Adipocyte Fatty Acid-Binding Protein As a Predictor of Outcome in Alcohol-induced Acute-On-Chronic Liver Failure

Background: Alcohol is the leading cause of acute-on-chronic liver failure (ACLF). Several severity scores predict the outcome of ACLF. However, there is a lack of simple biomarkers in predicting the outcome of these sick patients. Fatty acid-binding proteins (FABPs) are small cytosolic proteins that play a major role in lipid metabolism, energy homeostasis, and inflammation, but, have not been investigated in alcohol-induced ACLF (A-ACLF).

Objectives: The primary objective was to assess the correlation between serum adipocyte-FABP (A-FABP) and liver-FABP (L-FABP) levels on mortality at day 90. Secondary objectives were to compare the levels between controls and A-ACLF, correlate L-FABP, and A-FABP levels on the development of organ failure/sepsis at day 90.

Methods: In this prospective observational pilot study, we included patients with A-ACLF and age-matched healthy controls. FABP's were analyzed by enzyme-linked immunosorbent assay method. The patients were followed up for 90 days.

Results: Twenty-five patients with A-ACLF (mean age: 40years; mean model for end-stage liver disease NA: 29.8; median Modified Maddrey's discriminant function [mDF]: 95) and 12 controls (mean age: 36.83yrs) were included in the study. A-FABP and L-FABP levels were significantly high in patients with A-ACLF than controls. Forty-four percent of patients with A-ACLF developed sepsis, 48% developed organ failure, and 44% expired by day 90. On multivariate Cox regression analysis, A-FABP (hazard ratio [HR]: 1.27 1.08-1.5; = 0.003), Asian Pacific Association for the Study of Liver ACLF research consortium score HR 3.31.15-9.54; = 0.02, L-FABP HR 0.69 0.52-0.91; = 0.009 and serum protein levels HR 0.03 0.003-0.36; = 0.005 predicted mortality. A-FABP 1.17 1.07-1.29; = 0.001, and serum bilirubin 1.05 0.99-1.12; = 0.06 predicted development of organ failure and only mDF HR 1.04 1.01-1.07; = 0.009 predicted the development of sepsis on multivariate analysis. Fifteen patients received steroid therapy, of which 13.34% were nonresponders.

Conclusions: In a selected group of patients with A-ACLF, A-FABP is highly sensitive at predicting mortality and outcome. If validated in a large, diverse sample, A-FABP can be used as a simple biomarker for prognostication in A-ACLF.