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BACKGROUND: People living with HIV (PLHIV) may have concurrent Hepatitis B Virus (HBV) infection, and certain antiretroviral therapies are recommended for HBV-HIV co-infected individuals. Routine screening for Hepatitis B virus may influence management of antiretroviral therapy for PLHIV, but risk factors for co-infection have not been well defined. The objective of this study was to identify risk factors for HBV infection among PLHIV in South Africa. METHODS: We conducted a cross-sectional analysis of a prospective, clinic-based cohort study of adults seeking HIV testing from 2013-2017 in Umlazi township, South Africa. Patients newly diagnosed with HIV were enrolled and subsequently tested for Hepatitis B surface antigen positive (HBsAg +). We used a Poisson linear regression model to assess which factors, pertaining to sociodemographic status, medical history, clinical symptoms, mental health were associated with HBV. RESULTS: Among 3,105 PLHIV participants in South Africa, 6% were positive for HBV. Males had a higher HBV prevalence (10.4%) than females (5.2%). Within the HBV-positive group, the mean age was 33.2 years, with 38.3% females and 43.9% having completed high school or higher. About 39.9% reported alcohol use, 24.7% had a smoking history, and 8.3% reported substance use in the past year. Older participants born before 1995, when routine infant HBV vaccination was introduced, were more likely to have HBV. In multivariable analyses, smoking history increased HBV risk in females (aPR = 2.58; 95% CI 1.47-2.52), while alcohol use decreased HBV risk in males (aPR = 0.36; 95% CI 0.19-0.70). CONCLUSIONS: In a South African cohort, roughly one in 16 PLHIV had HBV co-infection, and this rate was higher in males. The most prominent risk factors for HBV infection in PLHIV were alcohol use, higher income, and smoking history, which may help inform targeted treatment and prevention strategies. Creating HBV-specific screening and prevention strategies for PLHIV may be useful for reducing HBV infections.

OBJECTIVES: Hepatitis B virus (HBV) infection remains a global health problem. Risk factors for HBV infection are usually assessed in prevalent rather than incident infections. To identify demographic and behavioral risks associated with incident HBV among South African blood donors. METHODS: A case-control study was performed between November 2014 and January 2018. Cases were blood donors testing positive for HBV DNA with or without hepatitis B surface antigen but negative for antibody to hepatitis B core antigen. Participants completed an audio computer-assisted structured interview on exposures during the previous 6 months. Sex-specific multivariable logistic regression yielded independent associations between risks and HBV infection. RESULTS: 56 females and 37 males with incident HBV were compared to 438 female and 439 male controls, respectively. For females, risk factors were accepting money or goods for sex, using agents to prepare ones anus prior to anal sex, penetrating injury, non-Black race, and lower educational status. Men reporting homosexual or bisexual orientation or sex with other men, previous injury, referral for HBV testing, or lack of medical insurance were at increased risk. For both sexes, having more than two male sexual partners increased risk. CONCLUSIONS: Sexual behaviors predominated over parenteral exposures as risks for incident HBV in both female and male blood donors.

BackgroundDue to shared modes of transmission, coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is common, and HBV vaccination is recommended for all persons with HCV who remain susceptible to HBV. To identify potential gaps in HBV vaccination among this high-risk population, we aimed to determine the patterns of HBV susceptibility in persons undergoing community-based HCV treatment.MethodsWe performed a cross-sectional study within two community-based HCV treatment programs in an urban US setting. Participants were identified for HCV screening and confirmatory testing via street-outreach recruitment directed at persons experiencing homelessness and currently using drugs. Participants were excluded if HBsAg was reactive. Cohort characteristics were obtained via intake surveys and descriptive analysis was performed by exposure status.ResultsAmong 150 participants without chronic HBV receiving community-based HCV treatment, 43% had evidence of prior HBV infection, 26% were immune from vaccination, and 31% were non-immune. Among the subset of the cohort reporting current injection drug use (IDU) (N = 100), 31% (n = 10) of those aged 24-40 and 47% (n = 23) of those aged 41-57 remained susceptible to HBV infection. By contrast only two participants aged 58-74 were HBV non-immune (11%), with 84% immune due to prior exposure.ConclusionsOur data reflect a high prevalence of HBV susceptibility among persons undergoing community-based HCV treatment. Although younger patients were more likely to be immune due to vaccination, a high proportion remained non-immune to HBV, particularly among those reporting current IDU. Our data reflect a gap in HBV vaccination among younger persons with HCV and suggest a potential role for co-localizing HBV vaccination with community-based HCV screening and treatment.

Background: Chronic hepatitis B virus (HBV) infection is still a major public health problem. In response to the World Health Organization (WHO), Tanzania implemented immunization and treatment to achieve the eradication of HBV infection by 2030. To achieve this goal, frequent updates of demographic data, antiviral therapy eligibility, and uptake are essential. We therefore evaluated demographic data, antiviral therapy eligibility, and uptake among chronically HBV-infected patients attending at Bugando Medical Centre (BMC), Tanzania. Methods: A cross-sectional study enrolled 196 chronic HBV patients from April 23, 2023, to October 10, 2023, at BMC, where 100 and 96 patients were retrospectively and prospectively enrolled, respectively. Study's ethical clearance and permission were observed by the Catholic University of Health and Allied Sciences/Bugando Medical Centre research ethics and review committee and the Bugando Medical Centre management respectively. For all patients, socio-demographic data and whole blood samples were obtained. Full blood picture, alanine and aspartate amino transferases, and HBV viral load parameters were determined. Aspartate-Platelet Ratio Index (APRI) and Fibrosis Four (FIB-4) scores were calculated according to their respective formulas. Therapy eligibility and uptake were evaluated according to the 2015 WHO HBV prevention, treatment, and care guidelines. The data were summarized and analysed using STATA version 15. Results: The median age for all patients was 39 [IQR: 32–47.5] years. Nearly all study patients, 99% (194/196), were older than 20 years old, with significant male dominance (73.5% [144/196] versus 26.5% [52/196]; p<0.0001). Anti-HBV antiviral therapy eligibility was 22.4%, while uptake was 6.8% (3/4), which was significantly lower than the WHO expectation of 80% (p <0.0001). Conclusion: Almost all chronically HBV-infected patients attending at BMC were older than 20 years old and were significantly dominated by males. Antiviral therapy uptake was remarkably lower than expected by the WHO towards combating HBV infection by 2030. [ABSTRACT FROM AUTHOR]

In recent years, hepatitis B virus (HBV) core protein allosteric modulators (CpAMs) have become a hot spot to develop new anti‐HBV drugs. Sulfonamide analogues are a new class of CpAMs targeting HBV core protein (Cp), while their biological activity is still needed to be improved and the binding mechanism is unclear still. In this study, we utilized molecular docking and molecular dynamics simulation to explore the binding mode between the novel compounds and HBV Cp. Combining with binding free energy calculation and decomposition, we inferred that TyrE132, ValE124, ThrE128, ThrD109, and IleD105 were key residues during the binding process, and especially, the conformational change of TryE132 was responsible for the stable binding. Besides, reasonable CoMFA (q2 = 0.515, r2ncv = 0.994, and r2pred = 0.628) and CoMSIA (q2 = 0.602, r2ncv = 0.988, and r2pred = 0.681) models were constructed to explore the 3D structure‐activity relationship of the novel compounds. The results suggested that it was favorable to increase the biological activity of sulfonamide analogues when introducing hydrophobic groups to R1 and electronegative groups to R2. In conclusion, we explored the binding mode and structure‐activity relationship between sulfonamides and HBV Cp and provided a theoretical basis for the optimization of this series of compounds. [ABSTRACT FROM AUTHOR]

Background and Aims: Molecular processes driving immune‐active chronic hepatitis B (CHB) with and without hepatitis B e antigen (HBeAg) remain incompletely understood. This study aimed to investigate expression profiles of serum and intrahepatic HBV markers and replicative activity of HBV in CHB patients with or without HBeAg. Methods: This study recruited 111 untreated immune‐active CHB (60 HBeAg‐positive and 51 HBeAg‐negative) patients and quantified intrahepatic covalently closed circular DNA (cccDNA), pre‐genomic RNA (pgRNA), total HBV DNA (tDNA), and replicative intermediates as well as serum HBV markers (HBV DNA, hepatitis B surface antigen, hepatitis B core‐related antigen). Correlations between HBV markers and clinico‐virological factors influencing expression levels of HBV markers were analysed. Results: Levels of all serum markers and intrahepatic cccDNA/tDNA as well as cccDNA transcriptional activity and virion productivity were significantly reduced in HBeAg‐negative patients compared to those in HBeAg‐positive patients. Additionally, correlations between intrahepatic cccDNA/pgRNA and serum markers were impaired in HBeAg‐negative individuals. Aminotransferase levels were positively correlated with cccDNA transcriptional activity in HBeAg‐positive patients, but not in HBeAg‐negative patients. Notably, among HBeAg‐positive patients, there was a progressive decline in pgRNA level, transcriptional activity, and serum HBV markers as liver fibrosis advanced, which was not observed in HBeAg‐negative patients. Conclusions: HBeAg loss is correlated with diminished intrahepatic HBV reservoirs and cccDNA transcription, leading to decreased serum HBV marker levels. Circulating HBV markers are not reliable indicators of intrahepatic HBV replicative activity for HBeAg‐negative patients. Our findings reveal distinct disease phenotypes between immune‐active CHB with and without HBeAg, highlighting the need to establish optimal surrogate biomarkers that can accurately mirror intrahepatic viral activity to aid in decision‐making for antiviral therapy for immune‐active CHB. [ABSTRACT FROM AUTHOR]

Background and Aims: We aimed to explore the risk factors associated with virological and clinical relapse, as well as their impact on overall mortality, in hepatitis B virus (HBV)‐infected patients receiving nucleos(t)ide analogues (NUCs) therapy prior to chemotherapy initiation. Methods: From 2010 to 2020, we conducted a prospective cohort study involving patients with HBV infection undergoing cytotoxic chemotherapy. We utilized the Kaplan–Meier method and Cox proportional hazard regression models to assess risk factors. Results: We observed that TDF or TAF (HR: 2.16, 95% CI 1.06–4.41; p =.034), anthracycline (HR: 1.73, 95% CI 1.10–2.73; p =.018), baseline HBV DNA (HR: 1.55, 95% CI 1.33–1.81; p <.001) and end‐of‐treatment HBsAg titre >100 IU/mL (HR: 7.81, 95% CI 1.94–31.51; p =.004) were associated with increased risk of virological relapse. Additionally, TDF or TAF (HR: 4.91, 95% CI 1.45–16.64; p =.011), baseline HBV DNA (HR: 1.48, 95% CI 1.10–1.99; p =.009) and end‐of‐treatment HBsAg titre >100 IU/mL (HR: 6.09, 95% CI.95–38.87; p =.056) were associated with increased risk of clinical relapse. Furthermore, we found that virological relapse (HR: 3.32, 95% CI 1.33–8.32; p =.010) and clinical relapse (HR: 3.59, 95% CI 1.47–8.80; p =.005) significantly correlated with all‐cause mortality in HBV patients receiving cytotoxic chemotherapy with prophylactic NUCs therapy. Conclusions: The risk of virological and clinical relapse was linked to baseline HBV DNA, end‐of‐treatment HBsAg levels and TDF or TAF for prophylaxis; additionally, experiencing relapse heightens the risk of all‐cause mortality. Further research is warranted to explore potential strategies for preventing virological and clinical relapse in high‐risk patients. [ABSTRACT FROM AUTHOR]

Background: Numerous observational studies have indicated that patients with Guillain-Barré syndrome (GBS) frequently had infections with various pathogens before the onset of the disease, particularly several viral infections. Some of these infections are linked to specific clinical and immunological subgroups of GBS, suggesting a potential correlation between viral infections and the development of GBS. However, observational studies have several limitations, including the presence of confounding factors. Method: We explored the potential correlation between HIV, SARS-CoV-2, varicella-zoster virus, herpes simplex virus, Epstein-Barr virus, hepatitis B virus, and influenza virus with GBS using a two-sample Mendelian randomization approach. The data was derived from published summary statistics from genome-wide association studies (GWAS). After removing linkage disequilibrium, selecting strong instrumental variables and addressing confounding factors, we would conduct a two-sample Mendelian randomization analysis along with sensitivity testing and the MR-Steiger directional test. Result: HIV may have a causal association with GBS (IVW: p = 0.010, OR [95% CI] 1.240 [1.052–1.463]), while no such relationship exists with COVID-19 (IVW: p = 0.275, OR [95% CI] 0.831[0.596–1.159]), varicella (IVW: p = 0.543, OR [95% CI] 0.919 [0.701–1.206]), herpes zoster (IVW: p = 0.563, OR [95% CI] 0.941 [0.766–1.156]), HSV (IVW: p = 0.280, OR [95% CI] 1.244 [0.837–1.851]), EBV (IVW: p = 0.218, OR [95% CI] 0.883 [0.724–1.076]), HBV (IVW: p = 0.179, OR [95% CI] 1.072 [0.969–1.187]), or influenza virus (IVW: p = 0.917, OR [95% CI] 0.971 [0.553–1.703]). We did not find any abnormal SNPs, pleiotropy, or heterogeneity, nor is there any reverse causation. Conclusion: Our study results indicate a causal relationship between HIV and GBS, providing new research directions for the etiology of GBS. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HBV-HCC) has poor prognosis and high mortality rate. Euphorbia helioscopia L. (EHL) is a classic Chinese medicinal herb. Aim: This study aimed to evaluate in vitro anti-HBV-HCC properties of EHL, and explore it targets in HBV-HCC based on molecular docking. Methods: The anti-tumor effect of EHL on HBV-HCC was evaluated using the cell viability, migration, invasion, and apoptosis of Hep 3B2.1–7 and HepG2.2.15 cells. Next, network pharmacological analysis was performed to predicted the key targets of EHL against HBV-HCC. Then the prognostic targets, including RAC-alpha serine/threonine-protein kinase (AKT1) and Caspase-3 (CASP3), were verified using molecular docking and rescue experiments. Results: EHL exhibited inhibitory effects on cell proliferation/migration/invasion and induced cell apoptosis. Network pharmacological analysis proposed 12 active compounds in EHL, which targeted 22 HBV-HCC-related genes. AKT1 and CASP3 were identified to be key targets for EHL against HBV-HCC. AKT1 and CASP3 had prognostic significance in liver cancer. Overexpression of AKT1 and caspase-3 inhibitor can counteract the EHL effect. Conclusion: EHL can exert anticancer effects on HBV-HCC by inhibiting migration/invasion, and inducing apoptosis, which may be achieved through AKT1 and CASP3. [ABSTRACT FROM AUTHOR]

Aim: Measurement of O‐glycosylated middle hepatitis B surface antigen (HBsAg glycan isomer, HBsAgGi) has been developed to quantify hepatitis B virus (HBV) infectious virions and distinguish them from subviral particles. This study aimed to evaluate the association between serum HBsAg seroclearance and serum HBV virions measured by HBsAgGi in patients with chronic hepatitis B (CHB). Methods: Serum HBsAgGi levels were quantified in 232 treatment‐naïve patients with CHB genotype C. Cox proportional hazards analysis was used to calculate hazard ratios (HRs) for factors associated with HBsAg seroclearance. Results: Baseline HBsAgGi levels showed significant differences among HBV phenotypes. During a median follow‐up period of 7.4 years, 22 of the 232 patients achieved HBsAg seroclearance. Multivariate analysis demonstrated that quantitative HBsAg, nucleoside/nucleotide analog therapy during the follow‐up period, and HBsAgGi levels were independent predictors of seroclearance. The adjusted HR indicated that the HBsAg seroclearance probability in patients with low HBsAgGi (≤3.5log ng/mL) was over five times higher than that in patients with high HBsAgGi. Kaplan–Meier analysis indicated that the 10‐year probabilities of HBsAg seroclearance were 21.0% and 3.0% in patients with low and high HBsAgGi levels, respectively (p < 0.001), and that patients with high HBsAgGi levels showed low seroclearance probabilities irrespective of the other predictors. Conclusion: Serum HBV infectious virion levels, measured using HBsAgGi, may be a novel predictor of HBsAg seroclearance. [ABSTRACT FROM AUTHOR]

Aim: Patients with chronic hepatitis B virus (HBV) infection experiencing viral breakthrough (BTH) or partial response (PR) during lamivudine (LAM) or entecavir hydrate (ETV) administration often took ETV plus tenofovir alafenamide fumarate (TAF) due to the emergence of a drug‐resistance mutation. However, in patients lacking drug‐resistance mutation against TAF, sufficient antiviral effects may be achievable with TAF monotherapy. We assessed the drug‐resistance profile through nucleotide sequences of HBV pregenome RNA, and subsequently changed to TAF monotherapy from ETV plus TAF. Methods: This prospective study included 25 patients with serum HBV‐DNA below 20 IU/mL under ETV plus TAF administration. Pregenome RNA nucleotide sequences of HBV in the sera were analyzed using direct sequencing and deep sequencing. ETV was discontinued in patients without rtA194T and rtS106C + rtH126Y + rtD134E + rtL269I quadruple mutations in direct sequencing. Results: LAM‐PR, LAM‐BTH, ETV‐PR, and ETV‐BTH were observed in 1, 16, 7, and 1 patient(s), respectively. Pregenome RNA nucleotide sequences were analyzable in 20 patients. Among the 12 patients classified as LAM‐BTH, six patients showed rtL180M + rtM204V/I in direct sequencing, and one patient showed minor clones containing rtL180M + rtM204V + A194T in deep sequencing at a frequency of 0.3%. In the six patients classified as ETV‐PR, one patient harbored rtM204I. No clones showing rtS106C + rtH126Y + rtD134E + rtL269I quadruple mutation were detected in deep sequencing. Subsequently, ETV was discontinued, and serum HBV‐DNA remained undetectable up to 48 weeks in all patients. Conclusion: Patients receiving ETV plus TAF due to partial response or BTH during initial LAM or ETV administration were able to safely transition to TAF monotherapy based on nucleotide sequences of HBV pregenome RNA in the sera. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) represents an estrogen-dependent tumor. The action of estrogen is regulated via estrogen receptor (ER). Polymorphisms in ERα gene, ESR1, are known to be related to HCC susceptibility among people carrying chronic hepatitis B (CHB). But the effect of ERβ on HCC is still largely unclear, and studies about the genetic variability of ESR2 and HCC are rare. For understanding ESR2's effect on HCC, this work tested two polymorphisms in the ESR2 gene promoter as well as the associations with CHB, HCC, and hepatitis B virus (HBV)-related liver cirrhosis (LC) among the Guangxi population. This work enrolled a total of 137 CHB, 136 LC, and 149 HBV-related HCC patients, together with 146 normal subjects. ESR2 polymorphisms rs3020449 and rs2978381 were examined using the SNaPshot genotyping technique. The AG genotype and dominant model of rs3020449 were related to the decreased CHB susceptibility. In both the overall and subgroup analyses, no associations were observed with the remaining models in all patient groups (those with CHB, HBV-related LC, and HCC), but associations were found between the dominant (TC+CC vs TT) and allele models (C vs T) of rs2978381 and increased HBV-related LC and HCC susceptibility, but not CHB. These findings suggest that rs3020449 polymorphism of ESR2 gene makes great contribution to the decreased CHB risk and that rs2978381 significantly contributed to higher risks of HBV-related LC and HCC. [ABSTRACT FROM AUTHOR]

Beclin 1 protein encoded by the BECN1 gene plays a critical role in the autophagy pathway which is utilized by the Hepatitis B virus (HBV) for its replication. HBV is known for the subversion of the host's autophagy process for its multiplication. The aim of this study was to determine the role of BECN1 intronic variants in HBV susceptibility. Intronic region variant rs9890617 was analyzed using Human splicing finder v3.1 and was found to alter splicing signals. A total of 712 individuals (494 HBV infected and 218 healthy controls) were recruited in the study and genotyped by applying Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR–RFLP). Statistical analysis revealed that the mutant allele T of rs9890617 was significantly associated with the overall disease risk in the allelic model (OR 1.41; 95%CI 1.00–1.99, p = 0.04). On stratifying the data based on the different stages of HBV infection, the mutant genotype showed a significant association with the chronic group in allelic (OR 1.62; 95%CI 1.11–2.39, p = 0.01), dominant (OR 1.64; 95%CI 1.07–2.52, p = 0.02), and co-dominant (OR 1.55; 95%CI 1.00–2.40, p = 0.04) models. Overall, this is the first study regarding beclin 1 variant rs9890617 and we found a significant association of the mutant T allele with the genetic predisposition to HBV infection. [ABSTRACT FROM AUTHOR]

The persistent presence of covalently closed circular DNA (cccDNA) in hepatocyte nuclei poses a significant obstacle to achieving a comprehensive cure for hepatitis B virus (HBV). Current applications of CRISPR/Cas9 for targeting and eliminating cccDNA have been confined to in vitro studies due to challenges in stable cccDNA expression in animal models and the limited non-immunogenicity of delivery systems. This study addresses these limitations by introducing a novel non-viral gene delivery system utilizing Gemini Surfactant (GS). The developed system creates stable and targeted CRISPR/Cas9 nanodrugs with a negatively charged surface through modification with red blood cell membranes (RBCM) or hepatocyte membranes (HCM), resulting in GS-pDNA@Cas9-CMs complexes. These GS-pDNA complexes demonstrated complete formation at a 4:1 w / w ratio. The in vitro transfection efficiency of GS-pDNA-HCM reached 54.61%, showing homotypic targeting and excellent safety. Additionally, the study identified the most effective single-guide RNA (sgRNA) from six sequences delivered by GS-pDNA@Cas9-HCM. Using GS-pDNA@Cas9-HCM, a significant reduction of 96.47% in in vitro HBV cccDNA and a 52.34% reduction in in vivo HBV cccDNA were observed, along with a notable decrease in other HBV-related markers. The investigation of GS complex uptake by AML-12 cells under varied time and temperature conditions revealed clathrin-mediated endocytosis (CME) for GS-pDNA and caveolin-mediated endocytosis (CVME) for GS-pDNA-HCM and GS-pDNA-RBCM. In summary, this research presents biomimetic gene-editing nanovectors based on GS (GS-pDNA@Cas9-CMs) and explores their precise and targeted clearance of cccDNA using CRISPR/Cas9, demonstrating good biocompatibility both in vitro and in vivo. This innovative approach provides a promising therapeutic strategy for advancing the cure of HBV. [Display omitted] [ABSTRACT FROM AUTHOR]

Bulevirtide (BLV), a first-in-class entry inhibitor, is approved in Europe for the treatment of chronic hepatitis delta (CHD). BLV monotherapy was superior to delayed treatment at week (W) 48, the primary efficacy endpoint, in the MYR301 study (NCT03852719). Here, we assessed if continued BLV therapy until W96 would improve virologic and biochemical response rates, particularly among patients who did not achieve virologic response at W24. In this ongoing, open-label, randomized phase III study, patients with CHD (N = 150) were randomized (1:1:1) to treatment with BLV 2 mg/day (n = 49) or 10 mg/day (n = 50), each for 144 weeks, or to delayed treatment for 48 weeks followed by BLV 10 mg/day for 96 weeks (n = 51). Combined response was defined as undetectable hepatitis delta virus (HDV) RNA or a decrease in HDV RNA by ≥2 log 10 IU/ml from baseline and alanine aminotransferase (ALT) normalization. Other endpoints included virologic response, ALT normalization, and change in HDV RNA. Of 150 patients, 143 (95%) completed 96 weeks of the study. Efficacy responses were maintained and/or improved between W48 and W96, with similar combined, virologic, and biochemical response rates between BLV 2 and 10 mg. Of the patients with a suboptimal early virologic response at W24, 43% of non-responders and 82% of partial responders achieved virologic response at W96. Biochemical improvement often occurred independently of virologic response. Adverse events were mostly mild, with no serious adverse events related to BLV. Virologic and biochemical responses were maintained and/or increased with longer term BLV therapy, including in those with suboptimal early virologic response. BLV monotherapy for CHD was safe and well tolerated through W96. In July 2023, bulevirtide was fully approved for the treatment of chronic hepatitis delta (CHD) in Europe based on clinical study results from up to 48 weeks of treatment. Understanding the efficacy and safety of bulevirtide over the longer term is important for healthcare providers. In this analysis, we demonstrate that bulevirtide monotherapy for 96 weeks in patients with CHD was associated with continued improvements in combined, virologic, and biochemical responses as well as liver stiffness from week 48 at both the 2 mg and 10 mg doses. Patients with suboptimal virologic responses to bulevirtide at week 24 also benefited from continued therapy, with the majority achieving virologic response or biochemical improvement by week 96. NCT03852719 [Display omitted] • BLV for 96 weeks maintained and/or improved responses compared to 48 weeks of treatment. • Efficacy was similar between the 2 mg and 10 mg doses of BLV. • In patients with a suboptimal early virologic response, improvements were observed with continued BLV. • Even in the absence of a virologic response, biochemical improvement can occur. • BLV was well tolerated with no discontinuations for adverse events through 96 weeks. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated fatty liver disease (MAFLD) and viral hepatitis due to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are common liver diseases worldwide. Excessive alcohol consumption and alcoholic liver disease (ALD) are also emerging health problems. Therefore, in clinical practice, we may encounter subjects with dual etiology of liver diseases such as coexisting MAFLD/HBV, MAFLD/HCV, and MAFLD/ALD. In this review, we summarize the epidemiology, clinical features, and mutual interactions of MAFLD with coexisting HBV, HCV, or ALD. The impact of MAFLD on the progression of liver diseases and treatment outcomes in patients with chronic viral hepatitis and the clinical questions to be addressed regarding dual MAFLD and ALD are also discussed. [ABSTRACT FROM AUTHOR]

ATG10S is a newly discovered subtype of the autophagy protein ATG10. It promotes complete macroautophagy/autophagy, degrades multiple viral proteins, and increases the expression of type III interferons. Here, we aimed to investigate the mechanism of ATG10S cooperation with IFNL1 to degrade viral proteins from different viruses. Using western blot, immunoprecipitation (IP), tandem sensor RFP-GFP-LC3B and in situ proximity ligation assays, we showed that exogenous recombinant ATG10S protein (rHsATG10S) could enter into cells through clathrin, and ATG10S combined with ATG7 with IFNL1 assistance to facilitate ATG12–ATG5 conjugation, thereby contributing to the autophagosome formation in multiple cell lines containing different virions or viral proteins. The results of DNA IP and luciferase assays also showed that ATG10S was able to directly bind to a core motif (CAAGGG) within a binding site of transcription factor ZNF460 on the IFNL1 promoter, by which IFNL1 transcription was activated. These results clarified that ATG10S promoted autophagosome formation with the assistance of IFNL1 to ensure autophagy flux and autophagic degradation of multiple viral proteins and that ATG10S could also act as a novel transcription factor to promote IFNL1 gene expression. Importantly, this study further explored the antiviral mechanism of ATG10S interaction with type III interferon and provided a theoretical basis for the development of ATG10S into a new broad-spectrum antiviral protein drug. Abbreviation: ATG: autophagy related; ATG10S: the shorter isoform of autophagy-related 10; CC50: half cytotoxicity concentration; CCV: clathrin-coated transport vesicle; CLTC: clathrin heavy chain; CM: core motif; co-IP: co-immunoprecipitation; CPZ: chlorpromazine; ER: endoplasmic reticulum; HCV: hepatitis C virus; HBV: hepatitis B virus; HsCoV-OC43: Human coronavirus OC43; IFN: interferon; PLA: proximity ligation assay; rHsATG10S: recombinant human ATG10S protein; RLU: relative light unit; SQSTM1: sequestosome 1; ZNF: zinc finger protein [ABSTRACT FROM AUTHOR]

Chronic hepatitis B (CHB) is consistently challenging to conquer with numerous complications and fatalities. Despite the effectiveness of antiviral therapies in suppressing hepatitis B virus (HBV) replication, there is an urgent need for novel and more effective treatment modalities. Current strategies predominantly emphasize immune activation but still face challenges in sufficiently eliciting T cell responses. Taking into account the targeted delivery of nanoparticles to the liver and spleen via intravenous injection, we have proposed a dual-pronged therapeutic strategy based on antigen-presenting cells (APCs)-derived exosomes. Specifically, exosomes targeted to the spleen can activate specific immune responses, while those targeted to the liver can modulate or reverse the liver's immunosuppressive microenvironment. After immunization, exosome formulations exhibit the remarkable ability to effectively activate APCs, thereby triggering the proliferation of CD8+T cells. Simultaneously, they also play an immunoregulatory role by converting M2 macrophages into M1 macrophages. This two-pronged therapeutic strategy precisely addresses the issues of T cell dysfunction and immune suppression, both characteristic features of CHB patients. When combined with Aluminum (Alum)-adjuvanted vaccine, these exosome formulations not only demonstrate a high level of cellular immune response but also secrete specific antibodies comparable to those induced by Alum adjuvant. This combined approach effectively enhances both cellular and humoral immunity, offering a promising avenue for the development of therapeutic hepatitis B vaccines based on exosome formulations. [ABSTRACT FROM AUTHOR]

Purpose: Peginterferon alfa-2b (Peg-IFN α-2b) has demonstrated superior efficacy over nucleos(t)ide analogs (NAs) in the treatment of chronic hepatitis B (CHB), particularly among patients with low levels of hepatitis B surface antigen (HBsAg). This study aims to determine whether patients with ultra-low HBsAg levels (< 200 IU/mL) can achieve significantly higher clinical cure rates with abbreviated courses of Peg-IFN α-2b therapy. Methods: In this retrospective analysis, CHB patients with HBsAg levels below 200 IU/mL were categorized into a Peg-IFN α-2b group and a control group. The Peg-IFN α-2b group received Peg-IFN α-2b for a minimum of 24 weeks, with the possibility of early discontinuation upon achieving HBsAg clearance, and were followed through week 48. The control group remained untreated for hepatitis B virus (HBV), and was observed for 24 weeks. HBsAg clearance rates were compared between groups. Univariate and multivariate logistic regression analyses were employed to identify factors associated with HBsAg clearance. Results: By week 24, the HBsAg clearance rate in the Peg-IFN α-2b group was notably 52.1% (38/73), contrasting sharply with the mere 1.3% (1/77) observed in the control group. Within the Peg-IFN α-2b group, a substantial 97.3% (71/73) of patients noted a reduction in HBsAg levels. Besides, the decision to continue or discontinue treatment after the 24-week mark had no significant impact on the HBsAg clearance rate at week 48. Multivariable analysis pinpointed baseline HBsAg levels (OR = 0.984, p = 0.001) and the presence of fatty liver (OR = 5.960, p = 0.033) as independent predictors of HBsAg clearance. Conclusion: Our findings confirm that a 24-week course of Peg-IFN α-2b yields robust efficacy in CHB patients with ultra-low HBsAg levels. Prolonging treatment beyond the 24-week threshold is deemed unnecessary. Both baseline HBsAg level and the presence of fatty liver emerged as significant predictors for HBsAg clearance. [ABSTRACT FROM AUTHOR]

Background: Malaria and hepatitis B are significant public health infections in Nigeria. Coinfection with both pathogens is common where both diseases are endemic. Epidemiological surveys are essential for determining the burden of diseases and possible coinfection with multiple pathogens in vulnerable populations. There has been a lack of reports on HBV/malaria coinfection, particularly among marginalized groups in Ondo State. Thus, we used malaria microscopy and the HBsAg serological test to examine the prevalence of asymptomatic malaria parasitemia and HBV infections respectively among inmates at the Nigerian Correctional Center in Owo, Ondo State, Nigeria. Results: Out of the 126 prisoners and staff members who were evaluated, 20.6% and 7.9% tested positive for malaria and HBV infections, respectively. It was discovered that 1.6% of the individuals were coinfected with malaria and HBV. Plasmodium falciparum was the only malaria species recovered in malaria-infected individuals. Except for HBV, where gender was found to differ considerably with the proportion of HBV infection, variations in single infections with either pathogen did not vary with demographic characteristics. Conclusion: We suggest that the prison system should be considered in healthcare programs to improve the health of inmates. [ABSTRACT FROM AUTHOR]

Background: The relationship between chronic hepatitis B (CHB) infection and natural killer (NK) cell dysfunction is well-established, but the specific role of HBV viral antigens in driving NK cell impairment in patients with CHB remains unclear. This study investigates the modulatory effects of hepatitis B virus subviral particles (HBVsvp, a representative model for HBsAg) on the phenotypic regulation (activating and inhibitory receptors), cytokine production and cytotoxic potential of peripheral blood mononuclear cell-derived natural killer cells (PBMCs-derived NK cell), which contributes to NK cell dysfunction in CHB infection, potentially serving as an effective HBV immune evasion strategy by the virus. Methods: NK cells were isolated from peripheral blood of patients with CHB (n=5) and healthy individuals (n=5), stimulated with HBVsvp. Subsequent flow cytometric characterization involved assessing changes in activating (NKp46 and NKG2D) and inhibitory (CD94) receptors expression, quantifying TNF-α and IFN-δ cytokine secretion, and evaluating the cytotoxic response against HepG2.2.15 cells with subsequent HBVsvp quantification. Results: In CHB patients, in vitro exposure of PBMCs-derived NK cell with HBVsvp (represent HBsAg model) significantly reduced NK cell-activating receptors expression (P = 0.022), increased expression of CD94 + NK cells (p = 0.029), accompanied with a reduced TNF-α-IFN-γ cytokine levels, and impaired cytotoxic capacity (evidenced by increased cell proliferation and elevated HBVsvp levels in co-cultures with HepG2.2.15 cells in a time-dependent), relative to healthy donors. Conclusion: These findings suggest that HBVsvp may induce dysfunctional NK cell responses characterized by phenotypic imbalance with subsequent reduction in cytokine and cytotoxic levels, indicating HBVsvp immunosuppressive effect that compromises antiviral defense in CHB patients. These data enhance our understanding of NK cell interactions with HBsAg and highlight the potential for targeting CD94 inhibitory receptors to restore NK cell function as an immunotherapeutic approach. Further clinical research is needed to validate these observations and establish their utility as reliable biomarkers. [ABSTRACT FROM AUTHOR]

Introduction: Hepatocellular carcinoma (HCC) is a pressing global issue, with Hepatitis B virus (HBV) infection remaining the primary. Emodin, an anthraquinone compound extracted from the natural plant's. This study investigates the molecular targets and possible mechanisms of emodin in treating HBV-related HCC based on network pharmacology and molecular docking and validates the screened molecular targets through in vitro experiments. Methods: Potential targets related to emodin were obtained through PubChem, CTD, PharmMapper, SuperPred, and TargetNet databases. Potential disease targets for HBV and HCC were identified using the DisGeNET, GeneCards, OMIM, and TTD databases. A Venn diagram was used to determine overlapping genes between the drug and the diseases. Enrichment analysis of these genes was performed using GO and KEGG via bioinformatics websites. The overlapping genes were imported into STRING to construct a protein-protein interaction network. Cytoscape 3.9.1 software was used for visualizing and analyzing the core targets. Molecular docking analysis of the drug and core targets was performed using Schrodinger. The regulatory effects of emodin on these core targets were validate through in vitro experiments. Results: A total of 43 overlapping genes were identified. GO analysis recognized 926 entries, and KEGG analysis identified 135 entries. The main pathways involved in the KEGG analysis included cancer, human cytomegalovirus infection and prostate cancer. The binding energies of emodin with HSP90AA1, PTGS2, GSTP1, SOD2, MAPK3, and PCNA were all less than -5 kcal/mol. Compared to normal liver tissue, themRNA levels of XRCC1,MAPK3, and PCNAwere significantly elevated in liver cancer tissue. The expression levels of XRCC1, HIF1A, MAPK3, and PCNA genes were closely related to HCC progression. High expressions of HSP90AA1, TGFB1, HIF1A, MAPK3, and PCNA were all closely associated with poor prognosis in HCC. In vitro experiments demonstrated that emodin significantly downregulated the expression of HSP90AA1, MAPK3, XRCC1, PCNA, and SOD2, while significantly upregulating the expression of PTGS2 and GSTP1. Conclusion: This study, based on network pharmacology and molecular docking validation, suggests that emodin may exert therapeutic effects on HBV-related HCC by downregulating the expression of XRCC1, MAPK3, PCNA, HSP90AA1, and SOD2, and upregulating the expression of PTGS2 and GSTP1. [ABSTRACT FROM AUTHOR]

ABSTRACT The WHO recommends hepatitis B birth‐dose vaccination (HepB‐BD), but it is not routinely given in most sub‐Saharan African countries. We aimed to assess the immunogenicity of HepB‐BD in addition to the existing hepatitis B vaccine (HepB3) schedule in Kinshasa, Democratic Republic of Congo among HBV‐unexposed and HBV‐exposed infants. Using an open‐label, randomised, controlled design, HBV‐unexposed infants were randomised (1:1) to receive the standard HepB3 vaccine series (group U3), or to receive HepB‐BD in addition to HepB3 (group U4). A supplemental cohort of HBV‐exposed infants (group E4) received HepB‐BD and HepB3. We compared the proportion of infants with protective antibodies against HBV (HBV surface antibody ≥ 10 mIU/mL) between groups U3 and U4 and groups U4 and E4 at 12 months of age. Between August 20 and October 9, 2019, we enrolled 281 mother/infant dyads; 88 (31.3%) returned at 12 months. Most infants had protective antibodies against HBV at 12 months: 92.9% (75.7%–98.2%) in group U3, 85.7% (67.5%–94.5%) in group U4 and 96.9% (95% CI: 81.2%–99.6%) in group E4. Trends held in estimates adjusted for loss‐to‐follow‐up (LTFU) and baseline imbalance across groups. In this first randomised trial assessing the addition of HepB‐BD to the hepatitis B vaccine schedule in SSA, we found that HBV‐unexposed infants who received the 3‐dose and 4‐dose vaccine series had similar immunogenicity against HBV at 12 months. A high proportion of infants, and notably HBV‐exposed infants, had protective antibodies. Though extrapolation of findings may be limited by LTFU, this study adds real‐world evidence regarding HepB‐BD implementation in sub‐Saharan Africa.Trial Registration: ClinicalTrials.gov identifier: NCT03897946 [ABSTRACT FROM AUTHOR]

Hepatitis B virus and hepatitis C virus remains one of the leading causes of morbidity and mortality worldwide, particularly in countries with limited resources. The two hepatotropic viruses have common mode of transmission. Hepatitis B virus and hepatitis C virus are the main causes of Cirrhosis, liver cancer and death. To determine the Seroprevalence of HBsAg and anti-HCV antibodies among clinically suspected cases of viral hepatitis visiting Guhalla Primary Hospital, Northwest Ethiopia. A hospital-based retrospective study was conducted at Guhalla Primary Hospital, Northwest Ethiopia. The study included serology registration logbook data from all patients who visited the hospital and were tested using a rapid test kit between September 1st, 2017 to August 30, 2021. Data were entered, cleaned, and analyzed using SPSS version 26 software. Bivariate analysis was computed and a multivariable analysis was conducted to provide an adjusted odds ratio (AOR). p-value < 0.05 at a 95% confidence interval was considered statistically significant. In this study, a total of 883(883 for HBV and 366 for HCV) study participants were included. The overall prevalence of HBsAg and anti-HCV were 124/883(14%) and 73/366 (19.9%), respectively. The prevalence of HBV and HCV among males from the total HBV and HCV screened was 70/410 (17.1%) and 53/366(14.4%) respectively. In this study, being female (AOR 1.53, 95% CI 1.03–2.27, p = 0.003) and age group of 31–40 years (AOR 2.85; 95% CI 1.56, 5.17, p = 0.001) were statistically significant factors to HBV infection. Similarly, being female (AOR 1.97, 95% CI 1.10–3.53, p = 0.02), age group of 21–30 years (AOR 2.71; 95% CI 1.15, 6.40, p = 0.02) and age group greater than 40 years (AOR 3.13; 95% CI 1.31, 7.44, p = 0.01) were significantly associated with HCV infection. In our study, high seroprevalence of HBV and HCV infection was detected among clinically suspected patients. Females and the age groups between 31 and 40 were more affected. Community awareness of the prevention and transmission of viral hepatitis infection should be strengthened through herd immunization and health education. The prospective study should be conducted in this area. [ABSTRACT FROM AUTHOR]

Background: Studies have found dysbiosis of the gut microbiota in individuals infected with the hepatitis B virus (HBV). Tenofovir dipivoxil (TDF) is one of the preferred oral antiviral drugs used for the treatment of chronic hepatitis B (CHB), but the extent to which TDF is able to affect the gut microbiota and inflammatory factors of a patient remains largely unexplored. In this study, we collected stool samples from HBV patients prior to medication and from CHB patients treated with TDF. Results: The gut microbiota and inflammatory factors were assessed in 42 healthy subjects (HC group), 109 HBV-infected subjects, including 48 CHB patients who were not medicated with nucleoside analogue drugs (No-NAs group), and 61 CHB patients who were medicated with TDF (TDF group). 16 S rRNA sequencing revealed that TDF treatment caused significant changes in the gut microbiota of HBV-infected individuals; however, the gut microbiota of HBV-infected individuals did not fully recover to a pre-dysbiosis state. The relative abundance of Bacteroidota gradually decreased from the HC group to the No-NAs and TDF groups. The relative abundance of Fusobacteriota was significantly higher in the No-NAs group than in the HC group. At the genus level, Dialister, Eubacterium_hallii_group, Halomonas, Collinsella, Sphingomonas, Xanthomonadaceae_unclassified, and Rhizobiaceae_unclassified were overrepresented; while the abundance of Bacteroides and Fusobacterium decreased significantly in the No-NAs and TDF groups. Conclusions: This study showed that TDF treatment significantly improved the regulation of the gut microbiota and aided in dysbiosis recovery. We did not observe significant improvement in serum inflammatory factor concentrations, which may be related to the relatively short duration of TDF administration in this study. [ABSTRACT FROM AUTHOR]

The structure of a novel computational hyperbolic tangent sigmoid deep neural network (HTS-DNN) is presented for the numerical solutions of the hepatitis B virus model, which is based on the antibody immune response. The mathematical model is categorized as healthy and hepatocytes, capsids, antibodies and free viruses. A novel process based on the HTS-DNN is exploited by using two hidden layers with 20 and 30 numbers of neurons. The optimization is performed through Bayesian regularization, which is one of the reliable procedures used in the optimization of various problems. A dataset is obtained through the Runge–Kutta solver, which is used to reduce the mean square error by dividing the training, testing and verification data as 70%, 16% and 14%. Moreover, the statistical representations in the sense of error histogram, regression, and state transitions also approve the accuracy of the scheme. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionChronic hepatitis B virus (HBV) infection is a major disease that seriously affects the health of patients. In this paper, the relationship among MTHFR gene polymorphism, MTRR gene polymorphism and 1762/1764 mutation in the BCP region of HBV gene with disease progression in chronic HBV patients was studied.A total of 144 chronic HBV infection patients from January 2021 to June 2022 in the Third People’s Hospital of Zigong City, were included as the study subjects. These patients were divided into hepatitis B primary liver cancer patients group (PLC) in 51 cases, Non-primary liver cancer patients group (Non-PLC) in 93 cases, Non-PLC is also divided into chronic hepatitis B virus carriers (CHC) in 49 cases, hepatitis B Live cirrhosis(LC) in 44 cases. MTHFR (C677T), MTRR (A66G) and MTHFR (A1298C) genes polymorphisms were detected by PCR-dissolution curve. The level of HBV-DNA was quantified by real-time PCR, and the 1762/1764 mutation site in the BCP region of the HBV gene were detected by ARMS-PCR. Data were statistically analyzed using the SPSS statistical software.The proportion of HBV mutations in BCP region 1762/1764 in PLC group was 82.4%, which was higher than that in LC group (63.6%) and CHC group (51.0%), and the differences were statistically significant (p < 0.05). There were no significant differences in the distribution of MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms among CHC, LC and PLC (p > 0.05). The polymorphism distribution of MTHFR C677T, MTRR A66G and MTHFR A1298C genes in patients with chronic hepatitis B virus infection at different stages (CHC, LC and PLC) showed no gender or age differences between and within groups (p > 0.05). Among the patients with MTHFR 677CT + TT, MTRR 66AG + GG and MTHFR 1298AA genotype, the proportion of HBV mutation in BCP region 1762/1764 in PLC group was higher than that in CHC group and LC group, and the differences were statistically significant (p < 0.05). Folate levels in the PLC group were lower than those in the non-PLC group (CHC and LC patients), and the difference was statistically significant compared with the CHC group (p < 0.05). In different MTHFR C677T and MTRR A66G genotypes, the serum GGT activity were statistically significant between mutant PLC and mutant Non-PLC (p < 0.05).MTHFR C677T, MTRR A66G and MTHFR A1298C gene polymorphisms distribution have no gender and age differences in chronic hepatitis B virus infection patients. The mutation of HBV gene BCP region 1762/1764 may be associated with the occurrence and development of liver cancer in patients with chronic HBV infection. Single difference of MTHFR C677T, MTHFR A1298C and MTRR A66G gene polymorphisms may have little effect on the disease progression in patients with chronic HBV infection. MTHFR 677CT + TT, MTRR 66AG + GG and MTHFR 1298AA genotype combined with HBV gene BCP region 1762/1764 mutation may be closely related to the occurrence and development of hepatitis B liver cancer. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions Patients with chronic hepatitis B (CHB) remain at risk for hepatocellular carcinoma (HCC) even with nucleos(t)ide analog therapy. We evaluated risk factors for HCC development, including serum hepatitis B virus (HBV) RNA, hepatitis B core‐related antigen level, and growth differentiation factor 15 (GDF15) level, a predictor of HCC development in patients with chronic hepatitis C.We collected clinical data and stored serum from CHB patients without a history of HCC who were receiving nucleos(t)ide analog treatment for more than 1 year and whose HBV DNA level was less than 3.0 log IU/mL. We measured the serum levels of HBV RNA and GDF15.Among 242 CHB patients, 57 had detectable HBV RNA, and GDF15 was quantified in all patients. The median GDF15 level was 0.86 ng/mL. Cox proportional hazards analysis revealed that male sex and higher GDF15, FIB‐4 index, alpha‐fetoprotein and gamma‐glutamyl transpeptidase were independent risk factors for HCC. The presence of HBV RNA above the lower limit of quantification was not a risk factor. When we set cutoff values based on the Youden index, the cumulative incidence of HCC was significantly higher in the male, AFP ≥3.0 ng/mL, gamma‐glutamyl transpeptidase ≥22 U/L, FIB‐4 index ≥1.93, and GDF‐15 ≥1.17 ng/mL groups. In patients with no or more than three of these five risk factors, the 10‐year HCC cumulative incidence rates were 0% and 41.0%, respectively.High serum GDF15 is an independent risk factor for the occurrence of HCC in CHB patients treated with nucleos(t)ide analogs. [ABSTRACT FROM AUTHOR]

The integration of Hepatitis B Virus (HBV) is now known to be closely associated with the occurrence of liver cancer and can impact the functionality of liver cells through multiple dimensions. However, despite the detailed understanding of the characteristics of HBV integration and the mechanisms involved, the subsequent effects on cellular function are still poorly understood in current research. This study first systematically discusses the relationship between HBV integration and the occurrence of liver cancer, and then analyzes the status of the viral genome produced by HBV replication, highlighting the close relationship and structure between double-stranded linear (DSL)-HBV DNA and the occurrence of viral integration. The integration of DSL-HBV DNA leads to a certain preference for HBV integration itself. Additionally, exploration of HBV integration hotspots reveals obvious hotspot areas of HBV integration on the human genome. Virus integration in these hotspot areas is often associated with the occurrence and development of liver cancer, and it has been determined that HBV integration can promote the occurrence of cancer by inducing genome instability and other aspects. Furthermore, a comprehensive study of viral integration explored the mechanisms of viral integration and the internal integration mode, discovering that HBV integration may form extrachromosomal DNA (ecDNA), which exists outside the chromosome and can integrate into the chromosome under certain conditions. The prospect of HBV integration as a biomarker was also probed, with the expectation that combining HBV integration research with CRISPR technology will vigorously promote the progress of HBV integration research in the future. In summary, exploring the characteristics and mechanisms in HBV integration holds significant importance for an in-depth comprehension of viral integration. [ABSTRACT FROM AUTHOR]

Background: The concurrent presence of chronic hepatitis B virus (CHB) infection and metabolic dysfunction-associated steatotic liver disease (MASLD) presents a unique clinical scenario with implications that are not yet fully understood. This study aims to characterize the distinct clinical and virological features of CHB in the context of MASLD and evaluate its impact on disease progression and outcomes. Methods: Utilizing a comprehensive health maintenance organization database, this study included 1186 patients with CHB from 2000–2020. Patients were categorized into two groups: CHB-MASLD (n = 188) and CHB alone (n = 998). CHB diagnosis was confirmed by serological markers, while MASLD was diagnosed based on imaging and cardiometabolic risk factors. Comparative analysis and multiple regression models were applied to assess variables related to viral parameters and clinical outcomes. Results: The CHB-MASLD group was older (mean age of 45.2 vs. 39.1, p < 0.001) with higher rates of obesity (46.8% vs. 23.8%, p < 0.001), diabetes (36.2% vs. 17.3%, p < 0.001), and dyslipidemia. Distinct viral profiles included higher HBeAg negativity (96.2%), a higher rate of HBeAg-negative infection (70.4% vs. 63.8%; p < 0.001), and increased HBeAg seroconversion under treatment. Cirrhosis was more prevalent in the CHB-MASLD group (9.6% vs. 4.4%, p = 0.007), while HCC rates were comparable. Multivariate analysis identified age, male gender, chronic active hepatitis, and diabetes as predictors of cirrhosis. Conclusions: CHB-MASLD patients were distinguished by a higher prevalence of metabolic features, along with a distinct viral profile marked by increased chronic HBeAg infection, higher rates of HBeAg seroconversion, and a potential association with worse disease outcomes. [ABSTRACT FROM AUTHOR]

Liver cancer, recognized as a significant global health issue, is increasingly correlated with Hepatitis B virus (HBV) infection, as evidenced by numerous scientific studies. This study aims to examine the correlation between HBV infection and the development of liver cancer, focusing on using RNA sequencing (RNA-seq) to detect HBV sequences and applying deep learning techniques to estimate the likelihood of oncogenic transformation in individuals with HBV. Our study utilized RNA-seq data and employed Pathseq software and sophisticated deep learning models, including a convolutional neural network (CNN), to analyze the prevalence of HBV sequences in the samples of patients with liver cancer. Our research successfully identified the prevalence of HBV sequences and demonstrated that the CNN model achieved an exceptional Area Under the Curve (AUC) of 0.998 in predicting cancerous transformations. We observed no viral synergism that enhanced the pathogenicity of HBV. A detailed analysis of sequences misclassified by the CNN model revealed that longer sequences were more conducive to accurate recognition. The findings from this study provide critical insights into the management and prognosis of patients infected with HBV, highlighting the potential of advanced analytical techniques in understanding the complex interactions between viral infections and cancer development. [ABSTRACT FROM AUTHOR]

The article discusses the challenges of treating and curing chronic hepatitis B virus (HBV) infection. Currently available oral antiviral treatments only suppress viral replication but do not eliminate viral genomes from the liver. Achieving hepatitis B surface antigen (HBsAg) loss, which is considered a functional cure, is difficult with nucleos(t)ide analogues (NUCs) therapy. The article highlights the importance of integrated HBV DNA (iDNA) as a major source of HBsAg and suggests that targeting iDNA may be necessary for achieving a functional cure. However, further research is needed to better understand iDNA and develop effective treatments. [Extracted from the article]

Background Hepatitis B virus (HBV) DNA may become integrated into the human genome of infected human hepatocytes. Expression of integrations can produce the surface antigen (HBsAg) that is required for synthesis of hepatitis D virus (HDV) particles and the abundant subviral particles in the blood of HBV- and HDV-infected subjects. Knowledge about the extent and variation of HBV integrations and impact on chronic HDV is still limited. Methods We investigated 50 pieces of liver explant tissue from 5 patients with hepatitis D-induced cirrhosis, using a deep-sequencing strategy targeting HBV RNA. Results We found that integrations were abundant and highly expressed, with large variation in the number of integration-derived (HBV/human chimeric) reads, both between and within patients. The median number of unique integrations for each patient correlated with serum levels of HBsAg. However, most of the HBV reads represented a few predominant integrations. Conclusions The results suggest that HBV DNA integrates in a large proportion of hepatocytes, and that the HBsAg output from these integrations vary >100-fold depending on clone size and expression rate. A small proportion of the integrations seems to determine the serum levels of HBsAg and HDV RNA in HBV/HDV coinfected patients with liver cirrhosis. [ABSTRACT FROM AUTHOR]

Background This study assessed the epidemiology of hepatitis delta virus (HDV) within the University of Utah UHealth health care system (2000–2021). Methods Analysis of HDV/HBV testing, diagnostic codes, liver enzymes, and comorbidities was performed. Results Among the 1962 HBV patients, only 22.2% underwent HDV testing, revealing an 8.3% positivity rate for HDV coinfections. This study observed a consistent increase in HBV and HDV cases, with higher HDV detection rates linked to increased testing. Limited HDV testing and potential screening biases were evident. Discussion Improved HDV testing and surveillance are crucial for early detection and implementation of targeted therapies. [ABSTRACT FROM AUTHOR]

AbstractThe determination of serum hepatitis B Virus (HBV) DNA is of paramount significance in the comprehensive management of HBV infection. It aids in diagnosis, disease staging, and treatment monitoring, ultimately improving patient outcomes and reducing the burden of HBV-related morbidity and mortality. In this work, serum HBV DNA detection was performed using a novel nucleic acid screening system. The sensitivity, selectivity, repeatability, cross reactivity, and HBV DNA stability were evaluated and compared with published data. The detection limit of 95% was 29.12 IU/mL and the 95% confidence interval was from 23.71 to 34.55 IU/mL. Blood samples that contain free hemoglobin (1 g/L, 2 g/L, 4 g/L) and triglycerides (3 mmol/L, 6 mmol/L and 9 mmol/L) were also analyzed. The results demonstrated that the system can also be used in the presence of free hemoglobin and triglycerides. The mean of the cycle threshold (Ct) in 5-day replicates was 35.71 ± 0.35 with a coefficient of variation (CV) of 0.97%. The results of negative samples in the anti-cross contamination experiment showed no response. The coincidence rate for 3001 samples over 20 days of real-time stability measurements and external quality assessment samples was 100%. The results demonstrate the effectiveness of the nucleic acid system for HBV-DNA, providing a theoretical basis for other small and medium-sized blood stations or hospitals to these devices. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy (ART) for HIV infection has evolved substantially. The development of long-acting drugs, such as cabotegravir (CAB) and rilpivirine (RPV) might improve treatment satisfaction among people living with HIV (PLWH). The real-world effectiveness of long-acting ART and its effect on patient satisfaction needs to be assessed. This study investigated antiviral effectiveness and treatment satisfaction in PLWH who switched from conventional to long-acting ART (CAB + RPV). Methods: This prospective cohort study included PLWH aged 18 years and older who switched to CAB + RPV and received the injections every 8 weeks between June 2022 and May 2023, after a 4-week oral lead-in phase. The eligibility criteria included viral suppression, absence of hepatitis B virus (HBV) DNA, and no prior RPV resistance mutations. Clinical data, including renal, lipid, and glucose biomarker levels, were monitored from the baseline to 44 weeks after switching. Treatment satisfaction was assessed using the HIV Treatment Satisfaction Questionnaire. A linear mixed-effects model was used to estimate changes in clinical data from baseline. Results: Thirty-eight male participants were enrolled. Some participants had detectable levels of viral replication; however, all participants maintained viral suppression (HIV-RNA < 50 copies/mL) at 44 weeks and no cases of virological failure were detected. The creatinine level decreased by − 0.04 mg/dL (95% confidence interval [CI]: − 0.07 to − 0.01), lipid and glucose profiles remained stable, and treatment satisfaction increased by 6.6 points (95% CI: 2.4 to 10.8) after switching to CAB + RPV. Conclusions: Long-acting ART provides effective viral suppression and enhances treatment satisfaction in PLWH switching from conventional ART. Long-acting ART can improve patient well-being; however, patient selection and monitoring to prevent HBV-related complications are important. [ABSTRACT FROM AUTHOR]

ABSTRACT Hepatitis D virus leads to a severe form of viral hepatitis and affects nearly 5% of people living with chronic hepatitis B. Chronic infection with hepatitis D virus leads to more rapid progression to cirrhosis, hepatocellular carcinoma and ultimately liver disease‐related death compared with hepatitis B monoinfection. Health outcomes and treatment adherence can be affected by patient perception of, engagement in, and satisfaction with care. Our objective was to better understand the experiences of people with chronic hepatitis D, identify their preferred sources of information, and recognise unmet needs from their perspectives. Sixty‐seven participants from the United States and the European Union took part in monthly, online, self‐guided surveys for a minimum of 3 months with an optional extension. Participants reported feeling anxious and scared at the time of diagnosis but over time came to accept living with chronic hepatitis D. They voiced a need for access to information from trusted sources, fewer barriers to care, and shorter wait times for provider visits and test results after diagnosis. Participants experienced both physical and psychological strain living with chronic hepatitis D. Although most participants reported the ability to continue their regular activities and employment, some stated such activities were done at a reduced pace. Self‐reported overall health appeared to be closely linked with emotional support. Understanding patient perspectives, with concurrent clinician perspectives, is crucial when working toward developing solutions to fulfil unmet patient needs associated with chronic hepatitis D management and advancing health equity. [ABSTRACT FROM AUTHOR]

Background Emerging evidence suggests that viral infections may contribute to Alzheimer's disease (AD) onset and/or progression. However, the extent of their involvement and the mechanisms through which specific viruses increase AD susceptibility risk remain elusive. Methods We used an integrative systems bioinformatics approach to identify viral-mediated pathogenic mechanisms, by which Herpes Simplex Virus 1 (HSV-1), Human Cytomegalovirus (HCMV), Epstein-Barr virus (EBV), Kaposi Sarcoma-associated Herpesvirus (KSHV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Influenza A Virus (IAV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) could facilitate AD pathogenesis via virus-host protein-protein interactions (PPIs). We also explored potential synergistic pathogenic effects resulting from herpesvirus reactivation (HSV-1, HCMV, and EBV) during acute SARS-CoV-2 infection, potentially increasing AD susceptibility. Results Herpesviridae members (HSV-1, EBV, KSHV, HCMV) impact AD-related processes like amyloid-β (Aβ) formation, neuronal death, and autophagy. Hepatitis viruses (HBV, HCV) influence processes crucial for cellular homeostasis and dysfunction, they also affect microglia activation via virus-host PPIs. Reactivation of HCMV during SARS-CoV-2 infection could potentially foster a lethal interplay of neurodegeneration, via synergistic pathogenic effects on AD-related processes like response to unfolded protein, regulation of autophagy, response to oxidative stress, and Aβ formation. Conclusions These findings underscore the complex link between viral infections and AD development. Viruses impact AD-related processes through shared and distinct mechanisms, potentially influencing variations in AD susceptibility. [ABSTRACT FROM AUTHOR]

ABSTRACT Hepatocellular carcinoma (HCC) is one of the most common malignant tumours in China, at high annual incidence and mortality. Chronic hepatitis B virus infection (CHB) is considered as a leading cause to bring about HCC in China. Serum albumin (ALB) level has been adopted to verify its risk with HCC development as a combination variable with other factors. However, the predictive value of a single ALB level on HBV‐related HCC risk remained unclear. The aim of this study was to evaluate the prediction ability of serum ALB concentration on the risk of HBV‐related HCC development. A prospectively enrolled clinical cohort compromising 2932 cases of CHB patients with at least 1‐year exclusion window was selected to explore the predictive role of serum ALB level on incident HCC risk. Baseline clinical data including host characters and laboratory test were collected at the initial period of hospitalisation. The hazard ratio of ALB level associated with HCC development was assessed by Cox proportional hazards regression model using univariate and multivariate analyses. We evaluated the discrimination accuracy of ALB level in predicting HCC development by receiver operating characteristic (ROC) curves. Dose‐dependent and time‐dependent effects of ALB level on HCC risk prediction were demonstrated, respectively, using a restricted cubic spline and a Fine and Grey competing risk model. Referred to patients with higher ALB level, those with lower ALB level exhibited significantly increased risk of HCC development after adjustment for host variables (dichotomised analyses: hazard ratio = 3.12, 95% confidence interval 1.63–5.97, p = 8.23 × 10−4, plog‐rank = 5.97 × 10−4; tertile analyses: hazard ratio = 2.07, 95% confidence interval 1.63–2.64, p = 3.77 × 10−9, plog‐rank < 2.00 × 10−16; quartile analyses: hazard ratio = 2.10, 95% confidence interval 1.56–2.84, p = 9.87 × 10−7, plog‐rank < 2.00 × 10−16). There was a statistically increasing trend on HCC risk which was found following by the decrease of ALB level (ptrend < 0.0001). Similar findings were present by the Kaplan–Meier analysis, cumulative incidences of HCC development were significantly higher in patients with lower ALB levels, with the p value obtained from log‐rank test were all < 0.0001. The result of dose‐dependent effect showed hazard ratio (HR) value of HCC risk was gradually decreasing as the increasing of ALB level, with non‐linear correlation being statistically significant (Wald χ2 = 20.59, p = 0.000). HR value in lower ALB level remained persistently prominent by fluctuating around 2.73 in the whole follow‐up time by adjusting for host variables. Sub‐cohort analysis by ROC revealed that the discrimination ability of the ALB model was performed better than Child‐Pugh (C‐P) model in both cohort of patients with 1‐year (area under curve [AUC] 0.762 vs. 0.720) and 2‐year exclusion window (AUC 0.768 vs. 0.728). The AUC added by ALB level was demonstrated significantly from host model to full model. Lower ALB level was significantly associated with an increased risk of HBV‐related HCC and could provide extra useful clinical utility to other host features, which might be a promising non‐invasive indicator for surveillance on HCC development. [ABSTRACT FROM AUTHOR]

Background: To identify the risk factors and construct a predictive model for early recurrence of hepatitis B virus(HBV-)- related hepatocellular carcinomas(HCCs) after radical resection. Data and methods: A total of 465 HBV-related HCC patients underwent radical resections between January 1, 2012 and August 31, 2018.Their data were collected through the inpatient information management system of the First Affiliated Hospital of University of Science and Technology of China. Survival and subgroup analyses of early recurrence among male and female patients were performed using Kaplan-Meier curves. The independent risk factors associated with early postoperative tumor recurrence were analyzed using multivariate Cox proportional hazards regression model. Based on these independent risk factors, a risk function model for early recurrence was fitted, and a column chart for the prediction model was drawn for internal and external validation. Results: A total of 181 patients developed early recurrences, including 156 males and 25 females. There was no difference in the early recurrence rates between males and females. Tumor diameters>5cm, microvascular invasion and albumin level<35 g/L were independent risk factors for early recurrence. A nomogram for the early recurrence prediction model was drawn; the areas under the curve for the model and for external verification were 0.638 and 0.655, respectively. Conclusion: Tumor diameter>5 cm, microvascular invasion, and albumin level<35 g/L were independent risk factors for early recurrence. The prediction model based on three clinical indicators could predict early recurrence, with good discrimination, calibration, and extrapolation. [ABSTRACT FROM AUTHOR]

Introduction: In Sub-Saharan Africa alone, about 40–65% of Hepatitis B Virus infections among HCWs were a result of percutaneous occupational exposures to contaminated blood and body fluids of patients. Occupational exposure to blood and body fluids among healthcare workers is on the rise in Ghana. However, the relationship between self-reported exposures to blood and body fluids suspected to be contaminated with the hepatitis B virus and actual serological evidence of exposure remains unknown. The aim of the study however was to assess the self-reported exposure to HBV as against the serological evidence of lifetime exposure to HBV and associated factors among Ghanaian HCWs. Methods: The study was a cross-sectional analytical survey that involved 340 HCWs who were recruited using a simple random sampling procedure from six cadres of staff from five districts in Greater Accra. The participants were surveyed using a validated instrument and 5mls of venous blood was aseptically withdrawn for qualitative detection of Anti-HBc. SPSS version 23.0 was used to analyze the data to obtain proportions, odds ratios and their corresponding confidence intervals with the level of significance set at 0.05. Results: The response rate was 94% with Nurses and Doctors in the majority with a mean age of 35.6 ± 7.2. Self-reported exposure to HBV was 63% whereas lifetime exposure to HBV (Anti-HBc) prevalence was 8.2% (95% CI = 5.0-11.0%). Females were 60% less likely to be exposed to HBV (aOR = 0.4; 95% CI = 0.1–0.9) than their male counterparts. HCWs without training in the prevention of blood-borne infections had almost three times higher odds of being exposed to HBV in their lifetime (aOR = 2.6; 95% CI = 1.0-6.4). Conclusions: The findings of this study suggest that self-reported exposure to HBV-contaminated biological materials was high with a corresponding high lifetime exposure to HBV. The female gender was protective of anti-HBc acquisition. Apart from direct interventions for preventing occupational exposures to HBV in the healthcare setting, periodic training of all categories of healthcare workers in infection prevention techniques could significantly reduce exposure to the Hepatitis B virus. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions Reactivation of hepatitis B virus (HBV) after liver transplantation (LT) remains a problem; thus, development of more effective HBV reactivation prophylaxis is desirable. We evaluated the efficacy of a combination of a long‐term nucleotide analog (NA), such as entecavir (ETV) or tenofovir alafenamide (TAF), and short‐term hepatitis B immunoglobulin (HBIG) in preventing HBV reactivation and compared it with conventional HBV prophylaxis.Between February 1999 and August 2023, 135 patients underwent living‐donor liver transplantation for liver cirrhosis or acute liver failure caused by HBV infection or received an LT from a hepatitis B core antibody‐positive donor. Recipients who had undergone LT were classified as being in the first or second era (namely until September 2017 and from October 2017), respectively, and outcomes of prophylaxis against HBV reactivation were compared between the two eras.In the second era, recipients with HBV‐related disease or who had received hepatitis B core antibody‐positive liver received combination therapy with short‐term HBIG and an NA such as TAF and ETV long‐term. The duration of HBIG treatment was markedly shorter than in the first era in both categories of patients and HBIG could be discontinued in all cases. Surprisingly, we observed HBV reactivation in the first era, but not in the second era, in both groups.We have established a protocol for prophylaxis against HBV reactivation using a combination of short‐term HBIG and long‐term NA. This protocol was found to be sufficient to prevent HBV reactivation after LT. [ABSTRACT FROM AUTHOR]

Summary Advances in antibody technologies have resulted in the development of potent antibody‐based therapeutics with proven clinical efficacy against infectious diseases. Several monoclonal antibodies (mAbs), mainly against viruses such as SARS‐CoV‐2, HIV‐1, Ebola virus, influenza virus, and hepatitis B virus, are currently undergoing clinical testing or are already in use. Although these mAbs exhibit potent neutralizing activity that effectively blocks host cell infection, their antiviral activity results not only from Fab‐mediated virus neutralization, but also from the protective effector functions mediated through the interaction of their Fc domains with Fcγ receptors (FcγRs) on effector leukocytes. Fc‐FcγR interactions confer pleiotropic protective activities, including the clearance of opsonized virions and infected cells, as well as the induction of antiviral T‐cell responses. However, excessive or inappropriate activation of specific FcγR pathways can lead to disease enhancement and exacerbated pathology, as seen in the context of dengue virus infections. A comprehensive understanding of the diversity of Fc effector functions during infection has guided the development of engineered antiviral antibodies optimized for maximal effector activity, as well as the design of targeted therapeutic approaches to prevent antibody‐dependent enhancement of disease. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection poses a major global health challenge with massive morbidity and mortality. Despite a preventive vaccine, current treatments provide limited virus clearance, necessitating lifelong commitment. The HBV surface antigen (HBsAg) is crucial for diagnosis and prognosis, yet its high-resolution structure and assembly on the virus envelope remain elusive. Utilizing extensive datasets and advanced cryo–electron microscopy analysis, we present structural insights into HBsAg at a near-atomic resolution of 3.7 angstroms. HBsAg homodimers assemble into subviral particles with D2- and D4-like quasisymmetry, elucidating the dense-packing rules and structural adaptability of HBsAg. These findings provide insights into how HBsAg assembles into higher-order filaments and interacts with the capsid to form virions. [ABSTRACT FROM AUTHOR]

Background: In patients with cirrhosis, esophageal variceal hemorrhage (EVH) is a devastating consequence of portal hypertension (PH). Upper endoscopy is considered the gold standard for the detection and diagnosis of esophageal varices (EVs), despite being invasive and costly. This study was aimed at identifying and evaluating the diagnostic accuracy of noninvasive tools in predicting EVs in patients with compensated cirrhosis. Methods: This cross‐sectional study included 50 patients with compensated cirrhosis at the Tygerberg Hospital Gastroenterology Clinic in Cape Town between November 2022 and May 2023. We collected clinical, anthropometric, and laboratory data from patients' physical and electronic charts. All patients underwent an abdominal ultrasound, vibration‐controlled transient elastography (VCTE) to assess liver and splenic stiffness, and upper endoscopy. In this comparative study, we evaluated the diagnostic accuracy of different noninvasive tools in detecting EVs in patients with compensated cirrhosis. Results: Of the 50 patients included in the study, 30 (60%) were female and 20 (40%) were male. The patients' age ranged from 18 to 83, with a mean age of 46.6 years. Cirrhosis was mainly due to alcohol use (n = 11, 22%), hepatitis B virus (HBV) infection (n = 11, 22%), and autoimmune hepatitis (n = 10, 20%). The patients included in the study were divided into two subgroups: with (n = 34, 68%) or without (n = 16, 32%) EVs. Statistically significant differences were detected between groups in platelet count (PC), liver stiffness measurement (LSM), spleen stiffness measurement (SSM), portal vein diameter (PVD), bipolar spleen diameter (SBD), aspartate aminotransferase‐to‐platelet ratio index (APRI), fibrosis‐4 index (FIB‐4), platelet/bipolar spleen diameter ratio (PSR), liver stiffness‐spleen size‐platelet ratio (LSPS), liver stiffness‐spleen stiffness‐platelet ratio score (LS3PS), and spleen stiffness‐spleen size‐platelet ratio score (SSPS) (p < 0.001). The highest diagnostic precision was observed with SSM (96%), SSPS (96%), LS3PS (94%), LSPS (94%), PSR (94%), and PC (92%). SBD (88%), LSM (86%), APRI (82%), and FIB‐4 (82%) had the lowest diagnostic accuracy. Conclusion: SSM and SSPS have the highest diagnostic accuracy for predicting the presence of EVs in patients with compensated cirrhosis. LSPS, LS3PS, and PSR come second at 94%. We recommend SSM and SSPS in institutions with transient elastography equipped with the software necessary to measure splenic stiffness. We introduce and propose LS3PS as a novel composite score for predicting the presence of EVs in patients with compensated cirrhosis. Large‐sample‐size studies are needed to validate these prediction scores and to allow direct comparison with Baveno VII. These prediction tools can help clinicians avoid unnecessary endoscopic procedures in patients with compensated cirrhosis, especially in developing countries with limited resources such as South Africa. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to analyze whether undergoing amniocentesis during pregnancy in women diagnosed with hepatitis B virus (HBV) infection leads to HBV transmission to newborns. Methods: Retrospective data collection was conducted from June 2019 to November 2022 on expectant mothers positive for hepatitis B surface antigen (HBsAg) who underwent amniocentesis at The Third Affiliated Hospital of Sun Yat-sen University, along with data on their newborns. The study summarized the HBV infection status of newborns born to mothers with different expressions of hepatitis B e antigen (HBeAg), antiviral treatment versus no treatment, and different HBV DNA viral loads before delivery. Results: In this study, 346 expectant mothers tested positive for HBsAg, along with 351 newborns (including 5 sets of twins, with 8 infants (2.28%) testing HBsAg-positive at birth. All newborns received dual immunotherapy and were followed up. At 7–12 months, retesting for HBsAg positivity and HBV DNA positivity among infants revealed that out of the infants born with HBsAg positivity, 7 cases had seroconverted to negative, while the remaining infant, who was positive for both HBsAg and HBeAg at birth, tested positive for both HBsAg and HBV DNA at 7–12 months. Thus, one case of vertical transmission of hepatitis B from mother to child occurred in this study. The proportion of infants born with HBsAg + among newborns born to HBeAg-positive mothers (4 cases, 6.06%) was significantly higher than that among newborns born to HBeAg-negative mothers (4 cases, 1.41%) (P < 0.05). The proportion of infants born with HBsAg + showed no significant difference between newborns born to mothers receiving antiviral therapy (2 cases, 2.90%) and those born to mothers not receiving antiviral therapy (6 cases, 2.13%) (P > 0.05). Among expectant mothers with viral load ≥ 6 log 10 IU/mL before delivery, 3 newborns (30.00%) were manifesting HBsAg positivity at birth, significantly higher than the group with viral load < 6 log 10 IU/mL before delivery (5 cases, 1.47%) (P < 0.05). Conclusion: Among HBsAg-positive expectant mothers, only a small number of infants are infected with the hepatitis B virus at birth, the proportion of which is relatively low. Infants born to mothers who are HBeAg-positive or have a viral load ≥ 6 log10 IU/mL have a higher risk of being born positive. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) exploits the endosomal sorting complexes required for transport (ESCRT)/multivesicular body (MVB) pathway for virion budding. In addition to enveloped virions, HBV-replicating cells nonlytically release non-enveloped (naked) capsids independent of the integral ESCRT machinery, but the exact secretory mechanism remains elusive. Here, we provide more detailed information about the existence and characteristics of naked capsid, as well as the viral and host regulations of naked capsid egress. HBV capsid/core protein has two highly conserved Lysine residues (K7/K96) that potentially undergo various types of posttranslational modifications for subsequent biological events. Mutagenesis study revealed that the K96 residue is critical for naked capsid egress, and the intracellular egress-competent capsids are associated with ubiquitinated host proteins. Consistent with a previous report, the ESCRT-III-binding protein Alix and its Bro1 domain are required for naked capsid secretion through binding to intracellular capsid, and we further found that the ubiquitinated Alix binds to wild type capsid but not K96R mutant. Moreover, screening of NEDD4 E3 ubiquitin ligase family members revealed that AIP4 stimulates the release of naked capsid, which relies on AIP4 protein integrity and E3 ligase activity. We further demonstrated that AIP4 interacts with Alix and promotes its ubiquitination, and AIP4 is essential for Alix-mediated naked capsid secretion. However, the Bro1 domain of Alix is non-ubiquitinated, indicating that Alix ubiquitination is not absolutely required for AIP4-induced naked capsid secretion. Taken together, our study sheds new light on the mechanism of HBV naked capsid egress in viral life cycle. Author summary: HBV-infected cells can produce various viral particles with different sizes and morphologies. Virions are complete particles with both nucleocapsids and surface antigen (HBsAg) envelope, which exploits the endosomal sorting complexes required for transport (ESCRT)/multivesicular body (MVB) pathway for budding. In addition to virion, HBV-infected cells also secrete non-enveloped (or naked) capsid particles. It remains unclear how HBV naked capsid is released from the infected cells. In this study, we further characterized the naked capsid and identified the Lysine 96 of HBV core protein as an important contact point for cellular protein Alix to mediate naked capsid secretion. We also determined NEDD4 E3 ubiquitin ligase family member AIP4 stimulates the release of naked capsid, regardless of their genome contents. AIP4 interacts with Alix and promotes its ubiquitination. However, the AIP4 protein per se rather than its E3 ubiquitin ligase activity is sufficient for Alix-induced naked capsid secretion. In summary, these findings provide new insights into a better understanding of HBV naked capsid egress. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) infection can exacerbate liver disease progression through multiple mechanisms, eventually leading to hepatocellular carcinoma (HCC). HBV-encoded oncogene X protein (HBx), a key regulatory protein of HBV infection, serves as a positive regulator of hepatocarcinogenesis. The indispensability of the M2 subunit of ribonucleotide-diphosphate reductase (RRM2) lies in its role in facilitating DNA replication and repair processes. In our previous investigation, it was postulated that the gene RRM2 exhibits elevated expression levels in several categories of malignant tumors, particularly in HBV-related HCC. Additionally, it was observed that RRM2 is present within protein complexes that are centered on HBx. In the present investigation, the objective of this work was to investigate the potential relationship between the elevated expression of RRM2 in HBV-related HCC and the influence of HBx on this expression. The study attempted to determine the specific mechanism by which RRM2 is implicated in the promotion of hepatocarcinogenesis by HBx. There have been multiple scholarly proposals suggesting that the induction of autophagy by HBx is a significant intermediary factor in the development of HCC. However, the precise carcinogenic function of HBx-induced autophagy remains a subject of debate. Results: This work initially investigated the impact of suppressing cellular autophagy on the malignant biological behaviors of HBx-promoted cells using an in vitro cellular model. The findings revealed that the suppression of cellular autophagy partially disrupted the oncogenic effects of HBx. In light of this, we proceeded to conduct more investigations into the regulatory association between RRM2 and HBx-induced autophagy in the upstream-downstream context. Our data indicate that HBx proteins increase the expression of RRM2. Suppression of RRM2 expression not only hinders HBx-induced autophagy, but also worsens the cellular G1/S blockage and reduces the HBx-induced malignant growth of hepatocellular carcinoma tumors, while stimulating apoptosis. Conclusions: Therefore, we hypothesised that RRM2 is a potential downstream target of HBx-induced hepatocarcinogenesis, and mining the oncogenic mechanism of RRM2 is significant in exploring the preventive treatment of HBV-related HCC. [ABSTRACT FROM AUTHOR]