LIVER FAILURE AND LIVER DISEASE Nonalcoholic Fatty Liver Disease: From Steatosis to Cirrhosis
LIVER FAILURE AND LIVER DISEASE Nonalcoholic Fatty Liver Disease: From Steatosis to Cirrhosis
复制标题
DOI：
--
复制
发表时间：
2006
影响因子：
0.7
通讯作者：
G. Farrell;C. Larter
中科院分区：
文献类型：
--
作者：
G. Farrell;C. Larter
非酒精性脂肪性肝炎（NASH）是非酒精性脂肪性肝病（NAFLD）谱系中介于脂肪变性和肝硬化之间的关键，在1981年几乎没有被认识到。NAFLD目前在17%至33%的美国人中存在，具有全球分布，与中心性肥胖、肥胖、胰岛素抵抗、代谢综合征和2型糖尿病的发病率相似。三分之一的NAFLD病例可能存在NASH。年龄、脂肪性肝炎的活动性和已确定的纤维化易导致肝硬化，肝硬化的7至10年肝脏相关死亡率为12%至25%。许多隐源性肝硬化病例可能是晚期NASH。虽然终末期NAFLD目前占肝移植的4%至10%，但这一比例可能很快会上升。NAFLD/NASH的致病概念必须考虑到与营养过剩和活动不足、胰岛素抵抗和遗传因素的密切联系。脂肪毒性、氧化应激、细胞因子和其他促炎介质都可能在脂肪变性向NASH的转变中发挥作用。目前NASH管理的“金标准”是适度减轻体重，特别是通过将饮食措施与增加体育活动相结合来纠正中心性肥胖。无论是通过“生活方式调整”还是减肥手术，这都能改善胰岛素抵抗，逆转脂肪变性、肝细胞损伤、炎症和纤维化。对过氧化物酶体增殖激活受体（PPAR）激动剂“格列酮”的研究表明，“解旋”纤维化NASH的潜力相同，但这些药物可能以恶化肥胖为代价改善肝脏疾病。今后的挑战是将NAFLD作为一项预防性公共卫生倡议来处理，并激励受影响的人采取更健康的生活方式。(肝脏病学2006;43:S99-S112。)
Nonalcoholic steatohepatitis (NASH), the lynchpin between steatosis and cirrhosis in the spectrum of nonalcoholic fatty liver disorders (NAFLD), was barely recognized in 1981. NAFLD is now present in 17% to 33% of Americans, has a worldwide distribution, and parallels the frequency of central adiposity, obesity, insulin resistance, metabolic syndrome and type 2 diabetes. NASH could be present in one third of NAFLD cases. Age, activity of steatohepatitis, and established fibrosis predispose to cirrhosis, which has a 7to 10-year liver-related mortality of 12% to 25%. Many cases of cryptogenic cirrhosis are likely endstage NASH. While endstage NAFLD currently accounts for 4% to 10% of liver transplants, this may soon rise. Pathogenic concepts for NAFLD/NASH must account for the strong links with overnutrition and underactivity, insulin resistance, and genetic factors. Lipotoxicity, oxidative stress, cytokines, and other proinflammatory mediators may each play a role in transition of steatosis to NASH. The present “gold standard” management of NASH is modest weight reduction, particularly correction of central obesity achieved by combining dietary measures with increased physical activity. Whether achieved by “lifestyle adjustment” or anti-obesity surgery, this improves insulin resistance and reverses steatosis, hepatocellular injury, inflammation, and fibrosis. The same potential for “unwinding” fibrotic NASH is indicated by studies of the peroxisome proliferation activator receptor (PPAR)agonist “glitazones,” but these agents may improve liver disease at the expense of worsening obesity. Future challenges are to approach NAFLD as a preventive public health initiative and to motivate affected persons to adopt a healthier lifestyle. (HEPATOLOGY 2006;43:S99-S112.)