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

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 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 Epigenetic Mechanisms Involved in HCV-Induced Hepatocellular Carcinoma (HCC)

2021 ◽  
Vol 11 ◽  
Author(s):  
Pin Zhao ◽  
Samiullah Malik ◽  
Shaojun Xing
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Hcv Infection ◽  
Specific Gene ◽  
Epigenetic Alterations ◽  
Chronic Hcv Infection ◽  
Mechanisms Of Carcinogenesis ◽  
Chronic Hcv ◽  
Insight Into

Hepatocellular carcinoma (HCC), is the third leading cause of cancer-related deaths, which is largely caused by virus infection. About 80% of the virus-infected people develop a chronic infection that eventually leads to liver cirrhosis and hepatocellular carcinoma (HCC). With approximately 71 million HCV chronic infected patients worldwide, they still have a high risk of HCC in the near future. However, the mechanisms of carcinogenesis in chronic HCV infection have not been still fully understood, which involve a complex epigenetic regulation and cellular signaling pathways. Here, we summarize 18 specific gene targets and different signaling pathways involved in recent findings. With these epigenetic alterations requiring histone modifications and DNA hyper or hypo-methylation of these specific genes, the dysregulation of gene expression is also associated with different signaling pathways for the HCV life cycle and HCC. These findings provide a novel insight into a correlation between HCV infection and HCC tumorigenesis, as well as potentially preventable approaches. Hepatitis C virus (HCV) infection largely causes hepatocellular carcinoma (HCC) worldwide with 3 to 4 million newly infected cases diagnosed each year. It is urgent to explore its underlying molecular mechanisms for therapeutic treatment and biomarker discovery. However, the mechanisms of carcinogenesis in chronic HCV infection have not been still fully understood, which involve a complex epigenetic regulation and cellular signaling pathways. Here, we summarize 18 specific gene targets and different signaling pathways involved in recent findings. With these epigenetic alterations requiring histone modifications and DNA hyper or hypo-methylation of these specific genes, the dysregulation of gene expression is also associated with different signaling pathways for the HCV life cycle and HCC. These findings provide a novel insight into a correlation between HCV infection and HCC tumorigenesis, as well as potentially preventable approaches.

scholarly journals Serum IGFBP-3 is a more effective predictor than IGF-1 and IGF-2 for the development of hepatocellular carcinoma in patients with chronic HCV infection

2011 ◽  
Vol 3 (3) ◽  
pp. 704-712 ◽  
Author(s):  
EIMAN ALEEM ◽  
AYMAN ELSHAYEB ◽  
NIHAL ELHABACHI ◽  
AMAL REFAAT MANSOUR ◽  
AHMED GOWILY ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hcv Infection ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Igfbp 3

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.

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