الفهرس 
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Abstract
HCV is considered as a significant health problem world wide. As more than 3% of the world population is infected with this virus. The disease is manifested by slowly progressive development of fibrosis, and over the course of 20 to 30 years, about 25% of the infected individuals will go on to develop cirrhosis, liver failure or HCC. Recently, HCV infection is recognized as a systemic disease involving lipid metabolism, oxidative stress, ER stress, mitochondrial function, gene expression and signaling pathways. HCV mainly affects the liver, but also several tissues outside the liver have been reported to be involved, resulting in a wide spectrum of extrahepatic manifestations. During the last decade, it has been hypothesized that diabetes could be one of these extrahepatic conditions attributable to HCV infection.
The pathogenic mechanism causing DM in patients with HCV infection is not well understood. Both insulin resistance and impaired insulin secretion have been considered to play an important role. The liver plays a central role in the synthesis and metabolism of Hcy, which is a sulfur-containing amino acid that is formed as an intermediate in methionine metabolism. HHcy unleashes mediators of inflammation, increases production of intracellular superoxide anion causing oxidative stress and reducing intracellular level of nitric oxide and induces ER stress, all of which can explain many processes of Hcy promoted cell injury such as apoptosis, fat accumulation and inflammation.
An association between HHcy and IR has been suggested. So, the aim of the present work is to evaluate Hcy plasma levels in chronic HCV patients and its relation to insulin status.
Forty five subjects were included in the present study. Fifteen healthy normal volunteers, free from any diseases served as the control group (group I). Thirty non-diabetic HCV patients constitute the patient groups: divided as fifteen non-cirrhotic patients (group II) and fifteen cirrhotic patients (group III). All subjects were subjected to the following: history taking, complete physical examination, abdominal ultrasonography and laboratory investigations including:
• Complete blood picture, determination of fasting plasma blood glucose, bilirubin, prothrombin time and activity, urea, creatinine, alanine and aspartate aminotransferases and albumin.
• Determination of plasma insulin and homocysteine using ELISA techniques. Assessment of insulin sensitivity by homeostasis model assessment (HOMA) score using the following equation:
Fasting insulin (µu/ml)
By ANOVA test no significant difference in plasma glucose levels was found between the three studied groups. Plasma insulin, Hcy and HOMA score, were significantly increased in HCV patients (group II, III) as compared to the control group. They were more significantly elevated in cirrhotic group (group III) as compared to non-cirrhotic (group II).
A significant positive correlation was found between Hcy and HOMA-IR in both control and cirrhotic groups (r=0.54, p=0.039), (r=0.94, p<0.001) respectively.
In the cirrhotic group, a significant positive correlation was also found between Hcy and insulin (r=0.91, p<0.001).
In conclusion
• This study could support the concept that HCV infection may be a risk factor for developing type 2DM. However, the specific mechanisms by which HCV leads to type 2DM are not fully understood but it seems that HHcy and IR could play a crucial role.
• According to our data, Hcy and IR are both elevated in HCV cirrhotic subjects more than in non cirrhotics indicating their pathophysiollogical role in steatosis, fibrogenesis and cirrhosis in these patients. However, this study doesn’t permit conclusions about whether Hcy is the cause or the result of insulin resistance.
• It could be hypothesized that IR and HHcy may create a deleterious feed back loop each promoting the development of the other. Large epidemiological studies are necessary to elucidate the different physiologic mechanisms mediating this link.
• Hcy, insulin and IR regular monitoring could be a beneficial tool for management of cirrhotic patients.
• Further clinical researches including diabetes screening, life style modifications and pharmaceutical therapy against high Hcy and IR are essential since those interventions would effectively prevent the progression of hepatic C and its associated consequences.