NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) - Weebly：非酒精性脂肪性肝病（NAFLD）- Weebly.ppt

NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) Joel M. Andres, M.D. University of Florida OBJECTIVES To understand the pathophysiology of nonalcoholic fatty liver disease (NAFLD) - The link between NAFLD and insulin R - The relationship of insulin R to steatosis - The “second hit” theory of steatosis to NASH To learn about adipocytokines and HSCs, implicated in the dev-ment of hepatic inflam and fibrosis in patients with NAFLD To understand the key items for diagnosis and management of NAFLD in children OBESITY BASIC FACTS DEFINITION Epidemic of obesity, probably the most common health issue of children Because BMI norms for children vary with age and gender, BMI %tiles rather than absolute BMI’s are determined % of children 6-11 yrs of age with BMI 95th more than doubled from 6.5 to 15.3 % betw late 70’s and 2000 Cut off values to define the heaviest children are the 85th and 95th %tiles (BMI’s of 25 and 30, respectively, as maturity is approached in adolescence) Above #’s double if one includes children with BMI 85th %tile National Center for Health Stats, 2003 Strauss RS. JAMA 2001; 286:2845 Medical Conditions Assoc’ed WithCHILDHOOD OBESITY Hypertension Hyperlipidemia Impaired Glucose Tolerance/ Diabetes Gallbladder Disease/ Gallstones Nonalcoholic Fatty Liver Disease (NAFLD) - Elevated Liver Transaminases Common - Severe Fibrosis and Cirrhosis Also Occur Rashid M, et al. JPGHAN 2000;30:48 Tomuinaga K, et al. Dig Dis Sci 1995;40:’02 ObesityInsulin Resistance and NAFLD CENTRAL OBESITY Intra-abdominal fat is the main adipose depot associated with insulin resistance Visceral adipocytes are more metabolically active than subcu adipocytes FFAs from visceral adipose sites drain directly to liver via the portal vein Ioannou GN, et al.Clin Gastro Hepatol 2005; 3:67. Thus, potentially exerting influence on hepatic glucose metabolism and fatty acid oxidation, ultimately con- tributing to the development of hepatic ste