Abstract
BackgroundHaemodynamic impairment, inflammatory mediators and glucose metabolism disturbances have been implicated in the pathogenesis of Non-Alcoholic Fatty Liver Disease (NAFLD).AimTo investigate the cytokine profile in NAFLD patients in peripheral (P) and hepatic venous (HV) blood and to compare with histology, haemodynamic and metabolic parameters.Methods40 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.ResultsA 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).ConclusionsA 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.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is characterized by the presence of hepatic steatosis, in the absence of primary causes of hepatic fat accumulation
The hepatic venous (HV)-M1/M2 ratio positively correlated with fasting insulin and Hepatic Venous Pressure Gradient (r = 0.47, p = 0.003)
A proinflammatory cytokine state is associated with more disturbed metabolic, histological, and haemodynamic features in Non-Alcoholic Fatty Liver Disease (NAFLD) obese patients
Summary
Non-alcoholic fatty liver disease (NAFLD) is characterized by the presence of hepatic steatosis, in the absence of primary causes of hepatic fat accumulation. The estimated prevalence of NAFLD is 25–30% in Europe [1]. The severity of the disease can range from steatosis (Nonalcoholic fatty liver, NAFL) to Non-alcoholic Steatohepatitis (NASH), which can be accompanied by increasing grades of fibrosis. NAFLD is associated with liver-related morbidity and mortality, and with an increased risk of developing cardiovascular disease, type 2 diabetes mellitus (DM) and the metabolic syndrome. NAFLD is considered to be the hepatic component of the metabolic syndrome, as insulin resistance constitutes a common pathophysiological mechanism [4]. Haemodynamic impairment, inflammatory mediators and glucose metabolism disturbances have been implicated in the pathogenesis of Non-Alcoholic Fatty Liver Disease (NAFLD)
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