Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disorder worldwide. The aim of our study was to assess the role of bilirubin, and the heme oxygenase 1 (HMOX1) and bilirubin UDP-glucuronosyl transferase (UGT1A1) promoter gene variants, which are involved in bilirubin homeostasis, in the NAFLD development in adult patients. The study was performed on 84 patients with NAFLD and 103 age/sex-matched controls. Routine biochemistry, inflammatory markers, adipokines, and the fibrosis/steatohepatitis stage were determined in the NAFLD patients. The (GT)n/(TA)n dinucleotide variations in HMOX1/UGT1A1 gene promoters, respectively, were analyzed by fragment analysis. Compared to controls, serum bilirubin concentrations in NAFLD patients tended to be decreased, while the prevalence of phenotypic Gilbert syndrome was significantly low. Genetic variations in HMOX1 and UGT1A1 gene promoters did not differ between NAFLD patients and controls, and no relationship was found in the NAFLD patients between these gene variants and any of the laboratory or histological parameters. In conclusion, metabolism of bilirubin is dysregulated in NAFLD patients, most likely due to increased oxidative stress, since frequencies of the major functional variants in the HMOX1 or UGT1A1 gene promoters did not have any effect on development of NAFLD in adult patients.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is comprised of a spectrum of conditions from simple steatosis, non-alcoholic steatohepatitis (NASH), to liver cirrhosis—with a dramatic impact on population health [2]
The aim of the present study was to assess the role of bilirubin, and the heme oxygenase 1 (HMOX1) and UGT1A1 promoter gene variants, which are involved in bilirubin homeostasis, in the NAFLD development in adult patients
NASH suffered from more advanced fibrosis compared to those with simple steatosis
Summary
Non-alcoholic fatty liver disease (NAFLD) constitutes the hepatic manifestation of the metabolic syndrome, affecting a large proportion of the population worldwide [1]. NAFLD is comprised of a spectrum of conditions from simple steatosis, non-alcoholic steatohepatitis (NASH), to liver cirrhosis—with a dramatic impact on population health [2]. While simple steatosis is usually considered a benign condition, NASH is already a potentially progressive disease of the liver, which might develop into liver fibrosis and Antioxidants 2021, 10, 2000. The factors leading to the progression of liver disease in selected patients with NAFLD are not completely understood. The initial model considered the development of simple steatosis as a “first hit”, increasing the sensitivity of the liver to hepatocyte injury (leading to inflammation and fibrosis) by a “second hit” [4]. The factors acting as a “second hit” were considered to be increased oxidative stress, elevated cytokines (like TNF-α), and reactive oxygen species (ROS)-mediated lipid peroxidation [5]
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