scholarly journals Combinations of siRNAs against La Autoantigen with NS5B or hVAP-A Have Additive Effect on Inhibition of HCV Replication

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Anirban Mandal ◽  
Krishna Kumar Ganta ◽  
Binay Chaubey
Keyword(s):  
Target Genes ◽  
Antiviral Effect ◽  
Hcv Rna ◽  
Chronic Liver Diseases ◽  
Therapeutic Tool ◽  
Direct Acting Antiviral ◽  
Single Target ◽  
Cellular Factors ◽  
Combination Of Sirnas ◽  
Direct Acting

Hepatitis C virus is major cause of chronic liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Presently available direct-acting antiviral drugs have improved success rate; however, high cost limits their utilization, especially in developing countries like India. In the present study, we evaluated anti-HCV potential of several siRNAs targeted against the HCV RNA-dependent RNA polymerase NS5B and cellular factors, La autoantigen, PSMA7, and human VAMP-associated protein to intercept different steps of viral life cycle. The target genes were downregulated individually as well as in combinations and their impact on viral replication was evaluated. Individual downregulation of La autoantigen, PSMA7, hVAP-A, and NS5B resulted in inhibition of HCV replication by about 67.2%, 50.7%, 39%, and 52%, respectively. However, antiviral effect was more pronounced when multiple genes were downregulated simultaneously. Combinations of siRNAs against La autoantigen with NS5B or hVAP-A resulted in greater inhibition in HCV replication. Our findings indicate that siRNA is a potential therapeutic tool for inhibiting HCV replication and simultaneously targeting multiple viral steps with the combination of siRNAs is more effective than silencing a single target.

scholarly journals A211 SPONTANEOUS HBV REMISSION AFTER HBV REACTIVATION FOLLOWING TREATMENT WITH SOFOSBUVIR AND VELPATASVIR IN A PATIENT WITH HCV AND HBV CO-INFECTION: CASE REPORT

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 242-243
Author(s):  
A Chiang ◽  
K Tsoi
Keyword(s):  
Hepatitis C ◽  
Hepatitis B ◽  
Antiviral Agents ◽  
Clinical Signs ◽  
Hbv Dna ◽  
Hcv Rna ◽  
Hbv Reactivation ◽  
Genotype 3 ◽  
Direct Acting Antiviral ◽  
Direct Acting

Abstract Background In co-infected patients with hepatitis B (HBV) and hepatitis C (HCV), the treatment of HCV with direct-acting antiviral agents (DAA) can cause HBV reactivation. However, there are no clear guidelines on the timing of treatment initiation, especially in the absence of clinical signs of flare. Aims Here we discuss the case of a 34-year-old female with HBV and HCV genotype 3 who had HBV reactivation following HCV treatment, but did not require nucleos(t)ide therapy. Methods She initially presented with chronic inactive hepatitis B and chronic hepatitis C with HBV DNA level of 67.5 IU/mL and HCV RNA level of 3.33 x 106 IU/mL. She completed a 12 week course of sofosbuvir and velpatasvir for HCV and achieved sustained virologic remission, but subsequently developed reactivation of her HBV with HBV DNA peaking at 3.41 x 104 IU/mL twelve weeks post-treatment. She did not develop any signs of hepatitis and a decision was made to monitor her clinically. Results Two years later, she spontaneously went into remission with her HBV DNA levels being <10 IU/mL. Conclusions The significance of this case is to illustrate HBV reactivation following treatment of HCV with DAAs may not necessitate immediate treatment, especially if there are no signs of flare. There have been similar reported cases, but larger prospective studies are required to determine the appropriate clinical context where monitoring may be acceptable instead of immediate treatment. Funding Agencies None

scholarly journals HCV Core Antigen as an alternative test to Quantitative HCV RNA for assessment of SVR in Chronic HCV infected patients treated with Direct Acting Antiviral agents

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
S M Mohamed ◽  
N I Musa ◽  
R S Ghait ◽  
B M Abdelrhiem
Keyword(s):  
Antiviral Agents ◽  
Virologic Response ◽  
Hcv Infection ◽  
Core Antigen ◽  
Hcv Rna ◽  
Viral Kinetics ◽  
Direct Acting Antiviral ◽  
Hcv Core Antigen ◽  
End Of Treatment ◽  
Direct Acting

Abstract Background and aims Widespread use of direct-acting antiviral (DAA) agents to treat patients with hepatitis C virus (HCV) infection has reduced the need for monitoring of HCV-RNA levels, because viral kinetics do not predict sustained virologic response (SVR) to these drugs. However, the performance of cheaper tests, such as the assay to quantify HCV core antigen (HCV Ag), has not been determined. This study was aimed at investigating the accuracy of the HCV Ag test in predicting which patients receiving DAAs will achieve SVR at week 12 (SVR12). Methods We performed a prospective study on 90 patients, chronically infected with HCV, receiving DAAs therapy from different NCCVH centers in Cairo during the period from August 2017 to June 2018. We collected blood samples and measured the levels of HCV core Ag and HCV-RNA at baseline and 12 weeks after end of treatment. We compared the ability of these assays to predict which patients would have SVR12. Results The median baseline level of HCV-RNA was 1688529.6 ± 994697.3 IU/ml (range, 312700 IU/ml to 3491100 IU/ml) and HCV Ag was 179.2 ± 83.5 pg/ml (range, 33.5 pg/ml to 315.6 pg/ml). HCV Ag became undetectable in 92.2% 12 weeks after the end of treatment. HCV-RNA became undetectable in 87.8% at the end of treatment (P<.0001). 79 out of 90 patients (87.8%) achieved an SVR12; the test for HCV Ag identified 63.6% of these patients. Conclusions Tests that measure HCV Ag monitor efficacy of DAA therapy for HCV infection as well as assays that measure HCV-RNA, and hence could be recommended for clinical practice.

scholarly journals Baseline Plasma Metabotype Correlates With Direct-Acting Antiviral Therapy Nonresponse for HCV in HIV–HCV Coinfected Patients

2022 ◽  
Vol 8 ◽  
Author(s):  
Gaurav Tripathi ◽  
Sheetalnath Rooge ◽  
Manisha Yadav ◽  
Babu Mathew ◽  
Nupur Sharma ◽  
...  
Keyword(s):  
Treatment Response ◽  
Linear Regression Analysis ◽  
Sustained Viral Response ◽  
Tryptophan Metabolism ◽  
Plasma Metabolites ◽  
Hcv Rna ◽  
Multivariate Linear Regression Analysis ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
Post Therapy

Introduction: With the advent of direct-acting antiviral (DAA) therapy for HCV, the cure is achieved at similar rates among HIV–HCV coinfected patients as in HCV mono-infected patients. The present study evaluates host plasma metabolites as putative indicators in predicting the treatment response in baseline HIV–HCV patients.Methods: Non-cirrhotic HIV–HCV (N = 43) coinfected patients were treated with sofosbuvir and daclatasvir for 12 weeks. Plasma metabolite profiling of pre- and post-therapy was analyzed in 20/43 patients. Of the 20 selected, 10 (50%) attained the sustained viral response [(SVR) (responders)] as defined by the absence of HCV RNA at 12 weeks after the treatment, and 10 (50%) did not attain the cure for HCV (nonresponders).Results: A total of 563 features were annotated (metabolomic/spectral databases). Before therapy, 39 metabolites differentiated (FC ±1.5, p < 0.05) nonresponders from responders. Of these, 20 upregulated and 19 downregulated were associated with tryptophan metabolism, nicotinamide metabolism, and others. Post therapy, 62 plasma metabolites (12 upregulated and 50 downregulated, FC±1.5, p < 0.05) differentiated nonresponders from responders and highlighted a significant increase in the steroid and histidine metabolism and significant decrease in tryptophan metabolism and ascorbate and pyruvate metabolism in the nonresponders. Based on random forest and multivariate linear regression analysis, the baseline level of N-acetylspermidine (FC > 2, AUC = 0.940, Bfactor = −0.267) and 2-acetolactate (FC > 2, AUC = 0.880, Bfactor = −0.713) significantly differentiated between nonresponders from responders in HIV–HCV coinfected patients and was able to predict the failure of treatment response.Conclusion: Increased baseline levels of N-acetylspermidine and 2-acetolactate levels are associated with the likeliness of failure to attain the cure for HCV in HIV–HCV coinfected patients.

Amino acid substitutions in the hepatitis C virus core region predict hepatocarcinogenesis following eradication of HCV RNA by all-oral direct-acting antiviral regimens

2018 ◽  
Vol 90 (6) ◽  
pp. 1087-1093 ◽  
Author(s):  
Fumihiro Ogata ◽  
Norio Akuta ◽  
Masahiro Kobayashi ◽  
Shunichiro Fujiyama ◽  
Yusuke Kawamura ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Core Region ◽  
Hcv Rna ◽  
Amino Acid Substitutions ◽  
Direct Acting Antiviral ◽  
Virus Core ◽  
Direct Acting

Importance of very early HCV RNA kinetics for prediction of treatment outcome of highly effective all oral direct acting antiviral combination therapy

2015 ◽  
Vol 214 ◽  
pp. 29-32 ◽  
Author(s):  
Christoph Sarrazin ◽  
Heiner Wedemeyer ◽  
Gavin Cloherty ◽  
Daniel E. Cohen ◽  
Stephane Chevaliez ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Combination Therapy ◽  
Hcv Rna ◽  
Direct Acting Antiviral ◽  
Highly Effective ◽  
Direct Acting

scholarly journals Potential Molecular Targets of Tenofovir Disoproxil Fumarate for Alleviating Chronic Liver Diseases via a Non-Antiviral Effect in a Normal Mouse Model

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuanqin Duan ◽  
Zhiwei Chen ◽  
Hu Li ◽  
Wei Shen ◽  
Yi Zeng ◽  
...  
Keyword(s):  
Tenofovir Disoproxil Fumarate ◽  
Liver Diseases ◽  
Target Genes ◽  
Molecular Targets ◽  
Underlying Mechanism ◽  
Antiviral Effect ◽  
Prima Facie ◽  
Chronic Liver ◽  
Chronic Liver Diseases ◽  
Ppi Networks

Accumulating evidence suggests that tenofovir disoproxil fumarate (TDF) can attenuate liver fibrosis directly, the mechanism of which, however, has not been fully elucidated, and there is a paucity of data concerning whether TDF can also mitigate other chronic liver diseases (CLDs). We aimed to identify the molecular targets and potential mechanism of TDF itself in ameliorating CLDs. RNA-sequencing was performed on mouse liver tissues treated with TDF or normal saline. Then the differentially expressed genes (DEGs) were screened, and enrichment analyses of the function and signaling pathways of DEGs were performed with Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Metascape. Next, protein-protein interaction (PPI) networks were constructed and module analyses were utilized to identify significant genes. Subsequently, the DisGeNET platform was used to identify the potential target genes of TDF in mitigating these diseases. Finally, prediction of the transcription factors (TFs) and microRNAs (miRNAs) of the target genes was done to conjecture the underlying mechanism by which TDF relieved CLDs. As a result, a total of 854 DEGs were identified, and the DEGs were involved mainly in “immunity,” “inflammation,” and “metabolism” processes. In addition, 50 significant genes were obtained via PPI construction and module analyses. Furthermore, by means of DisGeNET, 19 genes (Adra2a, Cxcl1, Itgam, Cxcl2, Ccr1, Ccl5, Cxcl5, Fabp5, Sell, Lilr4b, Ccr2, Tlr2, Lilrb4a, Tnf, Itgb2, Lgals3, Cxcr4, Sucnr1, and Mme) were identified to be associated with nine CLDs. Finally, 34 miRNAs (especially mmu-miR-155-5p) and 12 TFs (especially Nfkb1) were predicted to be upstream of the nine target genes (Cxcl1, Cxcl2, Ccl5, Ccr2, Sell, Tlr2, Tnf, Cxcr4, and Mme) of TDF in ameliorating CLDs. In conclusion, our study suggests that TDF have the potential to ameliorate CLDs independently of its antiviral activity by affecting the expression of genes involved in hepatic immune, inflammatory, and metabolic processes via mmu-miR-155-5p-NF-κB signaling. These findings provided prima facie evidence for using TDF in CHB patients with concurrent CLDs.

Detection of Occult Hepatitis C Virus Infection in Patients Who Achieved a Sustained Virologic Response to Direct-Acting Antiviral Agents

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Tarek Mohamed Yousef ◽  
Maha Mohsen Mohamed Kamal El Din ◽  
Tari Magdy Aziz George ◽  
Amr Adel Elzohary Mohamed
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Virologic Response ◽  
Hcv Rna ◽  
Occult Hepatitis ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
Occult Hepatitis C ◽  
Direct Acting Antiviral Agents

Abstract Background Occult infection with hepatitis C virus (HCV) is defined as the presence of the HCV genome in either liver tissue or peripheral blood monocytes, despite constant negative results from tests for HCV RNA in serum. Objectives The aim of the study to detect the prevalence of occult hepatitis C Virus infection in patients who achieved a sustained virologic response (SVR) to direct-acting antiviral agents and to outline predictors of OCI. Patients and Methods This study included 100 patients with chronic HCV infection without liver cirrhosis attending to hepatitis C clinics at Ain Shams University Hospital, Ahmed Maher Teaching hospital and Elgomhorya Teaching Hospital.who received sofosbuvir (400mg) plus daclatasvir (60mg) daily for 12 weeks with or without ribavirin according to National committee to combat viral hepatitis (NCCVH) protocol. Results We tested peripheral blood for HCV RNA in PBMCs to detect OCI. Occult HCV was found positive in 12% of the studied cases. Occult HCV was positive more in male cases. Positive cases had significantly lower age, and higher total bilirubin, direct bilirubin, AST and ALT levels. Age had significant moderate diagnostic performance in predicting occult HCV, while direct bilirubin has significant low diagnostic performance in predicting occult HCV. Conclusion OCI following direct antiviral therapy may be present in some cases, and this may require further testing of patients with SVR particularly in younger male patients with persistantly high liver enzymes.

scholarly journals Real-world Efficacy of Direct-Acting Antiviral Therapy for HCV Infection Affecting People Who Inject Drugs Delivered in a Multidisciplinary Setting

2018 ◽  
Vol 5 (6) ◽  
Author(s):  
Arshia Alimohammadi ◽  
Julie Holeksa ◽  
Astou Thiam ◽  
David Truong ◽  
Brian Conway
Keyword(s):  
Real World ◽  
People Who Inject Drugs ◽  
Hcv Rna ◽  
World Population ◽  
Model Of Care ◽  
Hcv Treatment ◽  
Direct Acting Antiviral ◽  
Hcv Therapy ◽  
Direct Acting ◽  
Multidisciplinary Model

Abstract Background Many clinicians and insurance providers are reluctant to embrace recent guidelines identifying people who inject drugs (PWID) as a priority population to receive hepatitis C virus (HCV) treatment. The aim of this study was to evaluate the efficacy of direct-acting antiviral (DAA) HCV therapy in a real-world population comprised predominantly of PWID. Methods A retrospective analysis was performed on all HCV-infected patients who were treated at the Vancouver Infectious Diseases Centre between March 2014 and December 2017. All subjects were enrolled in a multidisciplinary model of care, addressing medical, psychological, social, and addiction-related needs. The primary outcome was achievement of sustained virologic response (undetectable HCV RNA) 12 or more weeks after completion of HCV therapy (SVR-12). Results Overall, 291 individuals were enrolled and received interferon-free DAA HCV therapy. The mean age was 54 years, 88% were PWID, and 20% were HCV treatment experienced. At data lock, 62 individuals were still on treatment and 229 were eligible for evaluation of SVR by intent-to-treat (ITT) analysis. Overall, 207 individuals achieved SVR (90%), with 13 losses to follow-up, 7 relapses, and 2 premature treatment discontinuations. ITT SVR analysis show that active PWID and treatment-naïve patients were less likely to achieve SVR (P = .0185 and .0317, respectively). Modified ITT analysis of active PWID showed no difference in achieving SVR (P = .1157) compared with non-PWID. Conclusion Within a multidisciplinary model of care, the treatment of HCV-infected PWID with all-oral DAA regimens is safe and highly effective. These data justify targeted efforts to enhance access to HCV treatment in this vulnerable and marginalized population.

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