الفهرس 
Acknowledgement
Pathogenic mechanisms with metabolic implicationsOnly 14 pages are availabe for public view
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Abstract
Egypt, HCC is the second most common cancer in men and the 6th most common cancer in women. Hospital-based studies from Egypt have reported an overall increase in the relative frequency of all liver-related cancers in Egypt, from approximately 4% in 1993 to 7.3% in 2003. Former studies in Egypt have shown the increasing importance of HCV infection in the etiology of liver cancer, estimated to account for 40–50% of cases, and the declining influence of HBV and HBV/HCV infection (25% and 15%, respectively)(El-Zayadi et al., 2005)The diagnosis of HCC without a pathological diagnosis can be achieved by assessing serum α-fetoprotein (AFP) levels and diagnostic imaging, such as computed tomography (CT) and magnetic resonance imaging (MRI). Unfortunately, even this approach is inadequate, and very few HCC biomarkers demonstrate sufficient diagnostic performance for early stage HCC in clinical practice. However, current data suggest that no single biomarker alone is likely to have optimal sensitivity and specificity for the detection of HCC, particularly at early stages of development. (Aghoram et al., 2012)The ideal HCC biomarker is one that enables clinicians to diagnose asymptomatic patients and can be widely used in a screening process. In general, a biomarker valuable for clinical use achieves a level of sensitivity and specificity of 90%, and is noninvasive and cost-effective to allow widespread use. The most desirable biomarker is therefore tumorspecific and easily detectable in bodily fluids, such as serum, plasma, and bile. (Tsuchiya et al., 2015)The aim of the study to evaluate the epidemiology and risk factors for HCC and evaluate the diagnostic value of new markers as lamin b1, vimentin and anti ku86.400 patients were included in the study during the period of 2 years either newly diagnosed or previously diagnosed HCC cases, and we compared 37 of them with 37 CLD cases and healthy controlThe study revealed that HCC mostly develop in old age group (OR1.6) and males were affected more than females (OR 11.95), agricultural and farming related workers were more affected than others (OR 10.48, and 6.88 repectively).Our study show that residence has no effect (OR 0.87), smoking and passive smoking are major risk factors of developing HCC (OR 4.93).Environmental factors as pesticides exposure has role in HCC progress (OR 5.57).Family history of cancer, previous history of liver cirrhosis have effect in developing HCC (OR 26.48).The study showed that HCV and HBV infection are major risk factor for HCC development. As 66% of HCC cases were HCV (OR 2.61) and 30% were HBV (OR 7.74),4% had coinfection with HCV and HBV and 7% had no infection with either HCV or HBVAlso diabetes mellitus appear to have role in HCC (OR 6.90), together with obesity (OR 3.26) so other factors than viral hepatitis may have role in HCC progress as older age, male gander, diabetes and obesityMost of our patients discovered accidentally to have HCC, other have abdominal pain, hematemesis, weight loss and uncontrolled ascites.This study showed that vimentin was the highest accuracy (93%), with sensitivity (94%), specificity (92%), PPV (92.2%) and NPV (93.9%), followed by anti-KU86 with accuracy (87%), sensitivity (94%), specificity (80%), PPV (82.5%), NPV (93%) then followed by lamin B1 with accuracy accuracy is (80.5%), sensitivity (96%), specificity (65%), PPV (73.3%) and NPV (94.2%). These biomarkers showed higher accuracy than AFP which accuracy accuracy (77.5%) sensitivity (55%), specificity (100%), PPV (55%), NPV (69%)from this study it is concluded that HCC is a major health problem in Egypt and its incidence is increasing. the high prevalence of HCV infection makes screening programs, and the surveillance of those patients is a very important tool to early detect cases of small HCCs that can be successfully resected or ablated rather than palliative treatment, also occupational exposure may play role in the development of HCC in addition to viral infection, smoking may generate an excess risk of HCC. Metabolic factors as diabetes and obesity have great burden in HCC development. The study reveal that lamin B1, vimentin and anti KU86 are more sensitive, specific and accurate than AFP for diagnosis and early detection of HCC and in differentiating HCC from chronic liver disease.Recommendations:Most of HCC cases occur on top of HCV and HBV so we recommend surveillance of chronic HCV and chronic HBV, and early treatment of discovered cases to prevent HCC development.Health care workers vaccination against HBV.Liver cirrhosis should strictly screened for early detection of HCC.Multiple risk factors can play role in HCC development as occupation so we recommend further studies to evaluate its contribution in HCC progress.Pesticide exposure should be prevented as well as other industrial agents which approved to have carcinogenic effects.Metabolic comorbidities as diabetes mellitus and obesity should be followed up and controlled and further studies are needed to evaluate its role in carcinogenesis.NASH and NAFLD are common sequence of these metabolic problems so we recommend putting them in regular screening programs.Genetic factors also can play role so we recommend to screen patients with family history of HCC.Further studies on risk factors in other geographical area with multicenter study to evaluate other risk factors.AFP has lower accuracy in screening of HCC than the novel biomarkers so we recommend to use novel biomarkers as vimentin, anti-KU86, and lamin B1 in screening and early detection of HCC as in early stages of the disease it can be curable.We recommend large scale multicenter studies in Egypt to clarify the diagnostic performance of these new biomarkers and also as therapeutic target.