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"Key words: HBV"
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A Single Dose of Anti-HBsAg Antibody-Encoding mRNA-LNPs Suppressed HBsAg Expression: a Potential Cure of Chronic Hepatitis B Virus Infection
2022
It is the first time that mRNA-LNPs have been used to express anti-HBsAg antibodies (G12-scFv, G12-scFv-Fc, and G12-IgG). G12-scFv-Fc- and G12-IgG-encoding mRNA-LNPs exerted a sustained effect on HBsAg serum clearance in the adeno-associated virus (AAV)/HBV mouse model with persistent HBsAg expression. Hepatitis B virus (HBV) infection is a serious global health issue with more than 250 million chronic carriers. It causes liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Persistent suppression of the HBV surface antigen (HBsAg) is necessary for a functional cure of chronic hepatitis B (CHB) virus infection. However, this can hardly be achieved with currently approved drugs. Antibody treatment against HBsAg has shown promise in restoring HBV-specific immune responses and promoting HBV cure. To achieve long-lasting HBsAg suppression, we used an advanced mRNA drug to encode the genes of three anti-HBsAg antibodies, G12-scFv, G12-scFv-Fc, and G12-IgG. Antibody-encoding mRNA-lipid nanoparticles (LNPs), mL (G12-scFv-Fc) and mL (G12-IgG), substantially reduced serum HBsAg levels in treated mice within 30 days after a single dose. In contrast, exogenous antibodies lost effect on reducing HBsAg or HBV DNA levels 9 days postadministration. The high affinity of anti-HBsAg antibodies and the adjuvant activity of mRNA-LNPs resulted in long-term HBsAg seroclearance, which could contribute to the reestablishment of the immune system in HBV carriers. These findings highlight the great potential of antibody-encoding mRNA molecules against CHB infection. IMPORTANCE It is the first time that mRNA-LNPs have been used to express anti-HBsAg antibodies (G12-scFv, G12-scFv-Fc, and G12-IgG). G12-scFv-Fc- and G12-IgG-encoding mRNA-LNPs exerted a sustained effect on HBsAg serum clearance in the adeno-associated virus (AAV)/HBV mouse model with persistent HBsAg expression. These findings may provide a new design of combination therapy for functional cure of HBV. For example, this strategy could provide an alternative for antibodies in “sandwich” therapy and further enhance the immunization properties of the therapy. Overall, mRNA therapeutics are promising for treatment of infectious diseases because of their rapid development, economic value, and simplicity.
Journal Article
Management Of Patients With Hepatitis B Virus Reactivation Post–DAA Treatment Of Chronic Hepatitis C Virus Infection In HCV–HBV Coinfected Patients With Pretreatment HBeAg Seroconversion And Early Degree Of Hepatic Fibrosis
by
Ahmed Osman, Heba
,
Khodeary Mohamed, Ashraf
,
Mahdy, Reem E.
in
Antiviral agents
,
Automation
,
Bilirubin
2019
Hepatitis C virus (HCV)-HBV coinfection is a significant health problem with rapid progression of liver disease without precise diagnosis and treatment. We aimed in this study to identify if there were any role of HBV antiviral therapy in patients with HBV reactivation after direct-acting antiviral therapy in HCV-HBV coinfected patients.
A prospective random study was carried out on 140 patients presenting with chronic HCV and chronic HBV coinfection. All patients had pretreatment HBeAg seroconversion, HBV DNA <2,000 IU/mL, normal liver enzymes, and F0/F1 hepatic fibrosis. They treated with sofosbuvir 400 mg and daklatasvir 60 mg once daily for 3 months. All patients underwent pretreatment hepatic fibrosis assessment using Fibro Scan and laboratory investigations: platelet count, liver-function tests, quantitative HCV PCR, HBsAg, HBc IgG, HBeAg, and HBeAb. All patients were followed up at 1, 3, 6, and 12 months from the start of HCV therapy.
The study enrolled 140 HCV-HBV coinfected patients: 55% were F0 and the rest F1. All our patients had negative HCV PCR at 1 month posttreatment and had achieved sustained virologic response with negative HCV PCR 3 months after treatment end. Four patients showed HBV reactivation with raised HBV DNA PCR and liver enzymes. Their mean age was 23.7±2.7 years, and three were male. Regarding patients with HBV reactivation, at 12 months posttreatment they showed significant decreases in liver enzymes, bilirubin, and INR, with increased platelet count (
=0.001), each with undetectable HBV PCR (
=0.001).
HBV-HCV coinfected patients with no/mild hepatic fibrosis, HBeAg seroconversion, and HBV DNA <2,000 IU/mL can complete direct-acting antiviral therapy without HBV antiviral treatment with close monitoring.
Journal Article
Gender differences in demographic and clinical characteristics in patients with HBV-related liver diseases in China
by
Duan, Zhongping
,
Li, Lu
,
Zhao, Jing
in
Age groups
,
Alcohol
,
Carcinoma, Hepatocellular - epidemiology
2022
The gender differences in demographic and clinical characteristics were examined in patients with hepatitis B virus (HBV)-related liver diseases.
Overall, 634 patients (44.7 ± 13.8 years) were consecutively included. Data of demographic and clinical characteristics were collected during an assessment interview. Comparisons between male and female patients in terms of demographic and clinical data were carried out using univariate analyses. The independent associations between the demographic and clinical variables and gender were examined with either logistic regression or analysis of covariance as appropriate.
The study sample consisted of 452 male and 182 female patients. Multiple logistic regression analyses revealed that being employed (OR = 3.4), personal monthly income <3,000 yuan (OR = 0.3), being current alcohol users (OR = 6.4), Cirrhosis (OR = 5.9), Hepatocellular Carcinoma (HCC) (OR = 8.5) and having less severe insomnia (OR = 0.6) were independently associated with male gender. The analysis of covariance revealed that after controlling for other potential confounding variables, later onset of HBV-related diseases (
= 4.5,
= 0.03) and older age (
= 6.7,
= 0.009) were independently associated with male gender.
Given the significant clinical differences in male and female patients with HBV-related liver diseases, more attention should be given to gender-specific treatment and prevention for this population.
Journal Article
Non-coding RNA and hepatitis B virus-related hepatocellular carcinoma: A bibliometric analysis and systematic review
by
Wang, Ben-gang
,
Yan, Li-rong
,
Jiang, Li-yue
in
bibliometric analysis
,
Bibliometrics
,
Biomarkers
2022
ObjectivesA bibliometric analysis for non-coding RNA and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) was performed to describe international research status and visualize the research scope and emerging trends over the last two decades on this topic.Materials and methodsResearch data of non-coding RNA and HBV-related HCC were retrieved and extracted from the Web of Science Core Collection (WoSCC) database from 1 January 2003 to 13 June 2022 and then analyzed by means of bibliometric methods. A total of 1,036 articles published in this field were assessed for specific characteristics, including the year of publication, journal, author, institution, country/region, references, and keywords. VOSviewer was employed to perform co-authorship, co-occurrence, and co-citation analyses accompanied by constructing a visual network.ResultsOverall, 1,036 reports on non-coding RNA and HBV-related HCC from 2003 to 2022 were retrieved from WoSCC. The publication has gradually increased during the last two decades with 324 journals involved. Most research records (748 publications and 23,184 citations) were concentrated in China. A co-occurrence cluster analysis for the top 100 keywords was performed and four clusters were generated: (1) non-coding RNA as a molecular marker for the diagnosis and prognosis of HBV-related HCC; (2) dysregulation of non-coding RNA by hepatitis B virus X protein (HBx); (3) non-coding RNA affecting the biological behaviors of HBV-related HCC; and (4) epidemiological study for the effects of non-coding RNA on the risk of HBV-related HCC.ConclusionThe publications and citations involved in non-coding RNA and HBV-related HCC have increased over the last two decades associated with many countries, institutions, and authors. Our study revealed current development trends, global cooperation models, basic knowledge, research hotspots, and emerging frontiers in this field.
Journal Article
Prevalence of hepatitis B surface antigen among hemodialysis patients from Middle Eastern countries: a systematic review and meta-analysis
by
Monavari, Seyed Hamidreza
,
Alavian, Seyed Moayed
,
Tavakoli, Ahmad
in
EMRO
,
HBsAg
,
Hemodialysis
2017
The aim of this study was to determine the overall prevalence of hepatitis B surface antigen (HBsAg) among hemodialysis patients reported from the Eastern Mediterranean Regional Office of the WHO (EMRO) countries and the Middle East.
Several databases such as PubMed, ISI Web of Science, MEDLINE and Scopus were searched for publications reporting HBsAg prevalence among hemodialysis patients up to December 2016.
From all the samples, the pooled prevalence of HBsAg was estimated (95% CI) to be 4.4% (4.4-4.5%).
The prevalence of HBsAg in hemodialysis units in the Middle Eastern countries is decreasing over the recent years. Nevertheless, it is important to conduct more studies in these regions to achieve more representative results.
Journal Article