Serum Cytokeratin-18 Is Associated with NOX2-Generated Oxidative Stress in Patients with Nonalcoholic Fatty Liver

Background & Aims. Hepatocyte apoptosis may play a role in progression of nonalcoholic fatty liver and oxidative stress seems one of the key mechanisms responsible for liver damage. The aim was to determine the association of oxidative stress with cytokeratin-18 M30 fragment levels, a marker of...

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Main Authors: M. Del Ben, L. Polimeni, F. Baratta, S. Bartimoccia, R. Carnevale, L. Loffredo, P. Pignatelli, F. Violi, F. Angelico
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:International Journal of Hepatology
Online Access:http://dx.doi.org/10.1155/2014/784985
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author M. Del Ben
L. Polimeni
F. Baratta
S. Bartimoccia
R. Carnevale
L. Loffredo
P. Pignatelli
F. Violi
F. Angelico
author_facet M. Del Ben
L. Polimeni
F. Baratta
S. Bartimoccia
R. Carnevale
L. Loffredo
P. Pignatelli
F. Violi
F. Angelico
author_sort M. Del Ben
collection DOAJ
description Background & Aims. Hepatocyte apoptosis may play a role in progression of nonalcoholic fatty liver and oxidative stress seems one of the key mechanisms responsible for liver damage. The aim was to determine the association of oxidative stress with cytokeratin-18 M30 fragment levels, a marker of hepatocyte apoptosis. Methods. Steatosis severity was defined according to Hamaguchi’s echographic criteria in 209 patients with nonalcoholic fatty liver. Serum cytokeratin-18, urinary 8-iso-prostaglandin F2α, soluble NOX2-derived peptide, and adiponectin were measured. Results. Serum cytokeratin-18 progressively increased with steatosis severity (from 169.5 (129.3/183.8) to 176 (140/190) and 180 (169.5/192.5) μIU/mL in mild, moderate, and severe steatosis, respectively; P<0.01). After stratification by cytokeratin-18 tertiles, a significant progression of body mass index, HOMA-IR, triglycerides, urinary 8-iso-PGF2α, soluble NOX2-derived peptide, and of the prevalence of diabetes and severe steatosis was found, while HDL-cholesterol and adiponectin progressively decreased. A positive correlation between cytokeratin-18 and body mass index, HOMA-IR, Hamaguchi’s score, urinary 8-iso-PGF2α, and soluble NOX2-derived peptide and a negative correlation between cytokeratin-18 and HDL-cholesterol and adiponectin were found. Body mass index, adiponectin, and soluble NOX2-derived peptide were independent predictors of serum cytokeratin-18 levels (adjusted R2=0.36). Conclusion. We support an association between oxidative stress and severity of liver damage in patients with nonalcoholic fatty liver.
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spelling doaj-art-3bfeca690fdc4ab99a2b9419cf4d5b342025-02-03T06:05:10ZengWileyInternational Journal of Hepatology2090-34482090-34562014-01-01201410.1155/2014/784985784985Serum Cytokeratin-18 Is Associated with NOX2-Generated Oxidative Stress in Patients with Nonalcoholic Fatty LiverM. Del Ben0L. Polimeni1F. Baratta2S. Bartimoccia3R. Carnevale4L. Loffredo5P. Pignatelli6F. Violi7F. Angelico8Department of Internal Medicine and Medical Specialities, Sapienza University, Rome, ItalyDepartment of Internal Medicine and Medical Specialities, Sapienza University, Rome, ItalyDepartment of Internal Medicine and Medical Specialities, Sapienza University, Rome, ItalyDepartment of Internal Medicine and Medical Specialities, Sapienza University, Rome, ItalyDepartment of Internal Medicine and Medical Specialities, Sapienza University, Rome, ItalyDepartment of Internal Medicine and Medical Specialities, Sapienza University, Rome, ItalyDepartment of Internal Medicine and Medical Specialities, Sapienza University, Rome, ItalyDepartment of Internal Medicine and Medical Specialities, Sapienza University, Rome, ItalyDepartment of Internal Medicine and Medical Specialities, Sapienza University, Rome, ItalyBackground & Aims. Hepatocyte apoptosis may play a role in progression of nonalcoholic fatty liver and oxidative stress seems one of the key mechanisms responsible for liver damage. The aim was to determine the association of oxidative stress with cytokeratin-18 M30 fragment levels, a marker of hepatocyte apoptosis. Methods. Steatosis severity was defined according to Hamaguchi’s echographic criteria in 209 patients with nonalcoholic fatty liver. Serum cytokeratin-18, urinary 8-iso-prostaglandin F2α, soluble NOX2-derived peptide, and adiponectin were measured. Results. Serum cytokeratin-18 progressively increased with steatosis severity (from 169.5 (129.3/183.8) to 176 (140/190) and 180 (169.5/192.5) μIU/mL in mild, moderate, and severe steatosis, respectively; P<0.01). After stratification by cytokeratin-18 tertiles, a significant progression of body mass index, HOMA-IR, triglycerides, urinary 8-iso-PGF2α, soluble NOX2-derived peptide, and of the prevalence of diabetes and severe steatosis was found, while HDL-cholesterol and adiponectin progressively decreased. A positive correlation between cytokeratin-18 and body mass index, HOMA-IR, Hamaguchi’s score, urinary 8-iso-PGF2α, and soluble NOX2-derived peptide and a negative correlation between cytokeratin-18 and HDL-cholesterol and adiponectin were found. Body mass index, adiponectin, and soluble NOX2-derived peptide were independent predictors of serum cytokeratin-18 levels (adjusted R2=0.36). Conclusion. We support an association between oxidative stress and severity of liver damage in patients with nonalcoholic fatty liver.http://dx.doi.org/10.1155/2014/784985
spellingShingle M. Del Ben
L. Polimeni
F. Baratta
S. Bartimoccia
R. Carnevale
L. Loffredo
P. Pignatelli
F. Violi
F. Angelico
Serum Cytokeratin-18 Is Associated with NOX2-Generated Oxidative Stress in Patients with Nonalcoholic Fatty Liver
International Journal of Hepatology
title Serum Cytokeratin-18 Is Associated with NOX2-Generated Oxidative Stress in Patients with Nonalcoholic Fatty Liver
title_full Serum Cytokeratin-18 Is Associated with NOX2-Generated Oxidative Stress in Patients with Nonalcoholic Fatty Liver
title_fullStr Serum Cytokeratin-18 Is Associated with NOX2-Generated Oxidative Stress in Patients with Nonalcoholic Fatty Liver
title_full_unstemmed Serum Cytokeratin-18 Is Associated with NOX2-Generated Oxidative Stress in Patients with Nonalcoholic Fatty Liver
title_short Serum Cytokeratin-18 Is Associated with NOX2-Generated Oxidative Stress in Patients with Nonalcoholic Fatty Liver
title_sort serum cytokeratin 18 is associated with nox2 generated oxidative stress in patients with nonalcoholic fatty liver
url http://dx.doi.org/10.1155/2014/784985
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