Investigation of the relationship between stage of liver disease and serum branched chain amino acids and fructose level in NAFLD patients

Objective: This study was aimed to investigate the relationship between serum levels of fructose and branched chain amino acids (BCAA) and liver disease stage in patients NAFLD. Materials and Methods: The face-to-face interviews were done with all the participants for the history of liver disease, comorbidities and drug treatments, and anthropometric measurements were also made. The electronic system records were reviewed for laboratory results, radiologic imaging and liver biopsy findings. MR-PDFF and MRE were done in all participants who didn't underwent liver MRI within last year. A nutrient consumption questionnaire was administered to 62 of the NAFLD patients. A 10 cc sample of blood and urine were taken for further analysies. The serum levels of fructose, BCAA and other metabolites were measured using the "Gase Chromotography-Mass Spectroscopy (GC-MS)". Results: One hundred thirty-two participants included in the study were evaluated in 4 groups; 27 controls, 63 steatohepatitis, 29 early fibrosis and 13 advanced fibrosis. Of the 105 NAFLD patients, 56 (53%) were female, and the median age was 49 (20-71) years. The median fructose intake of NAFLD patients was 29.6±19.6 g/day, and its contribution to total energy was 4.8%. There was no correlation between daily consumptions of fructose or BCAA and clinical or liver parameters. Patients with NAFLD had higher serum levels for fructose (11.0 vs. 14.7 µmol/ml; p=0.03), isoleucine (13.9 vs. 16.7 µmol/ml; p=0.01) and leucine (48.0 vs. 60.2 µmol/ml; p=0.008) than controls, but serum valine level was similar (16.3 vs. 17.4 µmol/ml; p=0.41). There were strong positive correlation between serum level of fructose and fasting blood glucose (r= 0,25; p <0,004), as well as serum levels of isoleucine and leucine and liver fat content on MR-PDFF (r=0,18; p=0,04 and R=0,18; p=0,039) and ALT (R=0,29; p <0.01 and r=0,19; p=0.03). In addition, 178 metabolites related to amino acids, lipids, energy metabolisms and gut flora have been identified. Serum levels of some of these metabolites differed between NAFLD patients and controls, but the NAFLD subgroups were similar for them. Conclusion: Serum fructose, isoleucine and leucine levels were higher in NAFLD patients than in controls. The results suggested that serum fructose levels may be a biomarker for insulin resistance, and serum isoleucine and leucine levels may be a biomarker for the development of hepatosteatosis and steatohepatitis. In addition, other metabolites having different serum levels in NAFLD patients than controls should be investigate for their diagnostic, theuropathic and prognostic significance through clinical and laboratory studies. Keywords: Non-alcoholic fatty liver disease, NASH, fructose, branched chain amino acids.