Background: Retinol binding protein 4 (RBP-4), a 21 kilodalton plasma protein, is secreted from the liver and adipose tissue, and is known to transport retinol in the blood. RBP-4 levels have an inverse relationship with disease progression and decompensation. This study evaluates the role of RBP-4 on assessing the severity of decompensated liver disease Methods: 85 patients (n=85) (age=49.6±11.4, mean±SD) with moderate to -severe liver disease (mean MELD of 18) were recruited into three groups: Group AChronic liver disease with cirrhosis (n=30):20/30 HCV (67%) 8/30 HBV (27%) 2/30 Misc (6.6%) with mean MELD of 22; Group Bnon-cirrhotic (n=30) 13/20 HCV (43%), 4/20 HBV (13.3%), 5/30 Alcoholics (17%), and 5/30 misc (17%) with mean MELD of <10 Group Ccontrols (n=25) with MELD <10, Liver biopsy, insulin resistance (HOMA-score), MELD score, adiponectin, Leptin and serum RBP-4 (ELISA), APRI, Hyaluronic acid, and Hepascore for liver fibrosis were analyzed Results: There was a significant difference in RBP-4 across the cirrhotic, non-cirrhotic, and control groups (F(2, 82)=47.9, p<0.001; one-way ANOVA). Posthoc Bonferroni tests over controls (n=25, 4.21+/1.60; mean+/-SD). RBP4 is significantly decreased in Cirrhotics (p<0.001; n=30, 1.46+/0.51) over the non-Cirrhotics (p=0.015; n=30, 3.37+/0.97) and controls. Cirrhotics also had decreases in HOMA (1.09±0.09 vs. 1.51±0.60; p=0.001, Student's t-test),adiponectin (0.93±0.40 vs. 1.26±0.53; p=0.01), but with an increase in TNFalpha (11.23±3.81 vs. 3.72±3.37; p<0.001) compared to the non-cirrhotic patients. Leptin (8.20±3.23 vs. 10.93±9.44; p=0.14) and hepatic steatometry (BURNT score<4)-(0.73±0.83 vs. 1.10±1.21; p=0.19 showed no difference. RBP 4 has no relevant correlations with TNFalpha (r=-0.62, p<0.001), leptin (r=0.12, p=0.38) and hepatic steatometry (BURNT score<4)(r=0.12, p=0.41). RBP-4 correlated negatively with MELD score (r=-0.57, p=0.001) Conclusions: This pilot study proposed that RBP-4 has a role as a biomarker for endstage liver disease, with an independent, inverse relationship with severity of fibrosis, hepatic decompensation, MELD score, and complications of liver failure. There is a positive correlation with insulin resistance, metabolic syndrome, and Adipokines, but not with hepatic steatometry. A larger prospective clinical trial needs to be conducted to validate the unique role of RBP-4 in fibrosis and decompensated liver disease.