Aromatic amino acid metabolism during liver failure
Aromatic amino acid metabolism during liver failure
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DOI：
10.1093/jn/137.6.1579s
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发表时间：
2007-06-01
影响因子：
4.2
通讯作者：
Damink, Steven W. M. Olde
中科院分区：
文献类型：
--
作者：
Dejong, Cornelis H. C.;van de Poll, Marcel C. G.;Damink, Steven W. M. Olde
肝衰竭与肝性脑病（HE）有关。芳香族氨基酸（AAA）、苯丙氨酸、酪氨酸、色氨酸和支链氨基酸（BCAA）的血浆水平失衡及其BCAA/AAA比率已被认为通过增强脑AAA摄取和随后干扰神经传递在HE中发挥因果作用。直到最近，由于门静脉和肝静脉的不可及性，关于这一主题以及肝脏和内脏床的作用的数据还很少，特别是在人类中。在这里，我们讨论，在相关文献的背景下，在接受肝切除术或经颈静脉肝内门体分流术（TIPSS），这些静脉是可访问的患者中获得的数据。BCAA/AAA比率在主要肝切除术后保持不变，但血浆AAA水平与残余肝体积呈负相关（P < 0.001），与观察到的肝AAA摄取一致。在稳定性肝硬化和TIPSS患者中，血浆BCAA/AAA比值低于对照组0.19 +/- 0.09 vs.对照组：3.63 +/- 0.34）。TIPSS患者的胃肠道出血引起BCAA水平和BCAA/AAA比值的紊乱，并引起catabolism，这可以通过异亮氨酸给药部分纠正。AAA在HE的发病机制中可能是重要的，但它们不太可能是唯一的因素。HE很可能是一种多因素发病机制的综合征，其中高氨血症、AAA/BCAA失衡、炎症、脑水肿和神经递质变化相互作用。使肝衰竭患者AAA水平正常化的新疗法（如分子吸附再循环系统透析装置）可能应与补充异亮氨酸和增强肾脏氨排泄等联合使用。
Liver failure is associated with hepatic encephalopathy (HE). An imbalance in plasma levels of aromatic amino acids (AAA) phenylalanine, tyrosine, and tryptophan and branched chain amino acids (BCAA) and their BCAA/AAA ratio has been suggested to play a causal role in HE,by enhanced brain AAA uptake and subsequently disturbed neurotransmission. Until recently, data on this subject and the role of the liver and splanchnic bed were scarce, particularly in humans, due to inaccessibility of portal and hepatic veins. Here, we discuss, against a background of relevant literature, data obtained in patients undergoing liver resection or with a transjugular intrahepatic portasystemic stent shunt (TIPSS), where these veins are accessible. The BCAA/AAA ratio remained unchanged after major liver resection, but plasma AAA levels were inversely correlated (P < 0.001) with residual liver volume, in keeping with the observed hepatic AAA uptake. In patients with stable cirrhosis and a TIPSS, the plasma BCAA/AAA ratio was lower than in controls 0.19 +/- 0.09 vs. controls: 3.63 +/- 0.34). Gastrointestinal bleeding in cirrhotics with a TIPSS induced disturbances in BCAA levels and the BCAA/AAA ratio and induced catabolism, which could partly be corrected by isoleucine administration. AAA may be important in the pathogenesis of HE, but it is unlikely that they are the sole factors. HE most likely is a syndrome with multifactorial pathogenesis, where hyperammonemia, AAA/BCAA imbalances, inflammation, brain edema, and neurotransmitter changes interact. Novel therapies to normalize AAA levels in patients with liver failure (such as the molecular adsorbent recirculating system dialysis device) should probably be combined with supplementation of e.g. isoleucine and enhancing ammonia excretion by the kidneys.