Prevalence of hepatitis B and C viruses among migrant workers in Qatar.

Limited data exist on viral hepatitis among migrant populations. This study investigated the prevalence of current hepatitis B virus (HBV) infection and lifetime hepatitis C virus (HCV) infection among Qatar's migrant craft and manual workers (CMWs), constituting 60% of the country's population. Sera collected during a nationwide COVID-19 population-based cross-sectional survey on CMWs between July 26 and September 9, 2020, underwent testing for HBsAg and HCV antibodies. Reactive samples underwent confirmatory testing, and logistic regression analyses were employed to explore associations with HBV and HCV infections. Among 2528 specimens tested for HBV infection, 15 were reactive, with 8 subsequently confirmed positive. Three samples lacked sufficient sera for confirmatory testing but were included in the analysis through multiple imputations. Prevalence of current HBV infection was 0.4% (95% CI 0.2-0.7%). Educational attainment and occupation were significantly associated with current HBV infection. For HCV infection, out of 2607 specimens tested, 46 were reactive, and 23 were subsequently confirmed positive. Prevalence of lifetime HCV infection was 0.8% (95% CI 0.5-1.2%). Egyptians exhibited the highest prevalence at 6.5% (95% CI 3.1-13.1%), followed by Pakistanis at 3.1% (95% CI 1.1-8.0%). Nationality, geographic location, and occupation were significantly associated with lifetime HCV infection. HBV infection is relatively low among CMWs, while HCV infection falls within the intermediate range, both compared to global and regional levels.

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.

Nanoparticle/Engineered Bacteria Based Triple-Strategy Delivery System for Enhanced Hepatocellular Carcinoma Cancer Therapy.

Background: New treatment modalities for hepatocellular carcinoma (HCC) are desperately critically needed, given the lack of specificity, severe side effects, and drug resistance with single chemotherapy. Engineered bacteria can target and accumulate in tumor tissues, induce an immune response, and act as drug delivery vehicles. However, conventional bacterial therapy has limitations, such as drug loading capacity and difficult cargo release, resulting in inadequate therapeutic outcomes. Synthetic biotechnology can enhance the precision and efficacy of bacteria-based delivery systems. This enables the selective release of therapeutic payloads in vivo. Methods: In this study, we constructed a non-pathogenic Escherichia coli (E. coli) with a synchronized lysis circuit as both a drug/gene delivery vehicle and an in-situ (hepatitis B surface antigen) Ag (ASEc) producer. Polyethylene glycol (CHO-PEG2000-CHO)-poly(ethyleneimine) (PEI25k)-citraconic anhydride (CA)-doxorubicin (DOX) nanoparticles loaded with plasmid encoded human sulfatase 1 (hsulf-1) enzyme (PNPs) were anchored on the surface of ASEc (ASEc@PNPs). The composites were synthesized and characterized. The in vitro and in vivo anti-tumor effect of ASEc@PNPs was tested in HepG2 cell lines and a mouse subcutaneous tumor model. Results: The results demonstrated that upon intravenous injection into tumor-bearing mice, ASEc can actively target and colonise tumor sites. The lytic genes to achieve blast and concentrated release of Ag significantly increased cytokine secretion and the intratumoral infiltration of CD4/CD8+T cells, initiated a specific immune response. Simultaneously, the PNPs system releases hsulf-1 and DOX into the tumor cell resulting in rapid tumor regression and metastasis prevention. Conclusion: The novel drug delivery system significantly suppressed HCC in vivo with reduced side effects, indicating a potential strategy for clinical HCC therapy.

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.

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.

Investigating factors associated to HBV/HIV co-infected patients in antiretroviral treatment clinic, in Northeast Ethiopia.

BACKGROUND: Existing research in Ethiopia has primarily focused on the individual epidemiology of HIV and HBV, often overlooking the intricate dynamics of co-infection. This study aims to address this gap by comprehensively exploring the prevalence of HBV and HIV co-infection and the associated factors influencing co-infection rates within the specific context of ART clinics. The existing study provides limited insights into the unique challenges posed by this dual infection in the Ethiopian population receiving ART. METHODS: An institutional-based cross-sectional study was conducted among people living with HIV aged 18 years and above attending ART clinics in northeast Ethiopia from April to May 2022. A sample size of 350(97% response rate) participants was selected by using a systematic random sampling method. Data were collected using a pre-tested interviewer-administered structured questionnaire. Data was entered into Epi Data version software and was exported to SPSS version 25 for further analysis. Descriptive statistics using Frequency, proportion, and summary measures were done. Binary logistic regressions were done to identify independent variables associated with HBV infection among HIV patients. A P-value less than 0.05 and adjusted odds ratio with a 95% confidence interval non-inclusive of one was considered statistically significant. RESULTS: The prevalence of Hepatitis B Surface Antigen (HBsAg) was identified constituting 7.14% of the study population. Females [AOR] 0.14; 95% Confidence Interval [CI] [0.041-0.478]). Participants with an educational status of only reading and writing (AOR 8.7; 95% CI [1.143-66.5]). Single individuals (AOR 2.04; 95% CI [1.346-28.6]) were associated factors. Moreover, participants with a viral load exceeding 1000 copies/ml were 6.5 times more likely to be infected with HBV compared to those with undetectable viral loads (AOR 6.53, 95% CI [1.87-22.72]). Additionally, individuals with a CD4 count ranging from 351 to 500 cells/ml were 1.2 times more likely to be infected with HBV compared to those with a CD4 count of 500 cells/ml or above (AOR 10.4, 95% CI [1.28-85]). CONCLUSION: The prevalence of HBV infection was found to be intermediate in HIV-infected patients in the study area. Being male, marital status of single and divorced, educational level was only read and written, current viral load of > 1000 copies/ml &<1000 copies/ml, and current CD4 < 250 cells/ml were found statistically associated factors for HBV infection. Thus, we recommend the provision of routine screening for HBsAg and appropriate treatment with accurate information on risk factors for HBV to improve quality of life and reduce morbidity.

Hepatitis B virus infection among illegal drug users in Enugu State, Nigeria: prevalence, immune status, and related risk factors.

INTRODUCTION: Hepatitis B virus infection poses a global health challenge, particularly in low- and middle-income African countries. Illicit drug use exacerbates the problem, with drug users having a higher HBV infection risk and maintaining a quiet transmission pool. This study aimed to determine HBV infection prevalence, immune status, and risk factors among illegal drug users in Enugu State, Nigeria. MATERIALS AND METHODS: A cross-sectional study was conducted in Enugu State, using privileged access interviewer methods to enroll drug users. Pre-tested structured questionnaires were administered after informed consent was obtained. Blood samples were tested for HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb using immunochromatographic rapid test kits. Statistical analysis was performed using SPSS version 25. RESULTS: One hundred drug users were recruited into the study. Overall, 7% of the drug users had HBV infection. 61% were found to be susceptible to HBV infection, 15% showed serological evidence of immunity from HBV vaccination and 1% developed natural immunity from HBV exposure. Significant risk factors for HBV infection were age less than 20 years, young age (≤ 20 years) at drug initiation, being single, injecting drugs more than or equal to 20 times per month and injecting with used syringes. CONCLUSION: This study shows high intermediate endemicity of HBV infection among drug users, low vaccination uptake, and high susceptibility to HBV infection. This calls for the urgent inclusion of drug users in national HBV vaccination campaigns and the adoption of the World Health Organization's recommendations on the prevention of viral hepatitis among people who inject drugs.

Frequency of HBsAg variants in occult hepatitis B virus infected patients and detection by ARCHITECT HBsAg quantitative.

Objective: To analyze the amino acid substitution caused by mutations in the major hydrophilic region (MHR) of the S-region genes in the serum samples of occult hepatitis B virus infection (OBI), and to explore the reasons for the missed detection of HBsAg. Method: The full-length gene of the S-region in hepatitis B virus(HBV) in the chronic hepatitis B virus(CHB)(10 samples) and OBI groups(42 samples) was amplified using a lab-developed, two-round PCR amplification technology. The PCR amplification products were sequenced/clone sequenced, and the nucleotide sequences of the S-region gene in HBV were compared to the respective genotype consensus sequence. Results: Only 20 of the 42 samples in the OBI group had the S-region genes successfully amplified, with the lowest HBV DNA load of 20.1IU/ml. As S-region genes in HBV, 68 cloned strains were sequenced. In the OBI and CHB groups MHR region, with a mutation rate of 3.21% (155/4828) and 0.70% (5/710). The genetic mutation rate was significantly higher in the OBI group than in the CHB group (P<0.05). The common mutation types in the MHR region were: I126T, L162R, K122E, C124R, and C147Y.Mutations at s122, s126, and s162 were associated with subgenotypes, most of which being C genotypes. The high-frequency mutation sites L162R and K122E found in this study have not been reported in previous literature. Conclusion: The results of this study confirmed that MHR mutations can cause the missed detection of HBsAg, giving rise to OBI.

Decentralised same day test and treatment of hepatitis C levering existing peer support networks among men who inject drugs: feasibility and effectiveness.

BACKGROUND: Prevalence of hepatitis C virus (HCV) infection among people who inject drugs in the state of Manipur, India, is 43%; however, access to care is poor. We piloted a Community-led and comprehensive hepatitis care model that included same-day HCV treatment at drug treatment centres. METHODS: Screening was conducted through venipuncture samples collected by community peer PWID, using HCV antibody (HCV Ab) rapid screening and hepatitis B virus (HBV) surface antigen (HBsAg) rapid diagnostic tests. Reactive HCV Ab samples were tested for HCV RNA using near point-of-care Truenat® HCV on Truelab® Quattro. Eligible HCV RNA-positive participants were treated on the same day using direct-acting antivirals and followed for sustained virologic response (SVR). HBsAg-negative participants received rapid HBV vaccination regimen while those positive for HBsAg were tested for DNA and referred for treatment. RESULTS: Between November 2021 and August 2022, 643 individuals were approached and 503 consented and were screened. All screened were males with history of injection drug use, and a median age of 27 years (IQR 23-32). Of the 241 (47.9%) HCV Ab reactive all underwent RNA testing and 156 (64.7%) were RNA detectable. Of those with viraemia, 155 (99.4%) were initiated on treatment with 153 (98.1%) on same day, with 2 (1.2%) HBsAg positive and waiting for HBV DNA results. Among those 153, median time from HCV Ab screening to treatment was 6 h 38 min (IQR 5 h 42 min-8 h 23 min). In total 155 (100%) completed HCV treatment, of those 148 (95.5%) completed SVR testing and 130 (87.8%) achieved SVR12. 27 (5%) participants were HBsAg-positive, 3 (11.1%) were also living with HCV viraemia; 443 (97.6%) were eligible for vaccination and 436 (98.4%) received all 3 vaccine doses. CONCLUSION: Community-led hepatitis care incorporating same day "test and treat" for HCV was feasible and effective. HBV screening identified a large proportion who were unvaccinated. Peer support extended resulted in ensuring compliance to care and treatment cascade and completing all the three doses of HBV vaccination. As the screening, diagnostics infrastructure and vaccine are available in most countries with national viral hepatitis programs also in place, our model can be adapted or replicated to progress towards global elimination targets.

Therapeutic effectiveness analysis of tenofovir alafenamide and tenofovir disoproxil fumarate on the treatment for chronic hepatitis B.

To explore the therapeutic effectiveness of tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) on the treatment for chronic hepatitis B (CHB). Retrospectively analyzing 241 cases of chronic hepatitis B patients admitted to our hospital from January 2020 to December 2021, they were divided into a TAF group of 180 cases and a TDF group of 61 cases. The liver function, serum virus markers, clinical efficacy, adverse reactions and cost-effectiveness ratio (CER) analysis of 2 groups were compared. Two groups of patients had no statistically significant difference in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) before treatment. After treatment, the levels of ALT, AST and TBIL were lower than before treatment in both groups (P < .05), but the inter-group difference was not statistically significant (P > .05). After treatment, Hepatitis B surface antigen (HBsAg) conversion rate and Hepatitis B virus DNA (HBV-DNA) conversion rate in the 2 groups had no statistically significant difference. After treatment, the difference in total clinical cure rate between the 2 groups has no statistical significance (P > .05), adverse reactions rate of TAF group was lower than that of TDF group (P < .05). The drug cost median of TAF group was higher than that of TDF (P < .05), but Cost-effectiveness analysis showed the CER of TAF group was similar of TDF group. TAF or TDF therapy can both improve liver function and promote recovery in patients with CHB, achieving the goal of treatment. TAF have more cost but have similar CER to TDF. Moreover, TAF therapy has a higher safety profile.

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.

[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.

The association of the hepatitis B virus infection and diffuse large B-cell lymphoma.

OBJECTIVES: To investigate the basic characteristics of patients with diffuse large B-cell lymphoma (DLBCL) and whether hepatitis B surface antigen positive (HBsAg [+]) affects the survival of patients with DLBCL. METHODS: The study was carried out at Affiliated Hospital of Hebei University, Baoding, China, including 602 DLBCL cases from January 2011 to December 2021. We analyzed patients' general clinical data and applied multivariate and univariate Cox analyses to assess the factors influencing their survival times. RESULTS: The HBsAg(+) and HBsAg(-) groups comprised 154 (25.6%) and 448 (74.4%) of the 602 cases, respectively. HBsAg(+) cases tended to be later-stage (III-IV) with higher international prognostic index (IPI) points (3-5) and a greater tendency toward B symptoms, impaired liver function, and recurrence than HBsAg(-) cases (all p<0.05). After follow-up, 194 (32.2%) patients died. The median overall survival (OS) and 5-year OS rates in the HBsAg(+) and HBsAg(-) groups were 16.5 months (42%) and 35 months (63%), respectively. Cox analyses indicated that HBsAg(+) affected the prognosis of DLBCL cases (HR=1.46, 95%CI=1.07-1.99, p=0.017). CONCLUSION: The HBsAg(+) seems to be an independent hazard factor for the worse prognosis of DLBCL patients; hence, a focus on these patients in clinic is required.

Impact of Hepatitis B Surface and Core Antibody Levels on Hepatitis B Virus Reactivation.

Hepatitis B virus reactivation (HBV-R) is a serious complication that can occur in patients with resolved HBV infection during cancer chemotherapy. We examined the levels of HBV surface antibody (HBsAb) and HBV core antibody (HBcAb) to assess the incidence of HBV-R in cancer patients including hematopoietic stem cell transplantation (HSCT) and rituximab administration. This retrospective cohort study included 590 patients with resolved HBV infection. The incidence of HBV-R was evaluated 761.5 (range, 90-3898) days after the inititiation of chemotherapy. Of the patients, 13 (2.2%) developed HBV-R after the start of chemotherapy. All 13 patients exhibited lower HBsAb (<100 mIU/mL) levels at baseline. A higher level of HBcAb (≥100 cut off index (C.O.I.)) was a possible risk factor for HBV-R as well as HSCT and rituximab administration. The simultaneous presence of HBsAb <100 mIU/mL and HBcAb ≥100 C.O.I. increased the risk of HBV-R by 18.5%. Patients treated with rituximab were at a higher risk of HBV-R (18.4%) despite having HBcAb <100 C.O.I. Our results suggest that assessment of HBsAb and HBcAb levels prior to the chemotherapy is important for identifying patients at high risk of HBV-R, especially in solid cancers without HSCT and rituximab administration.

Genetic variability of hepatitis B virus in acute and in different phases of chronic infection in Brazil.

The selection pressure imposed by the host immune system impacts on hepatitis B virus (HBV) variability. This study evaluates HBV genetic diversity, nucleos(t)ide analogs resistance and HBsAg escape mutations in HBV patients under distinct selective pressures. One hundred and thirteen individuals in different phases of HBV infection were included: 13 HBeAg-positive chronic infection, 9 HBeAg-positive chronic hepatitis, 47 HBeAg-negative chronic infection (ENI), 29 HBeAg-negative chronic hepatitis (ENH) and 15 acute infected individuals. Samples were PCR amplified, sequenced and genetically analyzed for the overlapping POL/S genes. Most HBV carriers presented genotype A (84/113; 74.3%), subgenotype A1 (67/84; 79.7%), irrespective of group, followed by genotypes D (20/113; 17.7%), F (8/113; 7.1%) and E (1/113; 0.9%). Clinically relevant mutations in polymerase (tL180M/M204V) and in the Major Hydrophilic Region of HBsAg (sY100C, T118A/M, sM133T, sD144A and sG145R) were observed. Our findings, however, indicated that most polymorphic sites were located in the cytosolic loops (CYL1-2) and transmembrane domain 4 (TMD4) of HBsAg. Lower viral loads and higher HBV genetic diversity were observed in ENI and ENH groups (p < 0.001), suggesting that these groups are subjected to a higher selective pressure. Our results provide information on the molecular characteristics of HBV in a diverse clinical setting, and may guide future studies on the balance of HBV quasispecies at different stages of infection.

Synthesis and evaluation of pentacyclic triterpenoids conjugates as novel HBV entry inhibitors targeting NTCP receptor.

Chronic liver diseases caused by hepatitis B virus (HBV) are the accepted main cause leading to liver cirrhosis, hepatic fibrosis, and hepatic carcinoma. Sodium taurocholate cotransporting polypeptide (NTCP), a specific membrane receptor of hepatocytes for triggering HBV infection, is a promising target against HBV entry. In this study, pentacyclic triterpenoids (PTs) including glycyrrhetinic acid (GA), oleanolic acid (OA), ursolic acid (UA) and betulinic acid (BA) were modified via molecular hybridization with podophyllotoxin respectively, and resulted in thirty-two novel conjugates. The anti-HBV activities of conjugates were evaluated in HepG2.2.15 cells. The results showed that 66% of the conjugates exhibited lower toxicity to the host cells and had significant inhibitory effects on the two HBV antigens, especially HBsAg. Notably, the compounds BA-PPT1, BA-PPT3, BA-PPT4, and UA-PPT3 not only inhibited the secretion of HBsAg but also suppressed HBV DNA replication. A significant difference in the binding of active conjugates to NTCP compared to the HBV PreS1 antigen was observed by SPR assays. The mechanism of action was found to be the competitive binding of these compounds to the NTCP 157-165 epitopes, blocking HBV entry into host cells. Molecular docking results indicated that BA-PPT3 interacted with the amino acid residues of the target protein mainly through π-cation, hydrogen bond and hydrophobic interaction, suggesting its potential as a promising HBV entry inhibitor targeting the NTCP receptor.

The occurrence of immune-related adverse events is an independent risk factor both for serum HBsAg increase and HBV reactivation in HBsAg-positive cancer patients receiving PD-1 inhibitor combinational therapy.

Background: Previous studies have suggested the potential of PD-1/PD-L1 inhibitors in the treatment of chronic HBV infection. However, since phase III clinical trials have not yet been announced, additional clinical insights may be obtained by observing changes in serum hepatitis B surface antigen (HBsAg) and HBV-DNA levels in cancer patients undergoing PD-1 inhibitor therapy. Objective: To explore the effects of PD-1 inhibitor combinational therapy on serum HBsAg and HBV-DNA levels, investigate the incidence of HBsAg loss, HBV reactivation (HBVr), and immune-related adverse events (irAEs), and identify the risk factors associated with significant HBsAg fluctuations and HBVr. Methods: A retrospective study including 1195 HBsAg-positive cancer patients who received PD-1 inhibitors between July 2019 and June 2023 was conducted, and 180 patients were enrolled in this study. Serum HBsAg levels before and after PD-1 inhibitor administration were compared across different subgroups. The Pearson χ2 or Fisher exact test was performed to investigate the relationships between categorical variables. Univariable and multivariable analysis were performed to identify the risk factors associated with significant HBsAg fluctuations and HBVr. Results: With the concurrent use of antiviral agents, serum HBsAg levels decreased (Z=-3.966, P < 0.0001) in 129 patients and increased (t=-2.047, P=0.043) in 51 patients. Additionally, 7 patients (3.89%) achieved serum HBsAg loss. Virus replication was suppressed in most of the enrolled patients. When divided patients into different subgroups, significant HBsAg decreases after PD-1 inhibitor administration were discovered in lower baseline HBsAg group (Z=-2.277, P=0.023), HBeAg-seronegative group (Z=-2.200, P=0.028), non-irAEs occurrence group (Z=-2.007, P=0.045) and liver cancer group (Z=-1.987, P=0.047). Of note, 11 patients and 36 patients experienced HBVr (6.11%) and irAEs (20%), respectively, which could lead to discontinuation or delayed use of PD-1 inhibitors. After multivariable analysis, HBeAg-seropositive (OR, 7.236 [95% CI, 1.757-29.793], P=0.01) and the occurrence of irAEs (OR, 4.077 [95% CI, 1.252-13.273], P=0.02) were identified as the independent risk factors for significant HBsAg increase, the occurrence of irAEs (OR, 5.560 [95% CI, 1.252-13.273], P=0.01) was identified as the only independent risk factor for HBVr. Conclusion: PD-1 inhibitors combined with nucleos(t)ide analogues (NAs) may exert therapeutic potential for chronic HBV infection in cancer patients. However, attention also should be paid to the risk of significant elevation in HBsAg levels, HBVr, and irAEs associated with PD-1 inhibitor combinational therapy.

The effect of intrahepatic cholestasis in pregnancy combined with different stages of hepatitis B virus infection on pregnancy outcomes: a retrospective study.

BACKGROUND AND AIMS: To investigate the impact of intrahepatic cholestasis of pregnancy (ICP) with hepatitis B virus (HBV) infection on pregnancy outcomes. METHODS: We selected 512 pregnant women, collected the data including maternal demographics, main adverse pregnancy outcomes and maternal HBV infected markers HBeAg and HBV-DNA loads status, then have a comparative analysis. RESULTS: There were 319 solitary ICP patients without HBV infection (Group I) and 193 ICP patients with HBV infection. Of the latter, there were 118 cases with abnormal liver function(Group II) and 80 cases with normal liver function(Group III). All HBV-infected pregnant women with ICP were divided into hepatitis Be antigen (HBeAg)-positive group (102 cases) and HBeAg-negative group (91 cases), according to the level of the serum HBeAg status; and into high viral load group (92 cases), moderate viral load group (46 cases) and low viral load group (55 cases) according to the maternal HBV-DNA level. Group II had a higher level of serum total bile acids, transaminase, bilirubin as well as a higher percentage of premature delivery, neonatal intensive care unit (NICU) admission and meconium-stained amniotic fluid (MSAF) compared with the other two groups(P < 0.05), but there were no significant differences in the above indicators between the Group I and Group III. Among the HBV-infected patients with ICP, HBeAg-positive group had a higher level of serum transaminase, bilirubin and bile acid as well as earlier gestational weeks of delivery, lower birth weight of new-borns and a higher rate of NICU admission than HBeAg-negative group (P < 0.05). Those with a high viral load (HBV-DNA > 106 IU/ml) had a higher level of transaminase, bilirubin, and bile acid as well as shorter gestational weeks of delivery, lower birth weight of new-borns and a higher rate of NICU admission compared with those with a low or moderate viral load (P < 0.05). CONCLUSION: HBV-infected pregnant women with ICP combined with abnormal liver function have more severe liver damage, a higher percentage of preterm birth and NICU admission. HBeAg-positive status and a high HBV-DNA load will increase the severity of conditions in HBV-infected pregnant women with ICP. HBV-infected patients with ICP who have abnormal liver function, HBeAg-positive or a high viral load should be treated more actively.

[Analysis of clinical characteristics of persistent HBeAg positivity in patients with chronic hepatitis B treated with nucleos(t)ide analogues].

Objective: To explore the clinical characteristics of persistent HBeAg positivity in patients with chronic hepatitis B treated with nucleos(t)ide analogues. Methods: A retrospective analysis was performed according to different data types. An independent sample t-test, Mann-Whitney U test, chi-square test, or Fisher's exact probability method were used. Chronic hepatitis B patients followed up for four years were collected from the follow-up case database of the Department of Infectious Diseases of Zhongshan Third Hospital from January 2009 to December 2018 and were divided into two groups, A and B, with 87 and 145 cases respectively, according to the duration of HBeAg-negativity≤ 3 and persistent positivity >3 years. Statistical analysis was conducted on the age, gender, family history, baseline, follow-up visit duration, liver function, and other data among the two patient groups. Results: There were no statistically significant differences in gender, age, family history of liver cirrhosis, family history of liver cancer, liver cirrhosis condition before treatment, fatty liver disease combined condition before treatment, baseline HBsAg, anti-HBc, alanine aminotransferase, albumin, or total bilirubin between the two groups of patients (P > 0.05). HBV DNA and HBeAg were significantly higher in group B than those in group A at baseline, with P≤0.001. Aspartate aminotransferase and γ-glutamyl transferase were significantly higher in group A than those in group B at baseline. The proportion of family history of hepatitis B was significantly higher in group B (69.0%) than that in group A (50.6%) among the two groups of patients, and the difference was statistically significant (P = 0.005). The proportion of mothers with hepatitis B was significantly higher in group B (25.5%) than in group A (11.5%), P = 0.010. During the treatment process, the HBV DNA quantification was significantly higher in group B than that in group A at 0.5 and 1 years (P≤0.002). The proportion of HBV DNA <100IU/ml was also significantly different at six months and one year (χ(2)=30.327, P < 0.001 and χ(2)=11.779, P = 0.001). The HBsAg level was higher in group B than that of group A in the second and fourth years, P < 0.05. During the entire treatment process, the HBeAg level was significantly higher in group B than that in group A (P < 0.001). A total of seven cases developed liver cirrhosis or cancer during follow-up, including three cases in group A and four cases in group B (P > 0.05). Conclusion: HBeAg-positive patients with chronic hepatitis B have persistent HBeAg positivity when treated with long-term nucleos(t)ide analogues. Accordingly, a greater proportion of this kind of patient family and mothers have a remarkable history of hepatitis B and a reduced HBV DNA relapse rate in the early stages (within a year or less).

Risk of hepatitis B virus reactivation in oncological patients treated with tyrosine kinase inhibitors: A case report and literature analysis.

Hepatitis B virus (HBV) reactivation (HBVr) represents a severe and potentially life-threatening condition, and preventive measures are available through blood test screening or prophylactic therapy administration. The assessment of HBVr traditionally considers factors such as HBV profile, including hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen, along with type of medication (chemotherapy; immunomodulants). Nevertheless, consideration of possible patient's underlying tumor and the specific malignancy type (solid or hematologic) plays a crucial role and needs to be assessed for decision-making process.