الفهرس 
Hepatitis C InfectionOnly 14 pages are availabe for public view
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Abstract
Egypt has the highest prevalence of HCV in the world and is a major health problem that estimated nationally at 14.7%. The incidence of liver cancer is one of the highest in the world. HCC represents up to 90% of all liver malignancies. In Egypt, HCC constitutes a significant public health problem. where it is responsible for 33.63% and 13.54% of all cancers in males and females respectively.
MiRNAs are a class of single stranded, non-coding with 17-25 ribonucleotides long and evolutionarily conserved RNA sequences that have critical roles in HCC progression by targeting many critical protein-coding genes.MiR-34a is one of these miRNAs and has been shown as a non- invasive marker that frequently exhibited in human cancer including HCC.
Hepatocellular carcinoma is typically a hyper vascular tumor and angiogenesis plays an essential role in its progression. An important angiogenic factor is the VEGF which is the most widely known pro-angiogenic factor and is shown to play a central role in tumorigenesis, progression, and metastasis through the process of angiogenesis in a variety of cancers including HCC.
The present study aimed to the study of the expression profile of miRNA-34a and the serum levels of VEGF both in patients and control group and to find their association with disease progression in HCV patients and evaluate their significance as novel markers for HCV induced HCC.
This study was conducted on 75 patients with chronic liver disease and 15 healthy individuals, served as a control group, with normal routine laboratory investigations and negative for HCV Ab. Their age ranged from 26 to 72 years old. All individuals enrolled in this study were classified into 4 groups; group A: 32 patients with HCV infection, group B: 23 HCV patients with liver cirrhosis, group C: 20 HCV patients with HHC and group D: 15 apparently healthy volunteer (control group).
This study was carried out in the Medical Microbiology and Immunology Department, Benha Faculty of Medicine. The studied groups were selected from the inpatient wards and the outpatient clinics of the Hepatology, Gastroenterology and Infectious Diseases Department Benha University Hospital.
All patients and healthy control individuals under this study after taking their informed consent were subjected to complete history taking, full clinical examination and laboratory investigations for diagnosis of CHC, liver cirrhosis and HCC.
Under complete aseptic condition 5ml of venous blood was collected, from each participant, in sterile tubes without anticoagulant. Serum from each sample was separated, divided into two parts, stored in -80⁰C and subjected to determination of serum levels of VEGF by ELISA and assay of miRNA-34a expression by RT-PCR.
The results of the present study showed that the studied groups were age matched with no significant difference and as regard sex, there were male predominance being 71.9% in patients with HCV infection, 52.2% in patients with HCV infection with LC, 75% in patients with HCV infection with HCC and 66.7% in the control group with no significant difference between them.
Regarding the laboratory data among the different studied groups the results of this study showed that, hemoglobin concentration was significantly increased in the control group compared to the other groups with no significant differences among them the WBC count showed no significant differences among the studied groups.
On evaluating the serum levels of ALT, AST, bilirubin and AFP the results showed that they were significantly elevated in patients’ groups than in the control group while serum albumin level showed significant decrease in the diseased groups than in the control group.
The results of the present study showed that there is a down-regulation of the expression of the serum miR-34a levels in the patients’ groups compared to that of the control group, with more lower expression being found in HCV with HCC and HCV with LC groups than in HCV infected group.
Also the results revealed that the VEGF levels increased significantly in patient’s groups suffering from HCV infection with LC (p2<0.001), HCV infection with HCC (p3<0.001) compared to the control group. In patient groups suffering from HCV infection with LC (p4<0.001), HCV infection with HCC (p5<0.001) groups compared to the HCV infected group and in HCV infection with HCC group compared to HCV with LC group (p6<0.001).
Regarding the validity of miRNA-34a and VEGF levels in differentiating patients’ groups, the present study showed that on differentiating LC group from HCV group the VEGF had high accuracy (AUC=0.984) with sensitivity (95.7%) and specificity (90.6%) while miRNA-34a showed moderate accuracy (AUC= 0.859) with sensitivity (91.3%) and specificity (84.4 %). Meanwhile on differentiating HCC group from HCV group the VEGF had perfect AUC while miRNA -34a had moderate accuracy (AUC=0.881) with sensitivity (100%) and specificity (84.4%). For differentiating HCC group from LC group the VEGF had high accuracy (AUC=0.965) with sensitivity (100%) and specificity (95.7%), on the other hand, miRNA-34a had low accuracy (AUC=0.639) with sensitivity (60%) and specificity (60.9%).
In this study the miRNA-34a gene expression levels showed a significant negative correlation with serum AFP and VEGF levels, while the serum levels of VEGF showed a significant positive correlation with serum levels of AFP.
In addition, higher levels of serum VEGF and lower level of miRNA-34a gene expression were considered as independent predictors for progression of the liver disease in the patients’ groups.