| Objective:Previous studies have shown that significantly elevated serum levels of interleukin-6(IL-6) correlate with the severity of overt hepatic encephalopathy (OHE) or minimal hepatic encephalopathy (MHE) in cirrhotic patients. However, the correlation between serum IL-6and plasma ammonia levels in these patients remains unclear. Therefore, the present study investigated this correlation between both va-riables in cirrhotic patients with OHE or MHE in order to provide evidences of a po-tential synergistic interaction between proinflammatory cytokines and ammonia in the pathogenesis of OHE or MHE.Methods:1. According to the West-Haven criteria, fifty-five cirrhotic patients with OHE were recruited in the study. Venous blood samples from included patients were collected, and concentrations of plasma ammonia and serum IL-6were simulta-neously measured.2. According to the West-Haven criteria, eighty-five cirrhotic patients without OHE were included in the study. Psychometric tests including number connection test part A (NCT-A) and digit symbol test (DST) were performed to diagnose MHE. Simulta-neously, venous blood samples from recruited patients were collected, and concentra-tions of plasma ammonia and serum IL-6were measured.3. Single factor analysis was performed using chi-square test or Wilcoxon signed-rank test between OHE and non-HE patients or between MHE and non-HE patients. The significantly different factors in the univariate analyses were included in a multiva-riate logistic regression analysis in order to indentify the independent predictors of the presence of OHE or MHE.4. The correlation between levels of plasma ammonia or those of serum IL-6and the severity of OHE (West-Haven criteria) or that of MHE (results of NCT-A and DST) was investigated, respectively.5. The correlation between plasma ammonia and serum IL-6levels in cirrhotic pa-tients with OHE or MHE was investigated, respectively. In cirrhotic patients with OHE, the influence of infectious precipitating factors on this correlation was also evaluated.Results:1. The risk factors of the presence of OHE were Child-Pugh classification (OR=15.67,95%CI:4.15-58.67, P<0.01), plasma ammonia levels (OR=4.75,95%CI:2.15-9.49, P<0.01), and serum IL-6levels (OR=3.27,95%CI:1.36-8.43, P=0.01). In cirrhotic patients with OHE, the severity of OHE (West-Haven criteria) correlated with plasma ammonia levels (r=0.59, P<0.05) and serum IL-6levels (r=0.43, P<0.05), respectively. Moreover, there was a significant positive correlation between plasma ammonia levels and serum IL-6levels in these patients (r=0.58, P<0.05), but not in patients with non-MHE (r=0.22, P>0.05). The correlation between IL-6and ammonia in cirrhotic patients with OHE was independent of infectious pre-cipitating factors.2. In eighty-five cirrhotic patients without OHE, thirty-two patients (42.7%) were di-agnosed with MHE. Serum IL-6levels (OR=3.46,95%CI:1.58-8.26, P<0.01) and plasma ammonia levels (OR=5.38,95%CI:2.16-12.29, P<0.01) were considered as the risk factors of the presence of MHE. In cirrhotic patients with MHE, plasma am-monia levels correlated with the severity of MHE (NCT-A:r=0.39, P<0.05and DST:r=-0.47, P<0.05, respectively), and serum IL-6levels were also associated with the severity of MHE (NCT-A:r=0.56, P<0.05and DST:r=-0.38, P<0.05, respectively). Moreover, there was a significant positive correlation between plasma ammonia levels and serum IL-6levels in these patients (r=0.61, P<0.05), but not in patients with non-HE (r-0.22, P<0.05).Conclusion:In cirrhotic patients with OHE or MHE, plasma ammonia and serum IL-6levels are the risk factors of the presence of OHE or MHE, and the levels of both variables significantly correlate with the severity of OHE or MHE. Moreover, plasma ammonia levels are associated with serum IL-6levels. These results indicate that IL-6may be involved in the pathogenesis of OHE or MHE, and that IL-6may have a po-tential synergistic interaction with ammonia in the pathogenetic mechanism of OHE or MHE. |
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