A22 LIVER TYPE FATTY ACID BINDING PROTEIN (FABP1) LEVELS IMPROVE PERFORMANCE OF PROGNOSTIC MODELS IN ACETAMINOPHEN INDUCED ACUTE LIVER FAILURE

Acetaminophen (APAP) - induced acute liver failure (ALF) is associated with significant mortality. To date, traditional prognostic scores (King’s College Criteria ~ KCC; Acute Liver Failure Study Group (ALFSG) prognostic index) lack discrimination in identifying patients with APAP-ALF who will die without liver transplant (LT), and those who will survive with medical management alone. Liver-type fatty acid binding protein (FABP1) is a 15 kDa cytoplasmic protein abundantly expressed in hepatocytes with potential prognostic value in APAP-ALF patients. Our aims were to a) Determine if elevated serum levels of FABP1 in APAP-ALF are significantly associated with 21-day mortality after adjusting for other significant covariates. b) Determine if the addition of FABP1 improves the performance of previously described prognostic models in APAP-ALF (KCC, ALFSG prognostic index). With serial serum samples (early; day 1 or late; day 3–5) from 198 APAP-ALF patients (99 survivors, 99 non-survivors), FABP1 was measured using solid-phase enzyme-linked immunosorbent assay. No patients in this analysis received LT. With clinical data from the prospectively collected ALFSG registry, model performance (early and late) for KCC, ALFSG index, FABP1, FABP1+KCC, and FABP1+ALFSG index were assessed using AUROC statistics. Comparisons of AUROC statistics between models (e.g. KCC vs. FABP1 + KCC) were made using the Delong method. APAP-ALF survivors had significantly lower serum FABP1 levels early (238.6 vs. 690.8 ng/ml, p <0.0001) and late (148.4 vs. 612.3 ng/ml, p <0.0001) compared with non-survivors (Figure 1). FABP1 > 350 ng/ml was associated with significantly higher risk of death at early (p=0.0004) and late (p<0.0001) time points. Increased serum FABP1 early (log FABP1 odds ratio (OR) 1.31, p=0.027) and late (log FABP1 OR 1.50, p =0.005) were associated with significantly increased 21-day mortality after adjusting for significant covariates (MELD, vasopressor use). Areas under the receiver-operating curve (AUROC) for early and late multivariable models were 0.778 and 0.907 respectively. AUROC of the King’s College Criteria (KCC) (Early: 0.552 alone, 0.711 with FABP1; Late: 0.604 alone, 0.797 with FABP1) and ALFSG prognostic index (Early: 0.686 alone, 0.766 with FABP1; Late: 0.711 alone, 0.815 with FABP1) significantly improved with the addition of FABP1 (p <0.002 for all, Delong). In patients with APAP-ALF, FABP1 showed good potential to discriminate survivors from non-survivors at multiple time-points and significantly improved models currently used in clinical practice. Validation of FABP1 as a clinical prediction tool in APAP-ALF merits further investigation. Figure 1: Serum levels of FABP1 (ng/ml) in healthy controls, non-survivors (early ~ admission), survivors (early), non-survivors (late ~ day 3–5), survivors (late). The study was sponsored by NIH grant U-01 58369 (from NIDDK) and a grant from the University of Alberta Hospital Foundation (UHF).

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