Hepatitis B virus-specific CD4 T cell responses differentiate functional cure from chronic surface antigen+ infection.

BACKGROUND & AIMS: With or without antiviral treatment, few individuals achieve sustained functional cure of chronic hepatitis B virus (HBV) infection. A better definition of what mediates functional cure is essential for improving immunotherapeutic strategies. We aimed to compare HBV-specific T cell responses in patients with different degrees of viral control. METHODS: We obtained blood from 124 HBV-infected individuals, including those with acute self-limiting HBV infection, chronic infection, and chronic infection with functional cure. We screened for HBV-specific T cell specificities by ELISpot, assessed the function of HBV-specific T cells using intracellular cytokine staining, and characterized HBV-specific CD4 T cells using human leukocyte antigen (HLA) class II tetramer staining, all directly ex vivo. RESULTS: ELISpot screening readily identified HBV-specific CD4 and CD8 T cell responses in acute resolving infection compared with more limited reactivity in chronic infection. Applying more sensitive assays revealed higher frequencies of functional HBV-specific CD4 T cells, but not CD8 T cells, in functional cure compared to chronic infection. Function independent analysis using HLA multimers also identified more HBV-specific CD4 T cell responses in functional cure compared to chronic infection, with the emergence of CD4 T cell memory both after acute and chronic infection. CONCLUSIONS: Functional cure is associated with higher frequencies of functional HBV-specific CD4 memory T cell responses. Thus, immunotherapeutic approaches designed to induce HBV functional cure should also aim to improve CD4 T cell responses. LAY SUMMARY: Immunotherapy is a form of treatment that relies on harnessing the power of an individual's immune system to target a specific disease or pathogen. Such approaches are being developed for patients with chronic HBV infection, in an attempt to mimic the immune response in patients who control HBV infection spontaneously, achieving a so-called functional cure. However, what exactly defines protective immune responses remains unclear. Herein, we show that functional cure is associated with robust responses by HBV-specific CD4 T cells (a type of immune cell).

Enduring Challenges despite Progress in Preventing Mother-to-Child Transmission of Hepatitis B Virus in Angola.

Sub-Saharan Africa has one of the highest rates of hepatitis B virus (HBV) infection globally, with an incidence of 1.5 million and 0.8 million yearly deaths, which drives synergistic efforts towards its elimination. To assess the risk of mother-to-child transmission of HBV infection, a cross-sectional study was conducted on 1012 pregnant women in Angola to investigate HBV serological and molecular profiles. The prevalence of HBV was 8.7% (n = 88), with hepatitis B core IgM antibody (anti-HBc IgM) positivity identified in 12.8%, hepatitis B "e" antigen (HBeAg) positivity in 30%, and HBV DNA ≥ 200,000 IU/mL in 28.2%. Family tracking studied 44 children, of which 11 (25%) received at least two doses of the hepatitis B vaccine. HBV was detected in 10/44 (22.7%) children, with vaccination reported in one infected child. Further testing identified anti-HBc IgM positivity in 3/10 (30%), HBeAg positivity in 55%, and both seromarkers in 20%. The results revealed the importance of antenatal HBV screening, antiviral prophylaxis for mothers with high viral loads or HBeAg positivity, and timely first-dose hepatitis B vaccines in newborns. Anti-HBc IgM positivity among pregnant women and children highlights prophylactic measures worth considering, including antenatal hepatitis B vaccination and catch-up vaccination to young children.

Transfusion Transmissible Infections in Blood Donors in the Province of Bié, Angola, during a 15-Year Follow-Up, Imply the Need for Pathogen Reduction Technologies.

Transfusion transmissible infections (TTIs), caused by hepatitis B virus (HBV), human immunode-ficiency virus (HIV), hepatitis C virus (HCV), and syphilis, have a high global impact, especially in sub-Saharan Africa. We evaluated the trend of these infections over time in blood donors in Angola. A retrospective cross-sectional study was conducted among blood donors in Angola from 2005 to 2020. Additionally, frozen samples obtained from blood donors in 2007 were investigated to identify chronic HCV carriers and possible occult HBV infection (OBI). The overall prevalence of HBV, HCV, HIV, and syphilis was 8.5, 3, 2.1, and 4.4%, respectively, among 57,979 blood donors. HBV was predominant among male donors, while the remaining TTIs were predominant among women. Donors >50 years had a significantly high prevalence for all TTIs. Chronic HCV infection was ab-sent in 500 samples tested and OBI was present in 3%. Our results show the continued high prev-alence of TTIs among blood donors in Angola. Most infections showed a significantly low preva-lence in years with campaigns seeking voluntary blood donors, thus, reinforcing the importance of this type of donor to ensure safe blood. Africa, with a high prevalence of diverse pathogens, should consider cost-effective pathogen reduction technologies, once they are commercially accessible, to increase the availability of safe blood.

Prevalência das hepatites B e C em doadores de sangue e da hepatite B em gestante no Kuito, Biê, Angola / Prevalence of hepatitis B and C among blood donors and hepatitis B among pregnant women, in Kuito, Biê, Angola

A Organização Mundial de Saúde (OMS) estima que aproximadamente 720 milhões de indivíduos estejam infectados pelos vírus da hepatite B (HBV) ou C (HCV) com índice de mortalidade cerca de 25%, constituindo importante problema de saúde pública global. A escassez de dados sobre HBV e HCV em Angola e a identificação de alguns fatores de risco incentivaram a realização deste trabalho com objetivo de avaliar a frequência de marcadores de HBV em gestantes e HBV e HCV em doadores, e descrever os fatores de risco associados, visando adoção de estratégias voltadas à aplicação de medidas preventivas. No presente estudo utilizou-se os dados de registros dos doadores em banco de sangue para os anos 2005, 2006 e 2007 e investigou-se os possíveis fatores de risco através da aplicação do questionário epidemiológico em 500 doadores e 1014 gestantes no ano 2007. Os resultados dos marcadores de HBV e HCV nos doadores foram obtidos através dos registros e nas gestantes através de testes rápidos. A frequência de HBsAg em doadores de sangue manteve-se em 11% durante os anos 2005, 2006 e 2007, enquanto que nas gestantes foi de 9por cento. A prevalência de anti-HCV em doadores aumentou progressivamente de 0,3% para 1% entre os anos 2005 e 2007. Os fatores de risco que despertaram a atenção nos doadores foram à circuncisão, DTS, e escarificação, ao passo que nas gestantes foram à aplicação de piercing, uso de medicamento tradicionais na vagina, compartilha de instrumento de manicure.