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

Impaired insulin exocytosis in chronic hepatitis C infection: contributory role of p38δ MAPK–protein kinase D–golgi complex axis

2020 ◽  
Vol 134 (12) ◽  
pp. 1449-1456
Author(s):  
Parimala Narne
Keyword(s):  
Hepatitis C ◽  
Protein Kinase ◽  
Golgi Complex ◽  
Hcv Infection ◽  
Protein Kinase D ◽  
Cell Dysfunction ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Insulin Exocytosis

Abstract Hepatitis C virus (HCV) infection and chronic hepatitis C (CHC) are associated with a measurable risk of insulin resistance (IR)/impaired glucose tolerance (IGT)/diabetes mellitus (DM). While loss of hepatic endocrine function contributes to liver cirrhosis in diabetic patients, onset and progression of IR/IGT to diabetes and exacerbation of incident hyperglycemia are ostensibly linked with chronic HCV infection. In this regard, the study by Chen J et al. appearing in Clinical Science (2020) (134(5) https://doi.org/10.1042/CS20190900) attempts to understand the mechanisms underlying the savaging effects of chronic HCV infection on insulin-producing pancreatic β-cells and hence diabetic onset. The study investigated the role of mitogen-activated protein kinase (MAPK) p38δ–protein kinase D (PKD)–golgi complex axis in impacting insulin exocytosis. It was inferred that an insulin secretory defect of pancreatic β-cells, owing to disrupted insulin exocytosis, to an extent explains β-cell dysfunction in HCV-infected or CHC milieu. HCV infection negatively regulates first-phase and second-phase insulin secretion by impinging on PKD-dependent insulin secretory granule fission at trans-golgi network and insulin secretory vesicle membrane fusion events. This commentary highlights the study in question, that deciphered the contribution of p38δ MAPK–PKD–golgi complex axis to β-cell dysfunction in CHC milieu. This pivotal axis proffers a formidable therapeutic opportunity for alleviation of double burden of glucose abnormalities/DM and CHC.

scholarly journals Immunity in Chimpanzees Chronically Infected with Hepatitis C Virus: Role of Minor Quasispecies in Reinfection

1998 ◽  
Vol 72 (3) ◽  
pp. 1725-1730 ◽  
Author(s):  
Colby A. Wyatt ◽  
Linda Andrus ◽  
Betsy Brotman ◽  
Fannie Huang ◽  
Dong-Hun Lee ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Primary Infection ◽  
Hcv Infection ◽  
Natural Evolution ◽  
Genotype 1A ◽  
Natural Progression ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

ABSTRACT We have previously reported that chimpanzees chronically infected with hepatitis C virus (HCV) could be reinfected, even with the original infecting strain. In this study we tested the hypothesis that this might reflect the presence of minor quasispecies to which there was little or no immunity. To evaluate this hypothesis, we sequenced multiple clones taken at intervals after primary infection and rechallenge from four chronically infected chimpanzees. The inoculum used in these studies (HCV-H, genotype 1a) revealed 17 separate variants among 46 clones sequenced. Following challenge, each of the four challenged animals showed marked alterations of their quasispecies distribution. The new variants, which appeared 1 to 6 weeks after challenge, were either identical to or closely resembled variants present in the challenge inoculum. These results, paralleled by an increase in viremia in some of the challenged animals, suggest that quasispecies in the challenge inoculum were responsible for signs of reinfection and that there was little immunity. However, the newly emerged quasispecies completely took over infection in only one animal. In the remaining three chimpanzees the prechallenge quasispecies were able to persist. The natural evolution of infection within chimpanzees resulted in variants able to compete with the inoculum variants. Whether through reexposure or the natural progression of infection, newly emerged quasispecies are likely to play a role in the pathogenesis of chronic HCV infection.

Treatment of acute hepatitis C infection with interferon-alfa 2b monotherapy prevents development of chronic HCV infection

2001 ◽  
Vol 120 (5) ◽  
pp. A567-A567 ◽  
Author(s):  
E JAECKEL ◽  
M CORNBERG ◽  
T SANTANTONIO ◽  
J MAYER ◽  
H WEDEMEYER ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Acute Hepatitis ◽  
Interferon Alfa ◽  
Hcv Infection ◽  
Acute Hepatitis C ◽  
Hepatitis C Infection ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

When Coadministration Cannot Be Avoided: Real World Experience of Direct Acting Antivirals for the Treatment of Hepatitis C Virus Infection in Patients on First Generation Anticonvulsants

2020 ◽  
pp. 089719002097776
Author(s):  
Kayla M. Natali ◽  
Humberto R. Jimenez ◽  
Jihad Slim
Keyword(s):  
Drug Interaction ◽  
Hepatitis C ◽  
Clinical Cure ◽  
First Generation ◽  
Virologic Response ◽  
Hcv Infection ◽  
Direct Acting Antivirals ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Direct Acting

Background Coadministration of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection and first generation anticonvulsants is currently not recommended due to a drug-drug interaction that could potentially lead to subtherapeutic DAA levels and subsequent treatment failure. Currently, there is limited data evaluating this interaction and timely treatment of HCV infection with DAAs is imperative to prevent liver-related morbidity and mortality. Methods A retrospective case series evaluating clinical cure of chronic HCV infection, defined as sustained virologic response (SVR) 12 weeks after completion of DAA therapy, in patients from three inner-city clinics who remained on first generation anticonvulsants during the treatment course. Results A total of five patients received standard dose DAAs for treatment of chronic HCV infection while being maintained on first generation anticonvulsants. The most common HCV genotype was 1a (80%), followed by 1b (20%). The majority of patients were treated with glecaprevir/pibrentasvir (80%) for eight weeks and one patient was treated with ledipasvir/sofosbuvir for 12 weeks. Anticonvulsant regimens consisted of carbamazepine, phenytoin, phenytoin plus phenobarbital, phenytoin plus levetiracetam, and phenobarbital plus lacosamide. All five patients achieved sustained virologic response (SVR) despite this drug-drug interaction. Conclusion Although every effort to prevent concomitant use of DAAs and potent inducers should be made, clinical cure may still be achieved in patients whom cannot avoid this coadministration.

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.

scholarly journals Liver Biopsies for Chronic Hepatitis C: Should Nonultrasound-Guided Biopsies Be Abandoned?

2009 ◽  
Vol 23 (6) ◽  
pp. 425-430 ◽  
Author(s):  
Jennifer A Flemming ◽  
David J Hurlbut ◽  
Ben Mussari ◽  
Lawrence C Hookey
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Liver Biopsy ◽  
Chronic Hepatitis C ◽  
Hcv Infection ◽  
Significant Difference ◽  
The Us ◽  
Chronic Hcv Infection ◽  
Liver Biopsies ◽  
Chronic Hcv

BACKGROUND/OBJECTIVE: Liver biopsy has been the gold standard for grading and staging chronic hepatitis C virus (HCV)-mediated liver injury. Traditionally, this has been performed by trained practitioners using a nonimage-guided percutaneous technique at the bedside. Recent literature suggests an expanding role for radiologists in obtaining biopsies using an ultrasound (US)-guided technique. The present study was undertaken study to determine if the two techniques produced liver biopsy specimens of similar quality and hypothesized that at our institution, non-US-guided percutaneous liver biopsies for HCV would be of higher quality than US-guided specimens.METHODS: Liver biopsies from 100 patients with chronic HCV infection (50 consecutive US-guided and 50 consecutive non-US-guided), were retrospectively identified using a hospital histopathology database. All original biopsy slides were coded and prospectively reanalyzed by a single hepatopathologist who was blinded to the technique used in obtaining the biopsy. Additionally, all liver biopsies for chronic HCV infection completed at the centre from 1998 to 2007 were identified and the technique used was recorded. Biopsy quality was determined primarily by the number of complete portal tracts (CPTs) identifiable in the slides. The total length of specimen and the degree of fragmentation were secondary outcome measures.RESULTS: There was a slight difference observed between the US-guided and non-US-guided groups in mean age (46.3 years versus 42.5 years, repectively; P=0.018) but no differences in sex, presence of cirrhosis, bilirubin, creatinine, international normalized ratio, and grade or stage of disease. Biopsies obtained using the US-guided technique produced higher quality specimens than the non-US-guided technique based on our primary outcome of number of CPTs in the biopsy (11.8 versus 7.4; P<0.001). US-guided specimens also were longer (24.4 mm versus 19.7 mm; P=0.001), had less fragmentation (P=0.016), and a higher overall histopathological quality assessment (P=0.026) than the non-US-guided biopsies. However, there was no significant difference between the two groups in the ability to grade and stage the disease (96% US-guided versus 90% in non-US-guided (P=0.20). Over a 10-year period, 763 biopsies for chronic HCV infection were identified with an obvious trend toward the increased use of US-guided technique observed at 2% in 1998 to 85% in 2007.CONCLUSIONS: US-guided liver biopsies for chronic HCV are the most common method of obtaining specimens at the Kingston General Hospital, Kingston, Ontario, and are of higher quality than non-US-guided specimens. However, there is no significant difference in the two techniques in the ability to grade and stage chronic HCV.

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