Learning Objectives: Acetaminophen (APAP) - induced Acute Liver Failure (ALF) is associated with significant mortality related to intracranial hypertension (ICH). Brain type fatty acid binding protein (B-FABP) is a small (15 kDa) cytoplasmic protein abundantly expressed in astrocytes where there is active fatty acid metabolism. B-FABP levels have not been previously reported in ALF patients at high risk of ICH. We aimed to determine whether serum B-FABP early (day 1) or late (day 3-5) levels were associated with 21-day mortality and/or the presence of ICH in APAP-ALF patients.
Methods: Serum samples from 198 APAP-ALF patients (99 survivors, 99 non-survivors) were analyzed by ELIZA methods and assessed with clinical data from the US Acute Liver Failure Study Group (ALFSG) Registry (1998-2013). No patients received transplant in this analysis.
Results: APAP-ALF survivors had significantly lower serum B-FABP levels on admission (147.9 vs. 316.5 ng/ml, P=0.0002) and late (87.3 vs. 286.2 ng/ml, P<0.0001) compared with non-survivors. However using multivariable logistic regression, a significant association between 21-day mortality and increased serum B-FABP early (Log B-FABP Odds Ratio (OR) 1.16, P=0.32) and late (Log L-FABP OR 1.34, P=0.21) was not detected after adjusting for significant covariates (MELD, vasopressor use). Area under the receiver operating curve for early and late multivariable models were 0.760 and 0.892 respectively. In a second analysis where data were available, patients were stratified based on the presence of ICH (n=46) or absence (n=104) based on death summaries or clinical data (ICP monitor, computed tomography). A significant difference in B-FABP levels between patients with or without ICH at early (259.7 vs. 228.2 ng/ml, P=0.61) and late (223.8 vs. 192.0 ng/ml, P=0.19) time points was not identified.
Conclusions: Serum B-FABP levels were significantly higher in APAP-ALF non-survivors but not after adjusting for covariates. While elevated B-FABP levels likely reflect astrocyte inflammation, B-FABP did not differentiate clinically between APAP-ALF patients with and without ICH.