scholarly journals The dynamic changes of HBV quasispecies diversity in infancy after immunoprophylaxis failure: a prospective cohort study

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yi Li ◽  
Yiwei Xiao ◽  
Lili Li ◽  
Yarong Song ◽  
Xiangjun Zhai ◽  
...  
Keyword(s):  
Antiviral Therapy ◽  
Prospective Cohort ◽  
Immune Escape ◽  
Antiviral Treatment ◽  
Amino Acid Level ◽  
Underlying Mechanism ◽  
Full Length ◽  
Dynamic Changes ◽  
Chronic Hepatitis B Virus ◽  
Immunoprophylaxis Failure

Abstract Background Previous works have observed that younger infants with chronic hepatitis B virus (HBV) infection are more responsive to antiviral treatment. However, the underlying mechanism remains unclear. In this study, the dynamic changes of HBV quasispecies in infants with immunoprophylaxis failure were investigated to provide virological explanations for clinical management on infantile antiviral therapy. Methods Thirteen 7-month-old infants with immunoprophylaxis failure and their mothers were enrolled from a prospective cohort, and 8 of them were followed up to 3 years old. The sequences of HBV quasispecies were analyzed by the full-length genome clone-based sequencing, and compared among mothers and their infants at different ages. Results The results revealed that the complexity, mutation frequency and genetic distance of HBV quasispecies decreased significantly at full-length, partial open reading frames and regulatory regions of HBV genome at nucleotide level in 7-month-old infants comparing with their mothers, whereas increased significantly to near the maternal level when infants grew up to 3 years old. Furthermore, similar changes were also found in Core, PreS2, RT and P regions of HBV genome at amino acid level, especially for potential NAs-resistant mutants in RT region and immune-escape mutants in Core and PreS2 regions. Conclusions This study uncovered the evolution of HBV quasispecies in infancy after mother-to-child transmission, which may provide the virological evidence for explaning that younger children are more responsive to antiviral therapy.

scholarly journals The Dynamic Changes of HBV Quasispecies Diversity in Infancy after Immunoprophylaxis Failure: A Prospective Cohort Study

2021 ◽  
Author(s):  
Yi Li ◽  
Yiwei Xiao ◽  
Lili Li ◽  
Yarong Song ◽  
Xiangjun Zhai ◽  
...  
Keyword(s):  
Antiviral Therapy ◽  
Prospective Cohort ◽  
Immune Escape ◽  
Antiviral Treatment ◽  
Amino Acid Level ◽  
Underlying Mechanism ◽  
Full Length ◽  
Dynamic Changes ◽  
Chronic Hepatitis B Virus ◽  
Immunoprophylaxis Failure

Abstract Background: Previous works have observed that younger infants with chronic hepatitis B virus (HBV) infection are more responsive to antiviral treatment. However, the underlying mechanism remains unclear. In this study, the dynamic changes of HBV quasispecies in infants with immunoprophylaxis failure were investigated to provide virological explanations for clinical management on infantile antiviral therapy.Methods: Thirteen 7-month-old infants with immunoprophylaxis failure and their mothers were enrolled from a prospective cohort, and 8 of them were followed up to 3 years old. The sequences of HBV quasispecies were analyzed by the full-length genome clone-based sequencing, and compared among mothers and their infants at different ages.Results: The results revealed that the complexity, mutation frequency and genetic distance of HBV quasispecies decreased significantly at full-length, partial open reading frames and regulatory regions of HBV genome at nucleotide level in 7-month-old infants comparing with their mothers, whereas increased significantly to near the maternal level when infants grew up to 3 years old. Furthermore, similar changes were also found in Core, PreS2, RT and P regions of HBV genome at amino acid level, especially for potential NAs-resistant mutants in RT region and immune-escape mutants in Core and PreS2 regions.Conclusions: This study uncovered the evolution of HBV quasispecies in infancy after mother-to-child transmission, which may provide the virological evidence for explaning that younger children are more responsive to antiviral therapy.

scholarly journals A noninvasive model to predict liver histology for antiviral therapy decision in chronic hepatitis B with alanine aminotransferase < 2 upper limit of normal

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shanshan Chen ◽  
Haijun Huang ◽  
Wei Huang
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Liver Biopsy ◽  
Antiviral Therapy ◽  
Alanine Aminotransferase ◽  
Antiviral Treatment ◽  
Training Group ◽  
Liver Histology ◽  
Validation Group ◽  
Upper Limit

Abstract Background At present, most assessments of liver fibrosis staging mainly focus on non-invasive diagnostic methods. This study aims to construct a noninvasive model to predict liver histology for antiviral therapy in chronic hepatitis B (CHB) with alanine aminotransferase (ALT) < 2 times upper limit of normal (ULN). Methods We retrospectively analyzed 577 patients with CHB who received liver biopsy and whose ALT was less than 2 ULN. Then they were randomly divided into a training group and a validation group. Through logistic regression analysis, a novel predictive model was constructed in the training group to predict significant changes in liver histology [necro-inflammatory activity grade (G) ≥ 2 or fibrosis stage (S) ≥ 2] and then validated in the validation group. Results If liver biopsy showed moderate or severe inflammation or significant fibrosis, antiviral treatment was recommended. Aspartate aminotransferase (AST), anti-hepatitis B virus core antibody (anti-HBC) and glutamine transpeptidase (GGT) were identified as independent predictors for antiviral therapy, with area under the ROC curve (AUROC) of 0.649, 0.647 and 0.616, respectively. Our novel model index, which combined AST, anti- HBC and GGT with AUROC of 0.700 and 0.742 in training set and validation set. Conclusions This study established a noninvasive model to predict liver histology for antiviral treatment decision in patients with CHB with ALT < 2 ULN, which can reduce the clinical needs of liver biopsy.

scholarly journals Prospective Characterization of Full-Length Hepatitis C Virus NS5A Quasispecies during Induction and Combination Antiviral Therapy

2000 ◽  
Vol 74 (19) ◽  
pp. 9028-9038 ◽  
Author(s):  
J.-B. Nousbaum ◽  
S. J. Polyak ◽  
S. C. Ray ◽  
D. G. Sullivan ◽  
A. M. Larson ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Antiviral Therapy ◽  
Variable Region ◽  
Response To Therapy ◽  
Full Length ◽  
Variable Regions ◽  
C Terminus

ABSTRACT The hepatitis C virus (HCV) nonstructural 5A (NS5A) protein has been controversially implicated in the inherent resistance of HCV to interferon (IFN) antiviral therapy in clinical studies. In this study, the relationship between NS5A mutations and selection pressures before and during antiviral therapy and virologic response to therapy were investigated. Full-length NS5A clones were sequenced from 20 HCV genotype 1-infected patients in a prospective, randomized clinical trial of IFN induction (daily) therapy and IFN plus ribavirin combination therapy. Pretreatment NS5A nucleotide and amino acid phylogenies did not correlate with clinical IFN responses and domains involved in NS5A functions in vitro were all well conserved before and during treatment. A consensus IFN sensitivity-determining region (ISDR237–276) sequence associated with IFN resistance was not found, although the presence of Ala245 within the ISDR was associated with nonresponse to treatment in genotype 1a-infected patients (P < 0.01). There were more mutations in the 26 amino acids downstream of the ISDR required for PKR binding in pretreatment isolates from responders versus nonresponders in both HCV-1a- and HCV-1b-infected patients (P < 0.05). In HCV-1a patients, more amino acid changes were observed in isolates from IFN-sensitive patients (P < 0.001), and the mutations appeared to be concentrated in two variable regions in the C terminus of NS5A, that corresponded to the previously described V3 region and a new variable region, 310 to 330. Selection of pretreatment minor V3 quasispecies was observed within the first 2 to 6 weeks of therapy in responders but not nonresponders, whereas the ISDR and PKR binding domains did not change in either patient response group. These data suggest that host-mediated selective pressures act primarily on the C terminus of NS5A and that NS5A can perturb or evade the IFN-induced antiviral response using sequences outside of the putative ISDR. Mechanistic studies are needed to address the role of the C terminus of NS5A in HCV replication and antiviral resistance.

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

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.

Changes in Serum Level of Autotaxin with Direct-Acting Antiviral Therapy in Patients with Chronic Hepatitis C

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Khaled Mohamed Hussein Abdelwahab ◽  
Shereen Abou Bakr Saleh ◽  
Ghada Abdelrahman Ahmed ◽  
Asmaa Mady Gomaa Mady
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Serum Level ◽  
Antiviral Therapy ◽  
Chronic Hepatitis C ◽  
Antiviral Treatment ◽  
Post Treatment ◽  
Direct Acting Antiviral ◽  
Direct Acting

Abstract Background Hepatitis C virus virus is global health burden and major health hazard in Egypt, since the virus is the etiological factor of chronic hepatitis. Hepatitis C virus (HCV) accounts for approximately 15%-20% cases of acute hepatitis. After acute infection, around 50% to 80% of HCV patients will develop chronic infection. Approximately, HCV infects 170 million individuals worldwide). Chronic hepatitis C (CHC) patients are at high risk to develop lifethreatening complications, including cirrhosis in 20% of cases and hepatocellular carcinoma. Objectives The aim of this study was to validate Changes in serum level of autotaxin in patients with chronic hepatitis C before and after antiviral treatment. Patients and methods This study was designed as a prospective observational cohort study to evaluate Changes in serum levels of autotaxin with direct-acting antiviral therapy in patients with chronic hepatitis C before (baseline) and after (sustained virologic response week 12) treatment. This prospective study was conducted on 48 chronic HCV infected patients eligible for antiviral treatment with direct acting antivirals, agreeable to regular follow up, recruited from Hepatology and virology outpatient clinic at DMNI (Damanhour Medical National Institute) during the period from September 2018 till Mars 2019. Results This study showed that Autotaxin level significantly decreased from baseline to 12 weeks post-treatment. ATX therefore represents a novel non-invasive biomarker for liver fibrosis and a prognostic indicator of disease activity. Conclusion Serum Autotaxin was found to be higher in chronic hepatitis c and ATX levels became significantly decreased from baseline to 12 weeks post-treatment with direct acting antiviral drugs in patients achieving a SVR.

scholarly journals Increased CCR7loPD-1hiCXCR5+CD4+ T Cells in Peripheral Blood Mononuclear Cells Are Correlated with Immune Activation in Patients with Chronic HBV Infection

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Ya-Xin Huang ◽  
Qi-Yi Zhao ◽  
Li-Li Wu ◽  
Dong-Ying Xie ◽  
Zhi-Liang Gao ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Antiviral Treatment ◽  
Hbv Infection ◽  
Peripheral Blood Mononuclear ◽  
Chronic Hbv Infection ◽  
Chronic Hepatitis B Virus ◽  
Chronic Hbv ◽  
Immune Tolerant

T follicular helper cells (Tfh cells) affect essential immune pathogenesis in chronic hepatitis B virus (HBV) infection. The CCR7loPD-1hi Tfh subset has a partial Tfh effector phenotype and is associated with active Tfh differentiation, whereas the CCR7hiPD-1lo Tfh subset is a resting phenotype. We recruited 20 healthy volunteers and 77 patients with chronic HBV infection, including those in the immune tolerant (IT) phase (n=19), immune clearance (IC) phase (n=20), low replicative (LR) phase (n=18), and reactivation (RA) phase (n=20). The expression of CD4, CXCR5, PD-1, and CCR7 was detected in T cells from peripheral blood by flow cytometry. The frequency of the CCR7loPD-1hi T subset was significantly higher in the patients than in the healthy controls (14.92±4.87% vs 12.23±2.95%, p=0.018). The frequency of this Tfh subset in the IC group (18.42%±3.08) was increased compared with the IT group (11.94±2.87%, p=0.001) and LR group (13.65±4.93%, p=0.031) and was higher in the RA group than in the IT group (16.03±5.37% vs 11.94±2.87%, p=0.030). We observed a weak positive correlation between the CCR7loPD-1hi Tfh subset population and the alanine transaminase (ALT) level (r=0.370, p=0.001). The CCR7loPD-1h Tfh subset in the chronic HBV-infected patients was elevated to various degrees among the different immune phases. CCR7loPD-1hiCXCR5+CD4+ T cells are correlated with the immune status of chronic HBV infection patients and may be developed as a potential indicator for antiviral treatment.

scholarly journals Multiple Influenza A (H3N2) Mutations Conferring Resistance to Neuraminidase Inhibitors in a Bone Marrow Transplant Recipient

2014 ◽  
Vol 58 (12) ◽  
pp. 7188-7197 ◽  
Author(s):  
Alireza Eshaghi ◽  
Sarah Shalhoub ◽  
Paul Rosenfeld ◽  
Aimin Li ◽  
Rachel R. Higgins ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antiviral Therapy ◽  
Influenza A ◽  
Antiviral Treatment ◽  
Marrow Transplant ◽  
Viral Fitness ◽  
H3n2 Virus ◽  
Resistance Mutations ◽  
Depth Analysis ◽  
Resistant Strains

ABSTRACTImmunocompromised patients are predisposed to infections caused by influenza virus. Influenza virus may produce considerable morbidity, including protracted illness and prolonged viral shedding in these patients, thus prompting higher doses and prolonged courses of antiviral therapy. This approach may promote the emergence of resistant strains. Characterization of neuraminidase (NA) inhibitor (NAI)-resistant strains of influenza A virus is essential for documenting causes of resistance. In this study, using quantitative real-time PCR along with conventional Sanger sequencing, we identified an NAI-resistant strain of influenza A (H3N2) virus in an immunocompromised patient. In-depth analysis by deep gene sequencing revealed that various known markers of antiviral resistance, including transient R292K and Q136K substitutions and a sustained E119K (N2 numbering) substitution in the NA protein emerged during prolonged antiviral therapy. In addition, a combination of a 4-amino-acid deletion at residues 245 to 248 (Δ245-248) accompanied by the E119V substitution occurred, causing resistance to or reduced inhibition by NAIs (oseltamivir, zanamivir, and peramivir). Resistant variants within a pool of viral quasispecies arose during combined antiviral treatment. More research is needed to understand the interplay of drug resistance mutations, viral fitness, and transmission.

Viral fitness and antigenic determinants of porcine parvovirus at the amino acid level of the capsid protein

2021 ◽  
Author(s):  
André Felipe Streck ◽  
Cláudio Wageck Canal ◽  
Uwe Truyen
Keyword(s):  
Amino Acid ◽  
Capsid Protein ◽  
Immune Escape ◽  
Amino Acid Level ◽  
Binding Activity ◽  
Viral Fitness ◽  
Antigenic Determinants ◽  
Amino Acid Substitutions ◽  
Porcine Parvovirus ◽  
Predominant Factor

Since 2001, strains of porcine parvovirus (PPV), designated 27a -like strains, were observed in Europe, suggesting a predominance of these viruses over older strains. The reasons for the obvious evolutionary advantage are unknown. Here, a series of mutants containing amino acid replacements found in the predominant field strains were generated in a PPV-NADL2 background and their impact on replication efficiency and antibody binding activity was determined. Some amino acid substitutions observed in the 27a- like strains significantly increased viral fitness and decreased neutralization activity of sera raised against commercial vaccines and old virus strains (e.g. NADL2). These mutant viruses and a monoclonal antibody raised against a classical PPV strain defined an 27a-specific neutralizing epitope around amino acid 228 of the capsid protein VP2. Based on the analysis of the mutant viruses, it is hypothesized that the predominant factor for the global spread of the PPV-27a strain substitutions is an increased viral fitness of the 27a- like viruses, possibly supported by a partial immune selection. This is reminiscent to the evolution of canine parvovirus and worldwide replacement of the original virus by the so-called new antigenic types. Importance Porcine parvovirus is one of the most important causes of reproductive failure in swine. Recently, despite the continuous use of vaccines, “new” strains emerged, leading to the hypothesis that the emergence of new amino acid substitutions could be a viral adaptation to the immune response against the commercial vaccines. Our results indicate the amino acid substitutions observed in the 27a -like strains can modify viral fitness and antigenicity. However, an absolute immune escape was not evident.

scholarly journals Antidepressant Prophylaxis Reduces Depression Risk but Does Not Improve Sustained Virological Response in Hepatitis C Patients Receiving Interferon Without Depression at Baseline: A Systematic Review and Meta-Analysis

2013 ◽  
Vol 27 (10) ◽  
pp. 575-581 ◽  
Author(s):  
Awad Al-Omari ◽  
Juthaporn Cowan ◽  
Lucy Turner ◽  
Curtis Cooper
Keyword(s):  
Depressive Symptoms ◽  
Hepatitis C ◽  
Antiviral Therapy ◽  
Sustained Virological Response ◽  
Risk Ratio ◽  
Virological Response ◽  
Randomized Clinical Trials ◽  
Rating Scale ◽  
Antiviral Treatment ◽  
Well Being

BACKGROUND: Depression complicates interferon-based hepatitis C virus (HCV) antiviral therapy in 10% to 40% of cases, and diminishes patient well-being and ability to complete a full course of therapy. As a consequence, the likelihood of achieving a sustained virological response (SVR [ie, permanent viral eradication]) is reduced.OBJECTIVE: To systematically review the evidence of whether preemptive antidepressant prophylaxis started before HCV antiviral initiation is beneficial.METHODS: Inclusion was restricted to randomized controlled trials in which prophylactic antidepressant therapy was started at least two weeks before the initiation of HCV antiviral treatment. Studies pertaining to patients with active or recent depressive symptoms before commencing HCV antiviral therapy were excluded. English language articles from 1946 to July 2012 were included. The MEDLINE, Embase and Cochrane Central databases were searched. Where possible, meta-analyses were conducted evaluating the effect of antidepressant prophylaxis on SVR and major depression as well as on Montgomery-Asberg Depression Rating Scale and Beck Depression Index scores at four, 12 and 24 weeks. The Cochrane Collaboration tool was used to assess bias risk.RESULTS: Six randomized clinical trials involving 522 patients met the inclusion criteria. Although the frequency of on-treatment clinical depression was decreased with antidepressant prophylaxis (risk ratio 0.60 [95% CI 0.38 to 0.93]; P=0.02; I2=24%), no benefit to SVR was identified (risk ratio 1.08 [95% CI 0.74 to 1.57]; P=0.69; I2=58%).CONCLUSION: This practice is not justified to improve SVR in populations free of active depressive symptoms leading up to HCV antiviral therapy.

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