Hepatitis B Virus Genotype Research Articles

Hepatitis B virus (HBV) serum biomarkers for screening and monitoring infections at Rio de Janeiro, Brazil

HBV is a short-term disease and is one of the major causative agents of chronic liver illness. For others, it can become a long-term, chronic infection like liver disease or liver cancer. This paper was aimed to investigate the blood-based serum biomarkers for screening and monitoring of Brazilian patients collected in the All Lab at Rio de Janeiro city. This research were carried out using the chemiluminescence method. The presence (reactive) or absence of anti-HBV antibodies (non-reactive) was also investigated by the electrochemiluminescence. The serological diagnosis of hepatitis B involves the evaluation of antigens and antibodies. Our findings had been showed which it is possible to determine the different phases of the infection (reactive – positive or non-reactive – negative) and some samples can be resulted indeterminates or inconclusive by the choice method and the immune system or susceptible of the patients. The sum of numbers, average, standard deviation and coefficient of variation were calculated among the 2222 samples collected from 1660 patients and 477 samples from 411 patients from the year 2022 and 2023, respectively. So, irrespective of HBV genotype or infection phase, this paper provides a classic way fast-track to advance the HBV serum biomarkers detected in blood samples. Novel challenges of serum HBV biomarkers should be more discussed to mitigated weaknesses points and eliminate cross-reaction in clinical assays.

Incidence and factors associated with hepatitis B surface antigen seroclearance in patients co-infected with HBV/HIV during antiretroviral therapy in Guangdong, China.

Hepatitis B surface antigen (HBsAg) clearance is vital for a functional cure of hepatitis B virus (HBV) infection. However, the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus (HIV) remain largely unknown in Guangdong, China. Between 2009 and 2019, patients co-infected with HBV/HIV undergoing antiretroviral therapy (ART) in Guangzhou Eighth People's Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31, 2020. The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses. A total of 1550 HBV/HIV co-infected patients were included in the study, with the median age of 42 years and 86.0% (1333/1550) males. Further, 98.3% (1524/1550) received ART containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC). HBV DNA was examined in 1283 cases at the last follow-up. Over the median 4.7 years of follow-up, 8.1% (126/1550) patients achieved HBsAg seroclearance, among whom 50.8% (64/126) obtained hepatitis B surface antibody, 28.1% (137/488) acquired hepatitis B e antigen seroconversion, and 95.9% (1231/1283) undetectable HBV DNA. Compared with patients who maintained HBsAg positive, cases achieving HBsAg seroclearance showed no differences in age, gender, CD4 + T cell count, alanine aminotransferase (ALT) level, or fibrosis status; however, they presented lower HBV DNA levels, lower HBsAg levels, and higher rates of HBV genotype B at the baseline. Multivariate analysis showed that baseline HBsAg <1500 cutoff index (COI) (adjusted hazard ratio [aHR], 2.74, 95% confidence interval [95% CI]: 1.48-5.09), ALT elevation >2 × upper limit of normal during the first six months after receiving ART (aHR, 2.96, 95% CI: 1.53-5.77), and HBV genotype B (aHR, 3.73, 95% CI: 1.46-9.59) were independent predictors for HBsAg seroclearance (all P <0.01). Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients. Lower baseline HBsAg levels, HBV genotype B, and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.

Two genetic variants in the SRD5A2 gene are found to be associated with sex differences in the disease characteristics of patients with chronic hepatitis B virus infection

BackgroundTo examine the expression characteristics of single nucleotide polymorphisms (SNPs) in the SRD5A2 gene and investigate their potential association with differences in the clinical characteristics between sexes in patients with chronic hepatitis B virus (HBV) infection.MethodsA total of 30 loci in six genes primarily involved in the metabolism and signaling of sex hormones/sex hormone receptors, namely AKR1C2, AKR1C3, HSD17B6, SRD5A1, SRD5A2, and ESR1, were genotyped in 1007 patients from eight counties (cities) in Northeastern China with chronic HBV infection and 1040 healthy controls, and their association with viral replication characteristics and the differences in disease severity between sexes was assessed. Western blotting was conducted to determine the hepatic SRD5A2 protein level and its relationship with the inflammatory activity and fibrosis degree in male and female patients.ResultsTwo SNP loci in the SRD5A2 gene (rs12470143 and rs7594951) exhibited significant differences in genotype and allele frequencies between sexes, with the proportion of T alleles significantly higher in males than in females. It was found that the incidence and severity of HBV-related liver fibrosis were significantly higher in patients with the T/T genotype in SRD5A2 rs12470143 and rs7594951 than those with the non-T/T genotype. Additionally, serum HBV DNA levels were significantly elevated in T/T patients compared to non-T/T patients. Female patients exhibited significantly lower serum DNA levels compared to male patients. Western blot analysis indicated that greater hepatic SRD5A2 protein levels were associated with higher METAVIR inflammation and fibrosis scores. Furthermore, multivariate analysis showed that the two genetic variants in the SRD5A2 gene (rs12470143 C > T, r7594951 C > T), together with the male sex, age > 50 years old, HBeAg positive status, elevated serum HBsAg load, high serum HBV DNA load, and HBV genotype C, were independent risk factors for HBV-related liver fibrosis.ConclusionsThis study demonstrated that two genetic variants in the SRD5A2 gene (rs12470143 C > T, r7594951 C > T) are associated with sex differences in the clinical characteristics of patients with chronic HBV infection.

Lifetime risk of liver-related outcomes and determinants in male inactive carriers of chronic hepatitis B.

The full spectrum of risks for the life course of inactive hepatitis B virus (HBV) carriers remains unclear. In this study, 995 untreated HBV carriers (median age: 42.8 years; median follow-up: 30.2 years) were included. Their data were sourced from a population-based cohort study of male civil servants recruited in 1989-1992. Outcomes were identified by active follow-up examinations and linkage with national health insurance research database. At baseline, 483 subjects were inactive carriers, 385 with indeterminate phase, and 127 with other phases. The joint lifetime risk for incident cirrhosis, decompensation, hepatocellular carcinoma, and liver-related deaths was lower for inactive carriers compared to subjects in other phases (p < 0.0001). There was a trend of increase in incidence among inactive carriers; the 5-, 10-, and 20-year cumulative incidences were 1.86%, 6.03%, and 10.07%, respectively. Of the inactive carriers, 37.7% cleared HBsAg and 36.6% had biochemical relapse during the study. Biochemical relapse, obesity, and advanced age were predictors for disease progression in inactive carriers. Virological relapse was the predominant cause of biochemical relapse. Higher HBV-DNA levels (≥1000 copies/mL or 200 IU/mL) and HBV genotype B (vs. C) were associated with higher virological relapse rate. After 30 years, we found that one-time measure of inactive carrier state continued to have the lowest risk compared with other infection phases. Despite a more favorable prognosis, inactive carriers had a non-negligible risk. Our findings of lifetime risk may provide important clues for the management of such patients and consideration of therapeutic strategies aiming to achieve functional cure.

The 863C&gt;A and 1031T&gt;C Single Nucleotide Polymorphisms (SNPs) in the Tumor Necrosis Factor Alpha (TNF-α) Promoter Gene May Not Be Putative Predictors of HBV Endemicity

Background: Genetic polymorphisms within the gene loci of the promoter region of tumor necrosis factor (TNF) alpha have been associated with the pathogenesis of hepatitis B virus (HBV) infection. In Uganda, there is a wide variation in the HBV endemicity, ranging from low endemicity, through moderate endemicity, to hyper-endemicity. However, the underlying reasons for this disparity in HBV burden are not fully elucidated. Thus, we aimed to test the hypothesis that the TNF-α-863C/A and -1031T/C polymorphic sites may have an effect on the difference between the burden of HBV in our country. We screened 384 participants, from which a sample of 134 was drawn, to determine the HBV, TNF-α-863C/A, and TNF-α-863T/C genotypes. The nucleotide BLAST was used to match the unknown targeted sequence obtained from the Sanger sequence against the known deposited sequence. This process unveiled the base substitution mutation and the HBV genotypes. The odds ratio (OR) and Chi-square test of proportions were used for the analysis. All the analyses were performed using SPSS version 26.0 and MedCalc software version 20.010 at 95% CI. A p &lt; 0.05 was considered statistically significant. Results: The prevalence of both the TNF-α-863C/A and the TNF-α-1031T/C genotypes and their alleles did not differ significantly by endemicity (p &gt; 0.05). However, the prevalence of the nucleotide substitution mutations for TNF-α-863C&gt;A and TNF-α-1031T&gt;C was significantly low for all the study groups (p &lt; 0.05). Conclusion: The TNF-α gene promoter at the TNF-α-863C/A and 1031T/C positions is conserved in our population and may not affect the endemicity of HBV infection. However, future research should focus on the use of nationwide samples in order to reach concreate determinations regarding the role of the TNF-α polymorphisms in the risk/resolution of HBV infections in an African or Black population.

Development of a Reagent Kit for the Quantitative Determination of Hepatitis B Virus (HBV) DNA in Clinical Material by PCR with Hybridization-Fluorescence Detection

Relevance.Hepatitis B virus (HBV) is one of the most common viral infections affecting people worldwide and can lead to chronic hepatitis, cirrhosis and hepatocellular carcinoma. Currently 3% of the world's population are infected with hepatitis B virus and are at risk of developing life-threatening liver disease. Immunological and molecular biological methods of detection of HBV are currently used in laboratory diagnostics. The polymerase chain reaction (PCR) is currently the most sensitive method for the detection and quantification of HBV. HBV DNA quantification is widely used to monitor the antiviral treatment of HBV infection.Aim.To develop a real-time PCR kit for the quantification of HBV DNA.Materials and methods.A total of 200 plasma and serum samples positive and negative for HBV were used in the development. The performance of the developed kit was compared with the use of other commercially registered HBV diagnostic kits in Russia. Additionally, the nucleotide sequences of all existing virus genotypes analysed for the selection of primers using GeneBank system.Results and discussion.Comparison analysis of the results of quantitative determination by real-time PCR in 200 clinical serum and blood plasma samples showed that the diagnostic sensitivity of the developed kit was 100% and specificity 100%. The primers developed specific to the POL gene region. The kit is capable of detecting all types of virus genotypes.Conclusions.The developed reagent kit allows detection of hepatitis B virus and determination of its quantity within 70 minutes. In addition to a large number of genotypes and subgenotypes, the virus is characterized by mutational changes in the genome, which complicates its diagnosis and, as a consequence, the ongoing therapy with drugs. Conservative regions for primer and probe selection taken into account in the development, and the sequencing results obtained are applicable to all HBV genotypes. The reagent kit is designed to monitor HBV infected patients and will allow the analysis of different HBV viral loads.

Host and HBV Interactions and Their Potential Impact on Clinical Outcomes.

Hepatitis B virus (HBV) is a challenge for global health services, affecting millions and leading thousands to end-stage liver disease each year. This comprehensive review explores the interactions between HBV and the host, examining their impact on clinical outcomes. HBV infection encompasses a spectrum of severity, ranging from acute hepatitis B to chronic hepatitis B, which can potentially progress to cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B infection (OBI), characterized by low HBV DNA levels in hepatitis B surface antigen-negative individuals, can reactivate and cause acute hepatitis B. HBV genotyping has revealed unique geographical patterns and relationships with clinical outcomes. Moreover, single nucleotide polymorphisms (SNPs) within the human host genome have been linked to several clinical outcomes, including cirrhosis, HCC, OBI, hepatitis B reactivation, and spontaneous clearance. The immune response plays a key role in controlling HBV infection by eliminating infected cells and neutralizing HBV in the bloodstream. Furthermore, HBV can modulate host metabolic pathways involved in glucose and lipid metabolism and bile acid absorption, influencing disease progression. HBV clinical outcomes correlate with three levels of viral adaptation. In conclusion, the clinical outcomes of HBV infection could result from complex immune and metabolic interactions between the host and HBV. These outcomes can vary among populations and are influenced by HBV genotypes, host genetics, environmental factors, and lifestyle. Understanding the degrees of HBV adaptation is essential for developing region-specific control and prevention measures.

In silico Analysis Predicts that Mir-6770-5p Can Target the X Gene of All Hepatitis B Virus Genotypes

To date, effective medication against hepatitis B virus (HBV) has not been developed. MicroRNAs (miRNAs) comprise a promising therapeutic approach to inhibit the virus. In this study, 1917 miRNAs in the miRBase database were screened using bioinformatics software to obtain candidates that can target HBV genotype B. Two parameters, namely pairing pattern and minimum free energy were used to select the qualifying miRNAs. Three miRNAs targeting the X gene and one miRNA targeting the C gene were identified out of 39 initial candidates. Uniquely, miR-6770-5p was the only candidate that could target the X gene of all HBV genotypes, with a higher potency of inhibition compared to other candidates. The three other candidates also showed good potency for some genotypes; thus, the identified candidates show promise as therapeutics for hepatitis infection.

Hepatitis B virus serum RNA transcript isoform composition and proportion in chronic hepatitis B patients by nanopore long-read sequencing.

Serum hepatitis B virus (HBV) RNA is a promising new biomarker to manage and predict clinical outcomes of chronic hepatitis B (CHB) infection. However, the HBV serum transcriptome within encapsidated particles, which is the biomarker analyte measured in serum, remains poorly characterized. This study aimed to evaluate serum HBV RNA transcript composition and proportionality by PCR-cDNA nanopore sequencing of samples from CHB patients having varied HBV genotype (gt, A to F) and HBeAg status. Longitudinal specimens from 3 individuals during and following pregnancy (approximately 7 months between time points) were also investigated. HBV RNA extracted from 16 serum samples obtained from 13 patients (73.3% female, 84.6% Asian) was sequenced and serum HBV RNA isoform detection and quantification were performed using three bioinformatic workflows; FLAIR, RATTLE, and a GraphMap-based workflow within the Galaxy application. A spike-in RNA variant (SIRV) control mix was used to assess run quality and coverage. The proportionality of transcript isoforms was based on total HBV reads determined by each workflow. All chosen isoform detection workflows showed high agreement in transcript proportionality and composition for most samples. HBV pregenomic RNA (pgRNA) was the most frequently observed transcript isoform (93.8% of patient samples), while other detected transcripts included pgRNA spliced variants, 3' truncated variants and HBx mRNA, depending on the isoform detection method. Spliced variants of pgRNA were primarily observed in HBV gtB, C, E, or F-infected patients, with the Sp1 spliced variant detected most frequently. Twelve other pgRNA spliced variant transcripts were identified, including 3 previously unidentified transcripts, although spliced isoform identification was very dependent on the workflow used to analyze sequence data. Longitudinal sampling among pregnant and post-partum antiviral-treated individuals showed increasing proportions of 3' truncated pgRNA variants over time. This study demonstrated long-read sequencing as a promising tool for the characterization of the serum HBV transcriptome. However, further studies are needed to better understand how serum HBV RNA isoform type and proportion are linked to CHB disease progression and antiviral treatment response.

Hepatitis B virus genotypes influence clinical outcomes: A review.

Hepatitis B virus (HBV) is a hepatotropic virus that affects approximately 296 million people worldwide. A crucial step to HBV replication is the transcription of its infectious DNA from its viral RNA intermediate. The production of the RNA intermediate hinges on reverse transcription, and therefore the lack of proofreading in that process commonly yields mutants and has led to nine well-described genotypes (A-I) and over 30 known sub-genotypes of the virus. The influence of genotype on HBV infection outcomes, which include fibrosis progression, cirrhosis, and hepatocellular carcinoma (HCC), remain uncertain. This review aims to analyze the influence of HBV genotype on the risk of development of these outcomes. The response to current and future HBV therapies is considered. Further study of larger and more diverse samples will hopefully resolve outstanding uncertainties.

The Hepatitis B Virus Genotypes E to J: The Overlooked Genotypes.

Hepatitis B virus (HBV) genotypes E to J are understudied genotypes. Genotype E is found almost exclusively in West Africa. Genotypes F and H are found in America and are rare in other parts of the world. The distribution of genotype G is not completely known. Genotypes I and J are found in Asia and probably result from recombination events with other genotypes. The number of reported sequences for HBV genotypes E to J is small compared to other genotypes, which could impact phylogenetic and pairwise distance analyses. Genotype F is the most divergent of the HBV genotypes and is subdivided into six subgenotypes F1 to F6. Genotype E may be a recent genotype circulating almost exclusively in sub-Saharan Africa. Genotype J is a putative genotype originating from a single Japanese patient. The paucity of data from sub-Saharan Africa and Latin America is due to the under-representation of these regions in clinical and research cohorts. The purpose of this review is to highlight the need for further research on HBV genotypes E to J, which appear to be overlooked genotypes.

An Example of the Importance of Electronic Health Records from Mogadishu, Somalia: Hepatitis B Prevalence and Co-infections with Hepatitis C

The epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) has been discussed in detail from different aspects around the world. Current epidemiological data has critical importance in the planning and carrying out of public health policies for the prevention of transmission and spread of these infections, and the treatment of chronic infections, and to reduce the burden and mortality associated with complications such as cirrhosis and liver cancer by national health authorities and international health institutions, especially the World Health Organization. Elimination of a social health problem is possible by first raising awareness, then determining the dimensions of the problem, and planning and implementing interventions for a solution. Somalia was in the position of a region where access to diagnosis and treatment for many life-threatening diseases was difficult, aside from the monitoring of public health criteria due to the unstable situations that has continued for more than 40 years. Until recently, basic health parameters and epidemiological predictions in Somalia were monitored through estimates based on data from neighboring countries or on data obtained from small groups from Somalia immigrants settled different parts of the world. However, this situation is changing rapidly. A tertiary education and research hospital established in the capital, Mogadishu, with the coordination of the Türkiye and Somalia governments, and which has become the largest health center in the country today; contributes to understanding the extent of the serious health problems faced by the country by pioneering specialized training and scientific studies, in addition to providing health care. Electronic health records have been kept regularly since 2015 in this hospital, where hundreds of thousands of patients receive treatment or undergo health checks every year and it has been the source of numerous retrospective epidemiological studies some of which have exceeded 100 thousand cases, in different age groups and sub-populations. These studies include human immunodeficiency virus (HIV) prevalence and complications, HCV prevalence and genotype distribution, prevalence and epidemiology of parasitic infections, incidence of tuberculosis and related complications, cancer incidence and distribution, causes of blindness, thyroid diseases, antibiotic resistance profiles, and the epidemiology of various organ-specific diseases. Dozens of studies using the hospital records were included in the scientific literature between 2020 and 2023. In this study, a four-year period between November 2015 and November 2019, HBV serological test results of more than 100,000 different patients are presented. HBsAg and anti-HBs seropositivity for all age groups was found to be 8.1% (9,405/115,946) and 32.7% (25,988/79,410), respectively. When the anti-HCV test results of HBsAg positive patients were examined, the rate of HCV co-infections was found to be 0.9% (82/9,405). HBsAg and anti-HBs seropositivity were significantly higher in males than females (p&lt;0.001). HBV, HCV, and co-infection incidence tended to decrease. Conversely, vaccination rates (especially in children under one year of age) tended to increase. While the comprehensive data presented in this study provide us with important and new information about the prevalence and co-infection rates of viral hepatitis in the country, many topics including HBV genotypes, hepatitis D frequency, access to treatment rates, complication rates, and HBV vaccination rates are still waiting to be researched in Somalia. In the region where it is not possible to carry out field studies, epidemiological data provided by electronic health records have become a country's window to the world.

High frequency of Lamivudine and Telbivudine resistance mutations in hepatitis B virus isolates from human immunodeficiency virus co-infected patients on highly active antiretroviral therapy in Bucaramanga, Colombia.

Hepatitis B virus (HBV) antiviral Resistance-Associated Mutations (RAMs) in human immunodeficiency virus (HIV) coinfected patients undergoing highly active antiretroviral therapy (HAART) are complex and incompletely understood. We aimed to determine the prevalence of HBV coinfection, HBV genotypes, and RAMs in a cohort of people living with HIV (PLWH) in the northeastern region of Colombia. This cross-sectional study was carried out between February 2013 and February 2014. Virological, immunological and HAART data were collected from clinical records. In-house nested PCR and Sanger sequencing of the HBV pol gene were used to identify coinfections, genotypes, RAMs and HBV s antigen (HBsAg) escape mutants. Among 275 PLWH, HBV coinfection was confirmed in 32 patients (11.6%), of whom nine (28.2%) were HBsAg positive (active hepatitis B), and 23 (71.8%) were occult hepatitis B infections (OBI). All HBV sequences (n = 23) belonged to the genotype F3. Among HIV/HBV coinfections, 71.9% had CD4+ T cell counts above 200 cells/mm3 and 37.5% had undetectable HIV viral loads. The RAMs rtL80I, rtL180M, and rtM204V, which confer resistance to Lamivudine/Telbivudine and partially resistant to Entecavir, were found in all HBV isolates. An unknown rt236Y mutation to Tenofovir was also identified. Most patients under HAART received first-generation HBV antiviral therapy with a low genetic barrier to resistance. Antiviral Drug-associated Potential Vaccine-escape Mutations (ADAPVEMs) in the S gene were observed in all isolates ranging from 1-20 amino acid substitutions. However, no vaccine escape mutants were detected. In Conclusion, these findings highlight the importance of HBV molecular screening, antiviral resistance monitoring and new guidelines for PLWH to overcome RAMs and prevent HBV-related liver disease.

Host sex disparity and viral genotype dependence of the glycosylation level of small Hepatitis B surface protein in patients with HBeAg-positive chronic Hepatitis B

BackgroundHepatitis B surface antigen (HBsAg) consists of six components of large/middle/small HBs proteins (L/M/SHBs) with non-glycosylated (ng)- or glycosylated (g)- isomers at sN146 in their shared S domain. g-SHBs plays a crucial role in hepatitis B virus (HBV) secretion. However, the host and viral factors impacting sN146 status in natural HBV infection remain revealed mainly due to the technical difficulty in quantifying g-SHBs and ng-SHBs in serum samples.MethodsTo establish a standardized Western blot (WB) assay (WB-HBs) for quantifying the SHBs isomers in serum samples of 328 untreated hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with genotype B or C HBV infection. The 1.3-mer HBV genotype B or C plasmids were transiently transfected into HepG2 cells for in vitro study.ResultsThe median level of ng-SHBs was significantly higher than that of g-SHBs (N = 328) (2.6 vs. 2.0 log10, P < 0.0001). The median g-/ng-SHBs ratio in female patients (N = 75) was significantly higher than that of male patients (N = 253) (0.35 vs. 0.31, P < 0.01) and the median g-/ng-SHBs ratio in genotype C patients (N = 203) was significantly higher than that of the genotype B patients (N = 125) (0.33 vs. 0.29, P < 0.0001).ConclusionsOur findings suggest that the g-/ng-SHBs ratio is host-sex-biased and viral genotype dependent in treatment naïve patients with HBeAg-positive chronic hepatitis B, which indicates the glycosylation of SHBs could be regulated by both host and viral factors. The change of ratio may reflect the fitness of HBV in patients, which deserves further investigation in a variety of cohorts such as patients with interferon or nucleos(t)ide analogues treatment.

Potent broadly neutralizing antibody VIR-3434 controls hepatitis B and D virus infection and reduces HBsAg in humanized mice

Chronic hepatitis B is a global public health problem, and coinfection with hepatitis delta virus (HDV) worsens disease outcome. Here, we describe a hepatitis B virus (HBV) surface antigen (HBsAg)-targeting monoclonal antibody (mAb) with the potential to treat chronic hepatitis B and chronic hepatitis D. HBsAg-specific mAbs were isolated from memory B cells of HBV vaccinated individuals. Invitro neutralization was determined against HBV and HDV enveloped with HBsAg representing eight HBV genotypes. Human liver-chimeric mice were treated twice weekly with a candidate mAb starting 3 weeks post HBV inoculation (spreading phase) or during stable HBV or HBV/HDV coinfection (chronic phase). From a panel of human anti-HBs mAbs, VIR-3434 was selected and engineered for pre-clinical development. VIR-3434 targets a conserved, conformational epitope within the antigenic loop of HBsAg and neutralized HBV and HDV infection with higher potency than hepatitis B immunoglobulins invitro. Neutralization was pan-genotypic against strains representative of HBV genotypes A-H. In the spreading phase of HBV infection in human liver-chimeric mice, a parental mAb of VIR-3434 (HBC34) prevented HBV dissemination and the increase in intrahepatic HBV RNA and covalently closed circular DNA. In the chronic phase of HBV infection or co-infection with HDV, HBC34 treatment decreased circulating HBsAg by >1 log and HDV RNA by >2 logs. The potently neutralizing anti-HBs mAb VIR-3434 reduces circulating HBsAg and HBV/HDV viremia in human liver-chimeric mice. VIR-3434 is currently in clinical development for treatment of patients with chronic hepatitis B or D. Chronic infection with hepatitis B virus and co-infection with hepatitis D virus place approximately 290 million individuals worldwide at risk of severe liver disease and cancer. Available treatments result in low rates of functional cure or require lifelong therapy that does not eliminate the risk of liver disease. We isolated and characterized a potent human antibody that neutralizes hepatitis B and D viruses and reduces infection in a mouse model. This antibody could provide a new treatment for patients with chronic hepatitis B and D.

Comparative untargeted metabolomics analysis of serum metabolic alterations in patients infected with hepatitis B virus genotypes B and C

The clinicopathological characteristics and outcomes of patients infected with hepatitis B virus (HBV) differ between genotypes B and C. However, the potential metabolic mechanisms and differences in certain biological pathways associated with different HBV genotypes remain unclear to date. To obtain a better understanding of the effects of liver diseases caused by HBV genotypes B and C on host metabolism, an untargeted metabolomics analysis was performed to assess the differences among the serum metabolic profiles of healthy controls and patients infected with genotypes B or C. Here, a total of 54 serum samples were obtained from healthy controls and patients with chronic HBV infections caused by genotypes B and C, and the samples were subjected to metabolomics analysis. The serum metabolite profiles were analyzed using an ultrahigh-performance liquid chromatography-quadrupole-time-of-flight/mass spectrometry (UHPLC-Q-TOF/MS)-based untargeted metabolomics approach for identifying the differentially expressed metabolites that were upregulated or downregulated by at least 1.5-foldin the serum samples of patients infected with HBV genotypes B and C. A total of 63 metabolites were found to be differentially expressed between the serum samples of healthy controls and patients infected with HBV genotype B, while 57 metabolites were differentially expressed between the serum samples of healthy controls and patients infected with HBV genotype C. The majority of these metabolites were involved in regulating the bile acid (BA) metabolism pathways. The results also indicated that 8 differentially expressed metabolites can serve as potential metabolic biomarkers for distinguishing between individuals infected with the HBV genotype B and C. Altogether, the untargeted metabolomics analysis revealed that infection with HBV genotypes B and C is associated with different metabolic profiles, and the study provided fundamental information for further detailed investigations of the mechanism underlying metabolic dysregulation in HBV infections.

Hepatitis B virus associated cirrhosis: overview of prognostic and management

Hepatitis B virus (HBV) infection is a global public health problem ; two billion people worldwide have evidence of past or present infection with HBV, and 296 million individuals are chronic carriers (i.e., positive for hepatitis B surface antigen [HBsAg]), of whom approximately 887,000 dies annually from HBV-related liver disease: chronic hepatitis B-associated cirrhosis and hepatocellular carcinoma. There are described some risk factors to the development of cirrhosis to HBV-infected persons: alcohol consumption, HBeAg status, metabolic syndrome, HBV genotypes and variants, and the level of HBV replication. The observation of a strong association between the development and decompensation of cirrhosis as well as between the development of HCC and the level of HBV replication suggests that suppression of HBV replication by long-term antiviral treatment may decrease the risk of complications in patients with HBV-related cirrhosis. The indication for antiviral treatment is given if any HBV DNA levels are detectable in the serum of HBV-infected patients with cirrhosis. Into the new era of antiviral treatment with nucleos(t)ide analogs we can prevent the development of cirrhosis in patients with chronic HBV infection and hepatic decompensation in many patients with HBV-related cirrhosis.

Evaluation of three hepatitis b virus detection protocols in blood donors

Hepatitis B virus (HBV) DNA diagnosis plays a critical role in the transmission of HBV infections. Accurate protocols in HBV detection will reduce the spread of the virus from blood donors. Therefore, this research compared the HBV detecting potentials of three different HBV protocols in the virus detection. Blood from 200 donors at the University college blood bank Ibadan were sampled and tested for HBV using the ABON™ HBsAg Hepatitis B Surface Antigen Tests (strip test), Monolisa TM HBsAg ULTRA (ELISA test) and Huruian biology HBV detection kit (qPCR test). HBV positive samples were genotyped by sequencing to ascertain genotype identity. Results showed that of the 200 samples tested, both ABON™ HBsAg Hepatitis B Surface Antigen Tests and Monolisa TM HBsAg ULTRA (for ELISA) did not record any positive sample. However, Huruian biology HBV detection kit via qPCR recorded a total of twenty-three positive samples. Of the twenty-three samples, twenty were of genotype E while three were of genotype B. The results from this study showed that that qPCR is more accurate in HBV virus detection than ELISA technique and also HBV genotype E is the most common genotype isolated in Nigeria.

Strongylocentrotus nudus egg polysaccharide (SEP) suppresses HBV replication via activation of TLR4-induced immune pathway

Chronic hepatitis B virus (HBV) infection is a worldwide public health problem that causes significant liver-related morbidity and mortality. In our previous study, Strongylocentrotus nudus eggs polysaccharide (SEP), extracted from sea urchins, had immunomodulatory and antitumor effects. Whether SEP has anti-HBV activity is still obscure. This study demonstrated that SEP decreased the secretion of hepatitis B surface antigen (HBsAg) and e antigen (HBeAg), as well as the replication and transcription of HBV both in vitro and in vivo. Immunofluorescence and immunohistochemistry results showed that the level of HBV core antigen (HBcAg) was clearly reduced by SEP treatment. Mechanistically, RT-qPCR, western blot, and confocal microscopy analysis showed that SEP significantly increased the expression of toll-like receptor 4 (TLR4) and co-localization with TLR4. The downstream molecules of TLR4, including NF-κb and IRF3, were activated and the expression of IFN-β, TNF-α, IL-6, OAS, and MxA were also increased, which could suppress HBV replication. Moreover, SEP inhibited other genotypes of HBV and hepatitis C virus (HCV) replication in vitro. In summary, SEP could be investigated as a potential anti-HBV drug capable of modulating the innate immune.

Unexpected rise in the circulation of complex HBV variants enriched of HBsAg vaccine-escape mutations in HBV genotype-D: potential impact on HBsAg detection/quantification and vaccination strategies

ABSTRACT Specific HBsAg mutations are known to hamper HBsAg recognition by neutralizing antibodies thus challenging HBV-vaccination efficacy. Nevertheless, information on their impact and spreading over time is limited. Here, we characterize the circulation of vaccine-escape mutations from 2005 to 2019 and their correlation with virological parameters in a large cohort of patients infected with HBV genotype-D (N = 947), dominant in Europe. Overall, 17.7% of patients harbours ≥1 vaccine-escape mutation with the highest prevalence in subgenotype-D3. Notably, complex profiles (characterized by ≥2 vaccine-escape mutations) are revealed in 3.1% of patients with a prevalence rising from 0.4% in 2005–2009 to 3.0% in 2010–2014 and 5.1% in 2015–2019 (P = 0.007) (OR[95%CI]:11.04[1.42–85.58], P = 0.02, by multivariable-analysis). The presence of complex profiles correlates with lower HBsAg-levels (median[IQR]:40[0–2905]IU/mL for complex profiles vs 2078[115–6037]IU/ml and 1881[410–7622]IU/mL for single or no vaccine-escape mutation [P < 0.02]). Even more, the presence of complex profiles correlates with HBsAg-negativity despite HBV-DNA positivity (HBsAg-negativity in 34.8% with ≥2 vaccine-escape mutations vs 6.7% and 2.3% with a single or no vaccine-escape mutation, P < 0.007). These in-vivo findings are in keeping with our in-vitro results showing the ability of these mutations in hampering HBsAg secretion or HBsAg recognition by diagnostic antibodies. In conclusion, vaccine-escape mutations, single or in complex profiles, circulate in a not negligible fraction of HBV genotype-D infected patients with an increasing temporal trend, suggesting a progressive enrichment in the circulation of variants able to evade humoral responses. This should be considered for a proper clinical interpretation of HBsAg-results and for the development of novel vaccine formulations for prophylactic and therapeutic purposes.