Dejong Cornelis H C, van de Poll Marcel C G, Soeters Peter B, Jalan Rajiv, Olde Damink Steven W M
Department of Surgery, Nutrition and Toxicology Institute Maastricht, Maastricht University, the Netherlands.
J Nutr. 2007 Jun;137(6 Suppl 1):1579S-1585S; discussion 1597S-1598S. doi: 10.1093/jn/137.6.1579S.
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 (1.19 +/- 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.
肝衰竭与肝性脑病（HE）相关。血浆中芳香族氨基酸（AAA）苯丙氨酸、酪氨酸和色氨酸与支链氨基酸（BCAA）水平失衡及其BCAA/AAA比值，被认为通过增强脑内AAA摄取及随后扰乱神经传递，在HE发病中起因果作用。直到最近，由于门静脉和肝静脉难以接近，关于这一主题以及肝脏和内脏床作用的数据很少，尤其是在人类中。在此，我们结合相关文献背景，讨论在肝切除患者或经颈静脉肝内门体分流术（TIPSS）患者中获得的数据，这些患者的这些静脉是可接近的。肝大部切除术后BCAA/AAA比值保持不变，但血浆AAA水平与残余肝体积呈负相关（P < 0.001），这与观察到的肝脏AAA摄取情况一致。在患有稳定肝硬化且行TIPSS的患者中，血浆BCAA/AAA比值低于对照组（1.19±0.09 vs. 对照组：3.63±0.34）。行TIPSS的肝硬化患者发生胃肠道出血会导致BCAA水平和BCAA/AAA比值紊乱，并引发分解代谢，给予异亮氨酸可部分纠正。AAA可能在HE发病机制中起重要作用，但它们不太可能是唯一因素。HE很可能是一种具有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等以及增强肾脏氨排泄相结合。
