Hepatitis B virus (HBV) infection is endemic to southern Africa and parts of Asia where approximately 350 million individuals are chronically infected. Persistent infection increases risk for the serious complications of cirrhosis and hepatocellular carcinoma. Licensed HBV treatments rarely eradicate the virus, which makes developing new strategies for the treatment of chronic HBV a priority. Pol II-transcribed mono- and trimeric primary micro RNAs (primiRNAs) have previously been used to activate RNA interference (RNAi) and inhibit HBV gene expression, indicating that this approach holds promise for HBV therapy. Nevertheless, achieving safe and efficient delivery of anti-HBV RNAi expression cassettes remains an important objective before therapeutic application of this gene silencing technology is realized. Recombinant adenoviruses (Ads) are amongst the most efficient hepatotropic gene delivery vehicles, but a drawback of their use is transient transgene expression and toxicity that results from induction of host immune responses. To diminish immunostimulation of anti-HBV RNAi-activating vectors, helper-dependent (HD) Ads with all viral proteinencoding sequences removed from their genomes, were generated. A CMV Pol II promoter element was used to transcribe antiviral pri-miRNAs that target HBV. Processing of the anti-HBV pri-miRNA RNAi activators occurred according to intended design. Assessment in cultured cells and in a HBV transgenic model of the infection demonstrated that HD Ads delivered the silencing sequences efficiently and replication of the virus was inhibited without causing overt toxic effects. Collectively these data augur well for clinical use of HD Ads to deliver Pol II HBV-silencing cassettes to counter the persistent infection.
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http://dx.doi.org/10.2174/2211536611201010019 | DOI Listing |
PLoS One
January 2025
Department of Preventive Medicine and Public Health, Catholic Kwandong University College of Medicine, Gangneung, South Korea.
Background And Aims: We investigated associations between body mass index (BMI) and hepatocellular carcinoma (HCC) in patients with hepatitis B (HBV) C (HCV) virus infection, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), and liver cirrhosis (LC).
Methods: We followed 350,608 Korean patients with liver disease who underwent routine health examinations from 2003-2006 until December 2018 via national hospital discharge records. Multivariable adjusted hazard ratios (HRs) per 5-kg/m2 BMI increase (BMI ≥25 kg/m2) for HCC risk were calculated using Cox models.
PLoS One
January 2025
Department of Surgery, Asian Liver Center, Stanford University School of Medicine, Stanford, California, United States of America.
Patients with chronic hepatitis B infection (CHB) have an increased risk for death from liver cirrhosis and hepatocellular carcinoma (HCC). In the United States, only an estimated 37% of adults with chronic hepatitis B diagnosis without cirrhosis receive monitoring with at least an annual alanine transaminase (ALT) and hepatitis B deoxyribonucleic acid (DNA), and an estimated 59% receive antiviral treatment when they develop active hepatitis or cirrhosis. A Markov model was used to calculate the costs, health impact and cost-effectiveness of increased monitoring of adults with HBeAg negative inactive or HBeAg positive immune tolerant CHB who have no cirrhosis or significant fibrosis and are not recommended by the current American Association for the Study of Liver Diseases (AASLD) clinical practice guidelines to receive antiviral treatment, and to assess whether the addition of HCC surveillance would be cost-effective.
View Article and Find Full Text PDFJ Gastroenterol
January 2025
Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Background: Hepatitis B virus (HBV) RNA is an important serum biomarker of hepatic covalently closed circular DNA (cccDNA) transcriptional activity; however, its clinical characteristics remain unclear. This study evaluated the clinical utility of HBV RNA levels in patients with chronic hepatitis B (CHB).
Methods: We studied 87 CHB patients with serum HBV DNA levels ≥ 5.
J Virol
January 2025
Department of Viral Hepatitis and AIDS, The L.V. Gromashevskyi Institute of Epidemiology and Infectious Disease, Kyiv, Ukraine.
The outcomes of retreatment patients infected with hepatitis C virus genotype 3, cirrhosis, with velpatasvir may be affected by treatment failure with velpatasvir. The efficacy of SOF+GLE/PIB+RIB 16-24 weeks of treatment has been shown. The presence of NS5A resistance-associated substitution mutations, including Y93H, and the number and regimens of the past failed therapy do not influence the likelihood of achieving sustained virological response.
View Article and Find Full Text PDFLiver Int
February 2025
Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Aim: This research was aimed to uncover the hepatitis B virus (HBV) and hepatitis C virus (HCV) related diseases burden in Asia over the past 3 decades, estimating from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019.
Methods: Age-standardised rates, case numbers of prevalence, disability-adjusted life-years (DALYs), incidence and deaths with 95% uncertainty intervals (UI) for HBV/HCV-related diseases from 1990 to 2019 were derived from GBD 2019 database, with the estimated annual percentage changes (EAPCs) calculated. Our analysis also encompassed the association between the Sociodemographic Index (SDI) and the burden of HBV/HCV-related diseases, future disease burden predictions in six selected countries and various risk factors.
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