Maddrey W C
J Am Coll Nutr. 1985;4(6):639-50. doi: 10.1080/07315724.1985.10720106.
Patients with hepatic cirrhosis often are malnourished and wasted. If portal-systemic encephalopathy (PSE) develops, restriction of dietary protein in an attempt to treat encephalopathy may further promote negative nitrogen balance. There is considerable interest in providing nutritional supplements to patients with cirrhosis and PSE which would lead to improvement in nitrogen balance while improving or at least not worsening PSE. Amino acid supplements designed to correct the abnormal amino acid pattern characteristically found in patients with cirrhosis and PSE are under investigation as potential therapeutic agents. The levels of the branched chain amino acids (BCAAs) are decreased in almost all patients with cirrhosis and PSE. The exact mechanism for the reductions in BCAA concentrations is unknown. Furthermore, aromatic amino acids (AAA) and methionine (MET) concentrations are usually increased in these patients. It has been suggested that BCAAs and neutral amino acids compete for transport across the blood-brain barrier and that a decrease in BCAA concentrations promotes entrance of neutral amino acids into the brain. Aromatic amino acids, MET, and their derivatives may have a role in the production of PSE. These observations have increased interest in the potential therapeutic benefit of administering BCAAs to patients with cirrhosis and PSE in order to decrease the entrance of putative toxins into the brain. Treatment trials using BCAAs alone or in solutions containing other amino acids in patients with cirrhosis and PSE have given conflicting results. In one trial, there appeared to be less PSE induced by a BCAA-enriched solution when compared to equinitrogenous dietary protein. However, other controlled studies have not demonstrated any advantage to the addition of BCAAs as compared to placebo with regards to reducing mortality or improving cerebral function in patients with acute cirrhosis and PSE. Some of the differences in study outcomes may relate to the patient population evaluated; the type, amount, and duration of treatment; and whether other therapy was administered. BCAA supplements may also be useful in minimizing or reversing the catabolic state characteristic of patients with cirrhosis. A reduction of increased urinary 3-methylhistidine excretion by infusions of BCAAs in cirrhotic patients suggests an anticatabolic effect. These potential anticatabolic effects of BCAAs are most interesting and deserve further study.
肝硬化患者常伴有营养不良和消瘦。如果发生门体性脑病（PSE），为治疗脑病而限制膳食蛋白质可能会进一步加剧负氮平衡。为肝硬化和PSE患者提供营养补充剂，以改善氮平衡，同时改善或至少不加重PSE，这引起了人们极大的兴趣。旨在纠正肝硬化和PSE患者中典型的异常氨基酸模式的氨基酸补充剂正在作为潜在治疗药物进行研究。几乎所有肝硬化和PSE患者的支链氨基酸（BCAAs）水平都降低。BCAA浓度降低的确切机制尚不清楚。此外，这些患者的芳香族氨基酸（AAAs）和蛋氨酸（MET）浓度通常会升高。有人提出，BCAAs和中性氨基酸竞争通过血脑屏障的转运，BCAA浓度降低会促进中性氨基酸进入大脑。芳香族氨基酸、MET及其衍生物可能在PSE的发生中起作用。这些观察结果增加了人们对给肝硬化和PSE患者施用BCAAs以减少假定毒素进入大脑的潜在治疗益处的兴趣。在肝硬化和PSE患者中单独使用BCAAs或在含有其他氨基酸的溶液中进行治疗试验，结果相互矛盾。在一项试验中，与等氮膳食蛋白质相比，富含BCAA的溶液诱发的PSE似乎较少。然而，其他对照研究并未表明，与安慰剂相比，添加BCAAs在降低急性肝硬化和PSE患者的死亡率或改善脑功能方面有任何优势。研究结果的一些差异可能与评估的患者群体、治疗的类型、剂量和持续时间以及是否进行了其他治疗有关。BCAA补充剂也可能有助于最小化或逆转肝硬化患者特有的分解代谢状态。肝硬化患者输注BCAAs后，尿中3-甲基组氨酸排泄增加量减少，提示有抗分解代谢作用。BCAAs的这些潜在抗分解代谢作用非常有趣，值得进一步研究。
