Study Of Serum Dipeptidyle Peptidase IV (DPP IV, CD26 ) Activity In Patients With Non – Alcoholic Fatty Liver Disease And Its Role In Development Of Non – Alcoholic Steatohepatitis

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a clinico-pathological disorder characterized by the accumulation of triglycerides in hepatocytes. The incidence of NAFLD has increased markedly in recent years, accompanying the increased prevalence of obesity and type 2 diabetes mellitus (T2DM). More than 10% of patients with NAFLD progress to non-alcoholic steatohepatitis (NASH), which is charac¬terized by inflammatory cell infiltration and ballooning of hepatocytes in the liver. Liver cirrhosis and hepatocellular carcinoma occur in several patients with NASH. Obesity and insulin resistance (IR) are believed to be involved in the pathogenesis of NAFLD. Increased hepatic uptake of fatty acids as a result of elevated triglyceride degradation in adipose tissue causes hepatic fat accumulation. Prolonged intrahepatic inflammation as a result of elevated generation of ROS is a significant process underlying the progression of liver disease from NAFLD to NASH. Reactive oxygen species (ROS) produced during lipid oxidation may induce hepatocyte death and inflammatory reactions.Notably , IR is known to induce the release of tumor necrosis factor (TNF) and interlukins ,which cause chronic activation of systemic low –grade inflammation .IR also reduces glucose uptake in muscles and diminishes insulin-dependent suppression of gluconeogenesis, ultimately progressing to T2DM. Dipeptidyl peptidase-4 (DPP4) is a serine protease that metabolizesincretin hormonesincluding glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) which are secreted by intestinal endocrine cells upon food ingestion. DPP4 seems to influence inflam¬mation by regulating T cell proliferation and the cell cycle of NK cells. In addition, the enhanced tissue mRNA expression of DPP4 in diseases such as asthma or ulcerative colitis implies that DPP4 may play a role in the pathogenesis of several inflammatory diseases. It is suggested that circulating DDP4 may play a role in the progression of non – alcoholic fatty liver disease (NAFLD) to non – alcoholic steatohepatitisbecause of its ability to differentiate simple steatosis from steatohepatitis. This study was designed to study the role of serum dipeptidyle peptidaseIV activity in development and progression of simple steatosis to non-alcoholic steatohepatitisin patients with non-alcoholic fatty liver disease and its role in follow upthe progression to chronic liver disease. After approval of institutional review board, this study was conducted at Internal Medicine Department of Ain Shams University Hospital on thirty patients with non-alcoholic fatty liver, thirty patients with non-alcoholic steatohepatitis and thirty healthy individuals. An informed consent was obtained from all enrolled patients and the control personal.