Shawcross Debbie L, Davies Nathan A, Williams Roger, Jalan Rajiv
Liver Failure Group, Institute of Hepatology, University College London Medical School, 69-75, Chenies Mews, London WC1E 6HX, UK.
J Hepatol. 2004 Feb;40(2):247-54. doi: 10.1016/j.jhep.2003.10.016.
BACKGROUND/AIMS: Studies in acute liver failure show correlation between evidence of a systemic inflammatory response syndrome (SIRS) and progression of hepatic encephalopathy (HE). We tested the hypothesis that SIRS mediators, such as nitric oxide and proinflammatory cytokines, may exacerbate the neuropsychological effects of hyperammonemia in cirrhosis.
Ten patients with cirrhosis were studied, 24-36 h after admission with clinical evidence of infection, and following its resolution. Hyperammonemia was induced by oral administration of an amino-acid (aa) solution mimicking hemoglobin composition. Inflammatory mediators, nitrate/nitrite, ammonia, aa profiles and a battery of neuropsychological tests were measured.
The hyperammonemia generated in response to the aa solution was similar prior to, and after resolution, of the inflammation (P=0.77). With treatment of the infection there were significant reductions in white blood cell count (WBC), C-reactive protein (CRP), nitrate/nitrite, interleukin-6, interleukin-1beta and tumour necrosis factor alpha. Induced hyperammonemia resulted in significant worsening of the neuropsychological scores when patients showed evidence of SIRS but not after its resolution.
The significant deterioration of neuropsychological test scores following induced hyperammonemia during the inflammatory state, but not after its resolution, suggests that the inflammation and its mediators may be important in modulating the cerebral effect of ammonia in liver disease.
背景/目的：急性肝衰竭的研究表明，全身炎症反应综合征（SIRS）证据与肝性脑病（HE）进展之间存在相关性。我们检验了以下假设：一氧化氮和促炎细胞因子等SIRS介质可能会加重肝硬化患者高氨血症的神经心理学效应。
对10例肝硬化患者进行研究，在入院有感染临床证据后24 - 36小时以及感染消退后进行观察。通过口服模拟血红蛋白成分的氨基酸（aa）溶液诱导高氨血症。测量炎症介质、硝酸盐/亚硝酸盐、氨、氨基酸谱以及一系列神经心理学测试指标。
炎症发作前和消退后，对氨基酸溶液产生的高氨血症情况相似（P = 0.77）。随着感染的治疗，白细胞计数（WBC）、C反应蛋白（CRP）、硝酸盐/亚硝酸盐、白细胞介素 - 6、白细胞介素 - 1β和肿瘤坏死因子α均显著降低。当患者出现SIRS证据时，诱导的高氨血症导致神经心理学评分显著恶化，但在SIRS消退后则未出现这种情况。
在炎症状态下诱导高氨血症后神经心理学测试评分显著恶化，但在炎症消退后则未出现，这表明炎症及其介质可能在调节肝脏疾病中氨对大脑的影响方面具有重要作用。
