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BMC Medicine Mar 2024The key role of thrombospondin 1 (THBS1) in the pathogenesis of acute-on-chronic liver failure (ACLF) is unclear. Here, we present a transcriptome approach to evaluate...
BACKGROUND
The key role of thrombospondin 1 (THBS1) in the pathogenesis of acute-on-chronic liver failure (ACLF) is unclear. Here, we present a transcriptome approach to evaluate THBS1 as a potential biomarker in ACLF disease pathogenesis.
METHODS
Biobanked peripheral blood mononuclear cells (PBMCs) from 330 subjects with hepatitis B virus (HBV)-related etiologies, including HBV-ACLF, liver cirrhosis (LC), and chronic hepatitis B (CHB), and normal controls (NC) randomly selected from the Chinese Group on the Study of Severe Hepatitis B (COSSH) prospective multicenter cohort underwent transcriptome analyses (ACLF = 20; LC = 10; CHB = 10; NC = 15); the findings were externally validated in participants from COSSH cohort, an ACLF rat model and hepatocyte-specific THBS1 knockout mice.
RESULTS
THBS1 was the top significantly differentially expressed gene in the PBMC transcriptome, with the most significant upregulation in ACLF, and quantitative polymerase chain reaction (ACLF = 110; LC = 60; CHB = 60; NC = 45) was used to verify that THBS1 expression corresponded to ACLF disease severity outcome, including inflammation and hepatocellular apoptosis. THBS1 showed good predictive ability for ACLF short-term mortality, with an area under the receiver operating characteristic curve (AUROC) of 0.8438 and 0.7778 at 28 and 90 days, respectively. Enzyme-linked immunosorbent assay validation of the plasma THBS1 using an expanded COSSH cohort subjects (ACLF = 198; LC = 50; CHB = 50; NC = 50) showed significant correlation between THBS1 with ALT and γ-GT (P = 0.01), and offered a similarly good prognostication predictive ability (AUROC = 0.7445 and 0.7175) at 28 and 90 days, respectively. ACLF patients with high-risk short-term mortality were identified based on plasma THBS1 optimal cut-off value (< 28 µg/ml). External validation in ACLF rat serum and livers confirmed the functional association between THBS1, the immune response and hepatocellular apoptosis. Hepatocyte-specific THBS1 knockout improved mouse survival, significantly repressed major inflammatory cytokines, enhanced the expression of several anti-inflammatory mediators and impeded hepatocellular apoptosis.
CONCLUSIONS
THBS1 might be an ACLF disease development-related biomarker, promoting inflammatory responses and hepatocellular apoptosis, that could provide clinicians with a new molecular target for improving diagnostic and therapeutic strategies.
Topics: Animals; Humans; Mice; Rats; Acute-On-Chronic Liver Failure; Biomarkers; Hepatitis B virus; Inflammation; Leukocytes, Mononuclear; Liver Cirrhosis; Prospective Studies; Thrombospondin 1
PubMed: 38439091
DOI: 10.1186/s12916-024-03318-x -
Clinics and Research in Hepatology and... Aug 2023Hepatitis B virus (HBV) infection is a global public health burden, affecting nearly 300 million people around the world. Due to HBV population is considered to be... (Review)
Review
BACKGROUND
Hepatitis B virus (HBV) infection is a global public health burden, affecting nearly 300 million people around the world. Due to HBV population is considered to be represented as a viral quasispecies with genetic diversity, some reports showed that different genotypes of HBV have different viral effects, though the emergence of antiviral drugs that effectively inhibit viral replication, however, HBV infection has still not been eradicated and further research is needed.
SUMMARY
HBV has been classified into at least ten genotypes (A-J) and more than 40 subgenotypes based on an intergroup or intragroup nucleotide difference across the whole genome, respectively. Inter genotypic recombinants were also observed during the HBV evolution. HBV genotypes and subgenotypes have distinct ethno-geographical distributions, as well as evident differences in their biological characteristics. HBV genotypes and subgenotypes also have close association with disease severity, long-term clinical outcomes, and response to antiviral therapy.
KEYMESSAGES
In this review, we up-dated the epidemiological characteristics, clinical features and prognosis of HBV infection with dissimilar genotype/subgenotypes, to better understanding and developing individualized prevention and treatment strategies.
Topics: Humans; Hepatitis B virus; Clinical Relevance; Genetic Variation; Phylogeny; Hepatitis B; Genotype; DNA, Viral
PubMed: 37479136
DOI: 10.1016/j.clinre.2023.102180 -
Journal of Ethnopharmacology Jul 2023Schisandra Chinensis (Turcz.) Baill. is a long-term used traditional Chinese medicine with the functions of tonifying the kidney and calming the heart, tonifying qi and...
ETHNOPHARMACOLOGICAL RELEVANCE
Schisandra Chinensis (Turcz.) Baill. is a long-term used traditional Chinese medicine with the functions of tonifying the kidney and calming the heart, tonifying qi and engendering fluid. It can be used to treat insomnia and dreaminess, spermatorrhea, coughs, as well as liver and kidney deficiency of Yin or Yang Syndrome. Modern pharmacological studies have shown that Schisandra Chinensis regulates host immunity and exhibits anti-cancer, antiviral and liver-protecting effects. However, the specific mechanism by which Schisandra Chinensis modulates antiviral immunity is unknown.
AIM OF THE STUDY
We sought to explore the therapeutic effect of the active components of Schisandra Chinensis on anti-viral immunity and further investigate the underlying mechanism.
MATERIALS AND METHODS
Immunoblotting, quantitative real-time PCR, enzyme-linked immunosorbent assay, immunofluorescence, and immunoprecipitation were used to investigate the effect of schisandrin C (SC), one of the most abundant and biologically active components of Schisandra Chinensis, on the activation of cGAS-STING signaling pathway and the underlying mechanism. In addition, CMA-mediated STING activation and hydrodynamic injection-mediated HBV-replicating mouse model were used to investigate the effect of SC on the activation of STING signaling pathway and its antiviral effect in vivo.
RESULTS
SC promoted cGAS-STING pathway activation, accompanied by increased production of interferon β (IFN β) and downstream gene expression. Moreover, SC also exerted anti-HBV effects, reducing HBeAg, HBcAg, HBsAg, and HBV DNA levels in hydrodynamic injection-mediated HBV-replicating mouse model and elevating the production of IFN β and expression of interferon-stimulated genes (IFIT1, ISG15, and CXCL10). Mechanistically, SC could facilitate the interaction between TANK-binding kinase 1 (TBK1) and STING, which is important for IRF3 phosphorylation and production of IFN β.
CONCLUSIONS
Our study confirmed that SC enhances cGAS-STING pathway activation and inhibits HBV replication, as well as provides clues for chronic hepatitis B and other infectious diseases treated by SC.
Topics: Mice; Animals; Hepatitis B virus; Nucleotidyltransferases; Signal Transduction; Interferon-beta; Antiviral Agents; Immunity, Innate
PubMed: 37001770
DOI: 10.1016/j.jep.2023.116427 -
Nature Medicine Sep 2023Pay-it-forward incentives involve having a person receive a free test with community-generated messages and then asking if those who received a free test would like to... (Randomized Controlled Trial)
Randomized Controlled Trial
Pay-it-forward incentives involve having a person receive a free test with community-generated messages and then asking if those who received a free test would like to donate money to support others to receive free testing. Here we undertook a two-arm cluster-randomized trial to evaluate pay-it-forward incentives with active community participation to promote hepatitis B virus (HBV) and hepatitis C virus (HCV) testing among men who have sex with men in China. Men randomized to the pay-it-forward arm received free HBV and HCV testing and were offered a chance to pay-it-forward by donating money to support the testing of another anonymous person. Each participant paid for their HCV and HBV test at 7.7 USD per test in the standard-of-care arm. The primary outcome was the proportion of men who tested for HBV and HCV. Between 28 March and 6 November 2021, 32 groups (10 men per group) of men were randomized to the pay-it-forward (n = 160, 16 clusters) and standard-of-care (n = 162, 16 clusters) arms, respectively. HBV and HCV rapid testing were higher in the pay-it-forward arm (59.4%) than in the standard-of-care arm (25.3%) (proportion difference 35.2%, 95% confidence interval 24.1-46.3%). No adverse events were reported. The community-led pay-it-forward incentives improved HBV and HCV testing among men who have sex with men. Clinical Trial registration: ChiCTR 2100046140.
Topics: Male; Humans; Homosexuality, Male; Motivation; Sexual and Gender Minorities; Hepatitis Viruses; Hepacivirus; Hepatitis B virus; Hepatitis C
PubMed: 37640859
DOI: 10.1038/s41591-023-02519-w -
International Journal of Molecular... Aug 2023Infection with hepatitis B virus (HBV) is a main risk factor for hepatocellular carcinoma (HCC). Extracellular vesicles, such as exosomes, play an important role in...
Infection with hepatitis B virus (HBV) is a main risk factor for hepatocellular carcinoma (HCC). Extracellular vesicles, such as exosomes, play an important role in tumor development and metastasis, including regulation of HBV-related HCC. In this study, we have characterized exosome microRNA and proteins released in vitro from hepatitis B virus (HBV)-related HCC cell lines SNU-423 and SNU-182 and immortalized normal hepatocyte cell lines (THLE2 and THLE3) using microRNA sequencing and mass spectrometry. Bioinformatics, including functional enrichment and network analysis, combined with survival analysis using data related to HCC in The Cancer Genome Atlas (TCGA) database, were applied to examine the prognostic significance of the results. More than 40 microRNAs and 200 proteins were significantly dysregulated ( < 0.05) in the exosomes released from HCC cells in comparison with the normal liver cells. The functional analysis of the differentially expressed exosomal miRNAs (i.e., mir-483, mir-133a, mir-34a, mir-155, mir-183, mir-182), their predicted targets, and exosomal differentially expressed proteins (i.e., POSTN, STAM, EXOC8, SNX9, COL1A2, IDH1, FN1) showed correlation with pathways associated with HBV, virus activity and invasion, exosome formation and adhesion, and exogenous protein binding. The results from this study may help in our understanding of the role of HBV infection in the development of HCC and in the development of new targets for treatment or non-invasive predictive biomarkers of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Hepatitis B virus; Liver Neoplasms; Hepatocytes
PubMed: 37685904
DOI: 10.3390/ijms241713098 -
Biochemical Pharmacology Jan 2024Hepatitis B is an infectious disease caused by the HBV virus. It presents a significant challenge for treatment due to its chronic nature and the potential for... (Review)
Review
Hepatitis B is an infectious disease caused by the HBV virus. It presents a significant challenge for treatment due to its chronic nature and the potential for developing severe complications, including hepatocirrhosis and hepatocellular carcinoma. These complications not only cause physical and psychological distress to patients but also impose substantial economic and social burdens on both individuals and society as a whole. The internalization of HBV relies on endocytosis and necessitates the involvement of various proteins, including heparin sulfate proteoglycans, epidermal growth factor receptors, and NTCP. Among these proteins, NTCP is pivotal in HBV internalization and is primarily located in the liver's basement membrane. As a transporter of bile acids, NTCP also serves as a receptor facilitating HBV entry into cells. Numerous molecules have been identified to thwart HBV infection by stifling NTCP activity, although only a handful exhibit low IC values. In this systematic review, our primary focus dwells on the structure and regulation of NTCP, as well as the mechanism involved in HBV internalization. We underscore recent drug breakthroughs that specifically target NTCP to combat HBV infection. By shedding light on these advances, this review contributes novel insights into developing effective anti-HBV medications.
Topics: Humans; Hepatitis B virus; Virus Internalization; Hepatitis B; Symporters; Liver Neoplasms; Hepatocytes; Hep G2 Cells
PubMed: 38049009
DOI: 10.1016/j.bcp.2023.115956 -
Expert Review of Vaccines 2024There is a lack of synthesis of literature to determine hepatitis B vaccine (HepB) strategies for hepatitis B virus (HBV) supported by quality evidence. We aimed to... (Review)
Review
BACKGROUND
There is a lack of synthesis of literature to determine hepatitis B vaccine (HepB) strategies for hepatitis B virus (HBV) supported by quality evidence. We aimed to explore the efficacy and safety of HepB strategies among people with different characteristics.
RESEARCH DESIGN AND METHODS
PubMed, Cochrane Library, Embase, and Web of Science were searched for meta-analyses comparing the efficacy and safety of HepB up to July 2023.
RESULTS
Twenty-one meta-analyses comparing 83 associations were included, with 16 high quality, 4 moderate, and 1 low quality assessed by AMSTAR 2. Highly suggestive evidence supports HepB booster and HepB with 1018 adjuvant (HBsAg-1018) for improved seroprotection, and targeted and universal HepB vaccination reduced HBV infection Suggestive evidence indicated that targeted vaccination decreased the rate of hepatitis B surface antibody positivity and booster doses increased seroprotection in people aged 10-20. Weak evidence suggests potential local/systemic reaction risk with nucleotide analogs or HBsAg-1018. Convincing evidence shows HLA-DPB1*04:01 and DPB1*04:02 increased, while DPB1*05:01 decreased, hepatitis B antibody response. Obesity may reduce HepB seroprotection, as highly suggested.
CONCLUSION
Targeted vaccination could effectively reduce HBV infection, and adjuvant and booster vaccinations enhance seroprotection without significant reaction. Factors such as obesity and genetic polymorphisms may affect the efficacy.
Topics: Humans; Hepatitis B Vaccines; Hepatitis B Surface Antigens; Hepatitis B Antibodies; Vaccination; Hepatitis B virus; Hepatitis B; Adjuvants, Immunologic; Obesity
PubMed: 38055218
DOI: 10.1080/14760584.2023.2289566 -
Virologica Sinica Dec 2023Chronic hepatitis B virus (HBV) infection remains a major public health concern globally, and T cell responses are widely believed to play a pivotal role in mediating... (Review)
Review
Chronic hepatitis B virus (HBV) infection remains a major public health concern globally, and T cell responses are widely believed to play a pivotal role in mediating HBV clearance. Accordingly, research on the characteristics of HBV-specific T cell responses, from activation to exhaustion, has advanced rapidly. Here, we summarize recent developments in characterizing T cell immunity in HBV infection by reviewing basic and clinical research published in the last five years. We provide a comprehensive summary of the mechanisms that induce effective anti-HBV T cell immunity, as well as the latest developments in understanding T cell dysfunction in chronic HBV infection. Furthermore, we briefly discuss current novel treatment strategies aimed at restoring anti-HBV T cell responses.
Topics: Humans; Hepatitis B virus; Hepatitis B, Chronic; Hepatitis B; T-Lymphocytes; Immunity, Cellular
PubMed: 37866815
DOI: 10.1016/j.virs.2023.10.007 -
JAMA Network Open Aug 2023The association of hepatitis B virus (HBV) infection with reduced fecundability among reproductive-aged couples lacks large-population, in-depth study evidence.
IMPORTANCE
The association of hepatitis B virus (HBV) infection with reduced fecundability among reproductive-aged couples lacks large-population, in-depth study evidence.
OBJECTIVE
To investigate the association of HBV infection with time to pregnancy in couples planning pregnancy, and to explore whether this association varied by gravidity, health statuses, or lifestyles.
DESIGN, SETTING, AND PARTICIPANTS
This is a population-based cohort study of Chinese couples participating in the National Free Preconception Check-up Projects during 2015 to 2017. They were planning pregnancy and were followed-up every 3 months until getting pregnant, as confirmed by gynecologic ultrasonography, or were followed-up for 1 year. Data were analyzed between March 1, 2022, and September 30, 2022.
MAIN OUTCOMES AND MEASURES
The main outcome was time to pregnancy, assessed using fecundability hazard ratios (HRs). The Cox proportional hazards regression models were used to estimate the association of HBV infection with fecundability.
RESULTS
Among 2 419 848 couples (mean [SD] age, 27.87 [5.20] years for women and 29.58 [5.50] years for men), 126 728 women (5.24%) and 156 572 men (6.47%) were infected with HBV. Compared with the HBV-negative group, the fecundability of both women and men in the HBV-positive group decreased by 5% (HR, 0.95; 95% CI, 0.94-0.95). Compared with couples in which both partners were HBV negative, the fecundability of those in which both partners were HBV positive declined by 6% (HR, 0.94; 95% CI, 0.93-0.96) among all couples, by 3% (HR, 0.97; 95% CI, 0.95-0.99) among nulligravidas couples, and by 7% (HR, 0.93; 95% CI, 0.91-0.95) among multigravidas couples. Both the female-male and couple models suggested that the association of HBV infection with decreased fecundability was more pronounced in couples with multigravidas. The negative association was greater in people with overweight and obesity and was inconsistent in certain subgroups; in particular, it was more pronounced in women with reproductive tract infections, normal fasting plasma glucose, and no alcohol intake and in men with normal blood pressure.
CONCLUSIONS AND RELEVANCE
In this population-based cohort study, HBV infection was associated with decreased fecundability in a general reproductive-aged population, especially in couples with multigravidas. For women and men with certain health statuses and lifestyles, a comprehensive consideration of this association is recommended to provide personalized fertility guidance.
Topics: Pregnancy; Female; Male; Humans; Adult; Hepatitis B virus; Cohort Studies; Fertility; Hepatitis B; Alcohol Drinking
PubMed: 37651142
DOI: 10.1001/jamanetworkopen.2023.30870 -
Infectious Diseases of Poverty Sep 2023Immunotherapy shows promise as a treatment option for various cancers. However, there is growing concern over potential complications from hepatitis B virus (HBV)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Immunotherapy shows promise as a treatment option for various cancers. However, there is growing concern over potential complications from hepatitis B virus (HBV) reactivation after checkpoint blockade immunotherapy. Although most of the previous clinical trials on immune checkpoint inhibitors (ICIs) excluded patients with HBV, a few case reports and retrospective studies of HBV reactivation have been published. The aim of this study is to assess the risk of hepatitis B virus reactivation (HBVr) in patients receiving ICIs for advanced cancer.
METHODS
English and Chinese language literature published prior to April 30, 2023, was searched in PubMed, EMBASE, Web of Science, Cochrane, SinoMed, CNKI and Wanfang Data for studies reporting HBVr rates in cancer patients treated with ICIs. A pooled risk estimate was calculated for HBVr rates with 95% confidence intervals (CI).
RESULTS
Data from 34 studies including 7126 patients were retrieved and analyzed. The pooled HBVr rate in cancer patients treated with ICIs was 1.3% (I = 90.44%, 95% CI: 0.2-2.9%, P < 0.001). Subgroup analysis revealed that patients diagnosed with hepatocellular carcinoma (HCC), HBV carriers, and patients from Asian regions or in developing countries have a higher rate of HBVr.
CONCLUSIONS
Our meta-analysis demonstrated a low risk of HBVr in patients treated with ICIs for advanced cancer. ICI treatment may be safely used in patients with existing HBV infection or chronic hepatitis B, accompanied by regular monitoring and appropriate antiviral prophylaxis if necessary.
Topics: Humans; Immune Checkpoint Inhibitors; Carcinoma, Hepatocellular; Retrospective Studies; Liver Neoplasms; Hepatitis B; Hepatitis B virus
PubMed: 37736699
DOI: 10.1186/s40249-023-01128-6