Pro-inflammatory Cytokines Are Raised in Extrahepatic Portal Venous Obstruction, with Minimal Hepatic Encephalopathy

Background And Aims: Minimal hepatic encephalopathy (MHE) and hyperammonemia are seen in patients with extrahepatic portal venous obstruction (EHPVO). Inflammation has been shown to play an important role in the pathogenesis of hepatic encephalopathy in cirrhotics. This study assessed serum pro-inflammatory cytokines and their correlation with hyperammonemia, (1)H-magnetic resonance (MR) spectroscopy-derived brain glutamine, and diffusion tensor imaging (DTI)-derived metrics in patients with EPHVO, with and without MHE.

Methods: Neuropsychological tests, DTI, (1)H-MR spectroscopy, and estimation of blood ammonia and pro-inflammatory cytokines (tumor necrosis factor-α[TNF-α] and interleukin-6 [IL-6]) were done in 20 patients with EHPVO and eight healthy controls.

Results: Pro-inflammatory cytokines (TNF-α and IL-6), blood ammonia, brain glutamine, and mean diffusivity were increased in both patient groups, as compared to controls. Patients with MHE (n-12) had significantly higher TNF-α, IL-6, blood ammonia, brain glutamine, and mean diffusivity, signifying brain edema, than controls. A significant, positive correlation was seen between TNF-α and IL-6 and between blood ammonia and TNF-α, IL-6, and brain glutamine. Significant, positive correlations of TNF-α, IL-6, and blood ammonia with mean diffusivity values were seen in various brain regions, including spectroscopy voxel-derived mean diffusivity.

Conclusion: Patients with extrahepatic portal vein obstruction have inflammation and hyperammonemia made evident by higher blood TNF-α, IL-6, ammonia, and brain glutamine levels. A significant correlation between hyperammonemia, pro-inflammatory cytokines, and cerebral edema on DTI in various brain regions suggests that both these factors play a role in the pathogenesis of MHE in these patients.