Deoxycholic acid liganded HBs contributes to HBV maturation

Understanding the underlying mechanism of HBV maturation and subviral particle production is critical to control HBV infection and develop new antiviral strategies. Here, we demonstrate that deoxycholic acid (DCA) plays a central role in HBV production. HBV infection increased DCA levels, whereas elimination of DCA-producing microbiome decreased HBV viral load. DCA can bind to HBs antigen via LXXLL motif at TM1 and TM2 region to regulate HBs-HBc interaction and the production of mature HBV. Plasma DCA levels from patients undergoing antiviral therapy were significantly higher in those with positive HBV viral load. These results suggest that intestinal DCA-producing microbiome can affect the efficiency of antiviral therapy and provide a potential novel strategy for HBV antiviral therapy.

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Molecular characteristics of HBV infection among blood donors tested HBsAg reactive in a single ELISA test in southern China

BMC Infectious Diseases ◽

10.1186/s12879-020-05747-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xianlin Ye ◽

Tong Li ◽

Ran Li ◽

Heng Liu ◽

Junpeng Zhao ◽

...

Keyword(s):

Viral Load ◽

Hepatitis B ◽

Nested Pcr ◽

Blood Donors ◽

Southern China ◽

Core Promoter ◽

Elisa Test ◽

Hbv Infection ◽

Molecular Characteristics ◽

Blood Samples

Abstract Background Hepatitis B virus (HBV) infection is a major concern for blood safety in high-prevalence HBV countries such as China. In Shenzhen, dual hepatitis B surface antigen (HBsAg) enzyme-linked immunosorbent assays (ELISAs) have been adopted in parallel with nucleic acid testing (NAT) for donors for over a decade. A small proportion of blood donors test reactive (R) for HBsAg but negative through routine NAT, which can lead to HBV infection with an extremely low viral load. Objectives We aimed to investigate and analyze the molecular characteristics of HBV among blood donors that tested HBsAg R in a single ELISA test. Methods Blood donations were evaluated in this study if confirmed HBsAg R through one of two ELISA kits. Samples with non-reactive (NR) results by NAT were collected and tested for HBsAg by chemiluminescent microparticle immunoassay (CLIA) with a neutralization test. The level of HBsAg was further assessed by electrochemiluminescence immunoassay (ECLIA). The viral basic core promoter (BCP) and pre-core (PC) and S regions were amplified by nested PCR. Quantitative real-time PCR (qPCR) for viral load determination and individual donation (ID)-NAT were adopted simultaneously. HBsAg was confirmed with CLIA, ECLIA, nested PCR, qPCR, and ID-NAT. Results Of the 100,252 donations, 38 and 41 were identified as HBsAg R with Wantai and DiaSorin ELISA kits, respectively. Seventy-nine (0.077%, 79/100,252) blood samples with ELISA R-NR and NAT NR results were enrolled in the study. Of these, 17 (21.5%,17/79) were confirmed as HBsAg-positive. Of the 14 genotyped cases, 78.6% (11/14) were genotype B, and C and D were observed in two and one sample, respectively. Mutations were found in the S gene, including Y100C, Y103I, G145R, and L175S, which can affect the detection of HBsAg. A high-frequency mutation, T1719G (93.3%), was detected in the BCP/PC region, which reduced the viral replication. Conclusion A small number of blood samples with HBsAg ELISA R-NR and NAT NR results were confirmed as HBV infection, viral nucleic acids were found in most of the samples through routine NAT methods. It is necessary to employ more sensitive and specific assays for the detection of HBV infection among blood donors.

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EGCG modulates PKD1 and ferroptosis to promote recovery in ST rats

Translational Neuroscience ◽

10.1515/tnsci-2020-0119 ◽

2020 ◽

Vol 11 (1) ◽

pp. 173-181 ◽

Cited By ~ 1

Author(s):

Jianjun Wang ◽

Ying Chen ◽

Long Chen ◽

Yanzhi Duan ◽

Xuejun Kuang ◽

...

Keyword(s):

Spinal Cord ◽

Functional Recovery ◽

Antioxidant Properties ◽

Underlying Mechanism ◽

Maximal Effect ◽

Loss Of Function ◽

Protein Kinase D1 ◽

Erk Phosphorylation ◽

Cord Injury ◽

Novel Strategy

AbstractBackgroundSpinal cord injury (SCI) causes devastating loss of function and neuronal death without effective treatment. (−)-Epigallocatechin-3-gallate (EGCG) has antioxidant properties and plays an essential role in the nervous system. However, the underlying mechanism by which EGCG promotes neuronal survival and functional recovery in complete spinal cord transection (ST) remains unclear.MethodsIn the present study, we established primary cerebellar granule neurons (CGNs) and a T10 ST rat model to investigate the antioxidant effects of EGCG via its modulation of protein kinase D1 (PKD1) phosphorylation and inhibition of ferroptosis.ResultsWe revealed that EGCG significantly increased the cell survival rate of CGNs and PKD1 phosphorylation levels in comparison to the vehicle control, with a maximal effect observed at 50 µM. EGCG upregulated PKD1 phosphorylation levels and inhibited ferroptosis to reduce the cell death of CGNs under oxidative stress and to promote functional recovery and ERK phosphorylation in rats following complete ST.ConclusionTogether, these results lay the foundation for EGCG as a novel strategy for the treatment of SCI related to PKD1 phosphorylation and ferroptosis.

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SAT0140 SAFETY OF TOFACITINIB THERAPY IN HBSAG CARRIERS WITH RHEUMATOID ARTHRITIS: A PROSPECTIVE STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6353 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1008.2-1008

Author(s):

L. Fang ◽

Z. Lin ◽

Z. Liao ◽

O. Jin ◽

Y. Pan ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Viral Load ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Hbv Infection ◽

Hbsag Carriers ◽

B Virus ◽

Group 2 ◽

A Prospective Study ◽

Group 1

Background:Targeted synthetic DMARDs (ts-DMARDs) are becoming more available and affordable in developing countries, where the prevalence of hepatitis B virus (HBV) infection is still an important public health issue. The safety of ts-DMARDs therapy in terms of the reactivation of hepatitis B virus (HBV) infection need more concern. Rare data from a prospective study focus on the use of ts-DMARDs in patients with concurrent rheumatoid arthritis (RA) and HBV infection were available by now.Objectives:To evaluate the influence of tofacitinib on reactivation of HBV infection in HBsAg carriers with RA.Methods:In this 52 weeks observation, HBsAg carriers with active RA (DAS28>5.1) despite failed combined treatment with MTX and other non-biological DMARDs were enrolled. Patients must have normal liver function prior to study. All patients received therapy with tofacitinib (5mg twice daily) and concomitant MTX (10-12.5mg/w). Entecavir was prescribed preventively for patients who had a baseline HBV load >2000 copy/ml (group 1), and Lamivudin for patients with HBV load ≤ 2000 copy/ml (group 2). Liver enzymes (AST/ALT) and HBV viral load were monitored every 4 weeks. Increased viral load and abnormal liver function were managed according to expert opinion.Results:Thirteen patients (10 female) were recruited. Nine patients had a baseline viral load >2000 copy/ml (group 1, with preventive Entecavir), and the other 4 patients had a viral load ≤ 2000 copy/ml (group 2, with preventive Lamivudin). Two patients from group 1 discontinued tofacitinib at week 12 due to ineffectiveness, and both continued taking Entecavir for another 3 months after the discontinuation of tofacitinib.No reactivation of hepatitis B was observed in patients from group 1. One patients (female, 54 years old) from group 2 underwent a mild increase of both ALT and AST (67 and 56 IU/L, respectively) at week 16. An elevated viral load (4.9e6 copies/ml, baseline 1.4e3) and a HBV YMDD mutant was also found. The tofacitinib treatment continued. After prescription of Adefovir (combined with the pre-existing Lamivudin), both liver enzyme and viral load decreased to normal range in 8 weeks and remained normal throughout the study.Conclusion:An aggressive Tofacitinib + MTX therapy may be a safe option for HBsAg carriers with cs-DMARDs refractory RA. More active and effective prophylaxis strategy may be recommended to reduce the risk of HBV reactivation during the treatment.References:[1]Chen YM, Huang WN, Wu YD, et al. Reactivation of hepatitis B virus infection in patients with rheumatoid arthritis receiving tofacitinib: a real-world study. Ann Rheum Dis 2018; 77:780-2.Disclosure of Interests: :None declared

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Multicenter Evaluation of the Cepheid Xpert® HBV Viral Load Test

Diagnostics ◽

10.3390/diagnostics11020297 ◽

2021 ◽

Vol 11 (2) ◽

pp. 297

Author(s):

Fabbio Marcuccilli ◽

Stephane Chevaliez ◽

Thomas Muller ◽

Luna Colagrossi ◽

Giulia Abbondanza ◽

...

Keyword(s):

Viral Load ◽

Standard Deviation ◽

Hbv Infection ◽

Load Test ◽

Serum Samples ◽

Viral Load Test ◽

Deming Regression ◽

B Virus ◽

Edta Plasma ◽

Viral Load Assay

Accurate measurement of the hepatitis B virus (HBV) DNA is important for the management of patients with chronic HBV infection. Here, the performance of the Xpert® HBV Viral Load test (Xpert HBV Viral Load) versus the Roche COBAS® Ampliprep/COBAS® TaqMan® system (CAP/CTM HBV) HBV test v2.0 was evaluated. From September 2017 to December 2017, a total of 876 prospectively collected or archived serum or EDTA plasma specimens from subjects chronically infected with HBV were tested using the Xpert HBV Viral Load and the CAP/CTM HBV v2.0 assays. Of the 876 specimens tested, 560 were within the quantitative range of both assays. The agreement between the two methods was 90.0%. No difference in plasma or serum samples was observed. Deming regression analysis showed a good correlation of the Xpert HBV Viral Load assay with the CAP/CTM HBV v2.0 assay. The Bland–Altman analysis showed a good agreement between the results of the Xpert HBV Viral Load assay and the CAP/CTM HBV assay, with a mean difference (±1.96 standard deviation) of 0.0091 ± 0.3852 Log IU/mL. Comparing the two assays, only nineteen specimens (2.1%) had a difference greater than 1.96 times the standard deviation. The Xpert® HBV Viral Load test is suitable for monitoring patients with HBV infection and is useful in diagnostic settings.

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Hepatitis C Virus Clearance after Discontinuation of Pegylated Interferon Alpha-2a Monotherapy in a Child

Case Reports in Medicine ◽

10.1155/2012/597348 ◽

2012 ◽

Vol 2012 ◽

pp. 1-4

Author(s):

Takeshi Endo ◽

Koichi Ito ◽

Tokio Sugiura ◽

Kenji Goto

Keyword(s):

Hepatitis C Virus ◽

Viral Load ◽

Hepatitis C ◽

Antiviral Therapy ◽

Interferon Alpha ◽

Antiviral Treatment ◽

Pegylated Interferon ◽

Hcv Rna ◽

Pegylated Interferon Alpha ◽

Present Patient

The present patient was a 4-year-old boy. His hepatitis C virus genotype was 2a, and his viral load was high (1400,000 U/mL). The pretreatment liver biopsy revealed no fibrosis or malignancy and mild chronic hepatitis; his Knodell's histological activity (HAI) score was 4. Single nucleotide polymorphism of IL28B (rs8099917) was major type. The patient began antiviral treatment with pegylated interferon alpha 2a (90 μg/week). At week 9, serum HCV RNA became undetectable, with a sensitivity of 50 copies/mL. Antiviral treatment was discontinued at week 11 because the ALT level increased to 610 U/L. After discontinuation of therapy, the patient’s serum HCV RNA status became positive again. The serum viral load increased to 100,000 U/mL. During this period, he had been observed without medication. Sixteen months after stopping treatment, serum HCV became undetectable. Over a 4-year period, HCV RNA became negative and his anti-HCV antibody titer gradually decreased. In conclusion, though antiviral therapy resulted in failure or incomplete therapy, a reduced viral load resulted in viral clearance in the present patient. Interleukin 28B genotype might have association with the clearance of hepatitis C virus after discontinuation of antiviral therapy.

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Activation of ERAD Pathway by Human Hepatitis B Virus Modulates Viral and Subviral Particle Production

PLoS ONE ◽

10.1371/journal.pone.0034169 ◽

2012 ◽

Vol 7 (3) ◽

pp. e34169 ◽

Cited By ~ 49

Author(s):

Catalin Lazar ◽

Alina Macovei ◽

Stefana Petrescu ◽

Norica Branza-Nichita

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Particle Production ◽

Human Hepatitis ◽

B Virus ◽

Subviral Particle ◽

Erad Pathway

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Letter: the potential risk of HBV reactivation in patients with resolved HBV infection during direct-acting antiviral therapy

Alimentary Pharmacology & Therapeutics ◽

10.1111/apt.14227 ◽

2017 ◽

Vol 46 (7) ◽

pp. 702-703 ◽

Cited By ~ 1

Author(s):

R. Huang ◽

J. Wang ◽

Y. Hao ◽

X. Yan ◽

C. Wu

Keyword(s):

Antiviral Therapy ◽

Potential Risk ◽

Hbv Infection ◽

Hbv Reactivation ◽

Direct Acting Antiviral ◽

Direct Acting

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Recent Progress and Future Prospective in HBV Cure by CRISPR/Cas

Viruses ◽

10.3390/v14010004 ◽

2021 ◽

Vol 14 (1) ◽

pp. 4

Author(s):

Yu-Chan Yang ◽

Hung-Chih Yang

Keyword(s):

Hepatitis B ◽

Antiviral Therapy ◽

Hbv Infection ◽

Host Genome ◽

Attractive Potential ◽

Major Barrier ◽

Base Editing ◽

Promising Therapeutic Approach ◽

In Vivo Delivery

Hepatitis B virus (HBV) infection remains an important issue of global public health. Although current antiviral therapy has dramatically reduced the mortality and morbidity of chronic hepatitis B (CHB), it fails to cure it. Rebound viremia often occurs after stopping antiviral therapy. Persistent HBV covalently closed circular DNA (cccDNA) and integrated DNA under antiviral therapy form the major barrier to eradication of HBV infection. CRISPR-mediated genome editing has emerged as a promising therapeutic approach to specifically destroy persistent HBV genomes, both cccDNA and integrated DNA, for HBV cure. However, the cleavage of integrated HBV DNA by CRISPR-Cas9 will cause double-strand break (DSB) of host genome, raising a serious safety concern about genome instability and carcinogenesis. The newly developed CRISPR-derived base editors (BEs), which fuse a catalytically disabled nuclease with a nucleobase deaminase enzyme, can be used to permanently inactivate HBV genome by introducing irreversible point mutations for generation of premature stop codons without DSBs of host genome. Although promising, CRISPR-mediated base editing still faces daunting challenges before its clinical application, including the base-editing efficacy, the off-target effect, the difficulty in finding conserved target HBV sequences, and in vivo delivery efficiency. Several strategies have been adopted to optimize the efficiency and specificity of CRISPR-BEs and to improve in vivo delivery efficacy through novel viral and non-viral delivery approaches. Particularly, the non-viral delivery of Cas9 mRNA and ribonucleoprotein by lipid nanoparticles exhibits attractive potential for liver-targeted delivery in clinical. Along with all progress above, the CRISPR-mediated gene therapy will ultimately achieve HBV cure.

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