Aims: Acute-on-chronic liver failure (ACLF) represents an acute decompensation of liver cirrhosis. End-to-side portacaval anastomosis (PCA) followed by hepatic artery ligation (HAL) performed after 4 weeks represents a model of liver decompensation. In this model, the onset of coma is delayed compared to acute liver failure induced by hepatic devascularisation. As oxidative stress plays a role in brain edema in chronic liver failure, the objective of this study was to investigate the role of oxidative stress in the pathogenesis of brain edema in ACLF. Methods: Male Sprague-Dawley rats were subjected to PCA followed by hepatic artery ligation (HAL) either concomitantly (HAL-0) or 4 weeks (HAL-4W) following shunt surgery or to a SHAM intervention. Body temperature and blood glucose were monitored and maintained throughout the experiments. Brain edema (specific gravimetric technique) and glutathione levels (spectrophotometry) were measured in brain tissue of all groups. Results: Brain water content was significantly attenuated in “acute-on-chronic” rats (SHAM: 80.12±0.09 %; HAL-0: 81.39±0.15 % (p<0.01 vs SHAM); HAL-4W: 80.04±0.13 % (ns vs SHAM; p<0.01 vs HAL-0)). Arterial ammonia concentration followed a similar pattern (control: 0.060±0.007 mM; HAL-0: 1.340±0.090 mM (p<0.001 vs SHAM); HAL-4W: 0.350±0.070 mM (p<0.001 vs SHAM; p<0.001 vs HAL-0)). Glutathione levels did not change in HAL-4W compared to SHAM and were significantly decreased in the brains of HAL-0 rats (by 36% vs SHAM, p<0.05 and by 25% vs HAL-4W). These effects were not due to an improvement in liver function, as liver necrosis markers AST and ALT did not differ between HAL-4W and HAL-0 rats. Conclusions: Brain edema, ammonia levels and oxidative stress are reduced in ACLF rats compared to acute liver failure rats. These findings suggest that during chronic liver failure compensatory mechanisms are developed that prevent the apparition of brain edema and attenuate oxidative stress during an acute deterioration.
