scholarly journals A Genome-Wide Association Study on Liver Stiffness Changes during Hepatitis C Virus Infection Cure

Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1501
Author(s):  
Anaïs Corma-Gómez ◽  
Juan Macías ◽  
Antonio Rivero ◽  
Antonio Rivero-Juarez ◽  
Ignacio de los Santos ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Genetic Factors ◽  
Liver Stiffness ◽  
Dna Conformation ◽  
Factors Associated ◽  
Hcv Therapy ◽  
Genome Wide ◽  
Pre Treatment ◽  
The Moment

Liver stiffness (LS) at sustained virological response (SVR) after direct-acting antivirals (DAA)-based therapy is a predictor of liver events in hepatitis C virus (HCV)-infected patients. The study aim was to identify genetic factors associated with LS changes from the moment of starting anti-HCV therapy to SVR. This prospective study included HCV-infected patients from the GEHEP-011 cohort who achieved SVR with DAA-based therapy, with LS pre-treatment ≥ 9.5 kPa and LS measurement available at SVR. Plink and Magma software were used to carry out genome-wide single-nucleotide polymorphism (SNP)-based and gene-based association analyses, respectively. The ShinyGO application was used for exploring enrichment in Gene Ontology (GO) categories for biological processes. Overall, 242 patients were included. Median (quartile 1, quartile 3) LS values at pre-treatment and at SVR were 16.8 (12, 28) kPa and 12.0 (8.5, 19.3) kPa, respectively. Thirty-five SNPs and three genes reached suggestive association with LS changes from the moment of starting anti-HCV therapy to SVR. GO categories related to DNA packaging complex, DNA conformation change, chromosome organization and chromatin organization were significantly enriched. Our study reports possible genetic factors associated with LS changes during HCV-infection cure. In addition, our results suggest that processes related to DNA conformation are also involved in these changes.

scholarly journals Viral genome wide association study identifies novel hepatitis C virus polymorphisms associated with sofosbuvir treatment failure

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
David A. Smith ◽  
Carlota Fernandez-Antunez ◽  
Andrea Magri ◽  
Rory Bowden ◽  
Nimisha Chaturvedi ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Genome Wide Association Study ◽  
De Novo ◽  
Response To Treatment ◽  
Common Component ◽  
Genome Wide ◽  
Pre Treatment ◽  
Direct Acting

AbstractPersistent hepatitis C virus (HCV) infection is a major cause of chronic liver disease, worldwide. With the development of direct-acting antivirals, treatment of chronically infected patients has become highly effective, although a subset of patients responds less well to therapy. Sofosbuvir is a common component of current de novo or salvage combination therapies, that targets the HCV NS5B polymerase. We use pre-treatment whole-genome sequences of HCV from 507 patients infected with HCV subtype 3a and treated with sofosbuvir containing regimens to detect viral polymorphisms associated with response to treatment. We find three common polymorphisms in non-targeted HCV NS2 and NS3 proteins are associated with reduced treatment response. These polymorphisms are enriched in post-treatment HCV sequences of patients unresponsive to treatment. They are also associated with lower reductions in viral load in the first week of therapy. Using in vitro short-term dose-response assays, these polymorphisms do not cause any reduction in sofosbuvir potency, suggesting an indirect mechanism of action in decreasing sofosbuvir efficacy. The identification of polymorphisms in NS2 and NS3 proteins associated with poor treatment outcomes emphasises the value of systematic genome-wide analyses of viruses in uncovering clinically relevant polymorphisms that impact treatment.

scholarly journals Viral genome wide association study identifies novel hepatitis C virus polymorphisms associated with sofosbuvir treatment failure

2020 ◽  
Author(s):  
David A Smith ◽  
Andrea Magri ◽  
Rory Bowden ◽  
Nimisha Chaturvedi ◽  
Jacques Fellay ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Genome Wide Association Study ◽  
De Novo ◽  
Response To Treatment ◽  
Common Component ◽  
Genome Wide ◽  
Poor Treatment ◽  
Pre Treatment ◽  
Direct Acting

AbstractChronic hepatitis C virus (HCV) infection is a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma worldwide. With the recent development of direct acting antivirals (DAA), treatment of chronically infected patients has become highly effective although a subset of patients do not respond to therapy. Sofosbuvir is a common component of current de novo or salvage combination therapies. We used pre-treatment whole genome sequencing of HCV from 507 patients infected with HCV subtype 3a and treated with sofosbuvir containing regimens to detect viral polymorphisms associated with response to treatment. We found that three common polymorphisms present in HCV NS2 and NS3 proteins (not direct targets of sofosbuvir) were associated with reduced treatment response. These polymorphisms were enriched in post-treatment HCV sequences of patients unresponsive to treatment; they were also associated with lower reductions in viral load in the first week of therapy. The finding of polymorphisms in NS2 and NS3 proteins associated with poor treatment outcomes emphasises the value of more systematic genome-wide analyses of HCV in uncovering indirect but clinically relevant mechanisms of antiviral resistance.

Correlation between FIB4, liver stiffness and metabolic parameters in patients with HIV and hepatitis C virus co-infection

2011 ◽  
Vol 43 (7) ◽  
pp. 575-578 ◽  
Author(s):  
Raffaele Bruno ◽  
Paolo Sacchi ◽  
Serena Cima ◽  
Laura Maiocchi ◽  
Savino F.A. Patruno ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Liver Stiffness ◽  
Metabolic Parameters

The impact of direct-acting antivirals on liver fibrosis in Egyptian hepatitis C virus patients: a single center experience

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Nadia Abdelaaty Abdelkader ◽  
Amira Mahmoud AlBalakosy ◽  
Ahmed Fouad Helmy Sherief ◽  
Mohamed Soliman Gado
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
Transient Elastography ◽  
Liver Stiffness ◽  
Treatment Unit ◽  
Non Invasive ◽  
One Year ◽  
The Impact

Abstract Background Hepatitis C virus (HCV) infection affects approximately 170 million people worldwide, causing liver cirrhosis and hepatocellular carcinoma (HCC) and leading to liver transplantation and ultimately death. Accurate evaluation of liver fibrosis in patients with chronic liver diseases is crucial, as liver fibrosis is important in order to make therapeutic decisions, determine prognosis of liver disease and to follow-up disease progression. Multiple non-invasive methods have been used successfully in the prediction of fibrosis; however, early changes in noninvasive biomarkers of hepatic fibrosis under effective antiviral therapy are widely unknown. The aim of this study is to evaluate changes of transient elastography values as well as FIB-4 and AST to platelet ratio index (APRI) in patients treated with DAAs. Objectives The aim beyond this study is to evaluate the changes in liver stiffness in hepatitis C Egyptian patients before and at least one year after treatment with DAAs using transient elastography and non-invasive liver fibrosis indices as FIB-4 and APRI scores. Patients and methods The present study was conducted on 100 patients with chronic hepatitis C patients attended to Ain Shams University Hospitals, Viral hepatitis treatment unit between October 2017 and December 2018, who were followed-up during treatment and after treatment for at least one year (retrospective and prospective study). Total number of cases during the study period was 117 patients. 17 patients were excluded from the study due to missed follow-up. Eventually, 100 patients were enrolled in the study fulfilling the inclusion criteria. Results The mean age of our patients is 47.9 years with Male predominance (52 males and 48 females). There was a significant improvement of, platelets counts, ALT and AST levels, which in turn cause significant improvement in FIB-4 and APRI scores. There was a significant improvement of liver stiffness after end of treatment, regardless of the DAA regimen used, as evidenced by Fibroscan. Conclusion Fibrosis regression –assessed by non-invasive markers of fibrosis is achievable upon removal of the causative agent.

scholarly journals Genetic Diversity of Near Genome-Wide Hepatitis C Virus Sequences during Chronic Infection: Evidence for Protein Structural Conservation Over Time

PLoS ONE ◽  
2011 ◽  
Vol 6 (5) ◽  
pp. e19562 ◽  
Author(s):  
Hui Li ◽  
Austin L. Hughes ◽  
Nazneen Bano ◽  
Susan McArdle ◽  
Stephen Livingston ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Infection ◽  
Genome Wide ◽  
Structural Conservation ◽  
Over Time

scholarly journals Diffuse Alveolar Hemorrhage (DAH) in Hepatitis C Virus (HCV) Associated Cryoglobulinemia After Completion of HCV Therapy

CHEST Journal ◽  
2016 ◽  
Vol 150 (4) ◽  
pp. 530A
Author(s):  
Abhijai Singh ◽  
Chandrakanta Chuturvedula ◽  
Gurbir GIll ◽  
Reshma Abraham ◽  
Pieusha Malhotra
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Diffuse Alveolar Hemorrhage ◽  
Alveolar Hemorrhage ◽  
Hcv Therapy
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