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Critical Reviews in Eukaryotic Gene... 2022We aimed to explore the relationship between free triiodothyronine (FT3) level and severity of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). A...
We aimed to explore the relationship between free triiodothyronine (FT3) level and severity of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). A total of 122 patients with HBV-ACLF who were hospitalized in Beijing You'an Hospital Affiliated to Capital Medical University from September 2018 to February 2020 were included in this study. The FT3 level and the number of organs involved in patients with different stages of liver failure were analyzed. The patients were divided into four groups, Q1, Q2, Q3, and Q4, according to FT3 level. Correlation analysis was used to compare the correlation between FT3 level and Model for End-Stage Liver Disease (MELD) score, chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score, CLIF-consortium organ failure (CLIF-COF) score, and Asian Pacific Association for the Study of the Liver (APASL) acute-on-chronic liver failure (ACLF) Research Consortium (AARC) score. Multiple linear regression, logistic regression and receiver operating characteristic (ROC) curve were used to analyze the effect of FT3 on MELD score. The FT3 level was the lowest in patients with advanced HBV-ACLF, but the highest in patients with early-stage HBV-ACLF (P < 0.01). The more organs involved, the lower the level of FT3 (P < 0.01). The MELD score of Q4 group was the lowest, whereas that of Q1 group was the highest (P < 0.01). Pearson correlation coefficients of FT3 with MELD score, CLIF-SOFA score, CLIF-COF score and AARC score were -0.477, -0.359, -0.347, and -0.391, respectively (P < 0.001). Multiple linear regression analysis showed that the partial regression coefficients of FT3, natural log total bilirubin in milligrams per decaliter {ln[TBIL (mg/dL)]}, natural log creatinine in milligrams per decaliter {ln[CR (mg/dL)]}, and natural log international normalized ratio {ln[INR]} were -0.215, 0.346, 0.231, and 0.667, respectively (P < 0.001). The odds ratio (OR) values of FT3, ln[TBIL (mg/dL)], ln[CR (mg/dL)], and ln[INR] were 0.141 (0.082-0.244), 5.426 (2.697-9.059), 4.535 (2.432-8.455), and 8.642 (6.679-10.267) in the MELD ≥ 30 group compared with MELD < 30 group (P < 0.001). Furthermore, their area under the ROC curve (AUROC) values were 0.739 (0.686-0.792), 0.748 (0.696-0.800), 0.632 (0.562-0.702), and 0.933 (0.903-0.963), respectively (P < 0.001). FT3 level is correlated with the severity of HBV-ACLF, which may be one of the factors to judge the severity of this disease.
Topics: Acute-On-Chronic Liver Failure; End Stage Liver Disease; Hepatitis B virus; Humans; ROC Curve; Severity of Illness Index
PubMed: 35997117
DOI: 10.1615/CritRevEukaryotGeneExpr.2022041680 -
Journal of Hepatology Sep 2023
Topics: Hepatitis B virus; Hepatitis B Core Antigens; DNA, Viral; Hepatitis B e Antigens
PubMed: 36965779
DOI: 10.1016/j.jhep.2023.03.008 -
Viruses Oct 2023Chronic hepatitis B affects >300 million people worldwide and is a major cause of liver disease, causing ~800,000 deaths each year [...].
Chronic hepatitis B affects >300 million people worldwide and is a major cause of liver disease, causing ~800,000 deaths each year [...].
Topics: Humans; Hepatitis B virus; Hepatitis B, Chronic; Hepatitis B
PubMed: 38005851
DOI: 10.3390/v15112173 -
Alimentary Pharmacology & Therapeutics Jan 2020Treatment of hepatitis B virus (HBV) infection with current therapy suppresses HBV DNA, but loss of hepatitis B surface antigen (HBsAg; functional cure), is rare.... (Review)
Review
BACKGROUND
Treatment of hepatitis B virus (HBV) infection with current therapy suppresses HBV DNA, but loss of hepatitis B surface antigen (HBsAg; functional cure), is rare. Multiple compounds are under investigation.
AIMS
To describe the pharmacology, including drug interactions, efficacy, safety and mechanisms of action of investigational compounds for HBV infection.
METHODS
Descriptive review using PubMed and Google to identify literature/conference papers on investigational compounds (≥Phase 2) with data on efficacy and safety in HBV-infected patients.
RESULTS
Bulevirtide, JNJ-56136379, ABI-H0731, REP-2139, and inarigivir decrease HBV DNA/RNA, with greater potency than current nucleos(t)ide analogues. REP-2139 (25%-75% of patients, 20-48 weeks treatment) and inarigivir (26% of patients, 12-24 weeks treatment) induce HBsAg loss. ARO-HBV reduced (>1.5 log UI/mL) HBsAg in 85% of patients (12 weeks treatment). There are some safety concerns with investigational agents (e.g., increased bile acids with bulevirtide, and liver enzyme flares with REP-2139) which will require a risk benefit assessment compared with current therapies. Single and multidose pharmacokinetic data are available for bulevirtide, JNJ-56136379, ABI-H0731; no such data are available for REP-2139, ARO-HBV, inarigivir. Initial drug interaction assessments have been performed with bulevirtide and inarigivir (only in vitro).
CONCLUSIONS
There are promising investigational therapies for HBV infection. Increasing the potential for HBsAg loss may result in more patients achieving functional cure. However, many knowledge gaps remain such as pharmacokinetics in those with HBV, cirrhosis and renal impairment but also the interaction potential between investigational therapies, risk-benefit profiles, and potential for drug interactions with medications used to treat comorbidities associated with aging.
Topics: Antiviral Agents; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; Humans; Molecular Targeted Therapy; Nucleic Acids; Polymers; Therapies, Investigational; Treatment Outcome
PubMed: 31840863
DOI: 10.1111/apt.15581 -
Frontiers in Cellular and Infection... 2022DEAD/H-box helicases are an essential protein family with a conserved motif containing unique amino acid sequences (Asp-Glu-Ala-Asp/His). Current evidence indicates that... (Review)
Review
DEAD/H-box helicases are an essential protein family with a conserved motif containing unique amino acid sequences (Asp-Glu-Ala-Asp/His). Current evidence indicates that DEAD/H-box helicases regulate RNA metabolism and innate immune responses. In recent years, DEAD/H-box helicases have been reported to participate in the development of a variety of diseases, including hepatitis B virus (HBV) infection, which is a significant risk factor for hepatic fibrosis, cirrhosis, and liver cancer. Furthermore, emerging evidence suggests that different DEAD/H-box helicases play vital roles in the regulation of viral replication, based on the interaction of DEAD/H-box helicases with HBV and the modulation of innate signaling pathways mediated by DEAD/H-box helicases. Besides these, HBV can alter the expression and activity of DEAD/H-box helicases to facilitate its biosynthesis. More importantly, current investigation suggests that targeting DEAD/H-box helicases with appropriate compounds is an attractive treatment strategy for the virus infection. In this review, we delineate recent advances in molecular mechanisms relevant to the interplay of DEAD/H-box helicase and HBV and the potential of targeting DEAD/H-box helicase to eliminate HBV infection.
Topics: Humans; Hepatitis B virus; Hepatitis B; DNA Helicases; Liver Cirrhosis; Virus Replication
PubMed: 36506030
DOI: 10.3389/fcimb.2022.1062553 -
The Lancet. Infectious Diseases Jun 2024Social determinants of health are important in designing effective interventions for hepatitis B virus (HBV) infection. This systematic review characterises... (Review)
Review
Social determinants of health are important in designing effective interventions for hepatitis B virus (HBV) infection. This systematic review characterises equity-oriented, social determinants of health-focused HBV interventions, and describes their effectiveness in terms of the prevention, care, or treatment of HBV in high-income countries. We searched electronic databases for central concepts of 'HBV', 'equity', 'social determinants of health', 'intervention', and 'Organization for Economic Co-operation and Development (OECD) countries'. Screening and data abstraction were conducted independently by two reviewers. Data were abstracted from 66 studies; articles with a comparative study design (n=36) were included in the narrative synthesis, highlighting social determinants of health domains of interventions, HBV-relevant health outcomes, and extra-health social determinants of health effects (ie, those effects that extend beyond health outcomes). Synthesis aligned with six emergent themes corresponding to HBV prevention and care: knowledge and education, diagnosis and screening, immunisation, care initiation, engagement with clinical care and treatment, and upstream prevention. Studies presented a heterogeneous array of HBV-relevant health outcomes. Most interventions were tailored for social determinants of health domains of race, ethnicity, culture, and language; drug use; and socioeconomic status. Across the themes, at least two-thirds of interventions showed comparative effectiveness for addressing HBV. Extra-health social determinants of health outcomes were observed for two studies. Considerable diversity in population-level approaches was observed regarding intervention goals and effectiveness; most interventions were effective at enhancing the prevention, care, or treatment of HBV.
Topics: Humans; Social Determinants of Health; Hepatitis B; Hepatitis B virus
PubMed: 38184004
DOI: 10.1016/S1473-3099(23)00590-X -
Cellular and Molecular Gastroenterology... 2022
Topics: Hepatitis B virus
PubMed: 35691338
DOI: 10.1016/j.jcmgh.2022.05.009 -
Hepatology (Baltimore, Md.) Nov 2020
Topics: Hepatitis B; Hepatitis B virus; Humans; Immunotherapy; Receptors, Antigen, T-Cell
PubMed: 32865247
DOI: 10.1002/hep.31527 -
Medicine Dec 2021Hepatitis B virus (HBV) genotypes and subgenotypes have distinct geographical distributions and influence a number of clinical disease features and responses to... (Meta-Analysis)
Meta-Analysis
Hepatitis B virus (HBV) genotypes and subgenotypes have distinct geographical distributions and influence a number of clinical disease features and responses to treatment. There are many reports on the distribution of HBV genotypes, but great differences are present between studies. What's more, a meta-analysis of HBV genotype- and subgenotype-distribution by country is lacking.A comprehensive literature search was performed in PubMed and a systematic search of full-length HBV sequences and S gene sequences was conducted in the GenBank database. HBV genotypes were checked and subgenotypes were determined by phylogenetic comparison of full-length HBV sequences or S gene sequences. STATA 12.0 was used for the analysis for countries with multiple datasets. BEAST 2.5.2 was used for Bayesian phylogenetic analysis to infer the evolutionary time scales of HBV.This study includes 309 datasets from 110 countries, including 188 relevant studies, 58 full-length gene datasets, and 63 S gene datasets. The meta-analysis was performed on 274 datasets from 75 countries. The distribution of genotypes is more detailed than those described by previous studies. While the overall genotype distribution is similar to that reported in previous studies, some notable aspects were different. The main genotypes present in south-eastern Africa, North Africa, and West Africa are genotypes A, D, and E, respectively. Genotypes G and H are mainly distributed in Mexico. Genotype F is mainly distributed in central and South America, but genotypes A and D are also common in Brazil, Cuba, and Haiti.This study provides a more accurate description of the distribution of HBV genotypes and subgenotypes in different countries and suggests that the differences in genotype distribution may be related to ethnicity and human migration.
Topics: Bayes Theorem; DNA, Viral; Genotype; Hepatitis B; Hepatitis B virus; Humans; Phylogeny
PubMed: 34918643
DOI: 10.1097/MD.0000000000027941 -
Frontiers in Immunology 2022As a small DNA virus, hepatitis B virus (HBV) plays a pivotal role in the development of various liver diseases, including hepatitis, cirrhosis, and liver cancer. Among... (Review)
Review
As a small DNA virus, hepatitis B virus (HBV) plays a pivotal role in the development of various liver diseases, including hepatitis, cirrhosis, and liver cancer. Among the molecules encoded by this virus, the HBV X protein (HBX) is a viral transactivator that plays a vital role in HBV replication and virus-associated diseases. Accumulating evidence so far indicates that pattern recognition receptors (PRRs) are at the front-line of the host defense responses to restrict the virus by inducing the expression of interferons and various inflammatory factors. However, depending on HBX, the virus can control PRR signaling by modulating the expression and activity of essential molecules involved in the toll-like receptor (TLR), retinoic acid inducible gene I (RIG-I)-like receptor (RLR), and NOD-like receptor (NLR) signaling pathways, to not only facilitate HBV replication, but also promote the development of viral diseases. In this review, we provide an overview of the mechanisms that are linked to the regulation of PRR signaling mediated by HBX to inhibit innate immunity, regulation of viral propagation, virus-induced inflammation, and hepatocarcinogenesis. Given the importance of PRRs in the control of HBV replication, we propose that a comprehensive understanding of the modulation of cellular factors involved in PRR signaling induced by the viral protein may open new avenues for the treatment of HBV infection.
Topics: Hepatitis B; Hepatitis B virus; Humans; Immunity, Innate; Receptors, Pattern Recognition; Signal Transduction
PubMed: 35251017
DOI: 10.3389/fimmu.2022.829923