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Lipid peroxidation in hepatic steatosis in humans is associated with hepatic fibrosis and occurs predominately in acinar zone 3
Author(s) -
Macdonald Graeme A,
Bridle Kim R,
Ward Patrick J,
Walker Neal I,
Houglum Karl,
George D Keith,
Smith Jeffery L,
Powell Lawrie W,
Crawford Darrell Hg,
Ramm Grant A
Publication year - 2001
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1046/j.1440-1746.2001.02445.x
Subject(s) - steatosis , lipid peroxidation , medicine , endocrinology , fibrosis , fatty liver , hepatic fibrosis , hepatic stellate cell , steatohepatitis , chemistry , pathology , oxidative stress , disease
Background and Aims: Hepatic steatosis has been shown to be associated with lipid peroxidation and hepatic fibrosis in a variety of liver diseases including non‐alcoholic fatty liver disease. However, the lobular distribution of lipid peroxidation associated with hepatic steatosis, and the influence of hepatic iron stores on this are unknown. The aim of this study was to assess the distribution of lipid peroxidation in association with these factors, and the relationship of this to the fibrogenic cascade. Methods: Liver biopsies from 39 patients with varying degrees of hepatic steatosis were assessed for evidence of lipid peroxidation (malondialdehyde adducts), hepatic iron, inflammation, fibrosis, hepatic stellate cell activation (α‐smooth muscle actin and TGF‐β expression) and collagen type I synthesis (procollagen α 1 (I) mRNA). Results: Lipid peroxidation occurred in and adjacent to fat‐laden hepatocytes and was maximal in acinar zone 3. Fibrosis was associated with steatosis ( P < 0.04), lipid peroxidation ( P < 0.05) and hepatic iron stores ( P < 0.02). Multivariate logistic regression analysis confirmed the association between steatosis and lipid peroxidation within zone 3 hepatocytes ( P < 0.05), while for hepatic iron, lipid peroxidation was seen within sinusoidal cells ( P < 0.05), particularly in zone 1 ( P < 0.02). Steatosis was also associated with acinar inflammation ( P < 0.005). α‐Smooth muscle actin expression was present in association with both lipid peroxidation and fibrosis. Although the effects of steatosis and iron on lipid peroxidation and fibrosis were additive, there was no evidence of a specific synergistic interaction between them. Conclusions: These observations support a model where steatosis exerts an effect on fibrosis through lipid peroxidation, particularly in zone 3 hepatocytes.