title: Peripheral and Hepatic Vein Cytokine Levels in Correlation with Non-Alcoholic Fatty Liver Disease (NAFLD)-Related Metabolic, Histological, and Haemodynamic Features.
abstract: BACKGROUND
  Haemodynamic impairment, inflammatory mediators and glucose metabolism disturbances have been implicated in the pathogenesis of Non-Alcoholic Fatty Liver Disease (NAFLD).
  
  
  OBJECTIVE
  To investigate the cytokine profile in NAFLD patients in peripheral (P) and hepatic venous (HV) blood and to compare with histology, haemodynamic and metabolic parameters.
  
  
  METHODS
  40 obese patients with an indication for a transjugular liver biopsy were enrolled. Besides an extended liver and metabolic work-up, interleukin (IL) 1B, IL4, IL6, IL10, IL23, tumour necrosis factor (TNF) α and interferon (INF) γ were measured in plasma obtained from P and HV blood by means of multiplex immunoassay. The T helper (Th)1/Th2, the macrophage M1/M2 and the IL10/IL17a ratios were calculated.
  
  
  RESULTS
  A decrease of the P-IL10/IL17-ratio and an increase of the P-M1/M2-ratio (p<0.05) were observed in NASH versus no-NASH patients. A P-M1/M2-ratio increase was detected also in patients with portal hypertension in comparison with patients without it (p<0.05). Moreover diabetic patients showed an increase of the P-Th1/Th2-ratio in comparison with non-diabetic ones (p<0.05). The P-M1/M2 ratio positively correlated with steatosis grade (r = 0.39, p = 0.02) and insulin (r = 0.47, p = 0.003). The HV-M1/M2 ratio positively correlated with fasting insulin and Hepatic Venous Pressure Gradient (r = 0.47, p = 0.003). IL6 correlated with the visceral fat amount (r = 0.36, p = 0.02). The P- and HV-IL10/IL17 ratios negatively correlated with fasting insulin (respectively r = -0.4, p = 0.005 and r = 0.4, p = 0.01).
  
  
  CONCLUSIONS
  A proinflammatory cytokine state is associated with more disturbed metabolic, histological, and haemodynamic features in NAFLD obese patients. An increase of the M1/M2 ratio and a decrease of the IL10/IL17 ratio play a key role in this process.
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari, Bari, Italy.|Department of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerp, Belgium.
authors.forename: Luisa
authors.initials: L
authors.lastname: Vonghia
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari, Bari, Italy.
authors.forename: Thea
authors.initials: T
authors.lastname: Magrone
authors.affiliation: Department of Endocrinology, Diabetes and Metabolic Diseases, University Hospital Antwerp, Antwerp, Belgium.|Laboratory of Experimental Medicine and Paediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Verrijken
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari, Bari, Italy.|Laboratory of Experimental Medicine and Paediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Michielsen
authors.affiliation: Department of Endocrinology, Diabetes and Metabolic Diseases, University Hospital Antwerp, Antwerp, Belgium.|Laboratory of Experimental Medicine and Paediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Van Gaal
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari, Bari, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Jirillo
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari, Bari, Italy.|Laboratory of Experimental Medicine and Paediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium.
authors.forename: Sven
authors.initials: S
authors.lastname: Francque
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D001706:Biopsy; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D005260:Female; D006439:Hemodynamics; D006503:Hepatic Veins / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism* / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators