scholarly journals Transcriptional Suppression of miR-181c by Hepatitis C Virus Enhances Homeobox A1 Expression

2014 ◽  
Vol 88 (14) ◽  
pp. 7929-7940 ◽  
Author(s):  
Anupam Mukherjee ◽  
Shubham Shrivastava ◽  
Joydip Bhanja Chowdhury ◽  
Ranjit Ray ◽  
Ratna B. Ray
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Therapeutic Intervention ◽  
Growth Promotion ◽  
Hcv Infection ◽  
Exogenous Expression ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Hepatocyte Growth

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.

scholarly journals Role of Tgf-β1and Gremlin-1in the Pathogenesis of Chronic HCV Infection and Hepatocellular Carcinoma

2011 ◽  
Vol 3 (9) ◽  
pp. 75-78 ◽  
Author(s):  
Areej Atiyah Hussein ◽  
◽  
Basim Mohammed Khashman ◽  
Saad Muhmood Hussain
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hcv Infection ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

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

2013 ◽  
Vol 33 (3) ◽  
pp. 420-427 ◽  
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

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 Hepatic resection for two giant hepatocellular carcinoma after oral direct-acting antiviral therapy: Is there a relationship?

2018 ◽  
Vol 8 (2) ◽  
pp. 32 ◽  
Author(s):  
Mohamed Abdel Wahab ◽  
Ahmed Shehta ◽  
Mahmoud Ali
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antiviral Drugs ◽  
Hcv Infection ◽  
Dramatic Improvement ◽  
Direct Acting Antiviral ◽  
Increased Risk ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Direct Acting ◽  
The Relationship

Introduction: Direct-acting antiviral drugs have been recently introduced for management of chronic hepatitis C virus (HCV) patients. Those medications have achieved a dramatic improvement of sustained virologic response (SVR) reaching almost 90%. However, reports regarding the increased risk of occurrence or recurrence of hepatocellular carcinoma (HCC) in chronic HCV patients who achieved SVR after direct-acting antiviral drugs are controversial.Methods: We report two cases of giant HCCs complicating chronic HCV infection after direct-acting antiviral drugs-based therapies and were managed by major hepatic resection.Results: Two male patients with chronic HCV infection received several regimens oral direct acting antiviral drugs with a SVR for 3 and 6 months, respectively. They complained of progressive right hypochondrial pain and abdominal enlargement. Two large HCCs were diagnosed (16.2 cm * 17.6 cm * 16.9 cm, and 18 cm * 13 cm * 16.5 cm in dimensions) with markedly elevated serum alpha feto-protein (36,000 and 7,000 ng/ml, respectively). Due to the presence of adequate residual liver volume, the decision was to proceed for surgical resection. Central hepatectomy and extended right hemi-hepatectomy were performed, respectively. Patients had smooth postoperative course and were discharged after 10 and 9 days, respectively.Conclusion: The relationship between direct-acting antiviral drugs and HCC is controversial. Those cases add support to the accumulating literature suggesting the relationship of HCC development in chronic HCV patients receiving direct-acting antiviral drugs. Further prospective studies with adequate long term follow up are needed to prove or disprove this relationship.

scholarly journals HCV Infection and B-Cell Lymphomagenesis

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
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.

scholarly journals CHRONIC HEPATITIS C VIRUS INFECTION

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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