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World Journal of Gastroenterology May 2024Chronic viral hepatitis causes an increased risk of progressive liver disease and hepatocellular carcinoma. On the wave of the World Health Organization's goal to reduce...
Chronic viral hepatitis causes an increased risk of progressive liver disease and hepatocellular carcinoma. On the wave of the World Health Organization's goal to reduce new cases and deaths from hepatitis B and C by 2030, there is an increasing call to expand the indications for treatment of chronic hepatitis B. Currently, the main goal of treatment is to achieve a functional cure due to the inability of current drugs to completely eradicate the virus. There are still many discrepancies between available guidelines in terms of eligibility for treatment as well as an uncertainty about the appropriate treatment duration. This editorial addresses key questions about the topic and whether indications for treatment should be expanded.
Topics: Humans; Hepatitis B, Chronic; Antiviral Agents; Hepatitis B virus; Liver Neoplasms; Practice Guidelines as Topic; Carcinoma, Hepatocellular; Treatment Outcome; Patient Selection
PubMed: 38813053
DOI: 10.3748/wjg.v30.i17.2294 -
Internal Medicine (Tokyo, Japan) May 2024We herein report a 40-year-old Japanese man with chronic hepatitis B genotype C (viral load 6.7 LC/mL) who developed hepatocellular carcinoma (HCC) despite achieving...
A Case of Chronic Hepatitis B in which HBs Antigen Seroclearance was Induced by Pegpegylated-interferonα-2a after Hepatocellular Carcinoma Treatment with Nucleos(t)ide Analogues: A Five-year Follow-up.
We herein report a 40-year-old Japanese man with chronic hepatitis B genotype C (viral load 6.7 LC/mL) who developed hepatocellular carcinoma (HCC) despite achieving undetectable hepatitis B virus (HBV) DNA levels with nucleos (t) ide analog (NA) treatment (entecavir). Notably, his hepatitis B surface antigen (HBsAg) level remained elevated at 388.4 IU/mL. Given the continued risk of carcinogenesis associated with HBsAg positivity, we initiated pegylated interferon (PEG-IFN) therapy one month after HCC surgery. Following three periods of PEG-IFN treatment, HBsAg seroclearance (HBsAg-negative state) was achieved.
PubMed: 38811223
DOI: 10.2169/internalmedicine.3643-24 -
Poultry Science May 2024Duck hepatitis A virus 1 (DHAV-1) is the primary cause of duck viral hepatitis, leading to sudden mortality in ducklings and significant economic losses in the duck...
Duck hepatitis A virus 1 (DHAV-1) is the primary cause of duck viral hepatitis, leading to sudden mortality in ducklings and significant economic losses in the duck industry. However, little is known about how DHAV-1 affects duckling liver at the molecular level. We conducted an analysis comparing the expression patterns of mRNAs and miRNAs in DHAV-1-infected duckling livers to understand the underlying mechanisms and dynamic changes. We identified 6,818 differentially expressed mRNAs (DEGs) and 144 differentially expressed microRNAs (DEMs) during DHAV-1 infection. Functional enrichment analysis of DEGs and miRNA target genes using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed their potential involvement in innate antiviral immunity, mitophagy, and pyroptosis. We constructed coexpression networks of mRNA-miRNA interactions and confirmed key DEMs (novel-mir333, novel-mir288, novel-mir197, and novel-mir71) using RT-qPCR. Further investigation demonstrated that DHAV-1 activates the RLRs signaling pathway, disrupts mitophagy, and induces pyroptosis. In conclusion, DHAV-1-induced antiviral immunity is closely linked to mitophagy, suggesting it could be a promising therapeutic target.
PubMed: 38810565
DOI: 10.1016/j.psj.2024.103839 -
Clinical and Molecular Hepatology May 2024HBV-DNA integration in HBV-related hepatocellular carcinoma (HBV-HCC) can be targeted by HBV-specific T cells. SCG101 is an autologous, HBV-specific T-cell product...
BACKGROUND AND AIMS
HBV-DNA integration in HBV-related hepatocellular carcinoma (HBV-HCC) can be targeted by HBV-specific T cells. SCG101 is an autologous, HBV-specific T-cell product expressing a T-cell receptor (TCR) after lentiviral transduction recognizing the envelope-derived peptide (S20-28) on HLA-A2. We here validated its safety and efficacy preclinically and applied it in an HBV-related HCC patient (NCT05339321).
METHODS
GMP-grade manufactured cells were assessed for off-target reactivity and functionality against hepatoma cells. Subsequently, a patient with advanced HBV-HCC (Child-Pugh:A, BCLC:B, ECOG:0, HBeAg-, serum HBsAg+, hepatocytes 10% HBsAg+) received 7.9x107 cells/kg after lymphodepletion. Safety, T-cell persistence, and antiviral and antitumor efficacy were evaluated.
RESULTS
SCG101, produced at high numbers in a closed-bag system, showed HBV-specific functionality against HBV-hepatoma cells in vitro and in vivo. Clinically, treatment was well tolerated, and all adverse events, including transient hepatic damage, were reversible. On day 3, ALT levels increased to 1404 U/ml, and concurrently, serum HBsAg started decreasing by 3.84log and remained <1 IU/ml for over six months. HBsAg expressing hepatocytes in liver biopsies were undetectable after73 days. The patient achieved a partial response according to mRECIST score with a >70% reduction of target lesion size. Transferred T cells expanded, developed a stem cell-like memory phenotype, and were still detectable after six months in the patient's blood.
CONCLUSIONS
SCG101 T-cell therapy showed encouraging efficacy and safety in pre-clinical models and in a patient with primary HBV-HCC and concomitant chronic hepatitis B with the capability to eliminate HBsAg+ cells and achieve sustained tumor control after single dosing.
PubMed: 38808361
DOI: 10.3350/cmh.2024.0058 -
The Journal of Innovations in Cardiac... May 2024We report the case of a 7-year-old boy who presented with post-viral myositis, rhabdomyolysis, and hepatitis, who was later readmitted due to a seizure-like activity and...
We report the case of a 7-year-old boy who presented with post-viral myositis, rhabdomyolysis, and hepatitis, who was later readmitted due to a seizure-like activity and ultimately found to have episodes of recalcitrant polymorphic ventricular tachycardia secondary to simultaneous QT prolongation and severe hypothyroidism. Temporary transvenous atrial pacing was successful at controlling the ventricular arrhythmias in the intensive care unit. With levothyroxine therapy and cessation of QT-prolonging medications, the corrected QT (QTc) normalized. A comprehensive arrhythmia panel identified a pathogenic mutation in , consistent with long QT syndrome (LQTS) type 1. After the patient experienced progressive neurodegeneration and seizures, he was referred to a genetics clinic to rule out genetic epilepsy. On the epilepsy panel of genetic testing, he was found to have two pathogenic variants in . deficiency explains the initial presentation of myositis, rhabdomyolysis, hypothyroidism, and life-threatening arrhythmias surrounding a viral illness more so than the initial diagnosis of mere LQTS. However, the gene is not included in most comprehensive arrhythmia and cardiomyopathy panels. deficiency is a rare condition that often presents with arrhythmias but may be unfamiliar to many cardiologists and electrophysiologists. This case describes management strategies and caveats, which could aid in the successful diagnosis and treatment of deficiency at the time of presentation.
PubMed: 38808169
DOI: 10.19102/icrm.2024.15054 -
Harm Reduction Journal May 2024People in Connecticut are now more likely to die of a drug-related overdose than a traffic accident. While Connecticut has had some success in slowing the rise in...
BACKGROUND
People in Connecticut are now more likely to die of a drug-related overdose than a traffic accident. While Connecticut has had some success in slowing the rise in overdose death rates, substantial additional progress is necessary.
METHODS
We developed, verified, and calibrated a mechanistic simulation of alternative overdose prevention policy options, including scaling up naloxone (NLX) distribution in the community and medications for opioid use disorder (OUD) among people who are incarcerated (MOUD-INC) and in the community (MOUD-COM) in a simulated cohort of people with OUD in Connecticut. We estimated how maximally scaling up each option individually and in combinations would impact 5-year overdose deaths, life-years, and quality-adjusted life-years. All costs were assessed in 2021 USD, employing a health sector perspective in base-case analyses and a societal perspective in sensitivity analyses, using a 3% discount rate and 5-year and lifetime time horizons.
RESULTS
Maximally scaling NLX alone reduces overdose deaths 20% in the next 5 years at a favorable incremental cost-effectiveness ratio (ICER); if injectable rather than intranasal NLX was distributed, 240 additional overdose deaths could be prevented. Maximally scaling MOUD-COM and MOUD-INC alone reduce overdose deaths by 14% and 6% respectively at favorable ICERS. Considering all permutations of scaling up policies, scaling NLX and MOUD-COM together is the cost-effective choice, reducing overdose deaths 32% at ICER $19,000/QALY. In sensitivity analyses using a societal perspective, all policy options were cost saving and overdose deaths reduced 33% over 5 years while saving society $338,000 per capita over the simulated cohort lifetime.
CONCLUSIONS
Maximally scaling access to naloxone and MOUD in the community can reduce 5-year overdose deaths by 32% among people with OUD in Connecticut under realistic budget scenarios. If societal cost savings due to increased productivity and reduced crime costs are considered, one-third of overdose deaths can be reduced by maximally scaling all three policy options, while saving money.
Topics: Humans; Connecticut; Naloxone; Opioid-Related Disorders; Narcotic Antagonists; Cost-Benefit Analysis; Drug Overdose; Opiate Overdose; Harm Reduction; Adult; Male; Quality-Adjusted Life Years; Female; Prisoners
PubMed: 38807226
DOI: 10.1186/s12954-024-01026-6 -
Scientific Reports May 2024The Bovine Leukemia Virus (BLV) Envelope (Env) glycoprotein complex is instrumental in viral infectivity and shapes the host's immune response. This study presents the...
The Bovine Leukemia Virus (BLV) Envelope (Env) glycoprotein complex is instrumental in viral infectivity and shapes the host's immune response. This study presents the production and characterization of a soluble furin-mutated BLV Env ectodomain (sBLV-EnvFm) expressed in a stable S2 insect cell line. We purified a 63 kDa soluble protein, corresponding to the monomeric sBLV-EnvFm, which predominantly presented oligomannose and paucimannose N-glycans, with a high content of core fucose structures. Our results demonstrate that our recombinant protein can be recognized from specific antibodies in BLV infected cattle, suggesting its potential as a powerful diagnostic tool. Moreover, the robust humoral immune response it elicited in mice shows its potential contribution to the development of subunit-based vaccines against BLV.
Topics: Animals; Leukemia Virus, Bovine; Cattle; Recombinant Proteins; Mice; Viral Envelope Proteins; Antibodies, Viral; Enzootic Bovine Leukosis; Cell Line; Gene Products, env
PubMed: 38806566
DOI: 10.1038/s41598-024-62811-8 -
Scientific Reports May 2024Blood exchange therapy, specifically Whole blood exchange (WBE), is increasingly being utilized in clinical settings to effectively treat a range of diseases....
Blood exchange therapy, specifically Whole blood exchange (WBE), is increasingly being utilized in clinical settings to effectively treat a range of diseases. Consequently, there is an urgent requirement to establish convenient and clinically applicable animal models that can facilitate the exploration of blood exchange therapy mechanisms. Our study conducted continuous WBE in rats through femoral and tail vein catheterization using dual-directional syringe pumps. To demonstrate the applicability of continuous WBE, drug-induced hemolytic anemia (DIHA) was induced through phenylhydrazine hydrochloride (PHZ) injection. Notability, the rats of DIHA + WBE group all survived and recovered within the subsequent period. After the implementation of continuous WBE therapy day (Day 1), the DIHA + WBE group exhibited a statistically significant increase in red blood cells (RBC) (P = 0.0343) and hemoglobin (HGB) levels (P = 0.0090) compared to DIHA group. The rats in the DIHA + WBE group exhibited a faster recovery rate compared to the DIHA group, indicating the successful establishment of a continuous blood exchange protocol. This experimental approach demonstrates not just promising efficacy in the treatment of DIHA and offers a valuable tool for investigating the underlying mechanisms of blood exchange. Furthermore, it has a great potential to the advancement of biomedical research such as drug delivery exploration.
Topics: Animals; Rats; Phenylhydrazines; Male; Anemia, Hemolytic; Disease Models, Animal; Hemoglobins; Erythrocytes; Rats, Sprague-Dawley
PubMed: 38806542
DOI: 10.1038/s41598-024-63049-0 -
Heliyon May 2024Hepatitis Delta represents a greater risk in the progression of advanced liver disease and HCC compared with HBV. The exact mechanism that determines the spontaneous...
BACKGROUND
Hepatitis Delta represents a greater risk in the progression of advanced liver disease and HCC compared with HBV. The exact mechanism that determines the spontaneous clearance of delta virus or its progression to cirrhosis remains unknown. Therefore, this study aimed to analyze the clinical profile of HBV and HBV/HDV individuals in the Western Amazon.
METHODS
The study was carried out at the Specialized Outpatient Clinic for Viral Hepatitis belonging to the Centro de Pesquisa em Medicina Tropical de Rondônia/CEPEM. 100 individuals were included, stratified into two groups: 50 with hepatitis B virus and 50 with hepatitis Delta virus.
RESULTS
The overall mean age was 48 years. For the HBV and HDV groups, 66 % (33/50) and 54 % (27/50) were men and 56 % (28/50) and 58 % (29/50) were on antiviral treatment, respectively. Patients with detectable HDV-RNA demonstrated high levels of ALT and AST compared to individuals with undetectable HDV-RNA. Comparative analysis between HBV carriers and infected with HDV shows significant differences in terms of age, HBV-DNA levels, albumin, hepatomegaly and splenomegaly.
CONCLUSION
Several markers were important for differentiating HBV and HDV infections. HDV-RNA detectable showed significant changes in biomarkers compared to undetectable patients, suggesting a possible worse prognostic effect in this group.
PubMed: 38803893
DOI: 10.1016/j.heliyon.2024.e31065 -
Journal of Hepatocellular Carcinoma 2024To examine the association of the history of preoperative antiviral therapy (AVT) with the tumor recurrence and overall survival in HBV-related HCC patients undergoing...
BACKGROUND & AIMS
To examine the association of the history of preoperative antiviral therapy (AVT) with the tumor recurrence and overall survival in HBV-related HCC patients undergoing curative-intent hepatectomy.
METHODS
Patients who underwent curative-intent hepatectomy for HBV-related HCC between 2014 and 2019 at 4 Chinese hospitals were analyzed. Patients were categorized as having undergone preoperative antiviral therapy (AVT) > 1 year or without antiviral therapy (non-AVT). Patient clinical features, short-term outcomes, overall survival (OS), and time-to-recurrence (TTR) were also compared. Multivariate Cox regression analysis was performed to identify the impact of preoperative AVT on the OS and TTR.
RESULTS
Among the 565 patients, 190 (33.6%) underwent continuous AVT > 1 year before surgery. Patients in the non-AVT group were more likely to have worse liver function and more advanced tumor pathological characteristics than those in the AVT group. Postoperative morbidity and mortality rates were comparable between the two groups. Multivariate analyses revealed that a preoperative HBV viral level ≥ 2000 IU/mL was independently associated with poorer TTR (hazard ratio, 1.328; 95% CI, 1.049-1.682) and preoperative AVT was a protective factor for OS (hazard ratio, 0.691; 95% CI, 0.484-0.986).
CONCLUSION
A high preoperative HBV DNA level was an independent risk factor for tumor recurrence. Preoperative AVT > 1 year was associated with better OS and a reduced incidence of tumor recurrence by inhibiting the preoperative level of HBV DNA.
PubMed: 38803837
DOI: 10.2147/JHC.S457135