الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Hepatitis C virus (HCV) is considered as a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. HCV genotype 4 is the predominant genotype in the Middle East; its prevalence in Egypt is estimated to be approximately 90 %.Obesity and fatty liver are commonly observed among patients with chronic hepatitis C virus (HCV) and are risk factors for increased hepatic fibrosis.
Endocannabinoids (ECS) are lipid signaling molecules mimicking the activity of ∆-9-tetrahydrocannabinol (THC), the main psychotropic constituent of marijuana. The endocannabinoid system (ECS) consists of cannabinoid receptors, several endogenous ligands (anandamide and 2-arachidonylglycerol) and over a dozen ligand metabolizing enzymes. They are provided with a series of central and peripheral effects as they influence neuroprotection, pain, motor function, and energy balance. ECS act primarily via CB1 and CB2 receptors. The physiological expression of CB1 and CB2 receptors in the adult liver is very low or even absent. Recently, cannabinoid receptors have emerged as novel mediators of liver diseases. The aim of the present work is to evaluate cannabinoid receptors (CB1 & CB2) in liver of chronic Hepatitis C virus patients in relation to obesity and hepatic steatosis in those patients.
The study included forty adult male chronic HCV patients. They were recruited from Alexandria Governorate patients who attend Medical Research Institute Hospital Hepatology Unit. They were categorized into two groups: Group 1: 20 Chronic HCV non-obese patients (BMI < 24.9 kg/m2, WC ≤ 94 cm and WHR ≤ 0.8) and Group 2: 20 Chronic HCV obese patients (BMI ≥ 30 kg/m2, WC > 94 cm, WHR >1).Patients with chronic liver diseases due to other causes were excluded from the study.
Detailed medical history, clinical examination and anthropometric measurements, liver biopsy and Laboratory investigations were done to all patients, determination of CB1 and CB2 receptors by immune histochemical staining and histological examination.
Our statistical findings revealed significant differences in BMI, WHR, and HCV RNA, HDL-C, AND HOMA-IR found in obese as compared to non-obese HCV patients. In addition, determination of steatosis and hepatic lipase was also done. Histochemical findings of the present study showed intense CB1 receptors density and lower intense of CB2 receptors in obese HCV patients as compared to non-obese patients. Correlation revealed positive association between CB1 and BMI, liver enzymes, viral load, and HOMA-IR while these parameters showed negative association with CB2 receptors. Our results demonstrated also higher grade of steatosis and increased activity of hepatic lipase in obese group.
In conclusion, data of the present work indicates the possible role of ECS in the pathophysiology of HCV. CB1 receptor is widely expressed in the livers of patients with HCV specially the obese ones. The up regulation of hepatic CB1 receptors is associated with steatosis and insulin resistance in obese HCV patients while CB2 receptors is down regulated and is negatively associated with these complications. The present study confirms the profibrogenic role of CB1 receptors and also the antifibrogenic role of CB2 receptors.
Future studies involving a larger study should explore the effectiveness of usage of peripherally restricted CB1 antagonists or CB2 agonists in counteracting HCV associated metabolic complications.