Immune response towards lipid peroxidation products as a predictor of progression of non-alcoholic fatty liver disease to advanced fibrosis

Aims: Factors responsible for the progression of non-alcoholic fatty liver disease (NAFLD) to more severe liver injury are poorly understood. In the present study, we investigated the association between immune reactions triggered by oxidative stress and stage of NAFLD. Methods: Titres of IgG agains...

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Veröffentlicht in:	Gut Jg. 54; H. 7; S. 987 - 993
Hauptverfasser:	Albano, E, Mottaran, E, Vidali, M, Reale, E, Saksena, S, Occhino, G, Burt, A D, Day, C P
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.07.2005 BMJ BMJ Publishing Group LTD Copyright 2005 by Gut
Schlagworte:	4-dihydropyridine-3 4-HNE 4-hydroxynonenal 4-methyl-1 5-dicarbaldehyde AAHP-HSA Adult Aged arachidonic acid hydroperoxide adduct with human serum albumin aspartate aminotransferase/alanine aminotransferase AST/ALT Autoantibodies - blood Biological and medical sciences Biomarkers - blood BMI body mass index Diabetes. Impaired glucose tolerance Disease Progression ELISA Endocrine pancreas. Apud cells (diseases) Endocrinopathies enzyme linked immunoabsorbent assay Etiopathogenesis. Screening. Investigations. Target tissue resistance Fatty Liver - complications Fatty Liver - immunology Female Gastroenterology. Liver. Pancreas. Abdomen HSA HSC human hepatic stellate cells human serum albumin Humans immune mechanisms Immunoglobulin G - blood Laboratories Lipid Peroxidation - immunology Liver cirrhosis Liver Cirrhosis - etiology Liver Cirrhosis - immunology Liver Disease liver fibrosis Liver. Biliary tract. Portal circulation. Exocrine pancreas Logistic Models Male Malondialdehyde - immunology malondialdehyde adduct with human serum albumin MDA-HSA MDD Medical sciences Metabolic diseases Middle Aged NAFLD NASH non-alcoholic fatty liver disease non-alcoholic steatohepatitis Obesity Other diseases. Semiology Ox-CL oxidative stress Oxidative Stress - immunology oxidised cardiolipin PBS phosphate buffered saline Rodents Serum Albumin - immunology steatosis Studies Womens health Endocrinopathy Type 2 diabetes Obesity Prognosis Immune response Nutrition disorder Hepatic disease Metabolic diseases Lipids Product Arachidonic acid Stress Cirrhosis Non alcoholic steatohepatitis Fibrosis Gastroenterology Digestive diseases Evolution Predictive factor Nutritional status Peroxidation
ISSN:	0017-5749, 1468-3288, 1458-3288
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Zusammenfassung:	Aims: Factors responsible for the progression of non-alcoholic fatty liver disease (NAFLD) to more severe liver injury are poorly understood. In the present study, we investigated the association between immune reactions triggered by oxidative stress and stage of NAFLD. Methods: Titres of IgG against human serum albumin adducted with malondialdehyde (MDA-HSA) or arachidonic acid hydroperoxide (AAHP) and against oxidised cardiolipin (Ox-CL) were measured in 167 NAFLD patients with steatosis only (n = 79), steatohepatitis (n = 74), or steatosis plus cirrhosis (n = 14), and in 59 age and sex matched controls. Results: Circulating IgG against lipid peroxidation products was significantly higher (p<0.001) in NAFLD patients than in controls. Oxidative stress dependent immune responses were not associated with obesity, type 2 diabetes, or with serum cholesterol, ferritin, or aminotransferase levels. Titres of lipid peroxidation related antibodies were also independent of the extent of steatosis and were similarly distributed in patients with and without necroinflammation. In contrast, the same antibodies were significantly increased in patients with advanced fibrosis or cirrhosis. Logistic regression analysis confirmed that anti-MDA antibodies were independently associated with progression of NALFD and that NAFLD patients with titres of anti-MDA-HSA antibodies above the control threshold value had a threefold (relative risk 2.82 (95% confidence interval 1.35–5.90); p = 0.007) higher risk of having advanced fibrosis/cirrhosis than patients whose antibody titres were within the control range. Conclusions: These results indicate that the presence of immune reactions triggered by oxidative stress can be an independent predictor of progression of NAFLD to advanced fibrosis.
Bibliographie:	href:gutjnl-54-987.pdf ark:/67375/NVC-HDPT3TXT-7 local:0540987 istex:AB9C3243EA8A4CD3480D785FB88B48FCCF8E5906 PMID:15951547 Correspondence to:  Professor E Albano  Department of Medical Science, University “Amedeo Avogadro” of East Piedmont, Via Solaroli 17, 28100 Novara, Italy; albano@med.unipmn.it ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conflict of interest: None declared. Correspondence to: Professor E Albano Department of Medical Science, University “Amedeo Avogadro” of East Piedmont, Via Solaroli 17, 28100 Novara, Italy; albano@med.unipmn.it
ISSN:	0017-5749 1468-3288 1458-3288
DOI:	10.1136/gut.2004.057968