This study aimed to analyze the relationship between quantitative hepatitis B surface antigen and hepatitis B virus deoxyribonucleic acid in hepatitis B e antigen-positive and hepatitis B e antigen-negative chronic hepatitis B patients and to determine the best cut-off value for quantitative hepatitis B surface antigen to predict high hepatitis B virus deoxyribonucleic acid levels (≥2000 IU/mL).

(1) Background: Hepatitis B core antibodies (anti-HBc) are a marker of hepatitis B virus (HBV) exposure; hence, a normal HBV serology profile is characterized by HBV surface antigen (HBsAg) and anti-HBc positivity. However, atypical HBV serologies occur, and we aimed to determine the prevalence of an atypical profile (HBsAg+/anti-HBc-) in a cohort of people with HIV-1 (PWH) in Botswana. (2) Methods: Plasma samples from an HIV-1 cohort in Botswana (2013-2018) were used. The samples were screened for HBsAg and anti-HBc. Next-generation sequencing was performed using the GridION platform. The Wilcoxon rank-sum test and Chi-squared tests were used for the comparison of continuous and categorical variables, respectively. (3) Results: HBsAg+/anti-HBc- prevalence was 13.7% (95% CI 10.1-18.4) (36/263). HBsAg+/anti-HBc- participants were significantly younger (p < 0.001), female (p = 0.02) and ART-naïve (p = 0.04) and had a detectable HIV viral load (p = 0.02). There was no statistically significant difference in the number of mutations observed in participants with HBsAg+/anti-HBc- vs. those with HBsAg+/anti-HBc+ serology. (4) Conclusions: We report a high HBsAg+/anti-HBc- atypical serology profile prevalence among PWH in Botswana. We caution against HBV-testing algorithms that consider only anti-HBc+ samples for HBsAg testing, as they are likely to underestimate HBV prevalence. Studies to elucidate the mechanisms and implications of this profile are warranted.

Quantitative hepatitis B core-related antigen (qHBcrAg) has a better correlation with intrahepatic hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) than HBV DNA or hepatitis B e antigen (HBeAg), but data are still lacking for its clinical application.

Chronic infection with hepatitis B virus (HBV) increases the risk of developing fibrosis, cirrhosis or hepatocellular carcinoma. Current therapies are limited to type-I interferons and/or nucleos(t)ide analogues; however, these are only partially effective. The development of novel anti-HBV agents for new treatment strategies has been hampered by the lack of a suitable system that allows the in vitro replication of HBV. Studies of virus infection/replication at the molecular level using wild-type HBV are labor-intensive and time-consuming. To overcome these problems, we previously constructed a recombinant reporter HBV bearing the NanoLuc gene and showed its usefulness in identifying factors that affect HBV proliferation. Because this system mimics the early stage of the HBV life cycle faithfully, we conducted a quantitative analysis of HBV infectivity to several human hepatocyte cell lines as well as the effect of dimethyl sulfoxide and HBV protein X on the early stage of HBV proliferation using this system. Furthermore, we developed a system to produce a reporter HBV expressing a pol gene. These reporter HBV may provide an opportunity to enhance our understanding of the HBV life cycle and aid strategies for the development of new anti-HBV agents.

B cell hyperactivation and functional impairment were identified from patients with chronic hepatitis B virus (CHB) infection; however, the underlying mechanism remains unknown. Here, we aim to elucidate the mechanisms responsible for B cell hyperactivation during HBV infection. Peripheral CD19+  B cells isolated from 4 CHB patients and 4 healthy volunteers were analysed by RNA sequencing. A total of 1401 differentially expressed genes were identified from B cell transcriptome of CHB patients vs healthy volunteers. We found that B cells from CHB patients were functional impaired, with increased TLR4 expression, activated NF-κB pathway and altered mitochondrial function. The expression of B cell activation-related genes, including TLR4, was further validated using additional clinical samples. To further verify the role of TLR4 in B cell activation during CHB, B cell phenotypes were determined in wild-type (WT) and TLR4-/- HBV-carrier mice. Hyperactivated B cell and TLR4 signalling pathway were observed in WT HBV-carrier mice, while TLR4 ablation failed to induce B cell hyperactivation, and downstream MyD88 and NF-κB were also not altered. Taken together, TLR4 pathway plays a pivotal role in B cell hyperactivation during CHB, which might serve as a promising target for B cell function restoration.

Cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to investigate the changes of cytokines concentration and its correlation to alanine aminotransferase (ALT), HBV deoxyribonucleic acid (HBV-DNA), hepatitis B envelope antigen (HBeAg), and HBV surface antigen (HBsAg) in the development of chronic hepatitis B (CHB).

This study aimed to examine the correlations between serum hepatitis B core-related antigen (HBcrAg) and hepatitis B surface antigen (HBsAg) titers in patients with hepatitis B cirrhosis and a hepatitis B virus (HBV)-DNA-negative status.

We examined changes in hepatitis B core-related antigen (HBcrAg) during the four sequential phases of chronic hepatitis B virus (HBV) infection: hepatitis B e antigen (HBeAg)-positive chronic infection (EPCI) and hepatitis (EPCH), followed by HBeAg-negative chronic infection (ENCI) and hepatitis (ENCH). We compared the performance of serum HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA in predicting EPCH and ENCH.

To evaluate the efficacy of hepatitis B vaccination on hepatitis B prevention and on hepatocellular carcinoma.

The aim of this study was to determine the correlation between vaccine therapy and appearance of mutations in hepatitis B surface antigen (HBsAg)-positive chronic hepatitis B virus (HBV) patients.

HBV-X protein is associated with the pathogenesis of HBV related diseases, specially in hepatocellular carcinomas of chronic patients. Genetic variability of the X gene includes genotypic specific variations and mutations emerging during chronic infection. Its coding sequence overlaps important regions for virus replication, including the basal core promoter. Differences in the X gene may have implications in biological functions of the protein and thus, affect the evolution of the disease. There are controversial results about the consequences of mutations in this region and their relationship with pathogenesis. The purpose of this work was to describe the diversity of HBV-X gene in chronic hepatitis patients infected with different genotypes, according to liver disease.

To determine the prevalence of detectable serum hepatitis B virus (HBV) DNA in patients who are hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (HBcAb)-positive. The correlation between HBV DNA viral load and serological markers, as well as liver and coagulation function indicators were investigated. Furthermore, the effects of immunosuppressive therapy on DNA replication were assessed.

The detection of dual-positivity for both hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) is not typically performed for patients with hepatitis B virus (HBV). This cross-sectional study was designed to figure out the prevalence of dual-positivity for both HBeAg and anti-HBe (DEP) among hospitalized patients with chronic hepatitis B virus infection (C-HBVI).

Non-detection of hepatitis B virus (HBV) envelope protein (hepatitis B surface antigen, HBsAg) in a chronically HBV infected individual has been described as occult infection. One possible reason for this phenotype is alteration in large (L-HBsAg) to small (S-HBsAg) envelope protein ratio associated with reduced or non secretion of HBsAg. This results in quantitative levels of serum HBsAg below the detection limit of enzyme immunoassays. Genotype D of HBV has a characteristic 33 nucleotide (nt) deletion upstream of the pre-S2/S promoter. This deletion may reduce HBsAg secretion in occult infection patients infected with genotype D HBV. Additional deletions in the pre-S2/S promoter may further aggravate reduced HBsAg secretion in patients infected with genotype D HBV. Thus, the aim of the present study was to determine the role of genotype D specific 33nt deletion and additional pre-S2/S promoter deletions in causing reduced or no secretion of HBsAg, in occult infection. Since these deletions overlap virus polymerase, their effect on virus replication was also investigated.

In the Netherlands, a selective hepatitis B virus (HBV) vaccination programme started in 2002 for men having sex with men, drug users, commercial sex workers and heterosexuals with frequent partner changes. We assessed the programme's effectiveness to guide policy on HBV prevention.

BACKGROUND Hepatitis B surface antigen (HBsAg) loss/seroconversion is considered to be an ideal endpoint for antiviral therapy and a final therapeutic target for chronic hepatitis (CHB). This study aimed to evaluate the HBsAg kinetics in CHB patients during peginterferon-alpha (Peg-IFN-alpha) treatment. MATERIAL AND METHODS A retrospective cohort study was performed using a case database, which included 151 patients who received Peg-IFN-alpha treatment and with HBsAg load of no less than 4 time points from May 1, 2018 to January 31, 2019. The HBsAg kinetic pattern was analyzed by Q-type clustering, and a clinical prognostic empirical model was constructed based on the HBsAg kinetic pattern of uncured patients. RESULTS Changes of HBsAg in 13 functionally cured patients were attributed to 3 kinetic patterns by cluster analysis, and there was a significant positive correlation between functionally cure time and baseline HBsAg. For uncured 116 patients with treatment duration longer than or equal to 56 days, 5 HBsAg kinetic patterns were obtained by cluster analysis, and the clinical prognosis empirical model was established. Finally, 13 new functionally cured patients preliminarily confirmed the rationality of the proposed empirical model. CONCLUSIONS According to empirical model, we recommend that the therapeutic regime should be timely adjusted to improve sustained response rate and reduce patients' medical burden for patients with second (Z type) and fifth (Z+W type) kinds of patterns. While for the rest of patterns' patients, it is recommended to continue treatment for a longer period of time to achieve the desired therapeutic goal.

The nucleocapsids formation is a pivotal step of hepatitis B virus (HBV) life cycle. The inhibition of HBV nucleocapsids assembly is a promising strategy for the anti-HBV treatment. HBc78-117 is an internal fragment of hepatitis B core protein (HBc). In this study, we used lentiviral vector to deliver HBc78-117 cDNA sequence into HepG2.2.15 cells and examined the effect of HBc78-117 on HBV replication. We confirmed by immunoprecipitation analysis that HBc78-117 interacted with full-length HBc in HepG2.2.15 cells. The nucleocapsids and HBV DNA replication intermediates were markedly reduced in the cells expressing HBc78-117, although HBV pregenome RNA was not affected. The level of HBV DNA was also significantly reduced in culture supernatant. These suggest that HBc78-117 can inhibit HBV DNA replication by interfering with nucleocapsids assembly.

Nine subgenotypes from genotype B have been identified for hepatitis B virus (HBV). However, these subgenotypes were less conclusive as they were often designated based on a few representative strains. In addition, subgenotype B6 was designated twice for viruses of different origin.

Previous studies have suggested hepatitis B splice-generated protein (HBSP), when expressed, is involved in the pathogenesis of HBV infection.

Hepatitis B virus (HBV) can have mutations that include the a determinant, which causes breakthrough infection. In particular, a single mutation at amino acid 145 of the surface protein (G145) is frequently reported in the failure of prophylactic treatment. The aim of this study was to evaluate the frequency of the a determinant mutants, especially the G145 variant, in Japan, where universal vaccination has not been adopted.