scholarly journals Diminished viral replication and compartmentalization of hepatitis C virus in hepatocellular carcinoma tissue

2016 ◽  
Vol 113 (5) ◽  
pp. 1375-1380 ◽  
Author(s):  
Djamila Harouaka ◽  
Ronald E. Engle ◽  
Kurt Wollenberg ◽  
Giacomo Diaz ◽  
Ashley B. Tice ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Population ◽  
Hcv Rna ◽  
Carcinoma Tissue ◽  
Insight Into ◽  
Hepatocellular Carcinoma Tissue ◽  
Comprehensive Study

Analysis of hepatitis C virus (HCV) replication and quasispecies distribution within the tumor of patients with HCV-associated hepatocellular carcinoma (HCC) can provide insight into the role of HCV in hepatocarcinogenesis and, conversely, the effect of HCC on the HCV lifecycle. In a comprehensive study of serum and multiple liver specimens from patients with HCC who underwent liver transplantation, we found a sharp and significant decrease in HCV RNA in the tumor compared with surrounding nontumorous tissues, but found no differences in multiple areas of control non-HCC cirrhotic livers. Diminished HCV replication was not associated with changes in miR-122 expression. HCV genetic diversity was significantly higher in livers containing HCC compared with control non-HCC cirrhotic livers. Tracking of individual variants demonstrated changes in the viral population between tumorous and nontumorous areas, the extent of which correlated with the decline in HCV RNA, suggesting HCV compartmentalization within the tumor. In contrast, compartmentalization was not observed between nontumorous areas and serum, or in controls between different areas of the cirrhotic liver or between liver and serum. Our findings indicate that HCV replication within the tumor is restricted and compartmentalized, suggesting segregation of specific viral variants in malignant hepatocytes.

Diminished Replication and Viral Compartmentalization of Hepatitis C Virus in Hepatocellular Carcinoma Tissue

2016 ◽  
Vol 64 (2) ◽  
pp. S421
Author(s):  
D. Harouaka ◽  
R.E. Engle ◽  
K. Wollenberg ◽  
G. Diaz ◽  
A. Tice ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Carcinoma Tissue ◽  
Hepatocellular Carcinoma Tissue

scholarly journals Genotype Dependence of Hepatitis C Virus Load Measurement in Commercially Available Quantitative Assays

1999 ◽  
Vol 37 (8) ◽  
pp. 2525-2532 ◽  
Author(s):  
Janet Mellor ◽  
Anna Hawkins ◽  
Peter Simmonds
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Narrow Range ◽  
Antiviral Treatment ◽  
Hcv Rna ◽  
Clinical Specimens ◽  
Rna Transcripts ◽  
Relative Quantitation ◽  
Version 2.0

Standardization and genotype independence of methods used to quantify hepatitis C virus (HCV) RNA in clinical specimens are necessary for accurate assessment of the role of HCV quantitation as a prognostic marker for HCV infection and monitoring of the response to antiviral treatment. Commercially available methods used to measure HCV loads include PCR-based (Roche Monitor) and hybridization-based (Quantiplex bDNA-2) methods. Recently, a new version of the Roche Monitor assay (version 2.0) has become available; it has been modified to achieve more equal quantitation of different HCV genotypes. Consistent with previous reports, Roche Monitor version 1.0 substantially underestimated concentrations of RNA transcripts of types 2b, 3a, 4a, 5a, and 6a and virus loads in individuals infected with genotypes 2 to 6 relative to reference tests. However, version 2.0 achieved equivalent quantitation of each genotype over a narrow quantitative range (103 to 5 × 105 copies of RNA/ml) but significantly underestimated RNA concentrations above this range. The assay showed an equivalent inability to quantify high levels of HCV RNA in plasma samples, and this was responsible for the falsely narrow range of virus loads detected in HCV-infected individuals. In contrast, the Chiron bDNA-2 assay could only measure RNA concentrations in the upper quantitative range (2 × 105 to 5 × 107 copies of RNA/ml) but showed equivalent sensitivity for genotypes 1 to 5; however, concentrations of type 6a RNA transcripts and virus loads in clinical specimens from individuals infected with type 6a were underestimated by a factor of 2 to 4. Differences were observed between PCR- and hybridization-based assays in their relative quantitation of HCV RNA transcripts and HCV genomic RNA, which may cause problems with the use of transcripts for interassay calibration.

scholarly journals Risk Factors Contributing to the Occurrence and Recurrence of Hepatocellular Carcinoma in Hepatitis C Virus Patients Treated with Direct-Acting Antivirals

Biomedicines ◽  
2020 ◽  
Vol 8 (6) ◽  
pp. 175
Author(s):  
Sara Kishta ◽  
Ashraf Tabll ◽  
Tea Omanovic Kolaric ◽  
Robert Smolic ◽  
Martina Smolic
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Hepatitis C ◽  
Dna Ploidy ◽  
Hcv Rna ◽  
Direct Acting Antivirals ◽  
Hepatic Cells ◽  
Chronic Hcv ◽  
Direct Acting

Although hepatitis C virus (HCV) RNA may be eliminated from blood circulation by direct-acting antivirals (DAA) therapy as assessed by real-time polymerase chain reaction (PCR), HCV RNA can still be present in liver tissue, and this is known as occult HCV. There has been a lot of controversy surrounding the recurrence of hepatocellular carcinoma (HCC) after DAA treatment of hepatic cells infected with chronic HCV. One of the main risk factors that leads to de novo HCC is the chronicity of HCV in hepatic cells. There are many studies regarding the progression of HCV-infected hepatic cells to HCC. However, there is a lack of research on the different molecular mechanisms that lead to the progression of chronic HCV infection to HCC, as well as on the effect of HCV on the alteration of DNA ploidy, which eventually leads to a recurrence of HCC after DAA treatment. In this review article, we will address some risk factors that could lead to the development/recurrence of HCC after treatment of HCV with DAA therapy, such as the role of liver cirrhosis, the alteration of DNA ploidy, the reactivation of hepatitis B virus (HBV), the role of cytokines and the alteration of the immune system, concomitant non- alcoholic fatty liver disease (NAFLD), obesity, alcohol consumption and also occult HCV infection/co-infection. Clinicians should be cautious considering that full eradication of hepatocarcinogenesis cannot be successfully accomplished by anti-HCV treatment alone.

Role of Myeloperoxidase in hepatitis C virus related hepatocellular carcinoma

Meta Gene ◽  
2018 ◽  
Vol 18 ◽  
pp. 1-8 ◽  
Author(s):  
Mohamed Abdel-Hamid ◽  
Ola Hassan Nada ◽  
Doha El-Sayed Ellakwa ◽  
Lamiaa Khalaf Ahmed
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C

The role of cyclins and cyclin dependent kinases in development and progression of hepatitis C virus-genotype 4-associated hepatitis and hepatocellular carcinoma

2011 ◽  
Vol 91 (2) ◽  
pp. 643-652 ◽  
Author(s):  
Abeer A. Bahnassy ◽  
Abdel-Rahman N. Zekri ◽  
Samah A. Loutfy ◽  
Waleed S. Mohamed ◽  
Amrallah Abdel Moneim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Genotype ◽  
Genotype 4 ◽  
Cyclin Dependent Kinases

scholarly journals Hepatitis C Virus (HCV) Constitutively Activates STAT-3 via Oxidative Stress: Role of STAT-3 in HCV Replication

2005 ◽  
Vol 79 (3) ◽  
pp. 1569-1580 ◽  
Author(s):  
Gulam Waris ◽  
James Turkson ◽  
Tarek Hassanein ◽  
Aleem Siddiqui
Keyword(s):  
Oxidative Stress ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Dominant Negative ◽  
Mitogen Activated Protein Kinase ◽  
Hcv Rna ◽  
Pyrrolidine Dithiocarbamate ◽  
Constitutive Activation ◽  
Mitogen Activated Protein

ABSTRACT The hepatitis C virus (HCV) causes chronic hepatitis, which often results in liver cirrhosis and hepatocellular carcinoma. We have previously shown that HCV nonstructural proteins induce activation of STAT-3 via oxidative stress and Ca2+ signaling (G. Gong, G. Waris, R. Tanveer, and A. Siddiqui, Proc. Natl. Acad. Sci. USA 98:9599-9604, 2001). In this study, we focus on the signaling pathway leading to STAT-3 activation in response to oxidative stress induced by HCV translation and replication activities. Here, we demonstrate the constitutive activation of STAT-3 in HCV replicon-expressing cells. The HCV-induced STAT-3 activation was inhibited in the presence of antioxidant (pyrrolidine dithiocarbamate) and Ca2+ chelators (BAPTA-AM and TMB-8). Previous studies have shown that maximum STAT-3 transactivation requires Ser727 phosphorylation in addition to tyrosine phosphorylation. Using a series of inhibitors and dominant negative mutants, we show that HCV-induced activation of STAT-3 is mediated by oxidative stress and influenced by the activation of cellular kinases, including p38 mitogen-activated protein kinase, JNK, JAK-2, and Src. Our results also suggest a potential role of STAT-3 in HCV RNA replication. We also observed the constitutive activation of STAT-3 in the liver biopsy of an HCV-infected patient. These studies provide an insight into the mechanisms by which HCV induces intracellular events relevant to liver pathogenesis associated with the viral infection.

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