Cytokines Genotype‐Phenotype Correlation in Nonalcoholic Steatohepatitis

Abstract

NASH consists in lipid accumulation in hepatocytes that trigger oxidative stress, secretion of proinflammatory cytokines leading to steatohepatitis (NASH). The study aimed to investigate the levels of proinflammatory (TNF-α and IL-6) along with anti-inflammatory cytokine IL-10 in patients with NASH and to correlate the cytokines' level with their polymorphism. Sixty-six patients with NASH and 30 healthy volunteers were included in the study. The plasmatic level of IL-6, IL-10, and TNF-α were determined by ELISA. IL-10 -1082 G/A, IL-6 -174 G/C, and TNF-α -308 G/A polymorphisms were determined using the PCR-RFLP technique. IL-6, TNF-α, and CRP levels were significantly higher in patients with NASH. There was a positive correlation between proinflammatory cytokines and a negative correlation between IL-10 and proinflammatory markers. The G allele and GG genotype of IL-6 -174 G/C polymorphism were more frequently noticed in NASH patients. Regarding IL-10 -1082 G/A polymorphism, the AA genotype was correlated with NASH and with a low plasmatic level of IL-10. The A allele in position 308 of the TNF-α gene was associated with high level of cytokine. In conclusion, there was an imbalance between pro- and anti-inflammatory cytokines in NASH patients. IL-10 -1082 G/A and TNF-α -308 G/A genotypes were correlated with the plasmatic levels of cytokines.

Paraoxonase-1 Serum Concentration and PON1 Gene Polymorphisms: Relationship with Non-Alcoholic Fatty Liver Disease

“…These are factors which are extremely difficult to evaluate during clinical studies. Also, we have previously reinforced that patients with NAFLD/NASH have a high plasmatic level of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), so a potential cytokines imbalance (not evaluated in the present study) could interfere also with the serum concentration of PON1 [35].…”

A 3D human liver model of nonalcoholic steatohepatitis

“…Thus, the human 3D liver co-culture model displays steatosis and an activation of HSC leading to fibrosis, which are two main characteristics of NAFL/NASH. This model is able to respond to the inflammatory environment and to enhance the expression of proinflammatory cytokines like IL-6, as described in the literature (Bocsan et al, 2017, Rabelo et al, 2010. Several studies associated an increased CCL2 chemokine with steatohepatitis in chronic hepatic injury through an enhancement of pro-inflammatory monocyte/macrophage influx in the liver (Baeck et al, 2012, Tosello-Trampont et al, 2012, Narayanan et al, 2016, Krenkel and Tacke, 2017.…”

The cytokeratin 18, adiponectin and leptin levels in patients with non-alcoholic steatohepatitis and coronary heart disease

“…The high prevalence of non-alcoholic fatty liver disease (NAFLD) in the world requires the development of new non-invasive methods of diagnosis [1][2][3][4][5] . Although the disease is still histologically determined by means of a liver biopsy, this is not a practical tool for a mass screening 6 .…”

“…This peptide is detected in the blood even before the morphological signs of apoptosis occur. This allows to use CK-18 as a non-invasive biomarker of non-alcoholic steatohepatitis (NASH) [1][2][3][8][9][10][11] .…”