616 RELATIONSHIP BETWEEN PRO-INFLAMMATORY CYTOKINES AND CEREBRAL EDEMA IN ACUTE-ON-CHRONIC LIVER FAILURE

Abstract

1 H-MR spectroscopy ( 1 H-MRS). DTI studies provide mean diffusivity (MD) and spherical anisotropy (CS) values which estimate intracellular and extracellular water content respectively. While hyperammonemia is considered to play a major role in the pathogenesis of CE and HE, recent reports suggest that inflammation derived cytokines also contribute significantly. Data supporting this remain scanty. This study looked at the relationship between cytokines and glutamate/glutamine ratio (Glx) in 1 H-MRS, a measure of cerebral ammonia exposure and DTI derived metrics for CE, namely MD and CS, which are decreased and increased respectively in CE of ACLF patients. Methods: Seventeen patients with ACLF and 14 controls, matched for age and gender, were included in this study. Apart from clinical assessment and biochemical evaluations, all patients had undergone MRI studies ( 1 H-MRS and DTI). Serum pro-inflammatory cytokines (IL-6 and TNF-a), blood ammonia and Glx were measured in both groups and compared using independent t-test. Correlations between cytokines, blood ammonia, brain Glx ratio and DTI derived metrics for CE were assessed using Pearson's correlation coefficient. Results: Levels of Pro-inflammatory cytokines, blood ammonia and brain Glx were significantly increased in ACLF patients as compared to controls (p < 0.001). Significant positive correlation was present between cytokines and Glx ((r = 0.667, p = 0.003) for TNF-a and (r = 0.502, p = 0.04) for IL-6) as well as with spectroscopy voxel (SV) derived CS ((r = 0.578, p = 0.015) for TNF-a and (r = 0.681, p = 0.003) for IL-6), while a negative correlation was noted with SV derived MD ((r = −0.506, p = 0.038) for TNF-a and (r = −0.619, p = 0.008) for IL-6). These cytokines also had positive and negative correlations with CS and MD respectively, in various specific brain regions. Conclusions: Pro-inflammatory cytokines are elevated and correlate with CE metrics and brain Glx ratio in ACLF patients suggesting a role for them in the pathogenesis of CE in ACLF patients.