The association between FABP7 serum levels with survival and neurological complications in acetaminophen-induced acute liver failure: a nested case-control study

Constantine J Karvellas; Jaime L Speiser; Mélanie Tremblay; William M Lee; Christopher F Rose; US Acute Liver Failure Study Group

doi:10.1186/s13613-017-0323-0

The association between FABP7 serum levels with survival and neurological complications in acetaminophen-induced acute liver failure: a nested case-control study

Ann Intensive Care. 2017 Oct 5;7(1):99. doi: 10.1186/s13613-017-0323-0.

Authors

Constantine J Karvellas¹, Jaime L Speiser², Mélanie Tremblay³, William M Lee⁴, Christopher F Rose³; US Acute Liver Failure Study Group

Affiliations

¹ Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine, University of Alberta, 1-40 Zeidler Ledcor Building, Edmonton, AB, T6G-2X8, Canada. dean.karvellas@ualberta.ca.
² Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
³ Hepato-Neuro Laboratory, CRCHUM, Université de Montréal, Montreal, Canada.
⁴ Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Abstract

Background: Acetaminophen (APAP)-induced acute liver failure (ALF) is associated with significant mortality due to intracranial hypertension (ICH), a result of cerebral edema (CE) and astrocyte swelling. Brain-type fatty acid-binding protein (FABP7) is a small (15 kDa) cytoplasmic protein abundantly expressed in astrocytes. The aim of this study was to determine whether serum FABP7 levels early (day 1) or late (days 3-5) level were associated with 21-day mortality and/or the presence of ICH/CE in APAP-ALF patients.

Methods: Serum samples from 198 APAP-ALF patients (nested case-control study with 99 survivors and 99 non-survivors) were analyzed by ELISA methods and assessed with clinical data from the US Acute Liver Failure Study Group (ALFSG) Registry (1998-2014).

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 non-survivors. However, 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). Areas under the receiver-operating curve for early and late multivariable models were 0.760 and 0.892, respectively. In a second analysis, patients were grouped based on the presence (n = 46) or absence (n = 104) of ICH/CE. 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.

Conclusion: Serum FABP7 levels were significantly elevated at early and late time points in APAP-ALF non-survivors compared to survivors. However, significant differences in FABP7 levels by 21-day mortality were not ascertained after adjusting for significant covariates (reflecting severity of illness). Our study suggests that FABP7 may not discriminate between patients with or without intracranial complications.

Keywords: ALFSG index; Liver-type fatty acid-binding protein; Multiorgan failure; Prognosis.