The Association of Toll-Like Receptor 4 Polymorphism with Hepatitis C Virus Infection in Saudi Arabian Patients

Hepatitis C virus (HCV) is a single stranded RNA virus. It affects millions of people worldwide and is considered as a leading cause of liver diseases including cirrhosis and hepatocellular carcinoma. A recent study reported that TLR4 gene polymorphisms are good prognostic predictors and are associated with protection from liver fibrosis among Caucasians. This study aims to investigate the implication of genetic polymorphisms of TLR4 gene on the HCV infection in Saudi Arabian patients. Two SNPs in the TLR4 gene, rs4986790 (A/G) and rs4986791 (C/T), were genotyped in 450 HCV patients and 600 uninfected controls. The association analysis confirmed that both SNPs showed a significant difference in their distribution between HCV-infected patients and uninfected control subjects (P<0.0001;OR=0.404, 95%CI=0.281–0.581) and (P<0.0001;OR=0.298, 95%CI=0.201–0.443), respectively. More importantly, haplotype analysis revealed that four haplotypes, AC, GT, GC, and AT (rs4986790, rs4986791), were significantly associated with HCV infection when compared with control subjects. One haplotype AC was more prominently found when chronic HCV-infected patients were compared with cirrhosis/HCC patients (frequency = 94.7% andP=0.04). Both TLR4 SNPs under investigation were found to be significantly implicated with HCV-infection among Saudi Arabian population.

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Gut Microbiota Characterization in Patients with HCC Post Chronic HCV Infection

10.21203/rs.3.rs-29305/v1 ◽

2020 ◽

Author(s):

karim Montasser ◽

heba Ahmed osman ◽

Hanan Abozaid ◽

Abeer M. M. sabry

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Gut Microbiota ◽

Hcv Infection ◽

P Value ◽

Group I ◽

Significant Difference ◽

Healthy Control ◽

Chronic Hcv Infection ◽

Chronic Hcv

Abstract Aim: Dysbiosis of gut microbiota favors chronic hepatic inflammation with subsequent hepatic carcinogenesis. The current study aimed to evaluate the role of gut dysbiosis in the development of hepatocellular carcinoma in patients with chronic HCV infection.Methods: This descriptive cross-sectional cohort study carried out on 400 subjects recruited from the Internal Medicine Department and Tropical Medicine and Gastroenterology Department of Helwan and South Valley University Hospitals in Egypt. The study period was from January 2017 till January 2020. The subjects were divided clinically into three groups. Group I: One hundred patients with HCC, evaluated by Child Pugh, TNM and BCLC scoring systems. Group II: 200 chronic hepatitis C virus-infected patients. All patients infected with hepatitis C virus genotype 4. Group III: One hundred healthy control subjects with negative hepatitis marker and normal abdominal ultrasound. PCR of stool Microbiota, complete blood counts, complete liver function tests, INR, HCV antibodies and HBsAg were done for all included subjects. HCV PCR assessment and alpha-fetoprotein (AFP) were done for all patients.Results: No statistically significant difference was detected between HCC patients and control (p-value > 0.05) as regard Bacteroides fragilis & Akkermansia muciniphila. Faecalibacterium prausnitzii was less detected in HCC patients (51%), opposite to 70% of healthy control. With Statistically significant difference (p-value < 0.05). Bifidobacterium was less detected in HCC patients (43%), opposite to (76%) of healthy control. With highly statistically significant difference (p-value < 0.001). Lactobacillus & Enterobacteriaceae was more detected in HCC patients (80%) and (81%), in. Opposite to (36%) and (58%) in healthy control, respectively. With highly statistically significant difference (p-value < 0.001). no significant difference was detected between gut-microbiota and HCC progression with respect to Child or TNM systems. However, a significant difference was detected between number of positive stool isolate of Bacteroid Fragilis and BCLC staging system; where it was isolated from 66.7% of patients with BCLC stage IV opposite to 10.7% of patients with BCLC stage I.Conclusion: A characteristic pattern of Bifidobacterium, Lactobacillus and Enterobacteriaceae species in patients with chronic HCV and HCC was detected. Alteration of gut microbiota may be accused as a predisposing factor for liver disease progression.

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Genetic polymorphisms as the predictors of response to antiviral treatment in chronic hepatitis C virus infection

Orvosi Hetilap ◽

10.1556/oh.2011.29113 ◽

2011 ◽

Vol 152 (22) ◽

pp. 876-881

Author(s):

Alajos Pár

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Genetic Polymorphisms ◽

Chronic Hepatitis C ◽

Genome Wide Association Study ◽

Antiviral Treatment ◽

Hcv Infection ◽

Snp Analysis ◽

Chronic Hcv

The review discusses the genetic polymorphisms involved in the pathogenesis of hepatitis C virus (HCV) infection, that may determine the outcome of disease. In this field earlier both certain major histocompatibility complex (MHC) alleles and some cytokine gene variants have also been studied. Recently, the genome-wide association study (GWAS) and targeted single nucleotide polymorphism (SNP) analysis have revealed that a variant in the promoter region of interleukin-28B (IL-28B) gene is strongly linked to viral clearance and it may be the strongest pretreatment predictor of treatment response in chronic hepatitis C. Last year it was shown that two genetic variants leading to inosine triphosphatase deficiency protect against haemolytic anemia in patients receiving ribavirin during antiviral treatment for chronic HCV infection. Orv. Hetil., 2011, 152, 876–881.

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Prevalence of Hepatitis C Virus in the Population of Albania for the Period 2007-2010

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2014.094 ◽

2014 ◽

Vol 2 (3) ◽

pp. 525-528 ◽

Cited By ~ 1

Author(s):

Hysaj Vila Brunilda ◽

Shundi Lila ◽

Abazaj Erjona ◽

Bino Silva ◽

Rexha Tefta

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Age Groups ◽

Viral Disease ◽

Hcv Infection ◽

University Hospital ◽

P Value ◽

Hcv Rna ◽

Significant Difference ◽

Males And Females

BACKGROUND: Hepatitis C is a blood-borne, infectious, viral disease that is caused by a hepatotropic virus called Hepatitis C virus (HCV).AIM: The aim of this study is to determine the prevalence of active HCV infection (HCV–RNA) in the cases that were anti-HCV positive.MATERIAL AND METHODS: Plasma of 301 high-risk for HCV infection consecutive from University Hospital Centre “Mother Theresa” Tirana-Albania, during January 2007 to December 2010 was included in this study. To identify the presence of HCV RNA, the samples were examined by Cobas Amplicor HCV test (qualitative method).RESULTS: From 301 samples analyzed in total, 214 of them resulted positive for the presence of HCV-RNA's, corresponding to a prevalence of 71.1%, with 95% CI interval [65.8 - 75.9] for value of χ2 = 52.7 p value <0.0001. Divide by the sex 56% were males and 44% females, with statistically significant difference between them for value χ2 =4306 p value=0.0380. Among the age groups the highest prevalence was observed in the age groups > 25 years with a significant difference with other age groups for p value <0.001.CONCLUSION: Among tested samples, 71.1 % were confirmed to be positive for HCV –RNA infections. The prevalence of male was highest compared to female. For males and females infected the prevalence was highest in the age group of > 25 years.

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Immunoglobulin M reactivity towards the inununologically active region sp75 of the core protein of hepatitis C virus (HCV) in chronic HCV infection

Journal of Medical Virology ◽

10.1002/jmv.1890390412 ◽

1993 ◽

Vol 39 (4) ◽

pp. 325-332 ◽

Cited By ~ 28

Author(s):

U. B. Hellström ◽

S. P. E. Sylvan ◽

R. H. Decker ◽

A. Sönnerborg

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Active Region ◽

Core Protein ◽

Immunoglobulin M ◽

Hcv Infection ◽

The Core ◽

Chronic Hcv Infection ◽

Chronic Hcv

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

Canadian Journal of Gastroenterology ◽

10.1155/2009/370651 ◽

2009 ◽

Vol 23 (6) ◽

pp. 425-430 ◽

Cited By ~ 9

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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Proteasome Activator PA28γ-Dependent Nuclear Retention and Degradation of Hepatitis C Virus Core Protein

Journal of Virology ◽

10.1128/jvi.77.19.10237-10249.2003 ◽

2003 ◽

Vol 77 (19) ◽

pp. 10237-10249 ◽

Cited By ~ 116

Author(s):

Kohji Moriishi ◽

Tamaki Okabayashi ◽

Kousuke Nakai ◽

Kyoji Moriya ◽

Kazuhiko Koike ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Core Protein ◽

Regulatory Protein ◽

Hcv Infection ◽

Nuclear Retention ◽

Proteasome Activator ◽

Hcv Core Protein ◽

Core Proteins ◽

Chronic Hcv

ABSTRACT Hepatitis C virus (HCV) core protein plays an important role in the formation of the viral nucleocapsid and a regulatory protein involved in hepatocarcinogenesis. In this study, we have identified proteasome activator PA28γ (11S regulator γ) as an HCV core binding protein by using yeast two-hybrid system. This interaction was demonstrated not only in cell culture but also in the livers of HCV core transgenic mice. These findings are extended to human HCV infection by the observation of this interaction in liver specimens from a patient with chronic HCV infection. Neither the interaction of HCV core protein with other PA28 subtypes nor that of PA28γ with other Flavivirus core proteins was detected. Deletion of the PA28γ-binding region from the HCV core protein or knockout of the PA28γ gene led to the export of the HCV core protein from the nucleus to the cytoplasm. Overexpression of PA28γ enhanced the proteolysis of the HCV core protein. Thus, the nuclear retention and stability of the HCV core protein is regulated via a PA28γ-dependent pathway through which HCV pathogenesis may be exerted.

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Direct-acting Antivirals for Hepatitis C Virus in Patients on Maintenance Dialysis

The International Journal of Artificial Organs ◽

10.5301/ijao.5000613 ◽

2017 ◽

Vol 40 (10) ◽

pp. 531-541 ◽

Cited By ~ 6

Author(s):

Fabrizio Fabrizi ◽

Francesca M. Donato ◽

Piergiorgio Messa

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Severe Renal Impairment ◽

Controlled Trial ◽

Hcv Infection ◽

Direct Acting Antivirals ◽

Safety And Efficacy ◽

Maintenance Dialysis ◽

Chronic Hcv ◽

Direct Acting

The frequency of hepatitis C virus (HCV) infection remains high in patients with chronic kidney disease (CKD) and plays a detrimental role in mortality in this population. According to the latest survey, the adjusted hazard ratio for HCV-positive versus HCV-negative patients on long-term dialysis was 1.12 (95% CI, 1.05 to 1.20) and 1.10 (95% CI, 0.98 to 1.22) for all-cause and cardiovascular mortality, respectively. An impairment on quality of life has also been documented in HCV-infected patients undergoing regular dialysis. Most clinicians have been so far reluctant to treat hepatitis C in patients with advanced CKD, due to concerns regarding low efficacy and safety of interferon-based regimens. The advent of all-oral, direct-acting antivirals (DAAs) has revolutionized treatment paradigms for HCV, including patients with other comorbidities such as CKD. Two combinations of DAAs have been recently approved for the treatment of HCV in advanced CKD: elbasvir/grazoprevir (evaluated in 1 randomized controlled trial) and ombitasvir/paritaprevir/ritonavir/dasabuvir with or without ribavirin (examined in some observational, single-arm studies). These antiviral combinations have provided high safety and efficacy (SVR12 rates >90%) in HCV-infected patients with stage 4–5 CKD. Sofosbuvir, a nucleotide analogue inhibitor of the HCV NS5B polymerase, is the cornerstone of most anti-HCV current regimens but is not currently recommended for patients with severe renal insufficiency (eGFR <30 mL/min per 1.73 m2). However, several small-sized studies have been published on the safety and efficacy of sofosbuvir-based regimens for patients with hepatitis C on maintenance dialysis>; overall, the viral response was satisfactory (SVR12 rates ranging between 58% and 100%) with a few drug-related drop-outs. Studies are in progress to assess whether ribavirin-free antiviral combinations with novel DAAs are a viable option for patients with severe renal impairment and chronic HCV infection.

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Hepatitis C Virus Infection and B-Cell Non-Hodgkin’s Lymphoma.

Blood ◽

10.1182/blood.v106.11.4668.4668 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4668-4668

Author(s):

Janet G. Grudeva

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

B Cell ◽

Hcv Infection ◽

Control Group ◽

Cell Infection ◽

Serum Samples ◽

Pathogenetic Role ◽

Significant Difference

Backgroud: An increasing number of bacterial and viral infections have been linked with specific subtypes of lymphoma. Preliminary evidence suggests that hepatitis C virus (HCV) might play a pathogenetic role in autoimmune-related, non-malignant B-cell lymphoproliferation, as well as a subset of B-cell non-Hodgkin, s lymphomas (B-NHL), often with extranodal localization. Design and methods: The study was conducted in the Department of Hematology and consisted 149 (86 male, 63 female) untreated patients with a new diagnosis of B-NHL for 5-years period (2000–2004). HCV infection was investigated by testing for HCV antibodies in serum samples. The controls were 587 patients (without intravenous drug users) in other departments of the same hospital. Results: HCV infection was documented in 13 cases (8,4%) with NHL. The infected patients were not clinically relevant cryoglobulinemic activity, increased rate of autoimmune disorders and extranodal localizations prevalence. There was statistically significant difference between the NHL and control group (p<0,01) and no statistically significant difference between man/women carriers (p>0,05) into the NHL group. Overall, the clinical outcome of HCV-positive NHL does not seem to be different from that of NHL patients without HCV infection. However, the evidence of a significant liver injury may predict a worse prognosis in these cases. Conclusions: Our date suggest that HCV infection may be associated with B-NHL. With regard to the mechanism(s) by which HCV might favor B-cell expansion and malignant transformation, most date support an indirect pathogenetic role of the virus as an exogenous trigger. A direct oncogenetic role of HCV by direct cell infection and deregulation has only been hypothesized on the basis of the lymphotropism of the virus.

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