Virus Surface Antigen Research Articles

A recombinant human immunoglobulin with coherent avidity to hepatitis B virus surface antigens of various viral genotypes and clinical mutants.

The hepatitis B virus (HBV) envelope is composed of a lipid bilayer and three glycoproteins, referred to as the large (L), middle (M), and small (S) hepatitis B virus surface antigens (HBsAg). S protein constitutes the major portion of the viral envelope and an even greater proportion of subviral particles (SVP) that circulate in the blood. Recombinant S proteins are currently used as a preventive vaccine, while plasma fractions isolated from vaccinated people, referred to as hepatitis B immune globulin (HBIG), are used for short-term prophylaxis. Here, we characterized a recombinant human IgG1 type anti-S antibody named Lenvervimab regarding its binding property to a variety of cloned S antigens. Immunochemical data showed an overall consistent avidity of the antibody to S antigens of most viral genotypes distributed worldwide. Further, antibody binding was not affected by the mutations in the antigenic 'a' determinant found in many clinical variants, including the immune escape mutant G145R. In addition, mutations in the S gene sequence that confer drug resistance to the viral polymerase did not interfere with the antibody binding. These results support for a preventive use of the antibody against HBV infection.

Abstract 3630: Comprehensive integrated HBV DNA profiling in HCC patients with GGH by HBV-targeted NGS and PacBio sequencing analysis

Abstract Despite current antiviral therapy success in reducing viral load in patients with chronic hepatitis B virus (HBV), persistent viral surface antigen (HBsAg) remains a risk factor of HCC. Recent evidence has shown that integrated HBV can serve as a source for continued viral antigen expression, despite the lack of detectable replication. Given the oncogenicity of pre-S mutant proteins and its expression in type II ground glass hepatocytes (GGH) even in the absence of viral replication, we assessed the likelihood of GGH as a pre-malignant state as compared to other adjacent-to-tumor non-GGH “normal” tissue by investigating the integrity of integrated HBV DNA. We developed a sensitive HBV-targeted NGS and downstream bioinformatics pipeline, ChimericSeq, to identify HBV-host junctions. A pilot study of 10 HBV-HCC patients, each with six micro-dissected FFPE tissue sections (2 tumor, 2 GGH, 2 HBsAg-negative), was subjected to HBV-targeted NGS and ChimericSeq analysis. We identified integrated HBV DNA in 90% of HCC as well as its matched GGH, and identified PreS2 deletions, for instance, deletion at nt. 43-52. Surprisingly, the recurrent insertional driver mutations of TERT, CCNE1, and ABCC13 integration were detected in 9 of 10 (90%) of this GGH/HCC patient cohort. Next we performed PacBio amplicon sequencing of integrated HBV DNA including Pre-S sequences to comprehensively profile the integrity of the integrated HBV DNA, such as insertional mutations or deletion, and mutations across the different frozen tissue sections (tumor, GGH, HBsAg-negative). Our data suggest that HBV integration of cancer driver genes occurs early during course of infection and integrated DNA evolved over time during carcinogenesis. Overall, a sensitive workflow to comprehensively profile integrated HBV DNA in HCC patients enables further investigation of the role of HBV integration during tumorigenesis. Citation Format: Yu-Lan Kao, Yih-Ping Su, Hung-Wen Tsai, Ih-Jen Su, Selena Lin, Wei Song, Ying-Hsiu Su. Comprehensive integrated HBV DNA profiling in HCC patients with GGH by HBV-targeted NGS and PacBio sequencing analysis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3630.

Association between quantitative hepatitis B virus core antibody levels and surface antigen in chronic low viraemic patients

Association between quantitative hepatitis B virus core antibody levels and surface antigen in chronic low viraemic patients

AS067 - Hepatitis B virus (HBV) surface antigen (HBsAg) inhibition with isis 505358 in chronic hepatitis B (CHB) patients on stable nucleos (t)ide analogue (NA) regimen and in NA-naive CHB patients: phase 2a, randomized, double-blind, placebo-controlled study

AS067 - Hepatitis B virus (HBV) surface antigen (HBsAg) inhibition with isis 505358 in chronic hepatitis B (CHB) patients on stable nucleos (t)ide analogue (NA) regimen and in NA-naive CHB patients: phase 2a, randomized, double-blind, placebo-controlled study

Single center experience from Egypt about fulminant hepatic failure in children

Aim: To assess fulminant hepatic failure (FHF) in children and its interrelating factors. Methods and materials: A retrospective review study of 24 patients less than 17 years old who presented to the National Liver Institute with FHF over a period of two years was done. FHF was defined as the presence of acute liver failure with or without encephalopathy without pre-existing liver disease, within 8 weeks of the onset of clinical liver disease. Hepatitis A virus (HAV) IgM antibodies, Hepatitis B virus surface antigen (HBsAg), IgM-anti Hepatitis B core antigen (HBc), Hepatitis E virus (HEV) IgM and Hepatitis C virus (HCV) RNA in nested PCR were done in all patients. Special investigations like alpha fetoprotein, serum copper, blood culture, drug levels and other metabolic studies were carried out whenever indicated. Detailed clinical evaluations and routine hepatic laboratory profile were done. Results: Acute hepatitis-A virus was the commonest cause. Severe coma was significantly present among non-survivals and no ascites. Patients who survived had got significantly lower level of prothrombin time, they also had significantly lower rate of descent of prothrombin time. Conclusion: Hepatitis A virus was the commonest etiology of FHF. The peak level of total serum bilirubin, the rate of change of the prothrombin time/day and ammonia level were significant predictors of mortality.

Factors associated with clearance of hepatitis B virus surface antigen in patients infected with human immunodeficiency virus.

Owing to similar routes of transmission, hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection commonly occurs. Compared with patients infected with only HBV, coinfected patients develop persistent HBV infection followed by advanced liver diseases. However, the characteristics of HIV-infected patients who can achieve the clearance of HBV surface antigen (HBsAg) have not been clarified. In this study, we retrospectively examined patients coinfected with HBV and HIV and determined the host factors associated with HBsAg clearance.Among HIV-infected patients who visited our hospital between 1994 and 2017, we examined medical records of those who were seropositive for HBsAg at least once. Among them, patients who cleared HBsAg afterward were regarded as “cured,” while those who remained HBsAg-seropositive until 2017 were “chronic.”HBsAg seropositivity was found in 57 patients, and among them, 27 male patients were cured whereas 18 were chronic. The cured patients were significantly younger and had higher CD4 cell and platelet counts than the chronic patients. In addition, the cured patients had higher levels of transaminases after the detection of HBsAg. Multivariate analysis revealed age as an independent factor. Analyses of the patients infected with genotype A also showed that the cured patients had significantly higher CD4 cell counts.Considering that the CD4 cell and platelet counts were higher in the cured patients, immunological and liver functions were closely associated with HBsAg clearance. Higher levels of transaminases in the cured patients may also reflect the immunological function leading to HBsAg clearance.

Acidic pH Triggers Lipid Mixing Mediated by Lassa Virus GP.

Lassa virus (LASV) is the causative agent of Lassa hemorrhagic fever, a lethal disease endemic to Western Africa. LASV entry is mediated by the viral envelope glycoprotein (GP), a class I membrane fusogen and the sole viral surface antigen. Previous studies have identified components of the LASV entry pathway, including several cellular receptors and the requirement of endosomal acidification for infection. Here, we first demonstrate that incubation at a physiological temperature and pH consistent with the late endosome is sufficient to render pseudovirions, bearing LASV GP, non-infectious. Antibody binding indicates that this loss of infectivity is due to a conformational change in GP. Finally, we developed a single-particle fluorescence assay to directly visualize individual pseudovirions undergoing LASV GP-mediated lipid mixing with a supported planar bilayer. We report that exposure to endosomal pH at a physiologic temperature is sufficient to trigger GP-mediated lipid mixing. Furthermore, while a cellular receptor is not necessary to trigger lipid mixing, the presence of lysosomal-associated membrane protein 1 (LAMP1) increases the kinetics of lipid mixing at an endosomal pH. Furthermore, we find that LAMP1 permits robust lipid mixing under less acidic conditions than in its absence. These findings clarify our understanding of LASV GP-mediated fusion and the role of LAMP1 binding.

Prevalence and etiology of end-stage renal disease patients on maintenance hemodialysis

Objectives The objective of this work is to study the prevalence and etiology of end-stage renal disease (ESRD) patients on maintenance hemodialysis (HD) in a central governmental Hospital of El-Sharkia governorate, Egypt. Background ESRD has become a public health concern worldwide as the total number of ESRD patients requiring renal replacement therapy has been growing dramatically. The main problem in developing countries is the lack and inaccuracy of data registry. Patients and methods This descriptive study had been done in the El-Sharkia governorate central governmental hospitals on adult patients' resident in the El-Sharkia governorate with ESRD on maintenance HD for more than or equal to 3 months. The study was done during the period from February 2017 to November 2017. Results The prevalence of ESRD patients on maintenance HD in the Sharkia governorate is 442 per million populations (pmp). The etiology of the studied ESRD patients: hypertension (30.1%), undetermined etiology (19.5%), diabetes mellitus (17.6%), recurrent urinary stone (10.3%), recurrent urinary tract infection (8.5%), analgesic nephropathy (4.3%), chronic glomerulonephritis (4.1%), autosomal dominant polycystic kidney disease (2.9%), systemic lupus erythematosus (1.5%), and gout (1.1%). Of the studied ESRD patients, 44.7% had positive antibodies for hepatitis C virus (+ve) and patients with hepatitis B virus surface antigen (+ve) were 2.2%. Conclusion The total prevalence of ESRD patients on maintenance HD in 2017 in Sharkia governorate, Egypt is 442 per million populations (0.0442%). The highest proportion of patients with ESRD was between 50 and 59 years (30.8%). Most of the ESRD patients were from the rural area (60.4%).

The epidemiology of hepatitis delta virus infection in Cameroon

ObjectiveTo investigate the distribution and risk factors of hepatitis delta virus (HDV) infection in Cameroon.DesignWe tested for hepatitis B virus (HBV) surface antigen (HBsAg) and anti-HDV antibody 14 150 samples...

Occult Hepatitis B Virus Infection Prevalence Among Different Populations of Iran: A Systematic Review and Meta-Analysis

Context: Various frequency rates of occult hepatitis B virus infection (OBI) are reported from different parts of Iran. This systematic review and meta-analysis aimed to characterize the OBI epidemiology in Iran and estimate the pooled prevalence among different populations. Evidence Acquisition: Nine international and Persian electronic databases, as well as some conference proceedings, were searched. Original cross-sectional studies up to December 2018 were included if they investigated the prevalence of OBI by the detection of serum hepatitis B virus surface antigen and hepatitis B virus nucleic acid in at least 30 samples selected with any sampling methods. Comprehensive meta-analysis software was used to analyze the data, and Cochran’s Q-test and I-square statistics were applied to assess the heterogeneity. Meta-regression analysis was performed to assess the impact of the year of study on the OBI frequency. A P value < 0.05 was considered as the level of significance. Results: Of 412 citations found in electronic sources and 35 relevant citations added by searching the gray literature, 83 non-duplicated non-overlapping studies were evaluated. A total of 55 documents comprising 14,485 individuals from 16 provinces met the inclusion criteria and were used in the analysis. The prevalence of OBI considerably varied in different parts of the country with the highest prevalence (63.1%) reported among the HIV-positive population in Fars province. The rates of the OBI prevalence were estimated at 0.06% (95% CI: 0.02 - 0.16%) among blood donors (BDs) regardless of their anti-HBc status, 7.90% (95% CI: 4.33 - 13.99%) among anti-HBc positive BDs, 2.49% (95% CI: 1.2 - 4.81%) among hemodialysis (HD) patients, 4.44% (95% CI: 1.56 - 12.02%) among HIV-positive patients, and 7.76% (95% CI: 4.57 - 12.86%) among HCV-positive patients. No significant trends were observed in OBI prevalence rates among different groups over time (P > 0.05). Conclusions: This review revealed high rates of OBI prevalence among high-risk populations in Iran. It is strongly suggested that occult hepatitis B be investigated among populations with a high chance of its occurrence in our country.

Intracellular delivery of nanoparticles fabricated from monoclonal and polyclonal antibodies against influenza A and hepatitis B virus antigens

Specific antibodies (AB) may serve as molecular tools for both targeted, etiotropic and immunomodulation therapy of the infectious and oncological diseases. Despite their ability to bind with extracellular virions and isolated viral antigens AB may not pass through host cell membranes to inhibit intracellular infectious agents. Nanoparticles (NP) were fabricated from polyclonal and monoclonal AB against the influenza A structural and non-structural proteins as well as against the hepatitis B virus surface antigen (HBsAg). ELISA and immunofluorescent analysis revealed the ligand-binding activity of the AB NP comparable with the properties of the original AB. Fluorescent microscopy and quantitation showed efficient cellular uptake of the labeled AB NP and their degradation in 5 days posttreatment. Intracellular AB NP induced interferon (IFN) gene expression but not interleukin (IL) 4 and IL10 transcription. The cytokines mediated immunomodulation potential of the protein NP.

Routine Investigations in the Antenatal Booking Visit: An Epidemiological Survey

Abstract Background: The antenatal care investigations is very important to determine the antenatal care problems, manage these problems and decrease the maternal morbidity and mortality. Aim of Study: Is to identify the medical pattern in the egyptian pregnant women from Kafr El-Sheikh according to the results of the booking test. Patients and Methods: Cross sectional study was done over 1260 pregnant women from 2015 to 2017 from the outpatient clinic of Obstetrics and Gynecology in Kafr El-Sheikh General Hospital, out of them 260 pregnant women stepped out of the study, all the pregnant women was asked to do the following antenatal care laboratory investigations, complete blood count, random blood sugar, Rh typing, cy-tomegalovirus (CMV) IgG antibodies, hepatitis B virus surface antigen, hepatitis C virus antibodies, high vaginal swap for bacterial vaginosis, urine analysis, all the data gathered for each woman in a file with her name for the statistical analysis. Results: Percentage of anemia was 47.1% with negative significant correlation with age, percentage of DM was 8.1%, percentage of Rh negative was 12.6%, percentage of CMV IgG was 85.7%, percentage of HBV was 2.4%, percentage of HCV was 7.9% with positive significant correlation with history of previous CS, percentage of bacterial vaginosis was 27% and percentage of UTI was 62%. Conclusion: A lot of women in Kafr El-Sheikh do not know the importance of the antenatal investigations and the control of the antenatal problems. Recommendations: There is need for give more concern about routine antenatal care investigations and it's importance and routine screening for anemia, DM, Rh, CMV, HBV, HCV, BV and UTI.

Ultrasensitive and fast detection of pathogens using Europium-containing polystyrene nanospheres in a homemade portable NMR diagnostic system

The use of nuclear magnetic resonance (NMR) platforms to detect biological samples via magnetic nanoparticles has shown great importance in clinical applications. In numerous studies, superparamagnetic nanoparticles, including ferromagnetic nanoparticles, have been adopted to improve the performance of magnetic nanoparticles. Here we developed a simple and novel europium (Eu)-containing polystyrene nanosphere (PS NS)-based NMR system for rapid pathogen detection in clinical samples. Using this proposed portable NMR diagnostic system, we found that during pathogen detection, NPs with lower susceptibility (e.g., Eu-containing PS NSs) produced an unexpected detection effect compared with iron oxide NPs. Our Eu-containing PS NS-based NMR diagnostic system showed higher detection sensitivity, broader detection range, and higher stability than conventional iron oxide NP-based NMR platforms do. Using an inexpensive microcontact-printed Ag microcoil-based NMR probe, we demonstrated unprecedented detection sensitivity and speed with minimal sample preparation for pathogen analyses. The sample concentration of 0.2 ng/mL of hepatitis B virus surface antigen (HBsAg) and 10 CFU/mL of Clostridium difficile can be attained by the NMR diagnostic system within 5 s, and concentration-detection ranges spanned over three orders of magnitude. With advantages of low-cost NMR probe, a portable instrument, and convenient operation, our proposed NMR platform may provide a promising point-of-care diagnostic system in clinical applications.

Novel hepatitis B virus surface antigen mutations associated with occult genotype B hepatitis B virus infection affect HBsAg detection

The causative factors of occult hepatitis B infection are complicated and not yet been fully elucidated. Mutations in hepatitis B virus (HBV) S gene are one of the factors may contributing to occult infection. In this study, 89 blood donors with genotype B occult HBV infectionwere investigated. Fifty-seven hepatitis B surface antigen (HBsAg)-positive/HBV DNA-positive blood donors served as control group for comparison. Occult HBV-related mutations with a high incidence (P<.05) in the S gene were identified. To further verify these occult infection-related mutations, a conservative full-gene expression vector of HBV B genotype (pHBV1.3B) was constructed. Then, the mutant plasmids on the basis of pHBV1.3B were constructed and transfected into HepG2 cells. Extracellular as well as intracellular HBsAg was analysed by electrochemical luminescence and cellular immunohistochemistry. Ten occult infection-related mutations (E2G, Q101R, K122R, M133T, D144E, G145R, V168A, S174N, L175S and I226S) were significantly more frequent in the occult infection group (P<.05). Five of the ten mutations (E2G, D144E, G145R, V168A and S174N) strongly decreased extracellular HBsAg level (P<.05) in the transfection system. Notably, the E2G mutation had the most significant impact on the ratio of extracellular HBsAg (3.8% vs pHBV1.3B) and intracellular HBsAg (239.3% vs pHBV1.3B) (P<.05), and the fluorescence density of E2G mutant HBsAg was significantly higher than that of pHBV1.3B (P<.0001). Hence, ten mutations were associated with genotype B occult HBVinfection; E2G and V168A were novel mutations which we confirmed significantly affect HBsAg detection. E2G might cause HBsAg secretion impairment that results in intracellular accumulation and a decrease in HBsAg secretion.

A \u201cone stop liver shop\u201d approach improves the cascade-of-care for Aboriginal and Torres Strait Islander Australians living with chronic hepatitis B in the Northern Territory of Australia: results of a novel care delivery model

BackgroundAboriginal and Torres Strait Islander Australians are disproportionately affected by Chronic Hepatitis B (CHB) with a prevalence of 6.08% in the Northern Territory (NT) and liver cancer rates 6 times higher than non-Indigenous Australians. Without appropriate care, overall 25% of those living with CHB will die from either liver failure or liver cancer, outcomes that can be minimised with regular follow up, antiviral treatment and hepatocellular carcinoma (HCC) screening. This care including antiviral treatment is publicly funded in the Australian setting however the care cascade still shows inequities in access to treatment for Aboriginal Australians. We describe the impact of a mobile care delivery model, “One Stop Liver Shop”, on the cascade of care for people living with CHB in a remote Australian setting.MethodsA retrospective analysis was performed for CHB care received between 2013 and 2018 in one very remote Northern Territory community, where the “One Stop Liver Shop” was iteratively developed with the community. Patients with positive Hepatitis B virus surface antigen (HBsAg) were identified through electronic medical records. Proportions of patients who are up-to-date with monitoring investigations and HCC screening were evaluated and compared to national guidelines and targets.ResultsEighty-three HBsAg positive patients were evaluated. Eighty-eight percent were engaged in care, 16% of whom were receiving antiviral treatment. Liver function tests (LFT) were up to date in 71% of patients in 2013 and 88% in 2018. Viral load (VL) monitoring was up to date for 61 (73%) of patients. There were 44 patients in whom HCC screening was indicated. Of these, 38 (86.4%) were up to date with 6 monthly alpha-fetoprotein (AFP), 35 (79.5%) were up to date with 6 monthly liver ultrasound scan (USS), and 34 (77.3%) were up-to-date for both.ConclusionsA “One Stop Liver Shop” developed with and including Aboriginal Health Practitioners bridges gaps in the availability of services to those living with CHB in a very remote community and improves the cascade of care.

Blood transfusion safety in the country of Georgia: collateral benefit from a national hepatitis C elimination program.

In April 2015, the government of Georgia (country) initiated the world's first national hepatitis C elimination program. An analysis of blood donor infectious screening data was conducted to inform a strategic plan to advance blood transfusion safety in Georgia. Descriptive analysis of blood donation records (2015-2017) was performed to elucidate differences in demographics, donor type, remuneration status, and seroprevalence for infectious markers (hepatitis C virus antibody [anti-HCV], human immunodeficiency virus [HIV], hepatitis B virus surface antigen [HBsAg], and Treponema pallidum). For regression analysis, final models included all variables associated with the outcome in bivariate analysis (chi-square) with a p value of less than 0.05. During 2015 to 2017, there were 251,428 donations in Georgia, representing 112,093 unique donors; 68.5% were from male donors, and 51.2% of donors were paid or replacement (friends or family of intended recipient). The overall seroprevalence significantly declined from 2015 to 2017 for anti-HCV (2.3%-1.4%), HBsAg (1.5%-1.1%), and T. pallidum (1.1%-0.7%) [p < 0.0001]; the decline was not significant for HIV (0.2%-0.1%). Only 41.0% of anti-HCV seropositive donors underwent additional testing to confirm viremia. Infectious marker seroprevalence varied by age, sex, and geography. In multivariable analysis, first-time and paid donor status were associated with seropositivity for all four infectious markers. A decline during the study period in infectious markers suggests improvement in blood safety in Georgia. Areas that need further improvement are donor recruitment, standardization of screening and diagnostic follow-up, quality assurance, and posttransfusion surveillance.

Genetic immunization against hepatitis B virus with calcium phosphate nanoparticles in vitro and in vivo

Calcium phosphate nanoparticles were loaded with plasmid DNA and toll-like receptor ligands (TLR), i.e. CpG or flagellin, to activate antigen-presenting cells (APCs) like dendritic cells (DCs). The functionalized nanoparticles were studied in vitro on HeLa, C2C12 and BHK-21 cell lines, focusing on the expression of two specific proteins. EGFP-DNA, encoding for enhanced green fluorescent protein (EGFP), was used as a model plasmid to optimize the transfection efficiency in vitro by fluorescence microscopy and flow cytometry. Calcium phosphate nanoparticles loaded with TLR ligands and plasmid DNA encoding for the hepatitis B virus surface antigen (pHBsAg) were evaluated by in vitro and in vivo immunization experiments to identify a possible candidate for a prophylactic hepatitis B virus (HBV) vaccine. The nanoparticles induced a strong expression of HBsAg in the three cell lines. In splenocytes, the expression of the co-stimulatory molecules CD80 and CD86 was enhanced. After intramuscular injection in mice, the nanoparticles induced the expression of HBsAg, the antigen-specific T cell response, and the antigen-specific antibody response (IgG1). Statement of SignificanceHepatitis B is one of the most frequent viral infections worldwide. For preventive immunization, nanoparticles can be used which carry both an adjuvant (a stimulatory molecule) and DNA encoding for a viral antigen. After administration of such nanoparticles to cells, they are taken up by cells where the DNA is transcribed into the viral antigen (a protein). This viral antigen is inducing a virus-specific immune response. This was shown both by in vitro cell culture as well as by an extensive in vivo study in mice.

Innovations in structure-based antigen design and immune monitoring for next generation vaccines.

The recent explosion of atomic-level structures of glycoproteins that comprise the surface antigens of human enveloped viruses, such as RSV, influenza, and HIV, provide tremendous opportunities for rational, structure-based vaccine design. Several concepts in structure-based vaccine design have been put into practice and are are well along preclinical and clinical implementation. Testing of these designed immunogens will provide key insights into the ability to induce the desired immune responses, namely neutralizing antibodies. Many of these immunogens in human clinical trials represent only the first wave of designs and will likely require continued tweaking and elaboration to achieve the ultimate goal of enhanced breadth and potency. Considerable effort is now being invested in germline targeting, epitope focusing, and improved immune presentation such as multivalent nanoparticle incorporation. This review highlights some of the recent advances in these areas as we prepare for the next generation of immunogens for subsequent rounds of iterative vaccine development.

Efficacy of an Inhibitor of Hepatitis B Virus Expression in Combination With Entecavir and Interferon-α in Woodchucks Chronically Infected With Woodchuck Hepatitis Virus.

RG7834 is a small‐molecule inhibitor of hepatitis B virus (HBV) gene expression that significantly reduces the levels of hepatitis B surface antigen (HBsAg) and HBV DNA in a humanized liver HBV mouse model. In the current study, we evaluated the potency of RG7834 in the woodchuck model of chronic HBV infection, alone and in combination with entecavir (ETV) and/or woodchuck interferon‐α (wIFN‐α). RG7834 reduced woodchuck hepatitis virus (WHV) surface antigen (WHsAg) by a mean of 2.57 log10 from baseline and WHV DNA by a mean of 1.71 log10. ETV + wIFN‐α reduced WHsAg and WHV DNA by means of 2.40 log10 and 6.70 log10, respectively. The combination of RG7834, ETV, and wIFN‐α profoundly reduced WHsAg and WHV DNA levels by 5.00 log10 and 7.46 log10, respectively. However, both viral parameters rebounded to baseline after treatment was stopped and no antibody response against WHsAg was observed. Effects on viral RNAs were mainly seen with the triple combination treatment, reducing both pregenomic RNA (pgRNA) and WHsAg RNA, whereas RG7834 mainly reduced WHsAg RNA and ETV mainly affected pgRNA. When WHsAg was reduced by the triple combination, peripheral blood mononuclear cells (PBMCs) proliferated significantly in response to viral antigens, but the cellular response was diminished after WHsAg returned to baseline levels during the off‐treatment period. Consistent with this, Pearson correlation revealed a strong negative correlation between WHsAg levels and PBMC proliferation in response to peptides covering the entire WHsAg and WHV nucleocapsid antigen. Conclusion: A fast and robust reduction of WHsAg by combination therapy reduced WHV‐specific immune dysfunction in the periphery. However, the magnitude and/or duration of the induced cellular response were not sufficient to achieve a sustained antiviral response.

Prevalence and molecular characterization of occult hepatitis B virus in pregnant women from Gondar, Ethiopia

BACKGROUND: The greatest risk of chronic hepatitis B (CHB) is from mother-to-child transmission. Approximately 20% of individuals in sub-Saharan Africa are hepatitis B virus (HBV) surface antigen–positive (HBsAg+), but the prevalence of occult hepatitis B (OHB) is unknown. Aim: This study investigated CHB and OHB prevalence and viral variants in a cohort of pregnant women in Gondor, Ethiopia. METHODS: Patients were prospectively recruited from the University of Gondar Hospital ( N = 200; median age 27 [inter-quartile range] 8.3y) from March through June 2016. Data were collected using an investigator-administered questionnaire. Plasma was tested for HBsAg and HBV core antibody (anti-HBc), and HBV genotype and presence of HBV variants (ie, vaccine escape mutants [VEMs]) were determined by polymerase chain reaction, Sanger sequencing, and phylogenetic analysis. RESULTS: Of women tested, 1% (2/200) were HBsAg+; 26.8% (47/182) of HBsAg-negative patients were anti-HBc+, of whom 37/47 (78.7%) had detectable HBV DNA. The overall rate of OHB was 20.3%. Both HBsAg+ cases were HBV genotype D, and 36/37 (97.3%) of OHB individuals were genotype D. None carried VEM, but both HBsAg+ cases and 32/37 (86.5%) of the OHB cases showed lamivudine-resistant mutations. CONCLUSIONS: Twenty-seven percent of pregnant women in this cohort showed evidence of CHB or prior HBV exposure (ie, HBsAg+ or anti-HBc+) and clinically relevant HBV variants. Data from this single-centre study suggests high HBV prevalence, reinforcing the World Health Organization’s recommendation for universal prenatal HBV screening and infant vaccination.