Molecular epidemiology of hepatitis B among Indigenous Australians in Queensland and the Torres Strait Islands.

Background: Chronic hepatitis B virus (HBV) infection is a major health problem for all Indigenous Australians. Post-2000, Hepatitis B surface antigen prevalence has decreased, although remaining four times higher among Indigenous compared with non-Indigenous people.

Aims: This study aimed to characterise the HBV from Indigenous populations in Queensland and the Torres Strait Islands.

Hepatitis B virus haplotype number at baseline is a predictive marker of functional cure during antiviral therapy for patients with genotypes A and D HBeAg-positive chronic hepatitis B.

Backgrounds And Aims: We investigated associations between hepatitis B virus (HBV) genome-length haplotype number (HN) at baseline in subjects with HBeAg-positive chronic hepatitis B (CHB), and the likelihood of achieving functional cure during direct-acting antiviral therapy METHOD: We analysed 86 HBeAg-positive baseline samples from patients with HBV genotypes A and D who were enrolled in a Phase II trial of tenofovir disoproxil fumarate (TDF) to determine if HN was a biomarker of HBsAg loss during therapy. Findings were validated using baseline samples from 181 patients with HBV genotypes A and D from an independent clinical trial utilising TDF or tenofovir alafenamide therapy in HBeAg-positive CHB.

Results: In the HBeAg-positive test cohort, patients with genotypes A or D and ≤2 haplotypes had a minimum of 21-fold higher likelihood of achieving HBsAg loss on TDF.

Secreted hepatitis B virus splice variants differ by HBV genotype and across phases of chronic hepatitis B infection.

Chronic hepatitis B (CHB) is characterized by progression through different phases of hepatitis B virus (HBV) infection and disease. Although not necessary for HBV replication, there is increasing evidence that HBV splice variants are associated with liver disease progression and pathogenesis. However, there have been no studies till date on the frequency or diversity of splice variants for different HBV genotypes across the phases of CHB.

Hepatitis Delta Virus (HDV) and Delta-Like Agents: Insights Into Their Origin.

Hepatitis delta virus (HDV) is a human pathogen, and the only known species in the genus . HDV is a satellite virus and depends on the hepatitis B virus (HBV) for packaging, release, and transmission. Extracellular HDV virions contain the genomic HDV RNA, a single-stranded negative-sense and covalently closed circular RNA molecule, which is associated with the HDV-encoded delta antigen forming a ribonucleoprotein complex, and enveloped by the HBV surface antigens.

Origins and Evolution of the Primate Hepatitis B Virus.

Recent interest in the origins and subsequent evolution of the hepatitis B virus (HBV) has strengthened with the discovery of ancient HBV sequences in fossilized remains of humans dating back to the Neolithic period around 7,000 years ago. Metagenomic analysis identified a number of African non-human primate HBV sequences in the oldest samples collected, indicating that human HBV may have at some stage, evolved in Africa following zoonotic transmissions from higher primates. Ancestral genotype A and D isolates were also discovered from the Bronze Age, not in Africa but rather Eurasia, implying a more complex evolutionary and migratory history for HBV than previously recognized.

Autochthonous and Travel Acquired Hepatitis E Virus in Australia.

Background: Hepatitis E virus (HEV) is a common cause of acute viral hepatitis with significant morbidity and mortality, particularly in pregnant women. There are four major genotypes which can cause disease in humans. Genotypes 1 and 2 are usually associated with outbreaks and spread via facal/oral route or contaminated water.

Quantitative analysis of the splice variants expressed by the major hepatitis B virus genotypes.

Hepatitis B virus (HBV) is a major human pathogen that causes liver diseases. The main HBV RNAs are unspliced transcripts that encode the key viral proteins. Recent studies have shown that some of the HBV spliced transcript isoforms are predictive of liver cancer, yet the roles of these spliced transcripts remain elusive.

Analysis of Hepatitis B Virus Haplotype Diversity Detects Striking Sequence Conservation Across Genotypes and Chronic Disease Phase.

Background And Aims: We conducted haplotype analysis of complete hepatitis B virus (HBV) genomes following deep sequencing from 368 patients across multiple phases of chronic hepatitis B (CHB) infection from four major genotypes (A-D), analyzing 4,110 haplotypes to identify viral variants associated with treatment outcome and disease progression.

Approach And Results: Between 18.2% and 41.

Hepatitis B and D in the Pacific Islands of Kiribati.

Background: Historical reports indicate that hepatitis B and hepatitis D are highly endemic in the Pacific Island of Kiribati but current levels are unknown.

Objectives: To determine current prevalence of HBV and HDV in Kiribati, characterize the strains in both mono-infection and co-infection and assess individuals for antiviral therapy.

Study Design: Sera obtained from 219 patients were screened for HBsAg, HBeAg, HBV DNA, anti-HD, and HDV RNA.

The evolution and clinical impact of hepatitis B virus genome diversity.

The global burden of hepatitis B virus (HBV) is enormous, with 257 million persons chronically infected, resulting in more than 880,000 deaths per year worldwide. HBV exists as nine different genotypes, which differ in disease progression, natural history and response to therapy. HBV is an ancient virus, with the latest reports greatly expanding the host range of the Hepadnaviridae (to include fish and reptiles) and casting new light on the origins and evolution of this viral family.

HBV variants are common in the 'immune-tolerant' phase of chronic hepatitis B.

Nucleos(t)ide analogues (NUC) treatment prevents progression of liver fibrosis in subjects with chronic hepatitis B (CHB). However, risk of hepatocellular carcinoma (HCC) persists despite viral suppression. Specific HBV variants have been associated with adverse outcomes, including HCC; however, the frequency of these variants during the seemingly benign immunotolerant (IT) phase is unknown.

Predicting HBsAg clearance in genotype A chronic hepatitis B using HBsAg epitope profiling: A biomarker for functional cure.

Background And Aim: Functional cure is the major goal of chronic hepatitis B (CHB) therapy though few biomarkers predict this outcome. HBsAg epitope occupancy can be influenced by therapeutic and immune pressure. The aim of this study was to map the HBsAg epitope profiles during long-term nucleos(t)ide analogue therapy in patients with genotype A CHB, in the context of HBsAg loss (SL)/seroconversion.

Tracing Ancient Human Migrations into Sahul Using Hepatitis B Virus Genomes.

The entry point and timing of ancient human migration into continental Sahul (the combined landmass of Australia, New Guinea, and Tasmania) are subject to debate. Unique strains of hepatitis B virus (HBV) are endemic among modern-day Australian Aboriginals (HBV/C4) and Indigenous Melanesians (HBV/C3). We postulated that HBV genomes could be used to infer human population movements because the main HBV transmission route in endemic populations is via mother-to-child for genotypes B and C infections.

A Divergent Hepatitis D-Like Agent in Birds.

Hepatitis delta virus (HDV) is currently only found in humans and is a satellite virus that depends on hepatitis B virus (HBV) envelope proteins for assembly, release, and entry. Using meta-transcriptomics, we identified the genome of a novel HDV-like agent in ducks. Sequence analysis revealed secondary structures that were shared with HDV, including self-complementarity and ribozyme features.

Molecular characterization of hepatitis B virus (HBV) in African children living in Australia identifies genotypes and variants associated with poor clinical outcome.

Migration from sub-Saharan Africa is contributing to the rising incidence of chronic hepatitis B (CHB) infection and its complications in Australia. African CHB is associated with unique genotypes, such as E and A1, which are associated with reduced vaccine efficacy and early-onset hepatocellular carcinoma, respectively, although the prevalence of these genotypes outside Africa is poorly described. Treatment-naïve children of African origin with CHB were recruited at the Royal Children's Hospital Melbourne.

Stop codons in the hepatitis B surface proteins are enriched during antiviral therapy and are associated with host cell apoptosis.

Premature stop codons in the hepatitis B virus (HBV) surface protein can be associated with nucleos(t)ide analogue resistance due to overlap of the HBV surface and polymerase genes. The aim of this study was to determine the effect of the replication of three common surface stop codon variants on the hepatocyte. Cell lines were transfected with infectious HBV clones encoding surface stop codons rtM204I/sW196*, rtA181T/sW172*, rtV191I/sW182*, and a panel of substitutions in the surface proteins.

Genotypic profiles of hepatitis B in African immigrants and their clinical relevance.

Hepatitis B virus (HBV) from 40 adult African immigrants in Australia was characterized to determine the prevalence of different HBV genotypes and subgenotypes. A mutational analysis was then performed to determine the presence of clinically significant mutations and correlate them to clinical outcomes. Initial sequencing analysis revealed 13 with genotype A (32.

In Vitro Studies Show that Sequence Variability Contributes to Marked Variation in Hepatitis B Virus Replication, Protein Expression, and Function Observed across Genotypes.

Unlabelled: The hepatitis B virus (HBV) exists as 9 major genotypes (A to I), one minor strain (designated J) and multiple subtypes. Marked differences in HBV natural history, disease progression and treatment response are exhibited by many of these genotypes and subtypes. For example, HBV genotype C is associated with later hepatitis B e antigen (HBeAg) seroconversion and high rates of liver cancer compared to other HBV genotypes, whereas genotype A2 is rarely associated with HBeAg-negative disease or liver cancer.

Effects of long-term tenofovir-based combination antiretroviral therapy in HIV-hepatitis B virus coinfection on persistent hepatitis B virus viremia and the role of hepatitis B virus quasispecies diversity.

Objective: Hepatitis B virus (HBV) can persist in some HIV-HBV coinfected individuals on tenofovir disoproxil fumarate (TDF)-containing combination antiretroviral therapy (cART) but HBV resistance to TDF has not been reported and the source of persistent HBV DNA on TDF is poorly understood. The aims of this study were to assess long-term HBV suppression in HIV-HBV coinfected individuals receiving TDF and investigate quasispecies variation using ultradeep pyrosequencing (UDPS).

Methods: Ninety-two HIV-HBV coinfected participants on, or about to commence, TDF-containing cART were enrolled [Australia (n = 40), Thailand (n = 52)] and followed for 2 years with study visits every 6 months.

Origins and Evolution of Hepatitis B Virus and Hepatitis D Virus.

Members of the family Hepadnaviridae fall into two subgroups: mammalian and avian. The detection of endogenous avian hepadnavirus DNA integrated into the genomes of zebra finches has revealed a deep evolutionary origin of hepadnaviruses that was not previously recognized, dating back at least 40 million and possibly >80 million years ago. The nonprimate mammalian members of the Hepadnaviridae include the woodchuck hepatitis virus (WHV), the ground squirrel hepatitis virus, and arctic squirrel hepatitis virus, as well as a number of members of the recently described bat hepatitis virus.

Molecular epidemiology of hepatitis delta virus in the Western Pacific region.

Background: Hepatitis delta virus (HDV) is a defective RNA virus requiring the presence of the hepatitis B virus (HBV) for the completion of its life cycle. Active replication of HDV can lead to severe hepatitis, and although present worldwide has an irregular geographical distribution, especially in the Asian Pacific region.

Objectives: The aim of this study was to determine the prevalence and molecular epidemiology of HDV isolates in Oceania following the 1998 evaluation of the hepatitis B vaccine program.

Possible origins and evolution of the hepatitis B virus (HBV).

All members of the family Hepadnaviridae are primarily viruses which contain double-stranded DNA genomes that are replicated via reverse transcription of a pregenomic RNA template. There are two subgroups within this family: mammalian and avian. The avian member's include the duck hepatitis B virus (DHBV), heron hepatitis B virus, Ross goose hepatitis B virus, stork hepatitis B virus and the recently identified parrot hepatitis B virus.