Differences in hepatic expression of iron, inflammation and stress-related genes in patients with nonalcoholic steatohepatitis
Journal Title: Annals of Hepatology - Year 2017, Vol 16, Issue 1
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. We have previously shown that hepatic reticuloendothelial system (RES) iron deposition is associated with an advanced degree of nonalcoholic steatohepatitis (NASH) in humans. In this study, we aimed to determine differentially expressed genes related to iron overload, inflammation and oxidative stress pathways, with the goal of identifying factors associated with NASH progression. Seventy five patients with NAFLD were evaluated for their biochemical parameters and their liver tissue analyzed for NASH histological characteristics. Gene expression analysis of pathways related to iron homeostasis, inflammation and oxidative stress was performed using real-time PCR. Gene expression was compared between subjects based on disease status and presence of hepatic iron staining. We observed increased gene expression of hepcidin (HAMP) (2.3 fold, p = 0.027), transmembrane serine proteinase 6 (TMPRSS6) (8.4 fold, p = 0.003), signal transducer and activator of transcription 3 (STAT3) (5.5 fold, p = 0.004), proinflammatory cytokines; IL-1? (2.7 fold, p = 0.046) and TNF-? (3.8 fold, p = 0.001) in patients with NASH. TMPRSS6, a negative regulator of HAMP, is overexpressed in patients with NASH and HIF1? (hypoxia inducible factor-1) is downregulated. NAFLD patients with hepatic iron deposition exhibited higher hepcidin expression (3.1 fold, p = 0.04) but lower expression of cytokines. In conclusion, we observed elevated hepatic HAMP expression in patients with NASH and in NAFLD patients who had hepatic iron deposition, while proinflammatory cytokines displayed elevated expression only in patients with NASH, suggesting a regulatory role for hepcidin in NAFL to NASH transition and in mitigatinginflammatory responses.
Authors and Affiliations
Akhila Vemulakonda, Priya Handa, Vicki Morgan-Stevenson, Bryan Maliken, James Nelson, Barjinder Dhillon, Rohit Gupta, Kelly Hennessey, Matthew Yeh, Kris Kowdley
Keywords
Related Articles
- EP ID EP207244
- DOI -
- Views 110
- Downloads 0
Lysophosphatidic acid and atotaxin in patients with cholestasis and pruritus: Fine biology, anticipated discern
Embolization of porto-systemic shunt as treatment for recurrent hepatic encephalopathy
Alcohol use among patients with HIV infection
Objective. To evaluate alcohol use in patients with HIV infection, assess ethnic and social associations, and describe outcomes. Material and methods. Design: cohort study. Setting: Academic HIV-Liver Clinic. Patients: 4...
Evaluation of liver diseases in Iranian patients with primary antibody deficiencies
Introduction. Patients with primary antibody deficiency (PAD) can complicate with liver disease. This study was performed in order to study the prevalence and causes of hepatobiliary diseases in Iranian patients with PAD...
Mean platelet volume is a useful indicator of systemic inflammation in cirrhotic patients with ascitic fluid infection