Complications of cirrhosis III. Hepatic encephalopathy
Complications of cirrhosis III. Hepatic encephalopathy
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DOI：
10.1016/s0168-8278(00)80424-9
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发表时间：
2000-01-01
影响因子：
25.7
通讯作者：
Butterworth, RE
中科院分区：
文献类型：
--
作者：
Butterworth, RE
肝性脑病（HE）是肝硬化的主要神经精神并发症，HE在肝硬化患者中发展缓慢，从睡眠模式改变开始，最终进展为昏迷和昏迷。诱发因素是常见的，包括口服蛋白质负荷，胃肠道出血和镇静剂的使用。HE在经颈静脉肝内门体分流术（TIPS）后很常见。神经病理学上，阿尔茨海默病患者的HE特征为星形胶质细胞（而不是神经元）变化，称为阿尔茨海默病II型星形胶质细胞增多症，以及关键星形胶质细胞蛋白表达改变。磁共振成像显示，尤其是在苍白球的T-1加权成像，这可能是由于锰沉积的现象。质子（H-1）磁共振波谱显示大脑中谷氨酰胺共振增加，这一发现证实了先前的生化研究，结果无疑是大脑氨清除（谷氨酰胺合成）增加。使用正电子发射断层扫描和（NH 3）-N-13的研究提供了肝衰竭患者脑氨摄取和清除增加的其他证据。最近的分子生物学研究表明，慢性肝衰竭中神经递质相关蛋白编码基因的表达增加。这些基因包括单胺氧化酶（MAO-A同种型）、外周型苯二氮卓受体和一氧化氮合酶（nNOS同种型）。这些系统的激活有可能导致单胺和氨基酸神经递质功能的改变以及慢性肝功能衰竭中脑灌注的改变。肝硬化患者HE的预防和治疗仍然依赖于降氨策略，包括评估膳食蛋白质摄入量以及使用乳果糖、新霉素、苯甲酸钠和L-门冬氨酸-鸟苷酸。苯二氮卓类受体拮抗剂氟马西尼可能在某些情况下有效。更广泛地使用中枢神经系统作用的药物等待更完整地了解慢性肝功能衰竭中HE发病机制所涉及的精确神经递质系统。
Hepatic encephalopathy (HE) is a major neuropsychiatric complication of cirrhosis, HE develops slowly in cirrhotic patients, starting with altered sleep patterns and eventually progressing through asterixis to stupor and coma. Precipitating factors are common and include an oral protein load, gastrointestinal bleeding and the use of sedatives. HE is common following transjugular intrahepatic portosystemic stent shunts (TIPS), Neuropathologically, HE in cirrhotic patients is characterized by astrocytic (rather than neuronal) changes known as Alzheimer type II astrocytosis and in altered expression of key astrocytic proteins. Magnetic resonance imaging in cirrhotic patients reveals bilateral signal hyperintensities particularly in globus pallidus on T-1-weighted imaging, a phenomenon which may result from manganese deposition. Proton (H-1) magnetic resonance spectroscopy shows increases in the glutamine resonance in brain, a finding which confirms previous biochemical studies and results no doubt from increased brain ammonia removal (glutamine synthesis). Additional evidence for increased brain ammonia uptake and removal in cirrhotic patients is provided by studies using positron emission tomography and (NH3)-N-13, Recent molecular biological studies demonstrate increased expression of genes coding for neurotransmitter-related proteins in chronic liver failure. Such genes include monoamine oxidase (MAO-A isoform), the peripheral-type benzodiazepine receptor and nitric oxide synthase (nNOS isoform), Activation of these systems has the potential to lead to alterations of monoamine and amino acid neurotransmitter function as well as modified cerebral perfusion in chronic liver failure. Prevention and treatment of HE in cirrhotic patients continues to rely on ammonia-lowering strategies which include assessment of dietary protein intake and the use of lactulose, neomycin, sodium benzoate and L-ornithine-aspartate, The benzodiazepine receptor antagonist flumazenil may be effective in certain cases. A more widespread use of central nervous system-acting drugs awaits a more complete understanding of the precise neurotransmitter systems involved in the pathogenesis of HE in chronic liver failure.