Review article: role of oxidative stress in the progression of non-alcoholic steatosis.

The mechanisms responsible for the progression of nonalcoholic fatty liver disease (NAFLD) to more severe liver injury are still poorly understood. Data from animal models suggest that oxidative stress contributes to steatohepatitis and an increase of lipid peroxidation has been documented in human NAFLD. By measuring the titers of circulating antibodies against lipid peroxidation products as markers of oxidative stress we have observed that NAFLD patients have titers of these antibodies significantly higher than in controls.

Anti-phospholipid antibodies associated with alcoholic liver disease target oxidized phosphatidylserine on apoptotic cell plasma membranes.

Background/aims: Circulating anti-phospholipid antibodies (aPL) are often present in patients with alcoholic liver disease (ALD). The observations that defects in the disposal of apoptotic corpses leads to the development of aPL prompted us to investigate whether ALD-associated aPL might recognize antigens in apoptotic cells.

Methods: Apoptosis was induced in HuT-78 human T-lymphoma and HepG2 hepatoma cells by, respectively, FAS ligation with CH11 monoclonal antibodies or the incubation with ethanol (400 mmol/L).

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 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.

Use of molecular simulation for mapping conformational CYP2E1 epitopes.

The identification of the epitopes recognized by autoantibodies against cytochrome P450s (CYPs) associated with drug-induced hepatotoxicity is difficult because of their conformational nature. In the present investigation, we used a novel approach based on the analysis of the whole molecule antigenic capacity following single amino acid substitutions to identify the conformational epitopes on CYP2E1. A molecular model of CYP2E1 was generated based on the CYP2C5 crystal structure, and potential motifs for amino acid exchanges were selected by computer simulation in the surface of alpha helices and beta sheets.

Moderate alcohol consumption increases oxidative stress in patients with chronic hepatitis C.

The mechanisms by which alcohol consumption worsens the evolution of chronic hepatitis C (CHC) are poorly understood. We have investigated the possible interaction between hepatitis C virus (HCV) and ethanol in promoting oxidative stress. Circulating IgG against human serum albumin (HSA) adducted with malondialdehyde (MDA-HSA), 4-hydroxynonenal (HNE-HSA), or arachidonic acid hydroperoxide (AAHP-HSA) and against oxidized cardiolipin (Ox-CL) were evaluated as markers of oxidative stress in 145 CHC patients with different alcohol consumption, 20 HCV-free heavy drinkers (HD) without liver disease, and 50 healthy controls.