Introduction: A growing body of literature suggests that myokines, especially those associated with AMPK mediated fatty acid oxidation may play important roles in the development of non-alcoholic fatty liver disease (NAFLD). Aim: The aim of this pilot study is to explore circulating myokines in the context of two chronic liver diseases, chronic hepatitis-C viral infection (CH-C) and NAFLD. Methods: Serum, self reports of usual activity (Human Activity Profile (HAP AAS), and clinical, demographic, and laboratory data were collected from 87 subjects, including 23 subjects with no liver related diagnosis (Control 1), 36 patients positive for CH-C (Control 2), and 28 on the NAFLD spectrum (from simple steatosis to steatohepatitis). Circulating myokines (Apelin, Fractalkine, BDNF, Erythropoeitin, Osteonectin, LIF, IL-15, Myostatin, FABP-3, Irisin, FSTL-1, Oncostatin, IL-6, FGF, Osteocrin) were measured in serum by Human Magnetic Bead Panel (Millipore). Circulating myokine concentrations were analyzed by diagnostic group by Mann-Whitney U-Test and compared to relevant factors by Pearson correlation analysis. Results: Although circulating BDNF, FSTL1, and Oncostatin were significantly decreased in NAFLD patients compared to controls (22559pg/ml vs 14470pg/ml, P=0.0001, 100.7pg/ml vs 67.4pg/ml, P=0.01, and 166pg/ml vs 70.1pg/ml, P=0.02, respectively), only Oncostatin also showed differential expression between NAFLD and CH-C patients (CH-C=93.6pg/ml, P=0.05). However, pairwise comparison of circulating myokines from NAFLD and CH-C patients also revealed differential concentrations of Fractalkine (CH-C=29.25pg/ml, NAFLD=28pg/ml, P=0.006) and Erythropoeitin (CH-C=28.5pg/ml, NAFLD=27pg/ml, P=0.01). Both oncostatin and Fractalkine show modest but significant negative correlations with circulating triglycerides (TABLE). Irisin positively correlated with lean mass. BDNF, correlates positively with HAP AAS, but negatively with BMI, and AST. Conclusion: In addition to metabolic abnormalities associated with NAFLD and to a lesser degree CH-C, these data suggest associations for specific myokines such as Oncostatin, or Fractalkine. These included an ability to distinguish between NAFLD and CH-C with elevated triglycerides. The combination of high lean mass, low BMI, age and fatigue scores significantly correlates with BDNF. This preliminary observation may link BDNF to factors pertaining to exercise tolerance. Further study is required to elucidate the nature of these roles