P125 ROLE OF SIALIC-ACID-BINDING IMMUNOGLOBULIN-LIKE LECTIN-7 (SIGLEC-7) AS BIOMARKER OF LIVER DISEASE SEVERITY IN CHRONIC HCV INFECTION

ABSTRACTHepatitis C virus (HCV)-induced chronic liver disease is one of the leading causes of hepatocellular carcinoma (HCC). The molecular events leading to HCC following chronic HCV infection remain poorly defined. MicroRNAs (miRNAs) have been implicated in the control of many biological processes, and their deregulation is associated with different viral infections. In this study, we observed that HCV infection of hepatocytes transcriptionally downregulates miR-181c expression by modulating CCAAT/enhancer binding protein β (C/EBP-β). Reduced expression of the pri-miR-181c transcript was noted following HCV infection.In silicoprediction suggests that homeobox A1 (HOXA1) is a direct target of miR-181c. HOXA1 is a member of the homeodomain-containing transcription factor family and possesses pivotal roles in normal growth, development, and differentiation of mammalian tissues. Our results demonstrated that HOXA1 expression is enhanced in HCV-infected hepatocytes. Exogenous expression of the miR-181c mimic inhibits HOXA1 and its downstream molecules STAT3 and STAT5, which are involved in cell growth regulation. Interestingly, overexpression of miR-181c inhibited HCV replication by direct binding with E1 and NS5A sequences. Furthermore, accumulation of HCV genotype 2a RNA with miR-181c was observed in an RNA-induced silencing complex in Huh7.5 cells. Our results provide new mechanistic insights into the role of miR-181c in HCV-hepatocyte interactions, and miR-181c may act as a target for therapeutic intervention.IMPORTANCEChronic HCV infection is one of the major causes of end-stage liver disease, including hepatocellular carcinoma. An understanding of the molecular mechanisms of HCV-mediated hepatocyte growth promotion is necessary for therapeutic intervention against HCC. In this study, we have provided evidence of HCV-mediated transcriptional downregulation of miR-181c. HCV-infected liver biopsy specimens also displayed lower expression levels of miR-181c. We have further demonstrated that inhibition of miR-181c upregulates homeobox A1 (HOXA1), which is important for hepatocyte growth promotion. Exogenous expression of miR-181c inhibited HCV replication by directly binding with HCV E1 and NS5A sequences. Taken together, our results provided new mechanistic insights for an understanding of the role of miR-181c in HCV-hepatocyte interactions and revealed miR-181c as a potential target for therapeutic intervention.

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Liver disease in adult transfusion-dependent beta-thalassaemic patients: investigating the role of iron overload and chronic HCV infection

Liver International ◽

10.1111/liv.12095 ◽

2013 ◽

Vol 33 (3) ◽

pp. 420-427 ◽

Cited By ~ 11

Author(s):

Dimitrios Kountouras ◽

Nikolaos J. Tsagarakis ◽

Evangelia Fatourou ◽

Efthimios Dalagiorgos ◽

Nikolaos Chrysanthos ◽

...

Keyword(s):

Liver Disease ◽

Iron Overload ◽

Hcv Infection ◽

Chronic Hcv Infection ◽

Chronic Hcv

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

Journal of Biotechnology Research Center ◽

10.24126/jobrc.2016.10.1.457 ◽

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

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Safety of new DAAs for chronic HCV infection in a real life experience: role of a surveillance network based on clinician and hospital pharmacist

Infectious Agents and Cancer ◽

10.1186/s13027-017-0119-8 ◽

2017 ◽

Vol 12 (1) ◽

Cited By ~ 6

Author(s):

A. Nappi ◽

A. Perrella ◽

P. Bellopede ◽

A. Lanza ◽

A. Izzi ◽

...

Keyword(s):

Life Experience ◽

Hospital Pharmacist ◽

Real Life ◽

Hcv Infection ◽

Surveillance Network ◽

Chronic Hcv Infection ◽

Chronic Hcv

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HCV Infection and B-Cell Lymphomagenesis

Advances in Hematology ◽

10.1155/2011/835314 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 16

Author(s):

Masahiko Ito ◽

Hideki Kusunoki ◽

Keiko Mochida ◽

Kazunari Yamaguchi ◽

Toshiaki Mizuochi

Keyword(s):

B Cells ◽

B Cell ◽

Chronic Infection ◽

Recent Literature ◽

Epidemiological Data ◽

Mixed Cryoglobulinemia ◽

Hcv Infection ◽

Chronic Hcv Infection ◽

Chronic Hcv

Hepatitis C virus (HCV) has been recognized as a major cause of chronic liver diseases worldwide. It has been suggested that HCV infects not only hepatocytes but also mononuclear lymphocytes including B cells that express the CD81 molecule, a putative HCV receptor. HCV infection of B cells is the likely cause of B-cell dysregulation disorders such as mixed cryoglobulinemia, rheumatoid factor production, and B-cell lymphoproliferative disorders that may evolve into non-Hodgkin's lymphoma (NHL). Epidemiological data indicate an association between HCV chronic infection and the occurrence of B-cell NHL, suggesting that chronic HCV infection is associated at least in part with B-cell lymphomagenesis. In this paper, we aim to provide an overview of recent literature, including our own, to elucidate a possible role of HCV chronic infection in B-cell lymphomagenesis.

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CHRONIC HEPATITIS C VIRUS INFECTION

The Professional Medical Journal ◽

10.29309/tpmj/2010.17.04.2960 ◽

2010 ◽

Vol 17 (04) ◽

pp. 557-562

Author(s):

DILSHAD MUHAMMAD ◽

KHALID AMIN ◽

AMIN ANJUM ◽

Masood Javed

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Socioeconomic Status ◽

Type 2 Diabetes Mellitus ◽

Liver Disease ◽

Odds Ratio ◽

Hcv Infection ◽

Chronic Hcv Infection ◽

Chronic Hcv

Objectives: (1) To seek the association between chronic HCV infection and type 2 diabetes, mellitus. (2) To verify the effect of age, sex, socioeconomic status, obesity and presence of cirrhosis on the association of chronic HCV infection. Design. Case control study. Setting: DHQ Hospital, Faisalabad. Subjects: The subjects were divided into two groups. One was with positive anti-HCV antibody on ELISA method and other was without liver disease and negative for anti-HCV. Both the groups contained 500 subjects each and were selected according to the inclusion and exclusion criteria. Intervention: After a brief interview regarding age, residence, family history of diabetes, socioeconomic status, both the groups underwent weight and height measurements. The body mass was calculated according to the formulae. Ultrasonography of abdomen was done of all the patients of study groups to assess the liver status. Main outcome measures: Chi – squaretest was applied to see the association and then odds ratio was calculated to check the strength of association. Results: Diabetes mellitus was detected in 174 patients (34.8%) out of 500 patients in the group A as compared to 30 patients (6%) out of 500 patients in the group B. having chisquare value of 127.69 and significance of 0.000 with HCV +/ HCV- Odds ratio 0.120 and 95% CI0.079-0.181. Conclusions: There is strongassociation between HCV infection and type 2 diabetes mellitus. Severity of Liver Disease was strong associated factor.

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

Clinical Science ◽

10.1042/cs20200686 ◽

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.

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