الفهرس 
INTRODUCTION
HISTOPATHOLOGICAL STUDYOnly 14 pages are availabe for public view
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Abstract
Chronic liver disease is accompanied by hemodynamic changes as a part of the overall splanchnic vasodilation. Portal hypertension is one of its most serious complications. Schistosomiasis and post viral cirrhosis constitute a major health problem in Egypt.
The endothelium takes part in the regulation of vascular tone by producing relaxing and contracting factors both under basal condition and when activated by neurotransmitters, hormones and physical stimuli.
NO is a powerful vasoactive substance released from the endothelium in response to both humoral and mechanical stimuli affecting both the function and structure of the underlying vascular smooth muscle cells.
Endothelin-1 (ET-1) is a 21 amino acid peptide mainly produced by endothelial cells with the vascular endothelium being the most abundant source for it. It is a very potent vasoconstrictor for both systemic and portal circulation.
Plasma ET-1 level was found to be significantly elevated in patients with liver cirrhosis. ET-1 induces portal venous vasoconstriction and hence may play a role in increasing portal venous pressure i.e. aggravating portal hypertension in liver cirrhosis.
The aim of the present work was the evaluation of nitric oxide and endothelin-1 in patients with chronic liver disease and portal hypertension in both systemic and portal blood samples.
To achieve this goal, 45 patients were studied and they were categorized as follows:
Group I: The control group.
It included 15 subjects free from any liver disease and who were subjected to abdominal surgery not concerning the liver.
Group II: The patient group.
It included 30 patients with chronic liver disease and portal hypertension subjected to surgery.
All patients and control subjects were free from anaemia, cardiac, pulmonary, renal, endocrine disorders or collagenic disease to avoid haemodynamic changes from these diseases.
All patients included in this study were subjected to the following:
History taking, clinical examination, clinical investigations including abdominal ultrasonography, measurement of portal venous pressure by direct manometry, histopathological study and the severity of the liver disease was graded according to Child-Pugh scoring system.
Laboratory investigations included: CBC, prothrombin activity, serum bilirubin, AST, ALT, serum albumin, serum GT, serodetection of HBsAg, HBc Ab, anti-HCV Ab and evaluation of serum total nitric oxide (NO), Endothelin-1 (ET-1) and type III procollagen (PIIINP).
Statistical analysis of data obtained from the present study showed the following results:
Hepatitis C virus antibodies were detected in 14 patients. All patients and controls were negative for hepatitis B surface antigen (HBs-Ag) and anti-HBc. The mean serum transaminases (AST and ALT), GT, total and direct bilirubin were significantly higher in schistosomal hepatic fibrosis (SHF) patients group than the control group and in the anti-HCV antibody positive group than the control group.
Prothrombin activity and serum albumin were lower in the SHF group than the control group.
The mean portal pressure was significantly higher in SHF group than in the control group. PHT is a circulatory consequence of increased portal blood flow and increased resistance to hepatic sinusoidal blood flow. Resistance to portal flow is due to structural changes as fibrosis or because of humoral factors as NO which modulate sinusoidal blood flow. Evidence exists that elevated NO production is essential for PHT development.
Nitric oxide (NO) in both portal and systemic blood in SHF patients and in anti-HCV antibody positive and negative groups were significantly higher when compared to control group. Cirrhotic patients exhibit characteristic hemodynamic dysfunction and enhanced splanchnic production of NO which causes hyperdynamic circulation in cirrhosis and portal hypertension. PHT increases the shear stress and upregulates endothelial nitric oxide synthase (eNOS) contributing to NO over production in splanchnic circulation.
Endothelin-1 in both portal and systemic blood in SHF patients group and in the anti-HCV antibody positive and negative groups were significantly higher when compared to control group. The calculated percent increase of ET-1 in portal blood in comparison to systemic blood was significantly higher in SHF patients than in controls. ET-1 is implicated in both systemic and portal hemodynamic abnormalities in cirrhosis. Elevated peripheral ET-1 plasma concentration in cirrhosis may be partly of splanchnic origin, where ET-1 increases as a compensatory mechanism to antagonize the vasodilatory action of NO of endothelial origin.
When patients were subgrouped according to necro-inflammatory grade, it was found that as the degree of inflammation progressed, ET-1 level increased together with PIIINP.
The procollagen-III in both portal and systemic blood in SHF patients group was significantly higher than in the control group denoting that type III procollagen was a marker of collagen turnover in liver fibrosis.
The significantly higher value of portal procollagen III in stage 3 of periportal fibrosis than stage 1 and stage 2 PPF indicated the presence of both hepatocellular injury and active fibrogenic process.
The systemic nitric oxide and the portal endothelin both were significantly higher in Child class B than class A denoting that increased NO and ET-1 production were increased in advanced degree of cirrhosis.
The correlation study revealed that in SHF patients group the portal blood nitric oxide, endothelin-1 and procollagen-III showed a positive significant correlation with systemic blood nitric oxide, endothelin-1 and procollagen-III.
There was a positive significant correlation between ET-1 (P) and PIIINP(P) and PIIINP(S).
There was a negative significant correlation between NO(P) and
ET-1(S) and between NO(S) and ET-1(P).