The association between Brain Fatty Acid Binding protein serum levels with survival and intracranial hypertension in acetaminophen-induced acute liver failure patients: a case control study.
CCCF ePoster library. Speiser J. Nov 1, 2016; 150936; 57 Disclosure(s): None
Ms. Jaime Lynn Speiser
Ms. Jaime Lynn  Speiser
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Topic: Basic or Translational Science

The association between Brain Fatty Acid Binding protein serum levels with survival and intracranial hypertension in acetaminophen-induced acute liver failure patients: a case control study.


Karvellas, Constantine J1; Speiser, Jaime L2; Tremblay, Melanie3; Lee, William M.4; Leslie, Elaine M.5; Rose, Christopher F.3; for the US Acute Liver Failure Study Group

  1. Divisions of Hepatology and Critical Care Medicine, University of Alberta, Edmonton, Canada.
  2. Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
  3. Hepato-Neuro Laboratory, CRCHUM, Université de Montréal, Montréal, Canada.
  4. Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
  5. Department of Physiology, University of Alberta, Edmonton, Canada.

Grant acknowledgements:
Financial support: The study was sponsored by NIH grant U-01 58369 (from NIDDK) and a grant from the University of Alberta Hospital Foundation (UHF).

Abstract:

Background: Background: Acetaminophen (APAP) - induced Acute Liver Failure (ALF) is associated with significant morbidity and mortality related to cerebral edema (CE) and intracranial hypertension (ICH). Determination of ICH/CE often requires invasive neuromonitoring which carries significant risk (bleeding).  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 (1,2). B-FABP levels have not been previously reported in ALF patients at high risk of CE/ICH.

Aim:To determine whether serum Brain-type Fatty Acid Binding Protein (B-FABP) early (day 1) or late (day 3-5) levels were associated with 21-day mortality and/or the presence of ICH/CE in APAP-ALF patients in the absence of liver transplant. 

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).

Results: APAP-ALF survivors had significantly lower serum B-FABP levels early (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 (Figure 1). 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/CE (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/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.

Summary: Brain FABP levels were elevated in APAP-ALF patients with significantly higher serum levels at early and late time points in APAP-ALF non-survivors. However, significant differences in B-FABP levels by 21-day mortality were not ascertained after adjusting for significant covariates reflecting severity of illness (MELD, vasopressor dependence). No differences in the B-FABP levels were detected for APAP-ALF patients with and without evidence of 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, B-FABP appears to not discriminate between patients who did and did not have significant intracranial complications of APAP-ALF.


Figure Legend
Figure 1. Box and Whisker Plot of early and late time points for: a) healthy controls; and APAP-ALF b) non-survivors (early) c) survivors (early) d) non-survivors (late) and e) survivors (late). Differences at early (p=0.0002) and late (p< 0.0001) between APAP-ALF survivors and non-survivors were significant.


References:

[1]      Pelsers MM, Glatz JF. Detection of brain injury by fatty acid-binding proteins. Clinical chemistry and laboratory medicine : CCLM / FESCC 2005;43:802-809.

[2]      Bass NM, Barker ME, Manning JA, Jones AL, Ockner RK. Acinar heterogeneity of fatty acid binding protein expression in the livers of male, female and clofibrate-treated rats. Hepatology 1989;9:12-21.



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