الفهرس 
Material and methodsOnly 14 pages are availabe for public view
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Abstract
Aflatoxins are toxic compounds, and have shown to be immunosuppressive, mutagen, teratogen and carcinogen (Abdel-Wahhab et al., 2005, 2006, 2007, 2010; Liu and Wu, 2010). The occurrence of aflatoxin in food is a serious global health problem, particularly in developing countries. Aflatoxins are well documented as cancer potency factors as 4.6-28.2% of annual hepatocarcinoma cases worldwide are caused by these toxins (Zheng et al., 2010). Aflatoxins are potent liver carcinogens (IARC, 2002), and in young children chronic aflatoxin exposure at high levels has been associated with growth faltering (Gong et al., 2004; Galal et al., 2006; Polychronaki et al., 2007, 2008) and immune suppression (Turner et al., 2003; Abdel-Wahhab et al., 2011). The four naturally occurring aflatoxins are AFB1, AFB2, AFG1 and AFG2, though AFB1 is the most commonly occurring and carcinogenic (IARC, 2002).
Once AFB1 is absorbed into the cow’s body, the clearance of AFM1 in milk may take 5 to 7 days depending on the amount and duration of the AFB1 consumption (Whitlow and Hagler, 2005). AFB1 and AFM1 (metabolite) are found in feeds and milk, respectively. The AFB1 is rapidly absorbed in the digestive tract and primarily metabolized by liver enzymes, converting it to AFM1, which is then excreted in milk and urine which is considered as a biomarker for aflatoxin exposure. AFM1 is less toxic than AFB1; however, it has been demonstrated to be a carcinogen in rainbow trout and causes morphological changes in rat liver. The carcinogenic and highly toxic effects of aflatoxin and its metabolites have resulted in aflatoxin being highly regulated by most countries in the world (Sinnhuber et al., 1970).
Viral hepatitis is the leading cause of liver disease worldwide, accounting for about 70% of cases. However, less than 5% these viral infections will progress to liver disease (Lefilliatre and Villeneuve 2000). Patients with underlying liver disease and those who are older when infected appear to be at greater risk of developing liver disease. Viral hepatitis is caused by infection with any of at least five distinct viruses of which HAV, HBV, and HCV are the three most commonly identified worldwide (Lim et al., 2009). HCV is a single-stranded, positive-sense RNA virus in the flaviviraidae family (Szabo et al., 2003). In this virus family, viruses are also found as the Dengue virus and the animal pathogenic pestiviruses. HCV encodes a single polyprotein of ~3010 amino acids which is processed co- and post translationally into structural and nonstructural (NS) proteins. Today, there are about ten known products of this process. The HCV execute this process with help from a host cell signalases and two viral proteases (Bartenschlager and Lohmann 2000).
HCV infection is a major health problem with an estimated 175 million infected people worldwide (Hnatyszyn, 2005). At least 6 major HCV genotypes have been identified, and each one differs from the others by 30%-35% of its nucleotide site sequence (Hnatyszyn, 2005; Sharma, 2010). It was observed that HCV genotype 4 (HCV-4) is common in the Middle East and in Africa, where it is responsible for more than 80% of HCV infections and the highest number of infections is reported in Egypt (Nguyen ., 2005).
The use of paranteral antischistosomal therapy in Egypt is thought to have contributed to a prevalence of antibodies against HCV in various regions ranging from 6 to 28%, where hepatitis C is highly endemic, HCV-4 is the predominant subtype (Kamal and Nasser 2008). During an acute HCV infection only 20-30% of the infected persons develop symptoms. On the other hand, only about 20% of the infected can see a spontaneous clearance. The remaining 80% of the infected develop a chronic infection, 10-20% of these 80% develop cirrhosis and 1-5% with a chronic infection develops liver cancer within 20-30 years (WHO, 2003).
Poynard et al. (2001), reported that the risk and natural history of fibrosis associated with HCV have been greatly clarified as a result of several large clinical studies incorporating standardized assessments of fibrosis that combine detailed historical and clinical information. Previous reports of Kamal et al. (2005) and El-Zayadi et al. (2005a) showed that the combination of pegylated interferon α (PEG-IFN-α) with ribavirin markedly improves therapeutic outcomes, resulting in sustained virologic response (SVR) rates ranging between 44- 69%.
In Egypt, chronic liver diseases (CLD) are considered an important health problem (Strickland et al., 2002). They have a disastrous effect on health, hence economic potential of affected persons. Hepatitis B virus (HBV) infection showed a high prevalence in some communities in Egypt reaching up to 56.7%. However, infection was found in 6.7% who had HBsAg (Yang et al., 2002). Unfortunately, hepatitis C virus (HCV) infection showed also high prevalence. It was reported that the overall prevalence of anti-HCV antibody was 23.7% (Abdel-Aziz et al., 2000). Moreover, a high percentage of post HBV (70% to 90% of cirrhotic patients) and post HCV (44%) associated cirrhosis progress to hepatocellular carcinoma (HCC). Because of the fact that HCC is disastrous to health, epidemiological studies were much more concerned with it than with liver diseases in general (Okuda et al., 1982; Kaneko et al., 1994). Many risk factors are associated with liver disorders; these are infectious, parasitic, and environmental toxins. Synergism of more than one factor may enhance the process of liver damage. Several studies documented the associations and interactions between hepatitis, aflatoxins, especially aflatoxin B1, trace elements and heavy metals in the development of liver diseases (Badawi et al., 1999). Cirrhosis is a chronic disease of the liver in which diffuse destruction and regeneration of hepatic parenchymal cells has occurred, in which diffuse increase in connective tissue has resulted in disorganization of the lobular architecture. The triad of parenchymal necrosis, regeneration and scarring is always present regardless of individual clinical manifestations (Conn, 1975). The main causes of cirrhosis are: alcoholic liver disease (ALD), hepatitis B (HBV), hepatitis C (HCV), non-alcoholic steatohepatitis (NASH), haemochromatosis, auto-immune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) (Guha and Iredale, 2007). The natural history of cirrhosis can be divided into a preclinical and a subsequent clinical phase. The preclinical phase is usually prolonged over several years; once clinical events occur, such as, ascites, encephalopathy, variceal bleeding or the development of hepatocellular carcinoma the remaining course of the disease is much shorter and usually fatal (de Franchis and Dell’Era, 2007).