Low HBV knowledge is associated with low HBV vaccination uptake in general adult population despite incentivization of HBV vaccination.

BACKGROUND: Hepatitis B virus (HBV) vaccination in Vietnamese adults remains low and unequally distributed. We conducted a study on HBV-naïve adults living in Ho Chi Minh City, Viet Nam, to determine barriers associated with HBV vaccination uptake after removing the financial barrier by providing free coupons for HBV vaccination. METHODS: After being screened for HBsAg, anti-HBs, and anti-HBc, 284 HBV-naïve study participants aged 18 and over (i.e., negative for HBsAg, anti-HBs, and anti-HBc total) were provided free 3-dose HBV vaccine coupons. Next, study participants' receipt of 1st, 2nd, and 3rd doses of HBV vaccine was documented at a pre-specified study healthcare facility, where HBV vaccines were distributed at no cost to the participants. Upon study entry, participants answered questionnaires on sociodemographics, knowledge of HBV and HBV vaccination, and related social and behavioral factors. The proportions of three doses of HBV vaccine uptake and their confidence intervals were analyzed. Associations of HBV vaccine initiation with exposures at study entry were evaluated using modified Poisson regression. RESULTS: 98.9% (281 of 284) of study participants had complete data and were included in the analysis. The proportion of participants obtaining the 1st, 2nd, and 3rd doses of HBV vaccine was 11.7% (95% Confidence Interval [95% CI] 8.0-15.5%), 10.7% (95%CI 7.1-14.3%), and 8.9% (95%CI 5.6-12.2%), respectively. On the other hand, participants were more likely to initiate the 1st dose if they had adequate knowledge of transmission (adjusted relative risk [aRR] = 2.58, 95% CI 1.12-5.92), adequate knowledge of severity (aRR = 6.75, 95%CI 3.38-13.48), and annual health-checking seeking behavior (aRR = 2.04, 95%CI 1.07-3.87). CONCLUSION: We documented a low HBV vaccination uptake despite incentivization. However, increased vaccine initiation was associated with better HBV knowledge and annual health check-up adherence. When considering expanding HBV vaccination to the general adult population, we should appreciate that HBV knowledge is an independent predictor of vaccine uptake.

ViroISDC: a method for calling integration sites of hepatitis B virus based on feature encoding.

BACKGROUND: Hepatitis B virus (HBV) integrates into human chromosomes and can lead to genomic instability and hepatocarcinogenesis. Current tools for HBV integration site detection lack accuracy and stability. RESULTS: This study proposes a deep learning-based method, named ViroISDC, for detecting integration sites. ViroISDC generates corresponding grammar rules and encodes the characteristics of the language data to predict integration sites accurately. Compared with Lumpy, Pindel, Seeksv, and SurVirus, ViroISDC exhibits better overall performance and is less sensitive to sequencing depth and integration sequence length, displaying good reliability, stability, and generality. Further downstream analysis of integrated sites detected by ViroISDC reveals the integration patterns and features of HBV. It is observed that HBV integration exhibits specific chromosomal preferences and tends to integrate into cancerous tissue. Moreover, HBV integration frequency was higher in males than females, and high-frequency integration sites were more likely to be present on hepatocarcinogenesis- and anti-cancer-related genes, validating the reliability of the ViroISDC. CONCLUSIONS: ViroISDC pipeline exhibits superior precision, stability, and reliability across various datasets when compared to similar software. It is invaluable in exploring HBV infection in the human body, holding significant implications for the diagnosis, treatment, and prognosis assessment of HCC.

CARs derived from broadly neutralizing, human monoclonal antibodies identified by single B cell sorting target hepatitis B virus-positive cells.

To design new CARs targeting hepatitis B virus (HBV), we isolated human monoclonal antibodies recognizing the HBV envelope proteins from single B cells of a patient with a resolved infection. HBV-specific memory B cells were isolated by incubating peripheral blood mononuclear cells with biotinylated hepatitis B surface antigen (HBsAg), followed by single-cell flow cytometry-based sorting of live, CD19+ IgG+ HBsAg+ cells. Amplification and sequencing of immunoglobulin genes from single memory B cells identified variable heavy and light chain sequences. Corresponding immunoglobulin chains were cloned into IgG1 expression vectors and expressed in mammalian cells. Two antibodies named 4D06 and 4D08 were found to be highly specific for HBsAg, recognized a conformational and a linear epitope, respectively, and showed broad reactivity and neutralization capacity against all major HBV genotypes. 4D06 and 4D08 variable chain fragments were cloned into a 2nd generation CAR format with CD28 and CD3zeta intracellular signaling domains. The new CAR constructs displayed a high functional avidity when expressed on primary human T cells. CAR-grafted T cells proved to be polyfunctional regarding cytokine secretion and killed HBV-positive target cells. Interestingly, background activation of the 4D08-CAR recognizing a linear instead of a conformational epitope was consistently low. In a preclinical model of chronic HBV infection, murine T cells grafted with the 4D06 and the 4D08 CAR showed on target activity indicated by a transient increase in serum transaminases, and a lower number of HBV-positive hepatocytes in the mice treated. This study demonstrates an efficient and fast approach to identifying pathogen-specific monoclonal human antibodies from small donor cell numbers for the subsequent generation of new CARs.

Predictors of Nucleos(t)ide Analogues Discontinuation Relapse: Hepatitis B Virus RNA versus Hepatitis B Surface Antigen.

OBJECTIVE: To compare the predictive value of hepatitis B virus (HBV) RNA and HBsAg quantification upon discontinuation of nucleos(t)ide analogues (NAs) therapy for clinical and virological relapse in chronic hepatitis B (CHB). STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China, from July 2014 to December 2020. METHODOLOGY: CHB patients received single NAs and discontinued treatment following appropriate standards. HBsAg quantification was conducted using the i2000 Chemiluminescent Immunoassay (CLIA) Analyser, while serum HBV RNA quantification was performed using specific RNA target capture and simultaneous amplification and testing. The main observational endpoints included virological relapse and clinical relapse. RESULTS: Eighty-one patients were recruited, with 15 patients achieving HBsAg loss at cessation. Twenty-nine individuals encountered virological relapse, while 13 patients experienced clinical relapse. Thirty-one patients achieved HBsAg <100 IU/ml at NAs cessation, among whom 26 achieved undetectable HBV RNA, while four patients suffered virological relapse (15.4%). Serum HBV RNA emerged as an independent determinant of virological relapse (HR 1.850), clinical relapse (HR 2.020), and HBsAg loss after NAs cessation (HR 0.138). The presence of HBsAg <100 IU/ml at cessation did not serve as a predictor for virological relapse and clinical relapse. CONCLUSION: Lower HBV RNA levels predict a better off-treatment response. Discontinuation of prolonged NAs therapy appears as a viable and safe choice for patients with undetectable HBV RNA. In comparison to HBV RNA, HBsAg <100 IU/ml at cessation did not show sufficient predictive value for virological relapse and clinical relapse. KEY WORDS: HBV RNA, Hepatitis B surface antigen, Chronic hepatitis B, Relapse.

[Seroprevalence of Hepatitis B virus in pregnancy women at the time of delivery]. / Seroprevalencia de virus Hepatitis B en gestantes al momento del parto.

Worldwide, there is an alert due to the increase in the seroprevalence of hepatitis B virus (HBV). This can cause up to 3.5% of chronic diseases, of which 40% present secondary complications and/ or early death. OBJECTIVE: To determine the seroprevalence of HBV in pregnant women at the time of delivery. PATIENTS AND METHOD: Observational, descriptive, cross-sectional study with cross-association between 2018 and 2019 at the Hospital Carlos Van Buren (HCVB), in Valparaiso, Chile. All pregnant women admitted for delivery care or with an immediate newborn who had HBV surface antigen study were included. Data were collected from the pregnant woman (age, nationality, education level, parity, type of delivery, and peripartum HIV-syphilis serology) and the newborn (gestational age, weight, and APGAR score). Inferential and multivariate analysis was performed using the Stata software. RESULTS: 1,355 pregnant women were analyzed. 87.7% were Chilean, 5.5% Haitian, 4.2% Venezuelan, and 2.6% were of other nationalities. 0.3% were positive for HBV. The prevalence of HBV in Chileans was 0.08% and in Haitians 4%. Haitian nationality was at higher risk of HBV (OR = 83) vs. Chilean nationality (p = 0.0001). None presented coinfection with HIV and/or syphilis. CONCLUSIONS: HBV seroprevalence in HCVB pregnant women was 0.3%, similar to that described in the general population in Chile. There was no coinfection with other sexually transmitted diseases. The only predictor of HBV infection was Haitian nationality.

Discovery and mechanistic study of Imperatorin that inhibits HBsAg expression and cccDNA transcription.

Chronic hepatitis B virus (HBV) infection remains a significant global health challenge due to its link to severe conditions like HBV-related cirrhosis and hepatocellular carcinoma (HCC). Although current treatments effectively reduce viral levels, they have limited impact on certain HBV elements, namely hepatitis B surface antigen (HBsAg) and covalently closed circular DNA (cccDNA). This highlights the urgent need for innovative pharmaceutical and biological interventions that can disrupt HBsAg production originating from cccDNA. In this study, we identified a natural furanocoumarin compound, Imperatorin, which markedly inhibited the expression of HBsAg from cccDNA, by screening a library of natural compounds derived from Chinese herbal medicines using ELISA assay and qRT-PCR. The pharmacodynamics study of Imperatorin was explored on HBV infected HepG2-NTCP/PHHs and HBV-infected humanized mouse model. Proteome analysis was performed on HBV infected HepG2-NTCP cells following Imperatorin treatment. Molecular docking and bio-layer interferometry (BLI) were used for finding the target of Imperatorin. Our findings demonstrated Imperatorin remarkably reduced the level of HBsAg, HBV RNAs, HBV DNA and transcriptional activity of cccDNA both in vitro and in vivo. Additionally, Imperatorin effectively restrained the actions of HBV promoters responsible for cccDNA transcription. Mechanistic study revealed that Imperatorin directly binds to ERK and subsequently interfering with the activation of CAMP response element-binding protein (CREB), a crucial transcriptional factor for HBV and has been demonstrated to bind to the PreS2/S and X promoter regions of HBV. Importantly, the absence of ERK could nullify the antiviral impact triggered by Imperatorin. Collectively, the natural compound Imperatorin may be an effective candidate agent for inhibiting HBsAg production and cccDNA transcription by impeding the activities of HBV promoters through ERK-CREB axis.

Predictive role of early treatment dynamics of HBV RNA and HBcrAg for HBeAg seroconversion in children with chronic hepatitis B.

This study aimed to assess the predictive capacity of emerging serological markers, serum HBV RNA and HBcrAg, for HBeAg seroconversion in children with HBeAg-positive chronic hepatitis B (CHB). Treatment-naïve HBeAg-positive CHB children who admitted to the Liver Disease Center of Hunan Children's Hospital between April 2021 and September 2022 and received treatment with the combined entecavir and interferon-alpha treatment were recruited. Serum HBV RNA and HBcrAg were measured at baseline and Weeks 12, 24, and 48 of treatment. Our study showed that serum HBV RNA (HR = 0.71, 95% CI: 0.56-0.91, p = 0.006), HBcrAg (HR = 0.60, 95% CI: 0.43-0.84, p = 0.003), and HBsAg (HR = 0.49, 95%CI: 0.36-0.69, p < 0.001) at Week 12 were independent predictors of HBeAg seroconversion. ROC curve analysis presented that serum HBV RNA decline value (ΔHBV RNA) at Week 36 and HBcrAg decline value (ΔHBcrAg) at Week 12 (AUC = 0.871, p = 0.003 and AUC = 0.810, p = 0.003, respectively) could effectively predict HBeAg seroconversion. Furthermore, the optimal critical values were determined and the children with ΔHBV RNA > 3.759 log10 copies/mL at Week 36 or ΔHBcrAg >0.350 log10 U/mL at Week 12 more likely to achieve HBeAg seroconversion. The serum HBV RNA and HBcrAg provide new insights into the treatment of CHB in children. Early assessment of serum HBV RNA and HBcrAg during treatment can assist clinical decision-making and optimize individualized therapeutic approaches.

Metabolic self-feeding in HBV-associated hepatocarcinoma centered on feedback between circulation lipids and the cellular MAPK/mTOR axis.

INTRODUCTION: Hepatitis B Virus (HBV) is widely recognized as a "metabolic virus" that disrupts hepatic metabolic homeostasis, rendering it one of the foremost risk factors for hepatocellular carcinoma (HCC). Except for antiviral therapy, the fundamental principles underlying HBV- and HBV+ HCC have remained unchanged, limiting HCC treatment options. OBJECTIVES: In this study, we aim to identify the distinctive metabolic profile of HBV-associated HCC, with the promise of identifying novel metabolic targets that confer survival advantages and ultimately impede cancer progression. METHODS: We employed a comprehensive methodology to evaluate metabolic alterations systematically. Initially, we analyzed transcriptomic and proteomic data obtained from a public database, subsequently validating these findings within our test cohort at both the proteomic and transcriptomic levels. Additionally, we conducted a comprehensive analysis of tissue metabolomics profiles, lipidomics, and the activity of the MAPK and AKT signaling pathway to corroborate the abovementioned changes. RESULTS: Our multi-omics approach revealed distinct metabolic dysfunctions associated with HBV-associated HCC. Specifically, we observed upregulated steroid hormone biosynthesis, primary bile acid metabolism, and sphingolipid metabolism in HBV-associated HCC patients' serum. Notably, metabolites involved in primary bile acid and sphingolipids can activate the MAPK/mTOR pathway. Tissue metabolomics and lipidomics analyses further validated the serum metabolic alterations, particularly alterations in lipid composition and accumulation of unsaturated fatty acids. CONCLUSION: Our findings emphasize the pivotal role of HBV in HCC metabolism, elucidating the activation of a unique MAPK/mTOR signaling axis by primary bile acids and sphingolipids. Moreover, the hyperactive MAPK/mTOR signaling axis transduction leads to significant reprogramming in lipid metabolism within HCC cells, further triggering the activation of the MAPK/mTOR pathway in turn, thereby establishing a self-feeding circle driven by primary bile acids and sphingolipids.

Autophagy-related protein 5 (ATG5) interacts with bone marrow stromal cell antigen 2 (BST2) to stimulate HBV replication through antagonizing the antiviral activity of BST2.

Hepatitis B virus (HBV) infection is a major global health burden with 820 000 deaths per year. In our previous study, we found that the knockdown of autophagy-related protein 5 (ATG5) significantly upregulated the interferon-stimulated genes (ISGs) expression to exert the anti-HCV effect. However, the regulation of ATG5 on HBV replication and its underlying mechanism remains unclear. In this study, we screened the altered expression of type I interferon (IFN-I) pathway genes using RT² Profiler™ PCR array following ATG5 knock-down and we found the bone marrow stromal cell antigen 2 (BST2) expression was significantly increased. We then verified the upregulation of BST2 by ATG5 knockdown using RT-qPCR and found that the knockdown of ATG5 activated the Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling pathway. ATG5 knockdown or BST2 overexpression decreased Hepatitis B core Antigen (HBcAg) protein, HBV DNA levels in cells and supernatants of HepAD38 and HBV-infected NTCP-HepG2. Knockdown of BST2 abrogated the anti-HBV effect of ATG5 knockdown. Furthermore, we found that ATG5 interacted with BST2, and further formed a ternary complex together with HBV-X (HBx). In conclusion, our finding indicates that ATG5 promotes HBV replication through decreasing BST2 expression and interacting with it directly to antagonize its antiviral function.

Hepatitis B: Model Systems and Therapeutic Approaches.

Hepatitis B virus (HBV) infection is a major global health issue and ranks among the top causes of liver cirrhosis and hepatocellular carcinoma. Although current antiviral medications, including nucleot(s)ide analogs and interferons, could inhibit the replication of HBV and alleviate the disease, HBV cannot be fully eradicated. The development of cellular and animal models for HBV infection plays an important role in exploring effective anti-HBV medicine. During the past decades, advancements in several cell culture systems, such as HepG2.2.15, HepAD38, HepaRG, hepatocyte-like cells, and primary human hepatocytes, have propelled the research in inhibiting HBV replication and expression and thus enriched our comprehension of the viral life cycle and enhancing antiviral drug evaluation efficacy. Mouse models, in particular, have emerged as the most extensively studied HBV animal models. Additionally, the present landscape of HBV therapeutics research now encompasses a comprehensive assessment of the virus's life cycle, targeting numerous facets and employing a variety of immunomodulatory approaches, including entry inhibitors, strategies aimed at cccDNA, RNA interference technologies, toll-like receptor agonists, and, notably, traditional Chinese medicine (TCM). This review describes the attributes and limitations of existing HBV model systems and surveys novel advancements in HBV treatment modalities, which will offer deeper insights toward discovering potentially efficacious pharmaceutical interventions.

The value of dynamic changes in FT3 level for predicting 90-day prognosis of HBV-ACLF patients.

OBJECTIVE: To explore the effect of dynamic changes in free triiodothyronine (FT3) level for predicting the 90 day prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: The clinical data of 122 hospitalised patients with HBV-ACLF between September 2018 and January 2020 were collected and divided into a survival group (77 cases) and a death group (45 cases) according to the 90 day prognosis. We statistically analysed the characteristics of FT3 changes in the two groups of patients. Binary logistic regression one-way analysis was used to assess the degree of influence of each factor. The Kaplan-Meier survival curve and receiver operating characteristic curve were used to evaluate the effect of a single change in FT3 level difference (single △FT3) and the FT3 level change range (△FT3 range) in predicting the 90-day prognosis of patients. RESULTS: There were only three types of changes in FT3 levels, which included 19 (15.6%) cases of continuous normal type, 35 (28.7%) cases of continuous decrease type and 68 (55.7%) cases of U-shaped change type. The difference in survival curves between the three types of patients was statistically significant (P < 0.001). CONCLUSION: The dynamic change type of FT3 is related to the disease severity and 90-day prognosis of patients with HBV-ACLF. The single FT3 value and FT3 range could be used as a predictive factor for the 90-day prognosis of patients with HBV-ACLF. These results have a degree of research value and are worth further exploration in the future.

Analysis of hepatitis B virus infection in 1424 patients with different pathological types of lymphoma (2018-2022): A real-world, retrospective study.

OBJECTIVE: Recent studies have found a high prevalence of hepatitis B virus (HBV) infection in patients with non-Hodgkin's lymphoma (NHL), especially B-cell non-Hodgkin's lymphoma (B-NHL). However, most studies did not classify it and analyze the correlation between HBV and its various subtypes. METHODS: The authors retrospectively analyzed 1424 patients with lymphoma. Differences in the prevalence of HBV infection in patients with different pathological types of lymphoma were analyzed. The clinical characteristics, progression-free survival (PFS), and overall survival (OS) of HBV-positive and negative B-NHL subtypes were compared according to HBV infection. RESULTS: The HBV infection rate in NHL patients was 7.65%, which was higher than that in HL patients (2.59%, p < 0.05). The HBV infection rate in the B-NHL was higher than that in the T-cell non-Hodgkin's lymphoma (T-NHL) (8.14% vs. 4.95%). The HBV infection rate in the aggressive B-NHL was similar to that of the indolent B-NHL (8.30% vs. 7.88%), and the highest HBV infection rates were found in diffuse large B-cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, but no significant differences in clinical characteristics, PFS, and OS were seen between HBV-positive and negative patients in the two subtypes. CONCLUSIONS: There was an association between HBV infection and the development of NHL and HBV infection may play a role in the pathogenesis of B-NHL, but not T-NHL.

Hepatitis B and C viral coinfection and associated factors among HIV-positive patients attending ART clinics of Afar regional state, northeast Ethiopia.

BACKGROUND: Hepatitis B (HBV) and C virus (HCV) coinfection are the major causes of liver-related morbidity and mortality among people living with Human Immunodeficiency Virus (HIV). The burden of hepatitis among HIV-positive individuals has not been studied in the Afar region. Therefore, this study aimed to determine the prevalence of HBV and HCV coinfection and associated factors among HIV-positive patients in Afar Regional State, northeast Ethiopia. METHODS: A cross-sectional study was conducted on 477 HIV-positive patients between February 2019 and May 2019. A structured and pretested questionnaire was used to collect socio-demographic data and associated factors. Five milliliters of blood was collected, and Hepatitis B surface antigen (HBsAg) and HCV antibodies were detected using rapid test kits. Positive samples were confirmed using enzyme-linked immunosorbent assay (ELISA). Binary and multivariable logistic regression analyses were performed to identify associated factors. Statistical significance was set at P <0.05. RESULTS: Among the 477 study participants, 320/477(67.1%) of them were females and 157(32.9%) males. The overall prevalence of HIV-HBV and HIV-HCV coinfection was 25(5.2%) and 7(1.5%), respectively. Multi-sexual practice was significantly associated with HIV-HBV coinfection (AOR = 5.3; 95% CI: 1.2-24.4, P = 0.032). CONCLUSION: The prevalence of both HIV-HBV and HIV-HCV coinfection was intermediate. Multi-sexual practice was significantly associated with HIV-HBV coinfection. Screening of all HIV-positive patients for HBV and HCV and health education regarding the transmission modes should be considered.

[Research progress on novel antiviral therapeutic drugs for chronic hepatitis B].

The ideal goal of hepatitis B treatment is to achieve a functional cure, and the persistent cccDNA in the liver is a barrier to functional cure. Currently, antiviral drugs represented by pegylated interferon-α and nucleos (t) ide analogues cannot eliminate cccDNA, which is difficult to achieve functional cure. With the deepening of the exploration of various mechanisms and drug targets, significant progress has been made in the research and development of several novel drugs targeting the hepatitis B virus's life cycle and immune system, offering hope for a functional cure. This article presents an overview of the new progress in clinical research on antiviral therapy for chronic hepatitis B based on the literature published in recent years and international conference materials.

[Research progress on the effect of hepatitis B virus DNA integration on antiviral therapy].

Hepatitis B virus (HBV) DNA integration occurs during the reverse transcription process of HBV replication, which develops in the early stages of HBV infection and accompanies the entire disease course. The integration of HBV DNA is detrimental to the attainment of clinical cure goals and also raises the risk of developing liver cancer. Theoretically, nucleos(t)ide analogs can reduce the synthesis of new double-stranded linear DNA, but there is no clearance function for hepatocytes that have already integrated HBV. Therefore, patients with serum HBV DNA-negative conversions still have the risk of developing liver cancer. As an immunomodulatory drug, interferon can not only inhibit viral replication but also inhibit or even eliminate existing clonally amplified hepatocytes carrying integrated HBV DNA fragments. However, there are currently few studies on the effects of nucleos(t)ide analogues and interferon therapy on HBV DNA integration. Thus, large-scale clinical studies are urgently needed for further clarification.

[HBeAg-positive patients hepatic tissue inflammatory activity and influencing factors during normal ALT and indeterminate phases].

Objective: To analyze the hepatic tissue inflammatory activity and influencing factors in HBeAg-positive patients during normal alanine aminotransferase (ALT) and indeterminate phases so as to provide a basis for evaluating the disease condition. Methods: Patients with HBeAg-positive with normal ALT and HBV DNA levels below 2 × 10(7) IU/ml from January 2017 to December 2021 were selected as the study subjects. A histopathologic liver test was performed on these patients. Age, gender, time of HBV infection, liver function, HBsAg level, HBV DNA load, genotype, portal vein inner diameter, splenic vein inner diameter, splenic thickness, and others of the patients were collected. Significant influencing factors of inflammation were analyzed in patients using logistic regression analysis, and its effectiveness was evaluated using receiver operating characteristic (ROC) curves. Results: Of the 178 cases, there were 0 cases of inflammation in G0, 52 cases in G1, 101 cases in G2, 24 cases in G3, and one case in G4. 126 cases (70.8%) had inflammatory activity ≥ G2. Infection time (Z=-7.138, P<0.001), γ-glutamyltransferase (t =-2.940, P=0.004), aspartate aminotransferase (t =-2.749, P=0.007), ALT (t =-2.153, P=0.033), HBV DNA level (t =-4.771, P=0.010) and portal vein inner diameter (t =-4.771, P<0.001) between the ≥G2 group and < G2 group were statistically significantly different. A logistic regression analysis showed that significant inflammation in liver tissue was independently correlated with infection time [odds ratio (OR)=1.437, 95% confidence interval (CI): 1.267-1.630; P<0.001)] and portal vein inner diameter (OR=2.738, 95% CI: 1.641, 4.570; P<0.001). The area under the curve (AUROC), specificity, and sensitivity for infection time and portal vein inner diameter were 0.84, 0.71, 0.87, 0.72, 0.40, and 0.95, respectively. Conclusion: A considerable proportion of HBeAg-positive patients have inflammation grade ≥G2 during normal ALT and indeterminate phases, pointing to the need for antiviral therapy. Additionally, inflammatory activity has a close association with the time of infection and portal vein inner diameter.

[Inhibitory effect of small-molecule compound AM679 targeting elongation-factor binding protein 2 on hepatitis B virus in vitro].

Objective: To explore the antiviral activity of the small-molecule compound AM679 in hepatitis B virus (HBV) replication and infection cell models. Methods: The positive regulatory effect of AM679 on EFTUD2 expression was validated by qPCR and Western blotting. HepAD38 and HepG2-NTCP cells were treated with AM679 (0.5, 1, and 2 nmol/L). Negative control, positive control, and AM679 combined with the entecavir group were set up. HBV DNA intra-and extracellularly, as well as the expression levels of intracellular HBV total RNAs and 3.5kb-RNA changes, were detected with qPCR. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) levels were measured in the cell supernatant by an enzyme-linked immunosorbent assay (ELISA). The t-test method was used for the statistical analysis of the mean difference between groups. Results: EFTUD2 mRNA and protein expression levels were significantly increased in HepAD38 and HepG2-NTCP cells following AM679 treatment, with a statistically significant difference (P < 0.001). Intra-and extracellular indicators such as HBV DNA, HBV RNAs, HBV 3.5kb-RNA, HBsAg, and HBeAg were decreased to varying degrees in both cell models, and the decrease in these indicators was more pronounced with the increase in AM679 concentration and prolonged treatment duration, while the combined use of AM679 and entecavir had a more significant antiviral effect. The HBV DNA inhibition rates in the supernatant of HepAD38 cells with the use of 2 nmol/L AM679 were 21% and 48% on days three and nine, respectively. The AM679 combined with the ETV treatment group had the most significant inhibitory effect (62%), with a P < 0.01. More active HBV replication was observed after silencing EFTUD2, while the antiviral activity of AM679 was significantly weakened. Conclusion: AM679 exerts anti-HBV activity in vitro by targeting the regulation of EFTUD2 expression.

[New progress on diagnosis and treatment for indeterminate-phase chronic hepatitis B virus-infected patients].

Authoritative guidelines at home and abroad typically classify chronic hepatitis B virus (HBV) infection into four stages. However, in clinical practice, a considerable number of patients do not meet the guidelines for staging and are called "indeterminate phase" chronic HBV- infected patients. Studies have shown that patients in the indeterminate phase account for about 30%-50% of chronic HBV infection, have significant liver histological changes or even cirrhosis in a large proportion, and are at a higher risk of HCC and death if they do not receive antiviral therapy. Preliminary research shows that patients in the indeterminate phase who receive antiviral treatment have a good virological response and a remarkable reduced HCC risk. To this end, the 2022 publication "Expert Opinions on Expanding Antiviral Treatment for Chronic Hepatitis B" recommends aggressive treatment for patients with an indeterminate phase who have undergone more than a year of follow-up. However, there is still a lack of unified standards to refine the classification, as well as a lack of effective and rapid non-invasive diagnostic methods to identify patients in the indeterminate phase who are at risk for disease progression. This article aims to review the researches on the proportion, clinical characteristics, disease progression, and treatment benefits to further explore how to better manage indeterminate-phase chronic HBV-infected patients.

Release mechanism and pharmacodynamics of entecavir micro spheres.

Entecavir, an effective anti-hepatitis B drug with low resistance rate, was designed as sustained-release micro spheres in our previous study. Here, we aimed to reveal the drug-release mechanism by observing the drug distribution and degradation behavior of poly (lactic-co-glycolic acid) and to investigate the pharmacodynamics of entecavir micro spheres. Raman spectroscopy was used to analyze the distribution of active pharmaceutical ingredients in the micro spheres. The results showed that there was little entecavir near the micro sphere surface. With increasing micro sphere depth, the drug distribution gradually increased and larger-size entecavir crystals were mainly distributed near the spherical center. The degradation behavior of poly (lactic-co-glycolic acid) was investigated using gel permeation chromatography. Changes in poly (lactic-co-glycolic acid) molecular weights during micro sphere degradation revealed that dissolution dominated the release process, which proved our previous research results. Pharmacodynamics studies on transgenic mice indicated that the anti-hepatitis B virus replication effect was maintained for 42 days after a single injection of entecavir micro spheres, similar to the effect of daily oral administration of entecavir tablets for 28 days. The entecavir micro spheres prepared in this study had a good anti-hepatitis B virus replication effect and it is expected to be used in anti hepatitis B virus treatment against hepatitis B virus.