الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
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Abstract
According to World Health Organization (WHO) data, there are currently about 170 million HCV-infected persons worldwide, which is approximately 3% of the human population.
Pathological iron deposits have been observed in about 50% of patients with chronic HCV infection. The underlying mechanisms of the hepatic iron accumulation in HCV-infected liver are still poorly understood.
Parenchymal iron accumulation in HCV patients has been linked to suppressed levels of the systemic iron hormone hepcidin, in addition to the previously purposed two mechanisms that explain the iron overload in CHC patient as hemochromatosis gene mutations or as a result of turnover from damaged hepatocytes.
Hepcidin is a polypeptide synthesized in the liver and found in the serum and urine. It has a central role in iron homoeostasis, as it decreases iron release from macrophages and iron absorption from intestinal enterocytes through its binding to the iron exporter protein, ferroportin. Iron homoeostasis, hypoxia and inflammation are the major regulators of hepcidin production.
This is a cross-sectional descriptive study that was planned to assess the pro-hepcidin level, its relationship with iron status in the chronic hepatitis ”C” patients and its relation to progression of the disease. This study included 50 subjects classified into two groups:
Group A composed of 40 subjects of CHC infection not previously treated with antiviral therapy. And Group B (control group) composed of 10 apparently healthy volunteers.
All the studied patients and controls were subjected to:Complete clinical examination with full history taking, Laboratory investigations:Routine investigations as complete blood picture, Liver function tests including AST, ALT, bilirubin and albumin and Prothrombin time .Also Radiological investigations as Abdominal ultrasonography. Special investigations such as Detection of HCV antibodies by ELISA, Detection of HCV RNA by PCR for patients only, serum iron, serum ferritin, TIBC and transferrin saturation and Serum pro-hepcidin level.
The results of this study showed the following:
* There was no statistical significant difference between CHC group and control group regarding age, sex, weight, Alb, total bilirubin, WBCs, Platelets, INR and ALT, but there was statistical difference regarding AST and hemoglobin, where CHC group had higher mean level in comparison to control group as regard AST while the later has higher mean level of hemoglobin.
* the prohepcidin level was significantly elevated in cases than control group .
* Non-significant decrease in serum iron and ferritin in cases than control group.
* there was no significant correlation between prohepcidin and some other parameters of the cases as (age, sex, iron, TIBC, ferritin and transferrin saturation) .
* By comparison of different laboratory parameters in CHC patients with low activity grades (grade 0+1) and high activity grades (grade 2+3),it was found a significant difference between the two groups as regard AST, ALT and serum iron.
* There was a negative correlation between prohepcidin/ferritin ratio levels with haemoglobin, platelets, S. iron and fibrosis stage. And between prohepcidin / iron ratio levels with AST, ALT, and transferrin saturation .
* No association of prohepcidin levels with liver fibrosis stages, activity grades, nor with iron parameters was found in this study.
There are several limitations that need to be mentioned in this study. First, our study was cross-sectional and therefore doses not elucideate the causal relationships between prohepcidin levels and the presence of liver fibrosis. Therefore, we do not know whether prohepcidin levels could be mechanistically related to progression of liver disease in HCV-infected patients. Eventually, alongitudinal study is needed to clarify the causal relationship between prohepcidin levels and liver fibrosis. Second, the relatively small sample size limits the generalizability of our conclusions. We are fully aware that measurement of only prohepcidin levels may be a limitation of our study, and the lack of significant correlation between iron parameters and prohepcidin may be because of the measurement of prohepcidin instead of mature hepcidin.
Finally it is important to note that this study and most of the published studies in CHC patients or other hepatic disorders concentrated in its mRNA in the liver or its serum level or both regardless its source and didn’t take in consideration the extrahepatic sources of hepcidin and its influence on its serum level.
Recommendations
1. Further studies to asses serum hepcidin, hepcidin mRNA & IL6 in non cirrhotic & cirrhotic chronic hepatitis C patients whether compensated or not, taking in consideration the extrahepatic sources of hepcidin.
2. Further studies with larger sample size to estimate the percentage, severity and the effect of iron overload on the disease progression in our Egyptian CHC patients.
3. Further studies to assess the impact of iron overload on the response to interferon therapy.
4. Long-term prospective studies to evaluate hepcidin level in CHC patients responding and non-responding to interferon therapy.