably HBV-unvaccinated in infancy. HBV exposed babies tended to be born prematurely (< 37 weeks); 15.2% versus 9.9% in the HBV-unexposed, p = 0.009. In multivariate logistic regression-models with variable elimination, HIV-infection and reported tooth extractions predicted antenatal HBsAg-seropositivity; odds ratios (CI): 3.85 (1.61-10.7) and 2.46 (1.07-5.34), respectively. None of the exposed infants were HBsAg-seropositive neither before nor after 6 weeks of age. No HBs-antibodies were detected in 23.3% of HBsAg-exposed infants at two years despite having successfully completed the HBV vaccination schedule. CONCLUSION: Low and moderate HBV endemics were observed in HIV-uninfected and HIV-infected pregnant women, respectively. This underscores the need to routinely screen for HBV in pregnancy, especially the HIV-infected attending antenatal-care. Being HIV-infected and reported tooth extractions were independent risk factors for maternal HBsAg-seropositivity. Vertical and child horizontal transmissions were both absent, probably due to ~ the 50% frequency of antenatal anti-HBe-antibodies observed. Of concern was the absence of anti-HBs-antibodies in 23.3% of fully vaccinated/maternally HBV-exposed infants by two years. Absence of molecular diagnosis may have underestimated HBV burden. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , trial registration number: NCT04087239.

Stratified management based on surface antibody for the prevention of hepatitis B virus reactivation in lymphoma patients.

This study aimed to investigate a stratified approach based on hepatitis B virus (HBV) surface antibody (anti-HBs) for managing HBV reactivation (HBVr) in lymphoma patients with serological protection against HBV. A retrospective analysis was conducted on 209 lymphoma patients with a baseline anti-HBs titre of ≥10 iu/L, who were either positive or negative for HBV core antibody (anti-HBc). The results revealed that 15.7% of patients lost serological protection following 6-month anti-lymphoma therapy. With a median follow-up of 28.1 months, the cumulative rates of HBVr at 6 months, 2 years and 4 years were 2.9%, 4.7% and 6.3% respectively. Without intervention, the overall rate of reactivation was 2.0% for patients with isolated anti-HBs and 10.5% for those with positive anti-HBs and anti-HBc. To identify patients at high risk of losing seroprotection and susceptible to HBVr, a predictive model was developed. The high-risk group had significantly higher rates of serological protection loss (27.8% vs. 2.2%) and cumulative incidence of HBVr (22.0% vs. 0%) compared to the low-risk group. Overall, this study highlights the risk of HBVr in lymphoma patients with positive anti-HBs, with or without positive anti-HBc, and recommends periodic monitoring for low-risk patients and early intervention for high-risk patients.

Impact of hepatitis B virus infection on the risk of gallbladder polyps: a cohort study.

BACKGROUND/AIMS: We aimed to determine whether hepatitis B virus (HBV) or hepatitis C virus (HCV) infection remains an important risk factor for gallbladder polyps (GBPs) in the current context of reduced prevalence of these infections. METHODS: The cohort included 392,913 asymptomatic adults who underwent abdominal ultrasonography (US). RESULTS: The prevalence of GBP sized ≥ 5 mm, ≥ 10 mm, and overall (< 5, 5-9 and ≥ 10 mm) was 2.9%, 0.1%, and 12.8%, respectively. The prevalence of hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and hepatitis C antibody (anti-HCV) positivity was 3.2%, 26.7%, and 0.1%, respectively. The GBP risk was significantly increased in HBsAg-positive individuals, with an adjusted odds ratio of 1.66 (95% confidence interval, 1.49-1.85) for GBP ≥ 5 mm, 2.39 (1.53-3.75) for GBP ≥ 10 mm, and 1.49 (1.41-1.59) for overall, whereas there was no significant association between anti-HCV positivity and GBP risk. The GBP risk did not increase significantly in individuals who tested negative for HBsAg but positive for HBcAb. CONCLUSION: The presence of HBsAg may be an independent risk factor for GBP development in the current context of a indecreasing prevalence of HBsAg positivity. A more comprehensive evaluation of GBP during abdominal US surveillance of HBsAg-positive individuals may be necessary.

Hepatitis B virus reactivation in seronegative occult hepatitis B patient receiving ibrutinib therapy.

BACKGROUND: Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor approved for the treatment for several mature B-cell malignancies. Reactivation of hepatitis B virus (HBV) is a well-described complication in patients with chronic HBV infection or prior HBV exposure undergoing cytotoxic or immunosuppressive chemotherapy for hematologic malignancies. This phenomenon has been frequently reported with rituximab. However, published data on the risk of HBV reactivation induced by ibrutinib are scarce. Cases of HBV reactivation in hematologic patients receiving ibrutinib therapy have recently been described, but limited only to overt hepatitis B patients or seropositive occult hepatitis B patients. CASE PRESENTATION: We report the first case of HBV reactivation during ibrutinib treatment in an asymptomatic 82-year-old woman with seronegative occult hepatitis B patient (i.e., negative for HBsAg, anti-HBc and anti-HBs). Four months after ibrutinib treatment, her liver function test (LFT) was deranged, with seroconversion to HBsAg positivity. Serum hepatitis B virus DNA was quantified to be 1.92 × 108 IU/ml. Antiviral treatment was initiated, and viral load was gradually suppressed with improvement in LFT. CONCLUSIONS: Our case illustrated that in populations with a high incidence of HBV exposure, systematic screening for HBV exposure is essential prior to ibrutinib treatment, followed by serial monitoring of serologic and molecular markers of hepatitis B. There is a need for an international consensus to support the recommendation of antiviral prophylaxis against HBV reactivation in patients using ibrutinib.

High prevalence of past hepatitis B virus infection in diffuse large B cell lymphoma: a retrospective study from Italy.

Studies from high endemic areas, mostly China, indicate that surface antigen positive (HBsAgpos) chronic hepatitis B virus (HBV) infection is associated with an increased risk of developing diffuse large B-cell lymphoma (DLBCL), whereas studies in low endemic areas have provided conflicting results. Past infection, serologically defined by negative HBsAg and positive anti-core antibody (HBsAgnegHBcAbpos), has also been suggested to increase the risk of B-cell non-Hodgkin's lymphoma (NHL) in high endemic areas. We retrospectively reviewed unselected clinical records of 253 patients with DLBCL (54% male, aged 60.3 ± 14.6 years at diagnosis) and 694 patients with different types of indolent B-cell NHL (46% male, aged 61.7 ± 12.8 years). Patients were seen at a single center in Italy between 2001 and 2022 and HBV serological status (HBsAg, HBsAb, HBcAb, HBeAg, HBeAb, and HBV DNA) was analyzed through enzyme-linked immunosorbent assays and molecular assays; patients infected with hepatitis C virus or human immunodeficiency virus were excluded. We used an unconditional multiple logistic regression model including as matching variables gender, age at diagnosis, immigrant status, and HBV serological status. Patients with DLBCL had, compared to indolent NHL, a higher prevalence of HBsAgpos active infection (odds ratio (OR) 2.8, 95% confidence interval (95% CI) 1.2-6.3, p = 0.014). Strikingly, patients with DLBCL had also a significantly higher prevalence of past infection (OR 2.4, 95% CI 1.5-4.0, p = 0.0006). Male gender was associated with increased risk of DLBCL independently of the HBV serological status. These findings suggest that both past and active HBV infection may increase the risk of DLBCL in a low endemic area. Our study needs confirmation by studies in areas or populations with different rates of chronic or past HBV infection.