Background and aims: Minimal hepatic encephalopathy and hyperammonemia is seen in extra-hepatic portal venous obstruction patients. Inflammation has been shown to play an important role in pathogenesis of hepatic encephalopathy in cirrhotics. This study assessed the serum proinflammatory cytokines and their correlation with hyperammonemia, (1) H MR spectroscopy derived brain glutamine and diffusion tensor imaging derived metrics in extra-hepatic portal venous obstruction patients with and without minimal hepatic encephalopathy.

Methods: Neuropsychological tests, diffusion tensor imaging, (1) H magnetic resonance spectroscopy, estimation of blood ammonia and proinflammatory cytokines (TNF-α and IL-6) were done in 20 extra-hepatic portal venous obstruction patients and 8 healthy controls.

Results: Proinflammatory 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 minimal hepatic encephalopathy (n-12) had significantly higher TNF-α, IL6, 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 was seen in various brain regions including spectroscopy voxel derived mean diffusivity.

Conclusion: Extra-hepatic portal vein obstruction patients have inflammation and hyperammonemia as evident by higher blood TNF-α, IL-6, ammonia and brain glutamine levels. Significant correlation between hyperammonemia, proinflammatory cytokines and cerebral edema on diffusion tensor imaging in various brain regions suggests that both these factors play a role in pathogenesis of minimal hepatic encephalopathy in these patients.