scholarly journals The Impact of Interferon Lambda 3 Gene Polymorphism on Natural Course and Treatment of Hepatitis C

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
F. Bellanti ◽  
G. Vendemiale ◽  
E. Altomare ◽  
G. Serviddio
Keyword(s):  
Hepatitis C ◽  
Association Studies ◽  
Acute Infection ◽  
Sustained Viral Response ◽  
Hcv Infection ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Type Iii Ifn ◽  
Chronic Hcv ◽  
The Impact

Host genetic factors may predict the outcome and treatment response in hepatitis C virus (HCV) infection. Very recently, three landmark genome-wide association studies identified single nucleotide polymorphisms near the interleukin 28B (IL28B) region which were more frequent in responders to treatment. IL28B encodes interferon (IFN)λ3, a type III IFN involved in host antiviral immunity. Favourable variants of the two most widely studied IL28B polymorphisms, rs12979860 and rs8099917, are strong pretreatment predictors of early viral clearance and sustained viral response in patients with genotype 1 HCV infection. Further investigations have implicated IL28B in the development of chronic HCV infection versus spontaneous resolution of acute infection and suggest that IL28B may be a key factor involved in host immunity against HCV. This paper presents an overview about the biological activity and clinical applications of IL28B, summarizing the available data on its impact on HCV infection. Moreover, the potential usefulness of IFNλin the treatment and natural history of this disease is also discussed.

scholarly journals Genetic Variants in JAK1 Gene and Susceptibility to Hepatitis C Viral Infection in Iraq

2016 ◽  
Vol 10 (1) ◽  
pp. 37-41
Author(s):  
Fatima Abood Chaloob
Keyword(s):  
Hepatitis C ◽  
Hcv Infection ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Global Challenge ◽  
Pcr Products ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Apparently Healthy

Infection with hepatitis C virus (HCV) imposes a global challenge with over 180 million cases worldwide. Only few patients spontaneously had their virus neutralized, while most patients develop chronic HCV infection. This implies a key role of genetic factors in viral clearance or persistence. The current study aimed at clarifying the effect of certain single nucleotide polymorphisms (SNPs) on individual's susceptibility to HCV infection.  A total of 60 patients with confirmed HCV infection and 35 apparently healthy individuals were enrolled in this study. Blood sample was obtained from each participant, from which DNA was extracted. The JAK1gene was amplified with conventional PCR technique using three sets of primers targeting three SNPs in this gene: rs2780895, rs4244165 and rs17127024. Restriction fragment length polymorphism (RFLP) was used for genotyping of PCR products. Each of rs2780895 and rs17127024 had two genotypes in both patients and controls, however, only the heterozygous genotype of the SNP rs2780895 (CT) significantly associated with the susceptibility to HCV. The SNP rs4244165 appeared in only with homozygous wild genotype (GG) in both patients and controls. It can be concluded that allele T of the SNP rs2780895 could be considered as a risk factor for infection with HCV

scholarly journals French hepatitis C care cascade: substantial impact of direct-acting antivirals, but the road to elimination is still long

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Cécile Brouard ◽  
Josiane Pillonel ◽  
Marjorie Boussac ◽  
Victor de Lédinghen ◽  
Antoine Rachas ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Antiviral Treatment ◽  
Hcv Infection ◽  
World Health ◽  
Direct Acting Antivirals ◽  
Substantial Impact ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Direct Acting ◽  
The Impact

Abstract Background Hepatitis C virus (HCV) elimination by 2030, as targeted by the World Health Organization (WHO), requires that 90% of people with chronic infection be diagnosed and 80% treated. We estimated the cascade of care (CoC) for chronic HCV infection in mainland France in 2011 and 2016, before and after the introduction of direct-acting antivirals (DAAs). Methods The numbers of people (1) with chronic HCV infection, (2) aware of their infection, (3) receiving care for HCV and (4) on antiviral treatment, were estimated for 2011 and 2016. Estimates for 1) and 2) were based on modelling studies for 2011 and on a virological sub-study nested in a national cross-sectional survey among the general population for 2016. Estimates for 3) and 4) were made using the National Health Data System. Results Between 2011 and 2016, the number of people with chronic HCV infection decreased by 31%, from 192,700 (95% Credibility interval: 150,900-246,100) to 133,500 (95% Confidence interval: 56,900-312,600). The proportion of people aware of their infection rose from 57.7 to 80.6%. The number of people receiving care for HCV increased by 22.5% (representing 25.7% of those infected in 2016), while the number of people on treatment increased by 24.6% (representing 12.1% of those infected in 2016). Conclusions This study suggests that DAAs substantially impact CoC. However, access to care and treatment for infected people remained insufficient in 2016. Updating CoC estimates will help to assess the impact of new measures implemented since 2016 as part of the goal to eliminate HCV.

Universal Sustained Viral Response to the Combination of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir with/without Ribavirin in Patients on Hemodialysis Infected with Hepatitis C Virus Genotypes 1 and 4

2017 ◽  
Vol 45 (3) ◽  
pp. 267-272 ◽  
Author(s):  
Soraya Abad ◽  
Almudena Vega ◽  
Eduardo Hernández ◽  
Evangelina Mérida ◽  
Patricia de Sequera ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Transient Elastography ◽  
Sustained Viral Response ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Major Advance ◽  
Multicentric Study ◽  
Viral Response ◽  
The Impact

Background: Hepatitis C virus (HCV) infection is highly prevalent among patients on hemodialysis (HD) and is associated with poor prognosis. Treatment with interferon and ribavirin is poorly tolerated, and few data are available on the impact of new direct-acting antivirals (DAAs). This study was intended to analyze the efficacy and safety of treatment with a combination of ombitasvir/paritaprevir/ritonavir and dasabuvir with/without ribavirin in HCV-infected patients on HD from 3 hospitals. Methods: This is a multicentric study. We analyze the clinical course of all patients on HD with HCV infection who had been treated with the combination of ombitasvir/paritaprevir/ritonavir and dasabuvir in 3 hospitals in Madrid, Spain. All patients under treatment had undergone Transient elastography (FibroScan®) and HCV RNA (PCR) and HCV genotype were determined simultaneously. Results: Thirty-five patients aged 53.3 ± 8.9 years (68.6% males) and with genotypes 1 and 4 were treated with the DAA regimen, and 17 were also given ribavirin. The most common etiology was glomerular disease. Sustained viral response was achieved in 100% of patients. Adverse effects were negligible, and no patient had to discontinue treatment. The most significant side effect was anemia, which led to a significant increase in the dose of erythropoiesis-stimulating agents. Anemia was more marked in patients receiving ribavirin. No patients required transfusions. Conclusion: A combination of ombitasvir/paritaprevir/ritonavir and dasabuvir with/without ribavirin for the treatment of HCV in patients on HD is highly effective and causes minimal side effects. This regimen represents a major advance in disease management. A considerable improvement in prognosis seems likely.

scholarly journals Interferon lambda 4 impacts the genetic diversity of hepatitis C virus

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
M Azim Ansari ◽  
Elihu Aranday-Cortes ◽  
Camilla LC Ip ◽  
Ana da Silva Filipe ◽  
Siu Hin Lau ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Genome ◽  
Association Studies ◽  
Acute Infection ◽  
Adaptive Immune Response ◽  
Spontaneous Clearance ◽  
Genome Wide Association Studies ◽  
Direct Role ◽  
Interferon Lambda

Hepatitis C virus (HCV) is a highly variable pathogen that frequently establishes chronic infection. This genetic variability is affected by the adaptive immune response but the contribution of other host factors is unclear. Here, we examined the role played by interferon lambda-4 (IFN-λ4) on HCV diversity; IFN-λ4 plays a crucial role in spontaneous clearance or establishment of chronicity following acute infection. We performed viral genome-wide association studies using human and viral data from 485 patients of white ancestry infected with HCV genotype 3a. We demonstrate that combinations of host genetic variants, which determine IFN-λ4 protein production and activity, influence amino acid variation across the viral polyprotein - not restricted to specific viral proteins or HLA restricted epitopes - and modulate viral load. We also observed an association with viral di-nucleotide proportions. These results support a direct role for IFN-λ4 in exerting selective pressure across the viral genome, possibly by a novel mechanism.

scholarly journals The role of polymorphic ERAP1 in autoinflammatory disease

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Emma Reeves ◽  
Edward James
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Autoinflammatory Disease ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Single Nucleotide ◽  
Cell Functions ◽  
The Impact

Autoimmune and autoinflammatory conditions represent a group of disorders characterized by self-directed tissue damage due to aberrant changes in innate and adaptive immune responses. These disorders possess widely varying clinical phenotypes and etiology; however, they share a number of similarities in genetic associations and environmental influences. Whilst the pathogenic mechanisms of disease remain poorly understood, genome wide association studies (GWAS) have implicated a number of genetic loci that are shared between several autoimmune and autoinflammatory conditions. Association of particular HLA alleles with disease susceptibility represents one of the strongest genetic associations. Furthermore, recent GWAS findings reveal strong associations with single nucleotide polymorphisms in the endoplasmic reticulum aminopeptidase 1 (ERAP1) gene and susceptibility to a number of these HLA-associated conditions. ERAP1 plays a major role in regulating the repertoire of peptides presented on HLA class I alleles at the cell surface, with the presence of single nucleotide polymorphisms in ERAP1 having a significant impact on peptide processing function and the repertoire of peptides presented. The impact of this dysfunctional peptide generation on CD8+ T-cell responses has been proposed as a mechanism of pathogenesis diseases where HLA and ERAP1 are associated. More recently, studies have highlighted a role for ERAP1 in innate immune-mediated pathways involved in inflammatory responses. Here, we discuss the role of polymorphic ERAP1 in various immune cell functions, and in the context of autoimmune and autoinflammatory disease pathogenesis.

scholarly journals Determination of the human antibody response to the epitope defined by the hepatitis C virus-neutralizing monoclonal antibody AP33

2007 ◽  
Vol 88 (11) ◽  
pp. 2991-3001 ◽  
Author(s):  
Alexander W. Tarr ◽  
Ania M. Owsianka ◽  
Dhanya Jayaraj ◽  
Richard J. P. Brown ◽  
Timothy P. Hickling ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Natural Infection ◽  
Acute Infection ◽  
Hcv Infection ◽  
Human Antibody ◽  
Human Mabs ◽  
Chronic Hcv ◽  
New Treatments

Hepatitis C virus (HCV) is a major cause of liver disease worldwide and there is a pressing need for the development of a preventative vaccine as well as new treatments. It was recently demonstrated that the mouse monoclonal antibody (mAb) AP33 potently neutralizes infectivity of HCV pseudoparticles (HCVpp) carrying E1E2 envelopes representative of all of the major genotypes of HCV. This study determined the prevalence of human serum antibodies reactive to the region of HCV E2 recognized by AP33. Antibodies recognizing this region were present in less than 2.5 % of sera obtained from individuals with chronic HCV infection. A similar prevalence was found in a smaller cohort of individuals who had experienced an acute infection, suggesting that AP33-like antibodies do not play a major role in natural clearance of HCV infection. Sera exhibited different patterns of reactivity to a panel of peptides representing circulating variants, highlighting the presence of distinct epitopes in this region. Only two sera contained antibodies that could recognize a specific AP33-reactive peptide mimotope. AP33-like antibodies made a measurable contribution to the ability of these sera to inhibit E2–CD81 interaction, but not to the overall neutralization of cell entry. Together, these data show that antibodies to the AP33 epitope are not commonly generated during natural infection and that generation of such antibodies via vaccination may require modified immunogens to focus the generation of specific antibodies. Importantly, individuals harbouring AP33-like antibodies are an important potential source of human mAbs for future therapeutic development.

scholarly journals Separating the contributions of SLC26A9 and CFTR to anion secretion in primary human bronchial epithelia (HBE)

2021 ◽  
Author(s):  
Mads B Larsen ◽  
Jeannie J Choi ◽  
Xiaohui Wang ◽  
Michael M Myerburg ◽  
Raymond A Frizzell ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Association Studies ◽  
Primary Source ◽  
Airway Disease ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Anion Secretion ◽  
Anion Transporter ◽  
Bronchial Epithelia ◽  
The Impact

Aberrant anion secretion across the bronchial epithelium is associated with airway disease, most notably in cystic fibrosis. While the cystic fibrosis transmembrane conductance regulator (CFTR) is recognized as the primary source of airway anion secretion, alternative anion transport mechanisms play a contributing role. An alternative anion transporter of growing interest is SLC26A9, a constitutively active chloride channel which has been shown to interact with CFTR and may also contribute to bicarbonate secretion. Interest in SLC26A9 has been fueled by genome-wide association studies which suggest it is a significant modifier of CF disease severity. In spite of this growing evidence that SLC26A9 plays an important role in the airway, its presence and function in bronchial epithelia remains poorly understood, in part because its activity is difficult to separate from the activity of CFTR. Here we present results using primary, human bronchial epithelia (HBE) from multiple patient sources to confirm that SLC26A9 mRNA is present in HBE, and that its constitutive channel activity is unaffected by knock down of CFTR. Furthermore, SLC26A9 and CFTR show differential responses to common inhibitors of anion secretion. Finally, we assess the impact of bicarbonate on the activity of SLC26A9 and CFTR. These results confirm that SLC26A9 is the primary source of constitutive anion secretion across HBE, and should inform future studies focused on activation of SLC26A9 as an alternative anion channel in CF. These results should provide a strong foundation to investigate how single nucleotide polymorphisms in SLC26A9 modulate airway disease.

scholarly journals French hepatitis C care cascade: substantial impact of direct-acting antivirals, but the road to elimination is still long

2020 ◽  
Author(s):  
Cécile Brouard ◽  
Josiane Pillonel ◽  
Marjorie Boussac ◽  
Victor de Lédinghen ◽  
Antoine Rachas ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Antiviral Treatment ◽  
Hcv Infection ◽  
World Health ◽  
Direct Acting Antivirals ◽  
Substantial Impact ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Direct Acting ◽  
The Impact

Abstract Background: Hepatitis C virus (HCV) elimination by 2030, as targeted by the World Health Organization (WHO), requires that 90% of people with chronic infection be diagnosed and 80% treated. We estimated the cascade of care (CoC) for chronic HCV infection in mainland France in 2011 and 2016, before and after the introduction of direct-acting antivirals (DAAs).Methods: The numbers of people (1) with chronic HCV infection, (2) aware of their infection, (3) receiving care for HCV and (4) on antiviral treatment, were estimated for 2011 and 2016. Estimates for 1) and 2) were based on modelling studies for 2011 and on a virological sub-study nested in a national cross-sectional survey among the general population for 2016. Estimates for 3) and 4) were made using the National Health Data System.Results: Between 2011 and 2016, the number of people with chronic HCV infection decreased by 31%, from 192,700 (95% Credibility interval: 150,900-246,100) to 133,500 (95% Confidence interval: 56,900-312,600). The proportion of people aware of their infection rose from 57.7% to 80.6%. The number of people receiving care for HCV increased by 22.5% (representing 25.7% of those infected in 2016), while the number of people on treatment increased by 24.6% (representing 12.1% of those infected in 2016).Conclusions: This study suggests that DAAs substantially impact CoC. However, access to care and treatment for infected people remained insufficient in 2016. Updating CoC estimates will help to assess the impact of new measures implemented since 2016 as part of the goal to eliminate HCV.

scholarly journals French hepatitis C care cascade: substantial impact of direct-acting antivirals, but the road to elimination is still long

2020 ◽  
Author(s):  
Cécile Brouard ◽  
Josiane Pillonel ◽  
Marjorie Boussac ◽  
Victor de Lédinghen ◽  
Antoine Rachas ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Antiviral Treatment ◽  
Hcv Infection ◽  
World Health ◽  
Direct Acting Antivirals ◽  
Substantial Impact ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Direct Acting ◽  
The Impact

Abstract Background: Hepatitis C virus (HCV) elimination by 2030, as targeted by the World Health Organization (WHO), requires that 90% of people with chronic infection be diagnosed and 80% treated. We estimated the cascade of care (CoC) for chronic HCV infection in mainland France in 2011 and 2016, before and after the introduction of direct-acting antivirals (DAAs).Methods: The numbers of people (1) with chronic HCV infection, (2) aware of their infection, (3) receiving care for HCV and (4) on antiviral treatment, were estimated for 2011 and 2016. Estimates for 1) and 2) were based on modelling studies for 2011 and on a virological sub-study nested in a national cross-sectional survey among the general population for 2016. Estimates for 3) and 4) were made using the National Health Data System. Results: Between 2011 and 2016, the number of people with chronic HCV infection decreased by 31%, from 192,700 (95% Credibility interval: 150,900-246,100) to 133,500 (95% Confidence interval: 56,900-312,600). The proportion of people aware of their infection rose from 57.7% to 80.6%. The number of people receiving care for HCV increased by 22.5% (representing 25.7% of those infected in 2016), while the number of people on treatment increased by 24.6% (representing 12.1% of those infected in 2016).Conclusions: This study suggests that DAAs substantially impact CoC. However, access to care and treatment for infected people remained insufficient in 2016. Updating CoC estimates will help to assess the impact of new measures implemented since 2016 as part of the goal to eliminate HCV.

scholarly journals The efficacy and safety of direct-acting antiviral drugs in the management of hepatitis C virus-related arthritis

2020 ◽  
Vol 47 (1) ◽  
Author(s):  
Samah M. Alian ◽  
Mohamed Othman Wahba ◽  
Ahmed Fathy Gomaa ◽  
Sahar S. Khalil
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Viral Response ◽  
Hcv Infection ◽  
Direct Acting Antiviral ◽  
Group I ◽  
Group Ii ◽  
Chronic Hcv ◽  
Direct Acting ◽  
Post Therapy

Abstract Background Hepatitis C virus (HCV) infection is a worldwide disease. HCV-related arthritis is one of the extrahepatic manifestations of the disease. The treatment of chronic HCV has been revolutionized with the introduction of oral direct-acting antiviral (DAA) drugs. We aim to determine the outcomes of treatment by the combination of sofosbuvir-daclatasvir with or without ribavirin in patients with HCV-related arthritis. Results Post-therapy, all group I patients had sustained viral response. Significant improvement of the outcome parameters was found 12 weeks post-treatment in group I compared to baseline and group II. Complete and partial remission of articular symptoms in group I patients was observed in 80% and 5%, respectively, while 85% of patients in group II showed no remission. Few mild side effects were encountered with therapy. Conclusion The combination of sofosbuvir-daclatasvir with or without ribavirin is an effective and safe therapy for eradication of HCV infection and amelioration of HCV-related arthritis.

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