Department of Medicine, University of Montreal, 45143 Cabot Trail, Englishtown, NS, B0C 1H0, Canada.
Drugs R D. 2021 Jun;21(2):123-132. doi: 10.1007/s40268-021-00345-4. Epub 2021 Apr 22.
Effective lowering of circulating ammonia is the mainstay strategy in the prevention and treatment of hepatic encephalopathy in cirrhosis and there is increasing interest in agents with the metabolic potential for the active removal of ammonia by the liver and skeletal muscle by agents including L-ornithine L-aspartate, branched-chain amino acids, as well as the re-purposing of benzoate and phenylacetate currently employed for the control of hyperammonaemia in congenital urea-cycle enzymopathies. Based upon results of multiple systematic reviews with meta-analyses, L-ornithine L-aspartate demonstrably lowers circulating ammonia in patients with cirrhosis with concomitantly improved mental status. Distinct mechanisms responsible include optimisation of hepatic metabolic pathways for ammonia removal as well as direct hepatoprotective effects involving the release of glutathione and of nitric oxide with beneficial effects on hepatic microcirculation. L-ornithine L-aspartate also prevents cirrhosis-related sarcopenia, leading to increased capacity for ammonia removal by skeletal muscle. Branched-chain amino acids continue to be prescribed as nutritional supplements with the potential to result in improvements in liver function. Sodium benzoate, glycerol phenylbutyrate and an analogous compound L-ornithine phenylacetate were also evaluated. Glycerol phenylbutyrate was the only agent with a beneficial effect on both hyperammonaemia and hepatic encephalopathy. None were superior to lactulose for the lowering of blood ammonia.
有效降低循环氨是预防和治疗肝硬化肝性脑病的主要策略，人们对具有代谢潜力的药物越来越感兴趣，这些药物可以通过肝脏和骨骼肌主动清除氨，包括 L-鸟氨酸 L-天冬氨酸、支链氨基酸，以及目前用于控制先天性尿素循环酶病高氨血症的苯甲酸钠和苯乙酸的再利用。基于多项系统评价和荟萃分析的结果，L-鸟氨酸 L-天冬氨酸可明显降低肝硬化患者的循环氨，同时改善精神状态。其作用机制包括优化肝脏氨去除的代谢途径，以及直接的肝保护作用，涉及谷胱甘肽和一氧化氮的释放，对肝微循环有有益影响。L-鸟氨酸 L-天冬氨酸还可预防肝硬化相关的肌肉减少症，从而增加骨骼肌对氨的清除能力。支链氨基酸继续作为营养补充剂被开处方，有可能改善肝功能。苯甲酸钠、甘油苯丁酸和类似的化合物 L-苯丙氨酸 L-鸟氨酸也进行了评估。甘油苯丁酸是唯一对高氨血症和肝性脑病均有有益作用的药物。没有一种药物在降低血氨方面优于乳果糖。
