Background: Acetaminophen (APAP) - induced Acute Liver Failure (ALF) is associated with significant morbidity and mortality related to cerebral edema (CE) and intracranial hypertension (ICH). Brain type fatty acid binding protein (FABP7) is a small (15 kDa) cytoplasmic protein abundantly expressed in astrocytes where there is active fatty acid metabolism. FABP7 levels have not been previously reported in ALF patients at high risk of CE/ICH. Aims: One: To determine whether serum FABP7 early (day 1) or late (day 3-5) levels are associated with 21-day mortality in APAP-ALF patients in the absence of liver transplant. Two: To determine whether serum FABP7 levels at serial time points are associated with the presence of ICH/CE Methods: Nested case control study 198 APAP-ALF patients (99 survivors, 99 non-survivors) from the US Acute Liver Failure Study Group (ALFSG) registry. Patient samples were analyzed for FABP1 using solidphase enzyme-linked immunosorbent assay (ELISA) and assessed with clinical data. In a second analysis where data were available, patients were stratified based on the presence of ICH/CE (n=46) or absence (n=104) based on death summaries or clinical data (ICP monitor, computed tomography). Multivariable logistic regression was used to determine independent associations with 21-day mortality (n=198) and development of ICH/CE (n=150) Results: APAP-ALF survivors had significantly lower serum FABP7 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 nonsurvivors (Figure 1). However using multivariable logistic regression, a significant association between 21- day mortality and increased serum FABP7 early (Log FABP7 Odds Ratio (OR) 1.16, P=0.32) and late (Log FABP7 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. A significant difference in FABP7 levels between patients with or without ICH/CE 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. FABP7 was not significantly associated with the development of ICH/CE after adjusting for significant covariates (Early OR 1.0, p=0.65; Late OR 1.0, p=0.57 see Table 1). Summary: Brain type FABP (FABP7) levels were elevated in APAP-ALF patients with serum significantly higher serum levels at early and late time points in APAP-ALF non-survivors. However, significant differences in FABP7 levels by 21-day mortality were not ascertained after adjusting for significant covariates reflecting severity of illness (MELD, vasopressor dependence). FABP7 did not discriminate between the APAP-ALF patients with and without ICH/CE. Conclusions: This suggests that while all APAP-ALF patients have some evidence of astrocyte inflammation and increased permeability in the blood brain barrier, FABP7 appears to not discriminate between patients who did and did not have significant intracranial complications of APAP-ALF. Disclosure: The study was sponsored by NIH grant U-01 58369 (from NIDDK), TL1 001451 (from NCATS), and a grant from the University of Alberta Hospital Foundation (UHF).
