脂肪性肝病治疗进展课件.pptVIP

* Development of nonalcoholic hepatic steatosis. Insulin resistance enhances triglyceride (TG) lipolysis and inhibits esterification of free fatty acids (FFA) within adipose tissue. The result is increased serum FFA levels, which are taken up by the liver. Hepatic TG synthesis is driven by the increased influx of FFA and favoured by insulin upregulated lipogenic transcription factors, such as peroxisome proliferator-activated receptor gamma (PPARγ) and sterol regulatory element binding protein (SREBP)-1c. Alternative metabolism of FFA by oxidation is inhibited by insulin. TG export via very-low-density lipoproteins (VLDL) may be inhibited by decreased synthesis of apolipoprotein B (apo B) or reduced incorporation of TG with apo B by microsomal triglyceride transfer protein (MTP). See the animated figure at www.cmaj.ca/cgi/content/full/172/7/899/DC1. * Left: Histologic features of fibrosis in nonalcoholic steatohepatitis (NASH). Trichrome stain of liver (magnification × 200) demonstrating macrovesicular steatosis and fibrosis, most prominent in zone 3 near the central vein (CV) of the hepatic lobule. Typically early fibrosis is pericellular and perisinusoidal, giving the appearance of “chickenwire.” Right: Histologic features of necrotic inflammation in NASH. Hematoxylin and eosin stain of liver (magnification × 400) with injured ballooned hepatocytes (B) and a mild neutrophilic infiltrate (N). Aggregations of Mallory’s hyaline (MH) comprised of eosinophilic cytoskeleton filaments are also observed. UDCA治疗非酒精性脂肪性肝炎的临床试验 作者/年份 治疗方法 剂量和疗程 试验类型 样本量 生化 组织学 Abdelmalek 1995 UDCA N/A,12月 N/A 1 有（1/1） 有 Laurin 1996 UDCA 13-15mg/kg/d， 12月 小型 开放试验 24 有 有（12/19） Guma 1998 UDCA +节食 10mg/kg/d 6月 随机对照试验 24 有（10/13） N/A Ceriani 1998 UDCA +节食 10mg/kg/d， 6月 随机对照试验 31 有（14/16） N/A UDCA治疗非酒精性脂肪性肝炎的临床试验 作者/年份 治疗方法 剂量和疗程 试验类型 样本量 生化 组织学 Holoman 2000 UDCA 250mg,tid，6月 开放试验 24 有 N/A Vajro 2000 UDCA 和/或节食 10mg/kg/d 6月 小型开放试验 31 无 N/A Santos 2003 UDCA 10mg/kg/d 3月 随机对照双盲