Characterization of Cerebral Edema in Acute-on-Chronic Liver Failure

J Clin Exp Hepatol. 2017 Sep;7(3):190-197. doi: 10.1016/j.jceh.2017.04.001. Epub 2017 Apr 8.


Background and aims: The nature of cerebral edema in acute-on-chronic liver failure (ACLF) is not well studied. We aimed to characterize cerebral edema in ACLF using magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI).

Methods: Forty-six patients with cirrhosis and acute decompensation were included. Patients were divided into groups A (no cerebral failure, n = 39) and B (cerebral failure, n = 7). Group A was subdivided into no-ACLF (n = 11), grade 1 (n = 10), grade 2 (n = 9) and grade 3 (n = 9) ACLF as per CANONIC study. MRI brain and plasma TNF-alpha, IL-1beta and IL-6 were measured at baseline and 7-10 days after admission. Ten age- and sex-matched healthy controls were also included.

Results: Mean diffusivity (MD) values, an MRI marker of water content, progressively increased from controls to no-ACLF to ACLF grade 1, 2 and 3 in group A in frontal white matter (FWM) and basal ganglia (P < 0.0001). MD values improved only in survivors on follow-up. MD values correlated with IL-6 levels at baseline. On multivariate analysis MELD score ≥28 and MD values (>8 × 10-9 M2/s) in FWM were independent predictors of 90-day mortality. There was no significant difference in clinical and MRI parameters between group A and B.

Conclusion: Cerebral edema increases with severity of ACLF. Correlation between MD values and IL-6 levels suggests pathogenic role of inflammation in cerebral edema. Patients with grade 3 ACLF have cerebral edema irrespective of presence of clinically evident cerebral failure. MELD score and cerebral edema have prognostic significance in ACLF.

Keywords: ACLF, acute-on-chronic liver failure; AIH, autoimmune hepatitis; ALIC, anterior limb of internal capsule; APASL, Asian pacific association for study of liver diseases; AUROC, area under receiver operating characteristic; BBB, blood–brain barrier; BG, basal ganglia; CANONIC, chronic liver failure (CLIF) acute-on-chronic liver failure in cirrhosis; CI, confidence interval; CLIF-SOFA, chronic liver failure-sequential organ failure assessment; CTP, Child–Turcott–Pugh; DTI, diffusion tensor imaging; FA, fractional anisotropy; FLAIR, fluid attenuation inversion recovery; FWM, frontal white matter; HBV, hepatitis B virus; HE, hepatic encephalopathy; IC, internal capsule; IL-1 beta, interleukin 1 beta; IL-6, interleukin 6; MD, mean diffusivity; MELD, model for end-stage liver disease; MRI, magnetic resonance imaging; MTR, magnetization transfer ratio; PLIC, posterior limb of internal capsule; PWM, parietal white matter; ROI, regions of interest; SIRS, systemic inflammatory response syndrome; T1W, T1 weighted; T2W, T2 weighted; TE, echo-time; TNF-alpha, tumor necrosis factor-alpha; TR, repetition time; acute-on-chronic liver failure; cerebral edema; diffusion tensor imaging; magnetic resonance imaging.