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Despite high hepatitis B (HBV) prevalence among people of Vietnamese ethnicity in Australia and elsewhere, there is limited research on levels of HBV knowledge and factors associated with such knowledge. The aim of this study was to examine HBV knowledge and associated demographic and attitudinal factors among people of Vietnamese ethnicity in Australia. People of Vietnamese ethnicity ( n  = 966) were recruited through community events and social media groups to complete online surveys measuring HBV knowledge, attitudes towards HBV, levels of mistrust in Western medicine, and demographic characteristics. Findings of this study indicate that levels of knowledge are mixed, with gaps in knowledge related to transmission and treatment of the virus. Those with greater knowledge of HBV tended to be older, have higher levels of formal education, have been tested for HBV, and know someone living with HBV. Those with lower levels of knowledge tended to have more negative attitudes towards the virus and greater levels of mistrust in Western medicine. Given that health literacy is connected to effective communication from health providers, we suggest that there is a need for the development of health promotion and education resources targeted at people of Vietnamese ethnicity and translated into Vietnamese. We propose that such resources be developed in consultation with Vietnamese communities and health providers to ensure that they are culturally appropriate and sensitive to people of Vietnamese ethnicity living in Australia.

Research has shown that there are significant gaps in hepatitis B knowledge among migrant communities who are at risk of hepatitis B, such as Chinese and Vietnamese communities. Many students studying within Australia come from countries with high prevalence of hepatitis B. However, there is very little research examining hepatitis B knowledge, screening, or vaccination among university students in Australia or worldwide. The aim of this paper was to measure both levels of and demographic differences in hepatitis B screening and knowledge among Chinese and Vietnamese students in Australia. Online surveys were completed by 112 Chinese- and 95 Vietnamese-identifying students in Australia, measuring knowledge of hepatitis B, engagement in screening and vaccination, and demographic characteristics. Results show that although engagement in screening and vaccination for hepatitis B was high, there were significant gaps in knowledge around transmission of hepatitis B. There were also some key demographic differences in screening and knowledge. For instance, those born in Australia were more likely to have been screened compared to those born Mainland China, Hong Kong, or Vietnam. Chinese students born in Australia had lower levels of knowledge compared to those born in Mainland China or Hong Kong. Among both samples, knowing someone living with hepatitis B was associated with higher levels of knowledge. Findings underscore the need for education-based interventions to address the significant gaps that exist in knowledge around hepatitis B, with a specific need for culturally appropriate resources in a range of languages to cater to the diverse communities who may be at risk of hepatitis B., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To search for human protein-coding genes related to hepatocellular carcinoma (HCC) in the context of hepatitis B virus (HBV) infection, and perform prognosis risk assessment., Methods: Genes related to HBV-HCC were selected through literature screening and protein-protein interaction (PPI) network database analysis. Prognosis potential genes (PPGs) were identified using Cox regression analysis. Patients were divided into high-risk and low-risk groups based on PPGs, and risk scores were calculated. Kaplan-Meier plots were used to analyze overall survival rates, and the results were predicted based on clinicopathological variables. Association analysis was also conducted with immune infiltration, immune therapy, and drug sensitivity. Experimental verification of the expression of PPGs was done in patient liver cancer tissue and normal liver tissue adjacent to tumors., Results: The use of a prognosis potential genes risk assessment model can reliably predict the prognosis risk of patients, demonstrating strong predictive ability. Kaplan-Meier analysis showed that the overall survival rate of the low-risk group was significantly higher than that of the high-risk group. There were significant differences between the two subgroups in terms of immune infiltration and IC50 association analysis. Experimental verification revealed that CYP2C19, FLNC, and HNRNPC were highly expressed in liver cancer tissue, while UBE3A was expressed at a lower level., Conclusion: PPGs can be used to predict the prognosis risk of HBV-HCC patients and play an important role in the diagnosis and treatment of liver cancer. They also reveal their potential role in the tumor immune microenvironment, clinical-pathological characteristics, and prognosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: We sought to characterize in people with human immunodeficiency virus (PWH) the potential etiologies of elevated alanine aminotransferase (ALT) levels, which are common and often unexplained., Methods: Participants from the longitudinal observational AIDS Clinical Trials Group HAILO cohort without a history of hepatitis C virus (HCV) or hepatitis B virus (HBV) infection nor reported heavy alcohol use were included. Clinical and demographic characteristics, including medication use, the hepatic steatosis index (HSI), and metabolic syndrome (MetS) were compared between participants with and without ALT elevation., Results: Six hundred sixty-two participants were included; 444 (67%) had ≥1 and 229 (35%) ≥2 consecutive ALT elevations during a median of 4.0 years of follow-up. HSI and Hispanic or other (non-White or Black) race/ethnicity were consistently associated with higher odds of abnormal ALT (odds ratio [OR] 1.1 for HSI as a continuous variable, OR 1.9-2.8 for Hispanic/other race/ethnicity for ≥1 or ≥2 ALT elevations); older age and current smoking were associated with lower odds of abnormal ALT. Associations with metabolic disease, as well as with incident HBV and HCV infection, were strengthened by restricting outcomes to persistent and higher degrees of ALT elevation., Conclusions: ALT elevation was common in this cohort of PWH and associated with metabolic disease and hepatic steatosis markers. Nonalcoholic fatty liver disease is likely a common cause of liver inflammation in PWH receiving suppressive antiretrovirals, deserving targeted diagnosis and intervention., Competing Interests: Potential Conflicts of Interest. K. W. C. has received research funding to the institution from Merck Sharp & Dohme (grant) and Amgen (research contract), and served as a paid consultant for Pardes Biosciences, and reports payments and honoraria for CME presentations by a not-for-profit organization from International Antiviral Society-USA, and participation as Chair of a Safety Monitoring Committee for an investigator-initiated study where the sponsor is UCSF. F. J. P. has received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from ViiV, Janssen, Gilead, and Merck. S. N. has received research funding to the institution from Gilead Sciences and AbbVie Pharmaceuticals, served as a paid consultant for Pardes Biosciences, Theratechnologies, and Silverback Therapeutics, and served on an Advisory Board for Vir Biotechnology, a Data Safety Monitoring Board (DSMB) for Personal Health Insights, Inc, and an Event Adjudication Committee for Bristol-Myers Squibb/PRA, and reports stocks and stock options from Vir Biotechnology. E. T. O. has received research funding to the institution from Gilead Sciences and ViiV Healthcare, served as a consultant for ViiV Healthcare, Merck, and Theratechnologies, and reports stock or stock options from GSK, and since the completion of the analysis has become an employee of ViiV Healthcare. M. S. has served on a DSMB for Gilead and AbbVie, and on Advisory Boards for Abbvie, Arbutus, Assembly Bio, Antios, Gilead, GSK, Precision Bio, and Virion, and reports other financial or non-financial interests as the Editor, Journal of Viral Hepatitis, Wiley. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Hepatitis B virus (HBV) infection has been associated with an increased risk for B-cell lymphomas. We previously showed that 20% of diffuse large B-cell lymphoma (DLBCL) patients from China, an endemic area of HBV infection, have chronic HBV infection (surface antigen-positive, HBsAg+) and are characterized by distinct clinical and genetic features. Here, we showed that 24% of follicular lymphoma (FL) Chinese patients are HBsAg+. Compared with the HBsAg- FL patients, HBsAg+ patients are younger, have a higher histological grade at diagnosis, and have a higher incidence of disease progression within 24 months. Moreover, by sequencing the genomes of 109 FL tumors, we observed enhanced mutagenesis and distinct genetic profile in HBsAg+ FLs, with a unique set of preferentially mutated genes (TNFAIP3, FAS, HIST1H1C, KLF2, TP53, PIM1, TMSB4X, DUSP2, TAGAP, LYN, and SETD2) but lack of the hallmark of HBsAg- FLs (ie, IGH/BCL2 translocations and CREBBP mutations). Transcriptomic analyses further showed that HBsAg+ FLs displayed gene-expression signatures resembling the activated B-cell-like subtype of diffuse large B-cell lymphoma, involving IRF4-targeted genes and NF-κB/MYD88 signaling pathways. Finally, we identified an increased infiltration of CD8+ memory T cells, CD4+ Th1 cells, and M1 macrophages and higher T-cell exhaustion gene signature in HBsAg+ FL samples. Taken together, we present new genetic/epigenetic evidence that links chronic HBV infection to B-cell lymphomagenesis, and HBV-associated FL is likely to have a distinct cell-of-origin and represent as a separate subtype of FL. Targetable genetic/epigenetic alterations identified in tumors and their associated tumor microenvironment may provide potential novel therapeutic approaches for this subgroup of patients., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Hepatitis B virus (HBV) infection remains a major global health problem and the primary cause of cirrhosis and hepatocellular carcinoma (HCC). HBV intrusion into host cells is prompted by virus-receptor interactions in clathrin-mediated endocytosis. Here, we report a comprehensive view of the cellular endocytosis-associated transcriptome, proteome and ubiquitylome upon HBV infection. In this study, we quantified 273 genes in the transcriptome and 190 endocytosis-associated proteins in the proteome by performing multi-omics analysis. We further identified 221 Lys sites in 77 endocytosis-associated ubiquitinated proteins. A weak negative correlation was observed among endocytosis-associated transcriptome, proteome and ubiquitylome. We found 33 common differentially expressed genes (DEGs), differentially expressed proteins (DEPs), and Kub-sites. Notably, we reported the HBV-induced ubiquitination change of secretory carrier membrane protein (SCAMP1) for the first time, differentially expressed across all three omics data sets. Overexpression of SCAMP1 efficiently inhibited HBV RNAs/pgRNA and secreted viral proteins, whereas knockdown of SCAMP1 significantly increased viral production. Mechanistically, the EnhI/XP, SP1, and SP2 promoters were inhibited by SCAMP1, which accounts for HBV X and S mRNA inhibition. Overall, our study unveils the previously unknown role of SCAMP1 in viral replication and HBV pathogenesis and provides cumulative and novel information for a better understanding of endocytosis in response to HBV infection.

Purpose: To investigate the association between maternal HBsAg-positive status and pregnancy outcomes., Methods: The study enrolled women with singleton pregnancies who delivered during January-December 2018. Data of maternal demographics and main adverse pregnancy outcomes were collected from the institutional medical records and analyzed by univariate and multivariate logistic regression models to determine the association between maternal HBV markers (HBsAg/HBeAg/HBV-DNA loads status) and adverse pregnancy outcomes., Results: Total 1146 HBsAg-positive and 18,354 HBsAg-negative pregnant women were included. After adjusting for potential confounding variables, maternal HBsAg-positive status was associated with a high risk of gestational diabetes mellitus (GDM) [adjusted odds ratio (aOR) = 1.24; 95% confidence interval (CI) 1.07-1.43], intrahepatic cholestasis of pregnancy (ICP) (aOR = 3.83; 95% CI 3.14-4.68), preterm birth (aOR = 1.42; 95% CI 1.17-1.72), and neonatal asphyxia (aOR = 2.20; 95% CI 1.34-3.63). Further, higher risks of ICP and neonatal asphyxia remained with either HBeAg-positive status (aOR = 1.64; 95% CI 1.10-2.44; aOR = 3.08; 95% CI 1.17-8.00) or high HBV-DNA load during the second trimester (aOR = 1.52; 95% CI 1.06-2.35; aOR = 4.20; 95% CI 4.20-15.83) among HBsAg-positive pregnant women., Conclusion: Women with maternal HBsAg-positive status may have increased risks of GDM, ICP, preterm birth, and neonatal asphyxia; furthermore, the risks of ICP and neonatal asphyxia were higher in women with HBeAg-positive status and a high HBV-DNA load during the second trimester among the HBsAg-positive pregnant women, implying that careful surveillance for chronic HBV infection during pregnancy is warranted.

Hepatitis B virus (HBV) replication is controlled by four promoters (preS1, preS2, Cp, and Xp) and two enhancers (EnhI and EnhII). EnhII stimulates Cp activity to regulate the transcriptions of precore, core, polymerase, and pregenomic RNAs, and therefore, EnhII/Cp is essential for the regulation of HBV replication. This study revealed a distinct mechanism underlying the suppression of EnhII/Cp activation and HBV replication. On the one hand, the sex determining region Y box2 (SOX2), a transcription factor, is induced by HBV. On the other hand, SOX2, in turn, represses the expression levels of HBV RNAs, HBV core-associated DNA, hepatitis B surface antigen (HBsAg), and hepatitis B e antigen (HBeAg), thereby playing an inhibitory role during HBV replication. Further studies indicated that SOX2 bound to the EnhII/Cp DNA and repressed the promoter activation. With the deletion of the high mobility group (HMG) domain, SOX2 loses the ability to repress EnhII/Cp activation, viral RNA transcription, HBV core-associated DNA replication, HBsAg and HBeAg production, as well as fails to enter the nucleus, demonstrating that the HMG domain is required for the SOX2-mediated repression of HBV replication. Moreover, SOX2 represses HBsAg and HBeAg secretion in BALB/c mice sera, and attenuates HBV 3.5kb RNA transcription and hepatitis B virus core protein (HBc) production in the liver tissues, demonstrating that SOX2 suppresses HBV replication in mice. Furthermore, the results revealed that the HMG domain was required for SOX2-mediated repression of HBV replication in the mice. Taken together, the above facts indicate that SOX2 acts as a new host restriction factor to repress HBV replication by binding to the viral EnhII/Cp and inhibiting the promoter activation through the HMG domain., Competing Interests: The authors declare no conflict of interest.

Objective: Hepatitis B virus (HBV) causes inflammation of the liver and is the leading cause of both liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Serine protease inhibitor Kazal type 1 (SPINK1) is an acute-phase response protein that is overexpressed in liver cancer tissue. This study investigated the clinical value of SPINK1 with regard to the diagnosis of HBV-related diseases and its regulatory mechanism., Methods: Serum levels of SPINK1 in HBV-infected patients and healthy participants were detected by enzyme-linked immunosorbent assay (ELISA). Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting were used to detect differential expression of SPINK1 mRNA and protein in HepG2 and HepG2.2.15 cells. The HBV infectious clone pHBV1.3 and its individual genes were cotransfected into HepG2 cells with the SPINK1 promoter coupled to a luciferase reporter; luciferase activity was measured, and the expression levels of SPINK1 were examined., Results: Serum SPINK1 levels of HBV-infected patients were significantly higher than those of healthy participants, and the serum levels of SPINK1 in patients who tested positive for HBeAg were significantly higher than those in patients who tested negative for HBeAg. The serum SPINK1 levels of patients with LC or HCC were markedly higher than those of patients with chronic hepatitis. The HBV X protein (HBx) activated the SPINK1 promoter to upregulate expression of SPINK1 at both mRNA and protein levels., Conclusions: HBV enhances expression of SPINK1 through X. SPINK1 levels are increased during progression of HBV-related diseases and might be utilized as a biomarker for the diagnosis of HBV-related diseases.

Hepatitis B virus (HBV) infection is endemic in some parts of Asia, Africa, and South America and remains to be a significant public health problem in these areas. It is known as a leading risk factor for the development of hepatocellular carcinoma, but epidemiological studies have also shown that the infection may increase the incidence of several types of B-cell lymphoma. Here, by characterizing altogether 275 Chinese diffuse large B-cell lymphoma (DLBCL) patients, we showed that patients with concomitant HBV infection (surface antigen positive [HBsAg + ]) are characterized by a younger age, a more advanced disease stage at diagnosis, and reduced overall survival. Furthermore, by whole-genome/exome sequencing of 96 tumors and the respective peripheral blood samples and targeted sequencing of 179 tumors from these patients, we observed an enhanced rate of mutagenesis and a distinct set of mutation targets in HBsAg + DLBCL genomes, which could be partially explained by the activities of APOBEC and activation-induced cytidine deaminase. By transcriptome analysis, we further showed that the HBV-associated gene expression signature is contributed by the enrichment of genes regulated by BCL6, FOXO1, and ZFP36L1. Finally, by analysis of immunoglobulin heavy chain gene sequences, we showed that an antigen-independent mechanism, rather than a chronic antigenic simulation model, is favored in HBV-related lymphomagenesis. Taken together, we present the first comprehensive genomic and transcriptomic study that suggests a link between HBV infection and B-cell malignancy. The genetic alterations identified in this study may also provide opportunities for development of novel therapeutic strategies., (© 2018 by The American Society of Hematology.)

Hepatitis B virus (HBV) reactivation is a remarkable risk during the chemotherapy for solid tumour patients. Nucleos(t)ide analogues (NAs) are recommended as prophylaxis for the reactivation of HBV infection in some cancer patients prior to systemic chemotherapy. Therefore, we performed a meta-analysis aiming to determine the efficacy of prophylactic lamivudine on prevention of HBV reactivation and its related negative outcomes among solid tumour patients with chronic HBV infection receiving systemic chemotherapy. The primary outcome was HBV reactivation, and the secondary outcomes were HBV-related hepatitis, chemotherapy disruption, mortality and tyrosine-methio-nine-aspartate-aspartate (YMDD) mutations. Twelve original researches involving 1,101 patients were analysed in this study. The relative risk of HBV reactivation in patients with lamivudine prophylaxis was significantly lower than that without prophylaxis (RR = 0.17, 95% CL: 0.10-0.29, p < .00001). Lamivudine prophylaxis reduced the relative risk of hepatitis (p < .00001), chemotherapy disruptions (p = .01) and mortality (p = .08) due to HBV reactivation. Lamivudine prophylaxis is effective in reducing HBV reactivation and its related negative outcomes, such as hepatitis and chemotherapy disruption and mortality among chemotherapeutic solid tumour patients with chronic HBV infection. Future studies should lay more emphasis on the early HBV screening, mode of treatment and duration of NAs prophylaxis among solid tumour patients receiving chemotherapy., (© 2017 John Wiley & Sons Ltd.)

Hepatitis B virus (HBV) is a major etiologic agent of hepatocellular carcinoma (HCC). However, the molecular mechanism by which HBV infection contributes to HCC development is not fully understood. Here, we initially showed that HBV stimulates the production of cancer stem cells (CSCs)-related markers (CD133, CD117 and CD90) and CSCs-related genes (Klf4, Sox2, Nanog, c-Myc and Oct4) and facilitates the self-renewal of CSCs in human hepatoma cells. Cellular and clinical studies revealed that HBV facilitates hepatoma cell growth and migration, enhances white blood cell (WBC) production in the sera of patients, stimulates CD133 and CD117 expression in HCC tissues, and promotes the CSCs generation of human hepatoma cells and clinical cancer tissues. Detailed studies revealed that PreS1 protein of HBV is required for HBV-mediated CSCs generation. PreS1 activates CD133, CD117 and CD90 expression in normal hepatocyte derived cell line (L02) and human hepatoma cell line (HepG2 and Huh-7); facilitates L02 cells migration, growth and sphere formation; and finally enhances the abilities of L02 cells and HepG2 cells to induce tumorigeneses in nude mice. Thus, PreS1 acts as a new oncoprotein to play a key role in the appearance and self-renewal of CSCs during HCC development., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We performed a case-control study to investigate the prevalence and clinicopathological features of breast cancer patients with hepatitis B virus (HBV) infection in China. The clinical data for 2,796 female patients with newly diagnosed, primary breast cancer were evaluated. A total of 234 breast cancer patients with HBV infection (the case group; positive for hepatitis B surface antigen [HBsAg]) and 444 breast cancer patients without HBV infection (the control group; negative for HBsAg, hepatitis B surface antibody, hepatitis B envelope antigen, hepatitis B envelope antibody, and hepatitis B core antibody) were selected for study. Analysis of the clinicopathological features revealed that the metastatic axillary lymph node ratio was lower in the case group than the control group, as was the proportion of patients with pathological T stage ≥T2. No differences in the expression levels of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, p53, or Ki67 were observed between the case and control groups. These data indicate that the rate of HBV infection is high among female breast cancer patients in China, and that HBsAg-positive breast cancer patients were generally diagnosed at an earlier stage and had fewer lymph node metastases.

Our report aimed to investigate the physiopathological patterns of liver lesions patients during hepatitis. After being diagnosed clinically as hepatopathy (n=9), the liver biopsy samples were prepared to paraffin-sections and further subjected to routine and immunohistochemical stains. Among these lesioned livers invaded by viruses, immunity-regulatory molecules, such as CD20, CD4 and CD8, were significantly expressed. In addition, antigens of the hepatitis B virus (HBsAg and HBcAg) were positively detected in non-dependent way of hepatitis intervention. Furthermore, the pro-fibrotic promotor of vimentin (Vim) was labelled immunologically in mesenchymal cells within virus-attacked livers. These observations provide the clinicopathologic evidences that there is a potential association between immunodeficiency and collagenation in hepatitis patients when liver injury development. It also manifests that regulation of intrahepatic immunologic response may inhibition of excessive collagen generation prior to further progressing to hepatofibrosis.

Hepatitis B virus (HBV) infection is a major cause of liver diseases. However, the mechanisms underlying HBV infection and pathogenesis remain largely unknown. The sex-determining region Y box 4 (Sox4) is a transcriptional factor, which preferentially regulates the development of various organs, tissues, and cancers. But, the role of Sox4 in viral infection and pathogenesis has not been elucidated. Here, we demonstrated that Sox4 is up-regulated by HBV, and revealed the mechanism by which HBV regulates Sox4 expression. First, HBV stimulates Sox4 expression through transcriptional factor Yin Yang 1 (YY1), which binds to Sox4 promoter to activate Sox4 transcriptional activity. Second, miR-335, miR-129-2 and miR-203 inhibit Sox4 expression by targeting its mRNA 3'UTR, while HBV suppresses the microRNAs expression, resulting in up-regulating Sox4 post-transcriptionally. Third, Sox4 protein is degraded by proteasome, while HBV surface protein (HBsAg) prevents Sox4 from degradation by directly interacting with the protein, thereby enhancing Sox4 production post-translationlly. More interestingly, HBV-activated Sox4 in turn facilitates HBV replication by direct binding to the viral genome via its HMG box. Thus, this study revealed a novel positive feedback mechanism by which Sox4 production and HBV replication are tightly correlated.

Objectives: To characterize HIV/hepatitis B virus (HBV) coinfection in the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort and compare long-term HBV outcomes between regimens with 1 (MONO) or 2 (DUAL) anti-HBV agents., Design: A retrospective study of coinfected AIDS Clinical Trials Group Longitudinal Linked Randomized Trials subjects who received regimens containing anti-HBV agent(s)., Methods: Stored samples at baseline and weeks 16, 32, 48, 144, and 240 were tested for HBV DNA, HBV e antigen (HBeAg), HBV e antibody (HBeAb), and hepatitis D virus (HDV) antibody. Resistance and genotype were tested in samples with HBV DNA >600 IU/mL. MONO versus DUAL analyses were limited to HBV treatment-naive subjects (Naive-MONO, Naive-DUAL)., Results: Of 150 study subjects, median age was 40 years, 96% were male; 57% white, 26% black, 13% Hispanic. Baseline median CD4 was 224 cells per cubic millimeter, HIV RNA 4.48 log10 copies/mL, HBV DNA 6.30 log10 IU/mL; 59% HBeAg positive and 65% HBeAb negative; HBV genotypes A = 69%, G = 18%, D = 7%, <2% for A/G, B, C, F, H. Coinfection with HDV was 2%. There were 49 Naive-MONO (lamivudine) and 22 Naive-DUAL (11 lamivudine + tenofovir, 11 emtricitabine + tenofovir) with detectable HBV DNA. In the 240-week follow-up, HBV DNA suppression was not significantly higher in Naive-DUAL (P = 0.14); lower baseline HBV DNA (P < 0.01) was associated with suppression. Among 32 Naive-MONO subjects with detectable HBV DNA at baseline and results at week 48, 41% suppressed; among such 15 Naive-DUAL subjects, 53% suppressed. HBeAg and HBeAb analyses showed similar trends., Conclusions: While consistent trends toward increased HBV DNA suppression, HBeAg loss and HBeAb seroconversion were observed in Naive-DUAL compared with Naive-MONO, they were not statistically significant. Overall, HDV coinfection was low.

Objective: To explore seroepidemiological status and vaccine coverage of hepatitis B in children aging under 15 years old in Chaoyang district of Beijing., Methods: A total of 1602 children aging under 15 years old, residents or floating population who had lived here more than six months, were randomly selected by multistage cluster sampling, from Chaoyang district of Beijing in year 2010. The demographic information and vaccine coverage of hepatitis B vaccine (HepB) were collected by self-designed questionnaire.5 ml blood was collected from each subject and the serum HBsAg, anti-HBs and anti-HBc were detected by Abbott microparticle enzyme-linked immunoassay. Those whose HBsAg was positive were then tested HBeAg and anti-HBe. The positive rate of hepatitis B indicators and coverage rate of HepB in different population were compared., Results: The positive rate of HBsAg, anti-HBs and anti-HBc were 0.56% (9/1602), 64.17% (1028/1602) and 2.12% (34/1602), respectively; while the age standardized rates were separately 0.57%, 66.36% and 1.98%; and the gender-adjusted rates were 0.56%, 64.23% and 2.12% respectively. The positive rate of anti-HBs was statistically significant (χ(2) = 165.445, P = 0.000). The positive rate of anti-HBs was up to 90.73% (235/259) among 1-2 years old children, followed by 76.22% (141/185) among 13 - 15 years old children, 67.21% (166/247) among 3 - 4 years old children, 61.22% (150/245) among 9 - 10 years old children, 60.68% (142/234) among 11 - 12 years old children, 49.05% (103/210) among 5 - 6 years old children and 40.99% (91/222) among 7 - 8 years old children. The average coverage rate of HepB was 90.44% (1371/1516), separately 93.76% (661/705) in residents and 87.55% (719/811) in floating population. The difference was statistically significant (χ(2) = 16.829, P = 0.000)., Conclusion: HBsAg positive rate in children under 15 years old in Chaoyang district of Beijing dropped to less than 1% and the coverage rate of HepB had reached over 90%. It is suggested that we should pay more attention to increase the coverage rate of HepB among floating children under 15 years old.

Background: The aim of this study was to investigate the correlation between the expression of hepatitis B surface antigen (HBsAg) in human ovary and placenta and the vertical transmission of hepatitis B virus (HBV)., Methodology/principal Fidnings: Ovarian and placental tissue specimens of pregnant women infected with HBV were collected during cesarean section and immunostained for HBsAg. The sera of the corresponding newborns were tested for HBV markers and HBV DNA. HBsAg was detected in 15 out of 33 (45%) placental tissues and was further detected in capillary endothelial cells in 4 specimens (26%), of which 3 (75%) corresponding infants were infected with HBV in utero. Out of the 33 ovarian tissues, 7 (21%) were positive for HBsAg, of which 2 (28%) showed HBsAg in ovarian follicles and the 2 corresponding infants (100%) had intrauterine HBV infection., Conclusions/significance: HBsAg expression in cells of the ovarian follicle or placental capillary endothelium signal a higher risk for intrauterine HBV infection.

Unlabelled: The interaction between T cell immunoglobulin- and mucin-domain-containing molecule (Tim-3) expressed on T helper 1 (Th1) cells, and its ligand, galectin-9, negatively regulates Th1-mediated immune responses. However, it is poorly understood if and how the Tim-3/galectin-9 signaling pathway is involved in immune escape in patients with hepatocellular carcinoma (HCC). Here we studied the expression, function, and regulation of the Tim-3/galectin-9 pathway in patients with hepatitis B virus (HBV)-associated HCC. We detected different levels of galectin-9 expression on antigen-presenting cell (APC) subsets including Kupffer cells (KCs), myeloid dendritic cells (DCs), and plasmacytoid DCs in HCC. The highest galectin-9 expression was on KCs in HCC islets, not in the adjacent tissues. Furthermore, Tim-3 expression was increased on CD4(+) and CD8(+) T cells in HCC as compared to the adjacent tissues, and Tim-3(+) T cells were replicative senescent and expressed surface and genetic markers for senescence. Interestingly, tumor-infiltrating T-cell-derived interferon (IFN)-γ stimulated the expression of galectin-9 on APCs in the HCC microenvironment. Immunofluorescence staining revealed a colocalization of Tim-3(+) T cells and galectin-9(+) KCs in HCC. Functional studies demonstrated that blockade of the Tim-3/galectin-9 signaling pathway importantly increased the functionality of tumor-infiltrating Tim-3(+) T cells as shown by increased T-cell proliferation and effector cytokine production. Finally, we show that the numbers of Tim-3(+) tumor-infiltrating cells were negatively associated with patient survival., Conclusion: Our work demonstrates that the Tim-3/galectin-9 signaling pathway mediates T-cell senescence in HBV-associated HCC. The data suggest that this pathway could be an immunotherapeutic target in patients with HBV-associated HCC., (Copyright © 2012 American Association for the Study of Liver Diseases.)

The purpose of this study was to investigate the efficacy and safety of lamivudine (LAM) in stopping the vertical transmission of hepatitis B virus (HBV). Pregnant women with normal alanine transaminase (ALT) (n = 100) and with abnormal ALT (n = 100) who were positive for hepatitis B e antigen (HBeAg), and with HBV DNA (deoxyribonucleic acid) levels ≥1.0 × 107 copies/ml were enrolled in this study. One hundred volunteers (50 with normal ALT, 50 with abnormal ALT) received 100 mg of LAM daily from the 24th to 32nd week of gestation and the untreated 100 volunteers served as controls. All infants received passive-active immunoprophylaxis. Compared to the control group, the study group got a marked reduction in serum levels (P < 0.001) and high negativity (P < 0.001) of HBV DNA before delivery. They also got normalization in ALT levels as much as controls received general medication (P > 0.05). The prenatal transmission rate in the study group was significantly lower than that of the control group (P < 0.05). There were no differences in incidences of congenital malformation between the two groups (P > 0.05). LAM treatment can effectively and safely stop vertical transmission of HBV and normalize the ALT levels of pregnant women.

Objective: To explore the family aggregation and risk factors of hepatitis B virus (HBV) transmission in Chaoyang district of Beijing., Methods: A total of 5266 families were randomly selected for the multi-stage cluster sampling study in Chaoyang district of Beijing in 2010. The family members who aged between 1 and 70 years old and lived constantly in Beijing for over half a year, were recruited as subjects. There were 14 491 subjects in total, including temporary residents who did not have Beijing household account, except foreigners. 5 ml venous blood was drawn from every subject. A self-designed questionnaire was used to collect the basic information of the population and the risk factors of the hepatitis B transmission. Microparticle enzyme-linked immunoassay was applied to test five indicators of hepatitis B. Negative binomial distribution test was used among the HBsAg positive families to calculate the family aggregation rate of hepatitis B. Single factor analysis and multi-factor logistic regression model were used to analyze the risk factors of HBV transmission., Results: In all, 308 out of 5266 families had HBsAg positive members, accounting for 5.85%.383 out of 14 410 subjects were HBsAg positive, rating at 2.66%. The HBsAg positive rate among subjects under 14 years old was the lowest, at 0.56% (9/1603); and the positive rate among subjects aging between 35 and 44 years old was the highest, at 4.27% (47/1029). Negative binomial distribution test showed that the family aggregation rate of HBV infection was 7.66% (χ² = 15.10, P < 0.05). The analysis of family aggregation of HBsAg positive showed that 17.39% (8/46) of the transmission was from father to child, 13.04% (6/46) was from mother to child, 30.44% (14/46) was between couples, and another 39.13% (18/46) was between siblings or other relatives. Both single factor analysis and multi-factor logistic regression analysis showed that hepatitis B positive family members (OR = 5.40, 95%CI: 5.24 - 5.55), hepatitis B positive friends and colleagues (OR = 1.55, 95%CI: 1.11 - 1.99) and blood donation and transfusion history (OR = 1.96, 95%CI: 1.76 - 2.15) were the risk factors of HBV infection., Conclusion: HBV transmission showed family aggregation in Beijing, however, the risk factors needed further studies.

This study aimed to investigate the relationship between hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in the ovary and vertical transmission of HBV. HBV DNA and HBV cccDNA were assayed in the ovaries of 33 pregnant women who were positive for HBV DNA. The HBVM (HBV markers, including HBsAg, HBsAb, HBeAg, HBeAb, HBcAb) level and the HBV DNA content in peripheral blood of infants were measured. The overall positive rate of HBV DNA and HBV cccDNA in samples was 51·52% (17/33). The intrauterine infection rate of the infants was 12·12% (4/33). When HBV DNA and HBV cccDNA were both positive, the intrauterine infection rate of infants was significantly higher than when they were both negative (P<0·05). Levels of HBV cccDNA and the rate of positive samples were significantly higher in mothers with infants with intrauterine infection than in those without (P<0·01 and P<0·05, respectively). HBV can infect the human ovary and may transmit to the filial generation via the ovum.

Objective: To study the prevalence of hepatitis B infections and carrier status among general population in Chaoyang district, Beijing in 2010., Methods: From May to December 2010, 14 491 subjects over 12 months old were selected by multistage random cluster sampling method from residents in Chaoyang district, Beijing. Five millilitre venous blood specimens were collected from these subjects to test hepatitis B virus antigens and antibodies. Status of hepatitis B infections were analyzed in different age, sex and registered permanent residence groups., Results: The overall positive rate of surface antigen (HBsAg) was 2.66% (383/14 410). The lowest rate of 0.56% (9/1603) was found in the 1 to 14 years old group and the 35 to 44 years old group had the highest rate of 4.27% (92/2154). The rate in subjects younger than 24 years old was 1.03% (31/2986). The overall positive rate of surface antibody (anti-HBs) was 40.21% (5798/14 421). The highest positive rate of anti-HBs (80.59%, 407/505) was found in the 1 to 4 years old group. The overall positive rate of core antibody (anti-HBc) was 30.26% (4364/14 424). The overall hepatitis B virus infection rate was 30.32% (4364/14 393). For male and female groups, the positive rates of HBsAg were 2.93% (179/6108) and 2.44% (202/8287) respectively (χ² = 3.32, P > 0.05); anti-HBs were 41.93% (2563/6113) and 38.96% (3231/8293) respectively (χ² = 12.88, P < 0.01); and anti-HBc were 31.39% (1919/6114) and 29.39% (2438/8295) respectively (χ² = 6.65, P = 0.01). For local residents group and mobile population group, the positive rates of HBsAg were 2.46% (283/11 510) and 3.60% (98/2719) respectively (χ² = 11.08, P < 0.01); anti-HBs were 37.11% (4293/11 568) and 53.07% (1445/2723) respectively (χ² = 233.51, P < 0.01); and anti-HBc were 30.83% (3567/11 570), and 28.41% (774/2724) respectively (χ² = 6.08, P < 0.05)., Conclusion: The positive rate of HBsAg in population younger than 24 years old has reached a relatively low level. The mobile population has significantly higher positive rate of HBsAg than local residents, indicating the need for enhancing prevention and control measures for hepatitis B for the mobile population and local residents over 25 years old.

Objective: To investigate the efficacy of oral nucleosides in preventing hepatic failure during pregnancy (HFP) caused by hepatitis B virus (HBV) infection., Methods: Besides receiving standard treatment, 70 women with HFP caused by HBV infection joined a study group (n = 40) or a control group (n = 30) according to their preference. In the study group, 14 women were given lamivudine in the third trimester and an antiviral treatment was continued postpartum. The 26 remaining patients were treated postpartum only, with lamivudine (n = 16) or entecavir (n = 10)., Results: In the study group, the values for serum HBV DNA and hepatitis B envelope antigen were markedly lower at 1 and 2 months than they were at baseline (P < 0.001 and P < 0.001, respectively). Moreover, the HBV DNA values at 1 and 2 months were significantly lower in the study than in the control group (P < 0.05). Overall mortality and incidence of intrauterine infection were also significantly lower in the study group (P < 0.05). No newborns had any apparent abnormalities in either group., Conclusion: Treatment with nucleosides suppressed the replication of HBV DNA and led to biochemical improvement. It also reduced maternal mortality and safely decreased mother-to-child HBV transmission., (Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: To determine the best cutoff values of aspartate aminotransferase (AST) and alanine amino-transferase (ALT) in detecting viral hepatitis C infection among patients of continuous ambulatory peritoneal dialysis (CAPD)., Methods: 90 (44 male and 46 female) CAPD patients and 526 adult controls (266 male, 260 female) were enrolled. Serum AST and ALT were measured by an auto-analyser monthly. Serum HBsAg was examined using a RIA method and anti-HCV by an second-generation EIA method. The best cutoff values of AST and ALT for detecting viral hepatitis were obtained from the ROC (receiver-operating characteristic) curve., Results: The prevalence of anti-HCV(+) was significantly higher in CAPD patients (16.7%) than in normal controls (4.9%), while that of HBsAg(+) was similar in both groups. CAPD patients had significantly lower levels of serum aminotransferases compared to normal controls. Mean AST were 23.8 IU/l in normal control and 18.8 IU/l in the CAPD patients (P < 0.001). Mean ALT were 21.9 IU/l in normal controls and 15.3 IU/l in the CAPD patients (P < 0.001). CAPD patients with HCV infection had higher serum AST and ALT levels than those without. However, HBV infection did not cause significant serum aminotransferase elevation in patients. The conventional cutoff values of AST (40 IU/l) and ALT (40 IU/l) for detecting viral hepatitis yielded only a sensitivity of 27.3 and 18.2% respectively; on the contrary, our revised cutoff values of AST (24 IU/l) and ALT (17 IU/l) had better sensitivities (AST, 72.7%; ALT, 63.6%). For serial aminotransferase values, the sensitivity of AST and ALT for detecting HCV were 36.4 and 27.3% by conventional criteria, and were both 81.8%, by our newly revised criteria., Conclusions: Serum aminotransferase cutoff values should be modified for screening viral hepatitis in a CAPD population. Our new cutoff criteria had important clinical implications in providing benefits of earlier detection and possible prevention from chronic hepatic deteriorations.

Herein, we profiled the transcriptomes of 94,324 cells from 17 DLBCLs and 3 control samples using single-cell RNA-sequencing technology, creating a comprehensive single-cell map for tumor and infiltrating immune cells for DLBCL. Diffuse large B-cell lymphoma (DLBCL) is one of the most common yet aggressive types of B-cell lymphoma and remains incurable in 40% of patients. More than 2000 likely cell-cell interactions were further predicted in DLBCL, illustrating a complex and highly dynamic DLBCL tumor microenvironment. [Extracted from the article]

The X protein of human hepatitis B virus (HBV) acts as an indirect transcriptional transactivator to regulate the expression of many viral and cellular genes as well as playing a critical role in the development of hepatocellular carcinoma. While the biological importance of HBx has been well established, the cellular and molecular bases of its function remain largely undefined. In this study, we isolated a new HBV field strain from a patient with chronic viral infection. The X protein encoded by this virus was used as a bait protein for screening a human liver cDNA library using a yeast two-hybrid system. Several cell proteins were identified as new HBx interacting partners, including a transmembrane serine protease, Hepsin. Direct interaction between HBx and Hepsin proteins was confirmed byin vitroandin vivoco-immunoprecipitation assays. HBx also co-localized with Hepsin in human cells as determined by confocal immunofluorescence microscopy. The interaction between HBx and Hepsin protein appeared to play a role in both promoting cell proliferation and blocking apoptosis in human liver tumor cell and normal liver cell lines. In addition, the complex of HBx and Hepsin promoted the expression of HBeAg in Hep G2.2.1.5 cells indicating that the association of these two proteins stimulated viral replication. [ABSTRACT FROM AUTHOR]