Hepatitis B Virus (HBV) constitutes a chronic viral infection with limited therapeutic options and a significant global health challenge. The virus lifecycle intricacy significantly relies on the core protein crucial for virus structure stability and interaction with host cells thus contributing to the infection's persistence and severity. This study employs advanced techniques for the identification of novel core protein inhibitors through the screening of two chemical databases ZINC and BIMP utilizing computational methods such as structure-based virtual screening, drug-likeness, ADME, toxicity, consensus molecular docking, density functional theory, and 100 ns molecular dynamics simulation. The compound ZINC00674395 possesses high affinity and specificity towards core protein demonstrating drug-like properties, favorable ADME profiles, non-toxicity, and favorable electronic configuration with high stability at the core protein active site thus highlighting its potential as a therapeutic agent. These findings offer new insights into core protein interaction and pave the way for developing effective HBV therapeutics.

Occult hepatitis B virus infection (OBI) is characterized by the presence of HBV DNA in the absence of detectable HBsAg. OBI is an important risk factor for cirrhosis and hepatocellular carcinoma, but its pathogenesis has not been fully elucidated. Mutations in the HBV preS/S genes can lead to impaired secretion of either HBsAg or S-protein resulting in the accumulation of defective viruses or S protein in cells. In our previous work, the M133S mutation was present in the HBV S gene of maintenance hemodialysis (MHD) patients with OBI. In this study, we investigated the potential role of amino acid substitutions in S proteins in S protein production and secretion through the construction of mutant S gene plasmids, structural prediction, transcriptome sequencing analysis, and in vitro functional studies. Protein structure prediction showed that the S protein M133S mutant exhibited hydrophilic modifications, with greater aggregation and accumulation of the entire structure within the membrane phospholipid bilayer. Differential gene enrichment analysis of transcriptome sequencing data showed that differentially expressed genes were mainly concentrated in protein processing in the endoplasmic reticulum (ER). The expression of heat shock family proteins and ER chaperone molecules was significantly increased in the wild-type and mutant groups, whereas the expression of mitochondria-associated proteins was decreased. Immunofluorescence staining and protein blotting showed that the endoplasmic reticulum-associated protein PDI, the autophagy marker LC3, and the lysosome-associated protein LAMP2 co-localized with the S proteins in the wild-type and mutant strains, and their expression was increased. The mitochondria-associated TOMM20 protein was also co-expressed with the S protein, but expression was significantly reduced in the mutant. The M133S mutation in the S gene is expressed as a defective and misfolded protein that accumulates in the endoplasmic reticulum causing secretion-impaired endoplasmic reticulum stress, which in turn triggers mitochondrial autophagy and recruits lysosomes to fuse with the autophagosome, leading to mitochondrial clearance. This study preliminarily demonstrated that the mutation of M133S in the S gene can cause OBI and is associated with disease progression, providing a theoretical basis for the diagnosis and treatment of OBI.

Hepatitis B virus (HBV) infection presents with indicators of varying clinical significance. We aimed to evaluate the correlation among HBV Pre-S1 antigen (HBV PreS1-Ag), HBV e antigen (HBeAg), HBV DNA, and alanine aminotransferase (ALT) levels.

We retrospectively analyzed 6180 serum samples collected between 2020 and 2022 at the Shanghai General Hospital, China. Data regarding PreS1-Ag, HBeAg, ALT, and HBV DNA were compiled. Correlation analyses and cross-tabulations were employed to explore the diagnostic indicators.

The detection rates of both antigen indicators showed a proportional increase with HBV DNA loads. The correlation between PreS1-Ag and HBV DNA (r = 0.616) was stronger than that between HBeAg and HBV DNA (r = 0.391). The specificity of PreS1-Ag (84.30 %) was lower than that of HBeAg (97.44 %), whereas the sensitivity of HBeAg (91.13 %) significantly surpassed that of PreS1-Ag (29.56 %). Among the HBV DNA positive patients, 92.04 % tested positive for at least one indicator, which exceeded the rate of PreS1+HBeAg- and PreS1-HBeAg+ (52. 28 % and 68. 56 %, respectively). Only 1.75 % of the patients exhibited double negativity, which was lower than the percentage of patients with single negativity (1.95 % and 12.00 % for PreS1-Ag and HBeAg, respectively). The PreS1 levels correlated with ALT levels (r = 0.317); patients with PreS1-positive status had higher ALT levels than patients with PreS1-negative status.

PreS1-Ag is a more robust HBV replication indicator than HBeAg. PreS1-Ag displayed high sensitivity, whereas HBeAg demonstrated high specificity. Moreover, PreS1-Ag levels correlated with ALT levels. A combination of these indicators demonstrated dependable clinical value for detecting HBV infection and evaluating liver function.

NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) is an intracellular complex that upon external stimuli or contact with specific ligands, recruits other components, forming the NLRP3 inflammasome. The NLRP3 inflammasome mainly mediates pyroptosis, a highly inflammatory mode of regulated cell death, as well as IL-18 and IL-1β production. Acute and chronic liver diseases are characterized by a massive influx of pro-inflammatory stimuli enriched in reactive oxygen species (ROS) and damage-associated molecular patterns (DAMPs) that promote the assemblage and activation of the NLRP3 inflammasome. As the major cause of inflammatory cytokine storm, the NLRP3 inflammasome exacerbates liver diseases, even though it might exert protective effects in regards to hepatitis C and B virus infection (HCV and HBV). Here, we summarize the current knowledge concerning NLRP3 inflammasome function in both acute and chronic liver disease and in the post liver transplant setting, focusing on the molecular mechanisms involved in NLRP3 activity.

Hepatitis B virus (HBV) is a frequent cause of chronic hepatitis worldwide, with an estimated 5.6 million children under 5 years being infected. In Romania, there are no available epidemiology reports on large cohorts in children. We aimed to assess the profile of pediatric chronic HBV infection in southern Romania. We conducted an observational retrospective study on 506 HBV-infected children. Based on alaninaminotransferase (ALT), HBV serology and viremia, we identified four states of the disease. We correlated age, gender, household HBV infection, coinfection with other viruses and laboratory parameters. Most patients were in a positive HBV envelope antigen (HBeAg) immune-active state (65.4%). Age at diagnosis was significantly lower for those with household infection (p < 0.05). ALT values were not significantly different between positive or negative HBeAg patients in the immune-active state (p = 0.780). ALT values were higher in patients with hepatitis D virus (HDV)-associated infection (p < 0.001). Children with a household HBV infection had a high viraemia more frequently when compared to those with no infected relative (79.3% vs. 67.4%) (p < 0.001), but the ALT values were not significantly different (p = 0.21). Most of the patients are in an immune-active state (high ALT, high viremia). The percentages of HBV- and HDV-associated infections are high, but lower than the reported prevalence in Romania in the general population.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is potentially pathogenic and causes severe symptoms; in addition to respiratory syndromes, patients might experience other severe conditions such as digestive complications and liver complications injury. The abnormality in the liver is manifested by hepatobiliary dysfunction and enzymatic elevation, which is associated with morbidity and mortality. The direct cytopathic effect, immune dysfunction, cytokine storm, and adverse effects of therapeutic regimens have a crucial role in the severity of liver injury. According to aging and immune system alterations, cytokine patterns may also change in the elderly. Moreover, hyperproduction of cytokines in the inflammatory response to SARS-CoV-2 can lead to multi-organ dysfunction. The mortality rate in elderly patients, particularly those with other comorbidities, is also higher than in adults. Although the pathogenic effect of SARS-CoV-2 on the liver has been widely studied, the impact of age and immune-mediated responses at different ages remain unclear. This review discusses the association between immune system responses in coronavirus disease 2019 (COVID-19) patients of different ages and liver injury, focusing on cytokine alterations.

According to the World Health Organization (WHO), an estimated 296 million people are chronically infected with hepatitis B virus (HBV). Approximately 15-25% of these people develop complications such as advanced chronic liver diseases (ACLDs). Mortality due to HBV-related complications accounted for an estimated 882,000 deaths in 2019. Potent preventive vaccines have already restricted new HBV infections, and several drugs are available to treat chronic HBV infections. However, the positive impacts of these drugs have been recorded in only a few patients with chronic HBV infection. These drugs do not show long-term efficacy and cannot halt the progression to complications. Thus, more effective and evidence-based therapeutic strategies need to be urgently developed for patients with chronic HBV infection. CHB is a pathological entity induced by HBV that progresses due to impaired host immunity. This indicates the inherent limitations of antiviral-drug-based monotherapy for treating patients with chronic HBV infection. Additionally, commercially available antiviral drugs are not available to patients in developing and resource-constrained countries, posing a challenge to achieving the following WHO goal: "Elimination of Hepatitis by 2030". As such, this review aimed to provide insights regarding evidence-based and effective management strategies for chronic HBV infection.

The hepatitis B virus (HBV) is one of the major viral infection problems worldwide in public health. The exclusive proprietary Chinese medicine Ganweikang (GWK) tablet has been marketed for years in the treatment of chronic hepatitis B (CHB). However, the pharmacodynamic material basis and underlying mechanism of GWK are not completely clear. This study is aimed at investigating the pharmacological mechanism of the GWK tablet in the treatment of CHB. The chemical ingredient information was obtained from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP), Traditional Chinese Medicines Integrated Database (TCMID), and Shanghai Institute of Organic Chemistry of CAS. Ingredients and disease-related targets were defined by a combination of differentially expressed genes from CHB transcriptome data and open-source databases. Target-pathway-target (TPT) network analysis, molecular docking, and chemical composition analysis were adopted to further verify the key targets and corresponding active ingredients of GWK. Eight herbs of GWK were correlated to 330 compounds with positive oral bioavailability, and 199 correlated targets were identified. The TPT network was constructed based on the 146 enriched targets by KEGG pathway analysis, significantly associated with 95 pathways. Twenty-five nonvolatile components and 25 volatile components in GWK were identified in UPLC-QTOF/MS and GC-MS chromatograms. The key active ingredients of GWK include ferulic acid, oleanolic acid, ursolic acid, tormentic acid, 11-deoxyglycyrrhetic acid, dibenzoyl methane, anisaldehyde, wogonin, protocatechuic acid, psoralen, caffeate, dimethylcaffeic acid, vanillin, β-amyrenyl acetate, formonentin, aristololactam IIIa, and 7-methoxy-2-methyl isoflavone, associated with targets CA2, NFKB1, RELA, AKT1, JUN, CA1, CA6, IKBKG, FOS, EP300, CREB1, STAT1, MMP9, CDK2, ABCB1, and ABCG2.

Chronic hepatitis B (CHB) has a wide range of outcomes depending on host immune responses mainly Toll-like receptors (TLRs) signaling and released cytokines. Toll-like receptor 2 (TLR2) single nucleotide polymorphisms (SNPs) and interleukin 6 (IL-6) may influence the course of CHB. We aimed to elucidate the relation between TLR-2 polymorphism, IL-6 profile, and CHB progression. We analyzed TLR-2 polymorphism (SNP; rs3804099) in 185 CHB patients and 60 controls using TaqMan allelic discrimination assay. Serum IL-6 levels were assessed by ELISA. IL-6 levels were considerably higher in active CHB and cirrhotic patients compared with inactive carriers and controls (P < 0.001). IL-6 showed positive correlation with ALT and advanced fibrosis in active CHB patients (r = 0.31, P = 0.02). A significant positive correlation was noticed between IL-6 and HBV DNA PCR in all CHB groups. TT genotype of rs3804099/TLR-2 was significantly more prevalent in inactive carriers compared to active hepatitis patients (P = 0.04, OR = 0.39 and 95% CI: 0.16-0.95). Both heterozygous CT and mutant TT genotypes were significantly more frequent among inactive carriers compared to cirrhotic patients (P = 0.01, OR = 0.33, 95% CI: 0.13-0.81 and P = 0.009, OR = 0.32, 95% CI: 0.13-0.77). TT genotype was significantly related to lower IL-6 levels in active hepatitis and cirrhotic groups (P = 0.005 and P = 0.001, respectively) showing that TLR mutations would be associated with milder hepatitis activity and lower possibility for disease progression. There may be a positive association between TLR2 rs3804099 polymorphism and hepatitis B activity. IL-6 is a good indicator of CHB disease progression.

A total of 381 hepatitis B virus (HBV) DNA sequences collected from nine groups of Siberian native populations were phylogenetically analyzed along with 179 HBV strains sampled in different urban populations of former western USSR republics and 50 strains from Central Asian republics and Mongolia. Different HBV subgenotypes predominated in various native Siberian populations. Subgenotype D1 was dominant in Altaian Kazakhs (100%), Tuvans (100%), and Teleuts (100%) of southern Siberia as well as in Dolgans and Nganasans (69%), who inhabit the polar Taimyr Peninsula. D2 was the most prevalent subgenotype in the combined group of Nenets, Komi, and Khants of the northern Yamalo-Nenets Autonomous Region (71%) and in Yakuts (36%) from northeastern Siberia. D3 was the main subgenotype in South Altaians (76%) and Buryats (40%) of southeastern Siberia, and in Chukchi (51%) of the Russian Far East. Subgenotype C2 was found in Taimyr (19%) and Chukchi (27%), while subgenotype A2 was common in Yakuts (33%). In contrast, D2 was dominant (56%) in urban populations of the former western USSR, and D1 (62%) in Central Asian republics and Mongolia. Statistical analysis demonstrated that the studied groups are epidemiologically isolated from each other and might have contracted HBV from different sources during the settlement of Siberia.

In this special issue, we present collected updated data on the hepatitis viruses [...].