الفهرس 
Introduction and aim of the workOnly 14 pages are availabe for public view
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Abstract
HCV is a leading cause of chronic liver diseases including chronic hepatitis (CHC), liver cirrhosis and hepatocellular carcinoma as well as the most common indication of liver transplantation in many countries.
Hepatic fibrosis is the final event of chronic liver injury, independently from the etiological agent, it is characterized by excessive extracellular matrix (ECM) deposition that distorts the hepatic architecture by forming fibrotic scars, and the subsequent development of nodules of regenerating hepatocytes defines liver cirrhosis.
In addition to liver involvement, chronic HCV infection can result in several extra-hepatic conditions with haematological problems being one of them. Among these haematological derangements, the decrease of PLTs number seems to be the most common. Thrombocytopenia has a negative impact on the evolution of the disease, mainly in the advanced stages when PLTs number falls below 50,000/µl.
The pathophysiology of thrombocytopenia in patients with HCV- related chronic liver disease is not completely understood. However, it is universally agreed that multiple pathogenetic mechanisms that are complementary and often act in concert are involved.
The present study aimed to 1) Investigate whether intra hepatic platelets accumulation contribute to thrombocytopenia in a group of chronic HCV patients. 2) study the expression of platelets derived gro- wth factor receptor ß (PDGFR ß ) in the liver and its relation to the the grade and stage of CHC. 3) Assess the relationship of intra hepatic tumor necrosis factor α (TNF α) expression to platelets accumulation in the liver of these patients.
An analytical cross-sectional study was conducted. All patients were attending the outpatient clinic of Tropical Medicine and Gastro- enterology, Sohag University Hospital for pretreatment assessment of CHC.Fifty patients [40 males (80% and 10 females (20%)] were randomly recruited. Their ages ranged from 20 to 59 years and their mean age was 44.24 ±11.17 years.
The inclusion criteria were patients with positive HCV Ab and HCV RNA for ≥ 6 months and compensated liver disease. Whereas the exclusion criteria were: patients who received or are receiving any anti- HCV treatment, patients with liver cirrhosis or coagulopathy, patients whose PLT count less than 100,000 /µl, patients whose prothrombin time was more than three seconds over the control, patients with other diseases causing chronic hepatitis, hepatocellular carcinoma, and patients with chronic medical problems as cardiac and chronic renal failure.
All patients were subjected to, full medical history taking, full clinical examination. Blood samples were obtained for complete blood count and liver function tests. Abdominal ultrasound examination was done for all of them and liver biopsy was obtained from all patients for histopathological and immunohistochemical analysis. All specimens were stained with hematoxylin and eosin and examined under light microscopy for staging and grading of chronic hepatitis C using Scheuer et al. (1994) system. Monoclonal antibodies were used against CD41 (as a marker of PLTs), PDGFR- β by perisinusoidal mesenchymal cells, and TNF α expression by kupffer cells using commercially available staining kits.
Patients were categorized into two groups. group 1(10 patients) includes patients with PLTs count less than 150000/μL (thrombo-
cytopenia) . group 2 (40 patients) includes patients with normal PLTs count (150000-450000/μL).
All patients were then categorized according to the grades of inflammatory activity into patients with minimal and mild inflammation (G1 and G2, n= 32 patients) and those with moderate and severe inflammation (G3 and G4, n=18 patients).
Also, patients were categorized into two groups according to the histological stages of chronic hepatitis C as follows, group 1 includes 40 patients in stages 0,1, and 2. Whereas, group 2 includes 10 patients in
stage 3.
Our results showed that the mean AWS of CD41 (as a marker of PLTs) expression in hepatocytes, PDGFR-β (by perisinusoidal cells) and TNFα (by Kupffer cells) were significantly higher in thrombocytopenic group than normal PLTs group (P<0.001 for each). They were also significantly higher in patients with severe inflammation (Grade 3&4) than in those with minimal and mild inflammation (P=0.009, 0.05 and 0.0001 respectively). Similarly, the mean AWS of all three markers were significantly higher in stage 3 fibrosis than in lower stages (P<0.01, 0.04 and 0.0001).
The study also revealed that the mean peripheral PLTs count tended to be lower in advanced stage (3) of fibrosis than earlier stages (0- 1-2) and in cases of severe inflammation (G3 and 4) than those with minimal and mild grade.
The study demonstrated significant negative correlations between peripheral PLTs count and expression of each of CD41, PDGFR- β and TNFα in the liver.
Conclusion
Conclusion
We have demonstrated that:
• The accumulation of PLTs in the liver in patients with chronic hepatitis C could be an important factor involved in pathogenesis of thrombocytopenia in these patients.
• Intra-hepatic PLTs may also contribute to liver fibrosis through the action of PDGF ß on hepatic stellate cells.
• Expression of PDGFR- β, and TNFα markers in the liver play central roles in pathogenesis CHC as their expression is markedly elevated in association with progression of disease activity and fibrosis.
Recommendations
Recommendations
from the light of the present study, the followings could be recommended:
• Further studies of the biological characteristics and function of platelets in patients with chronic hepatitis C may contribute to improving the treatment of thrombocytopenia and liver fibrosis.
• Further studies of the biological characteristics and functions of TNF α, PDGF- β and other fibrogenic cytokines in the liver may help in identifying new treatment strategies for hepatic fibrosis in chronic hepatitis C patients.