Profiles of HBV DNA integration in humans with hepatitis B virus infection: Insights for antiviral treatment.

Background & Aims: HBV integration profiles in the natural history of chronic HBV infection (CHB) have not been well-defined. Hence, we aimed to determine HBV integration profiles across different CHB phases.

Methods: We delineated integration profiles from liver biopsies of 55 patients in different CHB phases (3 HBsAg-positive/HBeAg-positive infection; 13 HBsAg-positive/HBeAg-positive hepatitis; 7 HBsAg-positive/HBeAg-negative infection; 12 HBsAg-positive/HBeAg-negative hepatitis; 10 HBsAg seroclearance; 10 occult HBV).

Virological Insights from ARC-520 siRNA and Entecavir Treated Chronically HBV-Infected Patients and Chimpanzees.

In a previous study, eight chronically HBV-infected nucleos (t)ide analog (NA)-naïve patients began receiving entecavir (ETV) concomitant with a single ARC-520 HBV siRNA injection. This single dose of ARC-520 (SD) was followed by 6-8 months of ETV alone before the patients received 4-9 monthly doses of ARC-520, the multi-dose (MD) period, while continuing ETV. Quantities of HBV DNA, RNA, and antigens were measured from serum and a liver biopsy collected ~30 months after the last MD from five patients.

Combining serologic biomarkers with the PAGE B score improves risk stratification for hepatocellular carcinoma development among chronic hepatitis B patients.

Early-stage diagnosis of Hepatocellular Carcinoma (HCC) vastly improves outcomes for patients. However, most patients are diagnosed late-stage when their only option is palliative treatment. In this study we propose a risk stratification method that combines cutoffs for PAGE-B with cutoffs for a prototype serological immunoassay, LG2m, as well as 2 conformité européenne (CE)-certified serological immunoassays in AFP and PIVKA-II run on the high-throughput ARCHITECT (Abbott Laboratories, North Chicago, IL) instrument.

Large-scale profile study on hepatitis B surface antigen levels in chronic hepatitis B: implications for drug development targeting functional cure.

Background: Quantitative hepatitis B surface antigen (qHBsAg) is an important biomarker in chronic hepatitis B (CHB).

Objective: Establish qHBsAg profiles to guide novel drug development.

Design: Baseline qHBsAg profiles, longitudinal qHBsAg trajectories and predictors of HBsAg seroclearance were determined in a large CHB cohort.

Serum Tsukushi level is negatively associated with cholesterol efflux capacity in metabolic dysfunction-associated steatotic liver disease: a cross-sectional study.

Background Tsukushi (TSK), a recently identified hepatokine, has been shown to affect systemic cholesterol homeostasis and reduce HDL cholesterol (HDL-C) in murine studies. We have investigated whether TSK is associated with HDL-C and HDL function in subjects with and without MASLD. Methods Vibration-controlled transient elastography was performed in 896 subjects (63.

Rapid whole-blood immune profiling reveals heterogeneous HBV-specific T cell response patterns independent of clinical disease phases.

Background & Aims: There is an unmet need for immunological biomarkers in chronic HBV infection (CHB), where patient management relies on virological and biochemical markers despite the crucial role of virus-specific T cells in controlling viral replication and disease progression. Here, we developed the HBV-cytokine release assay (HBV-CRA), a rapid, point-of-care test, to define whether HBV-specific T cell functional patterns are linked with conventional disease phase classifications.

Methods: Peptides covering pan-genotype HBV proteomes were utilized to trigger cytokine release by HBV-specific T cells in whole blood.

Emerging therapies for HBsAg seroclearance: spotlight on novel combination strategies.

Introduction: Functional cure is a favorable endpoint in chronic hepatitis B (CHB), yet it is rarely achieved with currently approved drugs (nucleos[t]ide analogues and pegylated interferon alpha). A range of novel agents, broadly classified into virus-targeting agents and immunomodulators, are hence developed with functional cure as the treatment target. As the data on individual novel agents are maturing, the field has gradually shifted to novel combination strategies.

Small Extracellular Vesicle-Derived Nicotinamide Phosphoribosyltransferase (NAMPT) Induces Acyl-Coenzyme A Synthetase SLC27A4-Mediated Glycolysis to Promote Hepatocellular Carcinoma.

Tumour-derived small extracellular vesicles (sEV) are critical mediators within the tumour microenvironment (TME) and are known to regulate various metabolic pathways. In metastatic hepatocellular carcinoma (HCC), mass spectrometry protein analysis of HCC-derived sEV (HCC-sEV) identified an upregulation of nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in maintaining cellular nicotinamide adenine dinucleotide (NAD+) levels. Our study demonstrates that sEV-NAMPT enhances glycolysis, tumorigenesis, and metastasis in HCC.

Development and Validation of a High-Sensitivity Droplet Digital PCR Assay for Serum Hepatitis B Virus DNA Detection.

Real-time polymerase chain reaction (PCR) is the current standard for serum HBV DNA measurement. However, conventional real-time PCR assays have technical limitations, and are not sensitive enough to detect low-level residual viremia in chronic hepatitis B (CHB) patients. We developed and validated a droplet digital PCR (ddPCR) assay for high-sensitivity detection of serum HBV DNA.

Post-acute sequelae of hospitalised COVID-19 re-infection compared with hospitalised first-time infection: a population-based retrospective cohort study in Hong Kong.

Introduction: COVID-19 infection is associated with post-acute adverse outcomes affecting multiple organ systems. Although preliminary studies have suggested that COVID-19 re-infection may have a cumulative effect on long-term outcome, differential effects of COVID-19 re-infection severe enough to be hospitalised on post-acute sequelae compared with hospitalised first-time infection have not been explored.

Methods: Retrospective cohort study using territory-wide electronic medical records databases in Hong Kong.

Mechanism of entecavir-induced reduction of HBV DNA integration.

Nucleos(t)ide analogues (NUC) treatment can reduce the extent of HBV DNA integration in chronic hepatitis B (CHB) patients. However, the mechanism by which NUC reduces HBV integration is unclear. This study investigated the effects of entecavir (ETV), one of the commonly used NUC, on cells with HBV integration.

Expanding treatment indications in chronic hepatitis B: Should we treat all patients?

Nucleos(t)ide analogues (NUCs) are first-line agents for chronic hepatitis B (CHB). Current guidelines provide recommendations for NUC initiation, yet the guidelines are complex and restrictive. Accumulating data on hepatitis B virus (HBV) replication and HBV integration suggests that there are no real quiescent disease phases in CHB, and treatment-ineligible patients in current guidelines still have substantial risks of cirrhosis and hepatocellular carcinoma.

Impact of liver graft steatosis on long-term post-transplant hepatic steatosis and fibrosis via magnetic resonance quantification.

Background: The rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has led to an increased occurrence of steatotic liver grafts (SLG) in liver transplantation (LT). However, the implications of SLG on post-transplant hepatic steatosis (PTHS) and advanced fibrosis (≥F3) remain uncertain. This study aimed to characterize PTHS and ≥ F3 using magnetic resonance imaging (MRI) in patients who underwent LT for non-MASLD indications and to examine their relationship with SLG.

Characterization of Hepatitis B Virus Transcripts in Chronically HBV-Infected Chimpanzees and Patients Treated with ARC-520 siRNA Demonstrates Transcriptional Silencing of cccDNA.

Full-length hepatitis B virus (HBV) transcripts of chimpanzees and patients treated with multidose (MD) HBV siRNA ARC-520 and entecavir (ETV) were characterized by single-molecule real-time (SMRT) sequencing, identifying multiple types of transcripts with the potential to encode HBx, HBsAg, HBeAg, core, and polymerase, as well as transcripts likely to be derived from dimers of dslDNA, and these differed between HBeAg-positive (HBeAg+) and HBeAg-negative (HBeAg-) individuals. HBV transcripts from the last follow-up ~30 months post-ARC-520 treatment were categorized from one HBeAg+ (one of two previously highly viremic patients that became HBeAg- upon treatment and had greatly reduced cccDNA products) and four HBeAg- patients. The previously HBeAg+ patient received a biopsy that revealed that he had 3.

Longitudinal profile of plasma pregenomic RNA in patients with chronic hepatitis B infection on long-term nucleoside analogues and its interaction with clinical parameters.

Backgrounds/aims: Plasma pregenomic hepatitis B virus RNA (pgRNA) is a novel biomarker in chronic hepatitis B infection (CHB). We aimed to describe the longitudinal profile of pgRNA and factors influencing its levels in CHB patients on nucleoside analogue (NUC).

Methods: Serial plasma samples from 1,354 CHB patients started on first-line NUC were evaluated.

Investigational RNA Interference Agents for Hepatitis B.

Functional cure of chronic hepatitis B (CHB)-defined as sustained seroclearance of hepatitis B surface antigen (HBsAg) with unquantifiable hepatitis B virus (HBV) DNA at 24 weeks off treatment, is an optimal treatment endpoint. Nonetheless, it cannot be consistently attained by current treatment modalities. RNA interference (RNAi) is a novel treatment strategy using small-interfering RNA (siRNA) or antisense oligonucleotide (ASO) to target HBV post-transcriptional RNA, in turn suppressing viral protein production and replication.