World Journal of Research and Review (WJRR) ISSN:2455-3956, Volume-4, Issue-3, March 2017 Pages 01-07 1 www.wjrr.org Abstract— BACKGROUND Ghrelin is an inflammation inhibitor hormone. It is secreted from the gastrointestinal tract. It is involved in energy metabolism. Nuclear factor-kappa B (NF-κB) takes part in the initiation and the progression of the cardiovascular and adipose tissue inflammation. The combined role of Ghrelin and NF-κB in non-alcoholic fatty liver disease (NAFLD) pathogenesis is unclear. AIM: To investigate whether acyl-ghrelin level and NF-κB could interplay a role in lipid metabolism and inflammatory injury in NAFLD. PATIENTS AND METHODS: Ninety three adult participates were included in the study, 30 patients had proved nonalcoholic steatohepatitis (NASH), and 38 patients had simple steatosis, as well 25 healthy subjects, as a healthy control group. The control group matches the patients in age, gender and BMI. Full history and clinical examination, abdominal ultrasonography and liver biopsy were done when indicated. Liver function tests, lipid profile, blood sugar, insulin and C- peptide, fasting insulin, and plasma acyl-ghrelin concentrations were measured. Nuclear NF-kB mRNA expression was measured by quantitative RT-PCR. RESULTS: There are significant increase in fasting insulin, insulin C-peptide, HOMA-IR, AST, ALT and -GT and a significant decrease in HDL-C was in NAFLD patients compared to control group. In addition, a significant increase in ALT, -GT, fasting insulin, insulin C peptide and HOMA-IR were detected in the NASH group compared to group of simple steatosis. The plasma levels of Acyl-ghrelin was significantly decreased in NAFLD groups compared to normal control group, the lowest level was detected in NASH group as compared to group of simple steatosis. There was a significant increase in the expression of NF-kB mRNA in NAFLD groups more than in the normal control group. A significant increase in its level was in NASH than in simple steatosis patients. There was a positive correlation between NF-kB mRNA and BMI, HOMA-IR, ALT, fasting insulin, insulin C-peptide and liver histopathology and acyl-ghrelin was inversely correlated with BMI, HOMR-IR, ALT, fasting insulin, insulin C peptide and liver histopathology. Both were significantly correlated with HDL-C. CONCLUSION: Acyl ghrelin attenuated NAFLD-induced liver injury through down regulation of NF-κB and they are associated with disease progression. Mona El-Shafie , Clinical Pathology, Faculty of Medicine National Liver Institute, Menoufia University, Egypt Heba Allam Microbiology, Faculty of Medicine National Liver Institute, Menoufia University, Egypt Layla El-Shall Clinical Pathology, Faculty of Medicine for Girls, Al-Azhar University, C, Egypt. Mohamed Abdel-Samiee, HepatoGastroenterology, National Liver Institute, Menoufia University, Egypt El-Sayed Ibrahim HepatoGastroenterology, National Liver Institute, Menoufia University, Egypt Fatma Khalaf, Biochemistry, National Liver Institute, Menoufia University, Egypt Salwa Ali, Internal Medicine, Faculty of Medicine for Girls, Al-Azhar University, C, Egypt. Further large scale studies are recommended to consider ghrelin as promising drug for the prevention and treatment of NAFLD. Index Terms— Acyl-ghrelin; non-alcoholic fatty liver; Nuclear factor-kappa B. I. INTRODUCTION Nonalcoholic fatty liver disease (NAFLD) is a wide spectrum of diseases affecting the liver with grades of pathology. It causes fat accumulation use of alcohol. Disease spectrum may range from only simple steatosis to cirrhosis. It rarly can lead to hepatocellular carcinoma (HCC) (Bedogni et al., 2006; Vernon et al., 2011). Oxidative stress and resistance to insulin actions plays a major role initiation and progression of NAFLD (Kawano and Cohen, 2013). The oxidative stress causes injury liver cells with reactive oxygen species (ROS). This leads to hepatocytes inflammation and apoptosis (Natarajan et al., 2014). Kappa-B (NF-κB) is a nuclear factor that is composed of two subunits, p50 and p65. The two subunits associate with a third protein. IkB- α; is a regulatory protein that inhibits NF-B. This is done by forming a complex trapping it in the cytoplasm. The NF-κB is expressed in all cell types. It plays a main role as a transcriptional regulator in response to stress of cells (Paschetta et al., 2015). The pathway NF-κB is linked to oxidative stress and reactive oxygen species (ROS). This is accomplished through the production of inducible nitric oxide synthase (iNOS), cyclooxygenase- (COX-) 2, and metallo-proteinase-9. Hypoxic liver cells release ROS which directly activate hepatic stellate cell. This is through IkB-α phosphorylation and NF-κB signaling activation (Li et al., 2011). NF-κB takes part in initiation and progression of inflammation. NF-κB up regulates transcription of a wide range of inflammatory mediators leading to signaling pathway activation functions as a proinflammatory (Day, 2006). The NF-κB activation in liver cells and in stellate cells is associated with hepatic insulin resistance, hepatocytes apoptosis, and ultimately the development of NASH and HCC (Robinson and Mann, 2010; Luedde and Schwabe, 2011). A high-fat diet in mice proved to cause lipid accumulation in the liver leading to subacute hepatic inflammation. This occurs via NF-κB activation. It will lead to increased downstream cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β (Cai et al., 2005). Ghrelin is a peptide, present in the peripheral circulation in two forms: acylated and non-acylated. The stomach and small intestine produce the most amount of circulating Nuclear Factor-Kappa B Expression and Acyl-Ghrelin in Egyptian Patients with Non-Alcoholic Fatty Liver Mona El-Shafie , Heba Allam, Layla El-Shall, Mohamed Abdel-Samiee, El-Sayed Ibrahim, Fatma Khalaf ,Salwa Ali.