1、非酒精性脂肪肝（nonalcoholic fatty liver disease NAFLD) 发病机制和治疗,2004级住院医生 冯会芳,脂肪性肝病是指以肝小叶 内弥漫性肝细胞脂肪变性 大于1/3(每单位视野)为病 理特征的临床综合征,预后,预后较酒精性脂肪肝好 但并不是一种良性及静止的病变，它可在短期内发展为不可逆的肝损害，肝纤维化的发生率约高达25%，约1.5%8.0%患者可进展为肝硬化,分类,肥胖性脂肪肝 高脂血症性脂肪肝 糖尿病性脂肪肝 药物性脂肪肝,发病机制,胰岛素抵抗 游离脂肪酸(FFA) 氧化应激(oxygenstress,OS)和脂质过氧化(lipidperox2 ide,L
2、P) 瘦素抵抗(leptinresistance,LR) 铁超载 内毒素,胰岛素抵抗 (insulinresistance,IR),所谓IR是肝脏外周脂肪以及肌肉组织对胰岛素作用的生物反应低于正常水平 各种原因如肥胖，2型糖尿病，脂代谢紊乱等导致的胰岛素抵抗，游离脂肪酸增加，肝脏脂肪代谢障碍，从而使肝细胞内合成甘油三酯增加而输出减少，肝细胞内脂肪异位沉积，导致肝细胞脂肪变性,The state of insulin resistance in patients with nonalcoholic fatty liver and the intervention with Gankangyin.
3、 Chin J Integr Med. 2005 Jun;11(2):117-22.,Before treatment, the levels of blood glucose and insulin at different time points in OGTT test, and the insulin resistance index (IRI) were significantly higher (P 0.05 or P 0.01) while insulin sensitivity index (ISI) and insulin active index (IAI) were lo
4、wer (P 0.05 or P 0.01) in the NAFL patients than those in the healthy persons.,游离脂肪酸(FFA),FFA为具有肝细胞毒性的分子作用于肝细胞可以使线粒体肿胀和通透性增加，肝细胞变性，坏死和炎细胞浸润,诱导细胞凋亡 加强脂质过氧化反应损伤肝细胞 可以与细胞因子TNF-A，TNF-B，IL-1，IL-6等相互作用，导致生物膜损伤，诱发脂肪性肝炎,危险因素,代谢综合症（肥胖、糖尿病 、高血脂、动脉粥样硬化、高血压） 高龄 肝炎病毒感染史 冠心病,Incidence and risk factors for non-alc
5、oholic steatohepatitis: prospective study of 5408 women enrolled in Italian tamoxifen chemoprevention trial. BMJ. 2005 Apr 23;330(7497):932. Epub 2005 Mar 3,Other factors associated with the development of non-alcoholic fatty liver disease included overweight (2.4, 1.2 to 4.8), obesity (3.6, 1.7 to
6、7.6), hypercholesterolaemia (3.4, 1.4 to 7.8), and arterial ypertension (2.0, 1.0 to 3.8).,诊断,组织学 B 超 CT MRI“It is, however, common practice to use either sonography or computerized tomography scan. “ American Gastroenterological Association medical position statement: nonalcoholic fatty liver disea
7、se.,B超显示,肝脏增大，右肝最大斜径增大，实质近场回声增强，远场回声衰减，肝脏血管显示欠清。,治疗,治疗原发病 尤需注意易被忽视的病因，如药物性肝损害、磷中毒、肉碱缺乏状态、甲状腺功能亢进或减退。 饮食治疗 饮食应给高热量，高蛋白，并补充少量维生素，减少单糖和多价不饱和脂肪酸，但要有适量必需脂肪酸，脂肪以不超过总热量的15%20%为宜。 糖尿病性脂肪肝关键在于控制血糖,Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroen
8、terol. 2003 Nov;98(11):2348-50.,Vitamin treatment resulted in a statistically significant improvement in fibrosis score (p=0.002).,药物治疗,胰岛素增敏剂：二甲双胍等 血脂调节药 药物有阴离子交换树脂!（消胆胺）烟酸类!苯氧乙酸类!羟甲基戊二酸单酰辅酶A(HMG2COA),还原酶抑制剂包括普伐他汀、辛伐他汀等 可以降低总胆固醇的血浆浓度，提高HDL的血浆浓度,熊去氧胆酸(UDCA) （可降低血脂,并可稳定肝细胞膜和抑制单核细胞） 必需磷脂(肝得健) 谷胱甘肽(GSH
9、) 牛磺酸 马洛替酯 肝细胞生长因子(HGF) 中草药 （山楂，丹参，川芎，泽泻，柴胡）,二甲双胍,Open-label treatment with metformin for 24 weeks was notable for improvement in liver chemistry, liver fat, insulin sensitivity and quality of life. A large randomized-controlled trial is needed to definitively determine the efficacy of metformin for paediatric non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2005 Apr 1;21(7):871-9.,运动疗法,加强锻炼能有效改善人体脂质代谢，促进机体新陈代谢，提高脂蛋白酶的活性，加速脂质转运、分解和排泄使血清TC、TG、LDL和VLDL含量降低，而使HDL含量增高,谢谢！,
