Immune modulator and antiviral potential of dendritic cells pulsed with both hepatitis B surface antigen and core antigen for treating chronic HBV infection

Background The legacy of war in Northern Uganda continues to impact people’s health and wellbeing in the Acholi region. Despite increasing attention to Hepatitis B Virus (HBV) in Uganda and globally, concerns remain that unique drivers of infection, and barriers to screening, and treatment, persist among those affected by conflict. Methods Cango Lyec (Healing the Elephant) cohort survey involved conflict-affected adults aged 13–49 in three mid-Northern Uganda districts (Gulu, Amuru and Nwoya). Baseline (2011–2012) samples were tested for HBV surface antigen (HBsAg), HBV e-antigen (HBeAg), antibodies to HBV surface antigen (HBsAb), antibodies to HBV e-antigen (HBeAb), and antibodies to HBV core antigen (HBcAb). All HBsAg positive samples were tested for IgM antibodies to HBV B core antigen (HBc-IgM) and where available, >6-month follow-up samples were tested for HBeAg and HBV DNA. Data were analyzed using STATA 15 software. Logistic regression accounted for variance due to complex two-stage sampling that included stratification, unequal selection probabilities and community clustering. Odds ratios measured effect potential risk factors associated with chronic HBV infection. Results Among 2,421 participants, 45.7% were still susceptible to HBV infection. HBsAg seropositivity was 11.9% (10.9–13.0), chronic HBV was 11.6% (10.4–12.8), acquired immunity resulting from vaccination was 10.9%, and prior natural infection was 31.5%. Older age (OR:0.570; 95%CI:0.368–0.883) and higher education (OR:0.598; 95%CI:0.412–0.868) were associated with reduced odds of chronic HBV infection. Being male (OR:1.639; 95%CI:1.007–2.669) and having been abducted (OR:1.461; 95%CI:1.055–2.023) were associated with increased odds of infection. Among women, having 1 or 2 pregnancies (compared to none or >2) was associated with increased odds of infection (OR:1.764; 95%CI:1.009–3.084). Conclusion Chronic HBV is endemic in Gulu, Amuru and Nwoya districts. Recommended strategies to reduce post-conflict prevalence include establishment of Northern Uganda Liver Wellness Centres, integration of screening and treatment into antenatal care, and roll out of birth-dose vaccination.

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Hepatitis B surface antigen seroclearance during chronic HBV infection

Antiviral Therapy ◽

10.3851/imp1497 ◽

2010 ◽

Vol 15 (2) ◽

pp. 133-143 ◽

Cited By ~ 113

Author(s):

Chia-Ming Chu ◽

Yun-Fan Liaw

Keyword(s):

Hepatitis B ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

Hbv Infection ◽

Chronic Hbv Infection ◽

Chronic Hbv

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Recombinant hepatitis B core antigen carrying preS1 epitopes induce immune response against chronic HBV infection

Vaccine ◽

10.1016/j.vaccine.2003.07.014 ◽

2004 ◽

Vol 22 (3-4) ◽

pp. 439-446 ◽

Cited By ~ 31

Author(s):

Xinchun Chen ◽

Meizhong Li ◽

Xiaohua Le ◽

Weimin Ma ◽

Boping Zhou

Keyword(s):

Immune Response ◽

Hepatitis B ◽

Hbv Infection ◽

Core Antigen ◽

Recombinant Hepatitis ◽

Chronic Hbv Infection ◽

Chronic Hbv ◽

Hepatitis B Core Antigen

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Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection

10.21203/rs.3.rs-52170/v3 ◽

2020 ◽

Author(s):

Xiaoyi Li ◽

Qifan Zhang ◽

Wanyue Zhang ◽

Guofu Ye ◽

Yanchen Ma ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

B Cells ◽

Hepatitis B ◽

Immune Responses ◽

Cd4 T Cells ◽

Hbv Infection ◽

Follicular Dendritic Cells ◽

Chronic Hbv Infection ◽

Chronic Hbv

Abstract Background: The restoration of host hepatitis B virus (HBV)-specific antiviral immunity is an effective strategy for hepatitis B recovery. Follicular dendritic cells (FDCs) play a crucial role in immune regulation. The goal of the present study was to investigate the characteristics and functions of FDCs in chronic HBV infection. Methods: The frequencies of FDCs in peripheral blood, liver, and spleen were measured in patients with chronic HBV infection. Isolated FDCs from splenic tissues of HBV-related liver cirrhosis-induced hypersplenism patients were cultured with autologous intrasplenic CD4 + T cells and CD19 + B cells.Results: We found that patients with chronic HBV infection had a significantly increased frequency of circulating FDCs compared with that of healthy controls. Additionally, the frequency of circulating FDCs was positively correlated with that of intrahepatic and intrasplenic counterparts. Moreover, a positive correlation between the frequency of circulating FDCs and plasmablast and memory B cells, as well as C-X-C motif chemokine receptor type 5 (CXCR5) + CD4 + T cells and CXCR5 + CD8 + T cells was also observed. Notably, in vitro experiments demonstrated that FDCs derived from splenic tissues of chronic HBV patients facilitated interferon-γ and interleukin-21 production from autologous intrasplenic CD4 + T cells and promoted the proliferation of autologous intrasplenic CD19 + B cells. Conclusions: Expanded FDCs in patients with chronic HBV infection may favor the host immune responses against HBV. The identification of this unique population may contribute to a better understanding of the immune regulatory mechanisms and provide a potential immunotherapeutic target in chronic HBV infection.

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Hepatitis B seroprevalence in the U.S. military and its impact on potential screening strategies

Military Medicine ◽

10.1093/milmed/usaa131 ◽

2020 ◽

Vol 185 (9-10) ◽

pp. e1654-e1661

Author(s):

Paul T Scott ◽

Robert L Cohen ◽

David M Brett-Major ◽

Shilpa Hakre ◽

Jennifer A Malia ◽

...

Keyword(s):

Hepatitis B ◽

Surface Antigen ◽

Department Of Defense ◽

Military Service ◽

Screening Program ◽

Cost Model ◽

Linkage To Care ◽

Hbv Infection ◽

Chronic Hbv Infection ◽

Chronic Hbv

Abstract Introduction Knowledge of the contemporary epidemiology of hepatitis B virus (HBV) infection among military personnel can inform potential Department of Defense (DoD) screening policy and infection and disease control strategies. Materials and Methods HBV infection status at accession and following deployment was determined by evaluating reposed serum from 10,000 service members recently deployed to combat operations in Iraq and Afghanistan in the period from 2007 to 2010. A cost model was developed from the perspective of the Department of Defense for a program to integrate HBV infection screening of applicants for military service into the existing screening program of screening new accessions for vaccine-preventable infections. Results The prevalence of chronic HBV infection at accession was 2.3/1,000 (95% CI: 1.4, 3.2); most cases (16/21, 76%) identified after deployment were present at accession. There were 110 military service-related HBV infections identified. Screening accessions who are identified as HBV susceptible with HBV surface antigen followed by HBV surface antigen neutralization for confirmation offered no cost advantage over not screening and resulted in a net annual increase in cost of $5.78 million. However, screening would exclude as many as 514 HBV cases each year from accession. Conclusions Screening for HBV infection at service entry would potentially reduce chronic HBV infection in the force, decrease the threat of transfusion-transmitted HBV infection in the battlefield blood supply, and lead to earlier diagnosis and linkage to care; however, applicant screening is not cost saving. Service-related incident infections indicate a durable threat, the need for improved laboratory-based surveillance tools, and mandate review of immunization policy and practice.

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Antiviral Activity and Pharmacokinetics of the HBV Capsid Assembly Modulator GLS4 in Patients with Chronic HBV Infection

Clinical Infectious Diseases ◽

10.1093/cid/ciaa961 ◽

2020 ◽

Author(s):

Hong Zhang ◽

Fengjiao Wang ◽

Xiaoxue Zhu ◽

Yunfu Chen ◽

Hong Chen ◽

...

Keyword(s):

Hepatitis B ◽

Antiviral Activity ◽

Accumulation Rate ◽

Hbv Infection ◽

Controlled Study ◽

Core Antigen ◽

Capsid Assembly ◽

Chronic Hbv Infection ◽

Chronic Hbv ◽

The Mean

Abstract Background GLS4 is a first-in-class hepatitis B virus (HBV) capsid assembly modulator (class I) that can inhibit HBV replication by interfering with the assembly and disassembly of HBV nucleocapsid. Here, we evaluated its antiviral activity, pharmacokinetics (PK), and tolerability in a double-blind, randomized, parallel, entecavir-controlled study. Methods Twenty four chronic HBV patients were randomized to receive a 28-day course of GLS4 (120 or 240 mg) and ritonavir (100 mg) combination (cohorts A and B, respectively) or entecavir treatment (cohort C) at a 1:1:1 ratio. Patients were followed-up for 40 days in a phase 1b study. Results The GLS4/ritonavir combination was a tolerated combination for the treatment of chronic HBV infection. A total of two, three, and three subjects presented with alanine aminotransferase flare in cohorts A, B and C, respectively. This contributed to the withdrawal of one, two, and one patient from cohorts A, B and C, respectively. The mean Ctrough of GLS4 was 205–218 ng/mL, which was approximately 3.7–3.9 times the EC90 (55.8 ng/mL), with a lower accumulation (accumulation rate: 1.1–2.0). In cohorts A, B and C, the mean declines in HBV DNA after 28 days of treatment were -1.42, -2.13, and -3.5 log10 IU/mL; in hepatitis B surface antigen were -0.06, -0.14, and -0.33 log10 IU/mL; in pregenomic RNA were -0.75, -1.78, and -0.96 log10 copies/mL; and in hepatitis B core antigen (were -0.23, -0.5, and -0.44 log10 U/mL, respectively. Conclusions Treatment with 120 mg GLS4 was tolerated and had antiviral activity in patients with chronic HBV infection.

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Plasmacytoid dendritic cells and their role in the immunopathogenesis of viral infections for example hepatitis B

Journal Infectology ◽

10.22625/2072-6732-2019-11-2-14-19 ◽

2019 ◽

Vol 11 (2) ◽

pp. 14-19 ◽

Cited By ~ 1

Author(s):

R. R. Khodzhibekov ◽

O. N. Khokhlova ◽

A. R. Reizis ◽

G. M. Kozhevnikova

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Hbv Infection ◽

Unique Type ◽

Antiviral Immune Response ◽

Chronic Hbv Infection ◽

B Virus ◽

Chronic Hbv

A new approach in understanding the mechanisms of immune response in viral hepatitis is the discovery of a unique type of immune cells – plasmocytoid dendritic cells (pDCs). Plasmocytoid dendritic cells (pDCs) are cells of lymphoid origin and morphologically resemble plasma cells. Functionally, they are professional IFN-a-producing cells that play an important role in antiviral immune response. Data on the mechanisms of PDCs participation in hepatitis B virus infection are few and contradictory. In chronic HBV infection, the role of pDCs remains mysterious and poorly understood with conflicting circulating blood pDCs results that show differently that they are not affected or reduced. However, functional disorders of pDCs were observed in patients with chronic HBV infection. The establishment of these mechanisms, as well as the search for the cause of hepatitis B virus latency and the formation of chronic infection remains one of the important and promising areas of scientific activities today.

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