Excess iron modulates endoplasmic reticulum stress-associated pathways in a mouse model of alcohol and high-fat diet-induced liver injury.

Endoplasmic reticulum (ER) stress is an important pathogenic mechanism for alcoholic (ALD) and nonalcoholic fatty liver disease (NAFLD). Iron overload is an important cofactor for liver injury in ALD and NAFLD, but its role in ER stress and associated stress signaling pathways is unclear. To investigate this, we developed a murine model of combined liver injury by co-feeding the mildly iron overloaded, the hemochromatosis gene-null (Hfe(-/)) mouse ad libitum with ethanol and a high-fat diet (HFD) for 8 weeks.

A corn oil-based diet protects against combined ethanol and iron-induced liver injury in a mouse model of hemochromatosis.

Background: Combined iron overload and alcohol may promote synergistic chronic liver injury and toxicity. The role of specific dietary fats in influencing the development of co-toxic alcoholic liver disease needs further evaluation and is investigated in this study.

Methods: Wild-type (WT) and the iron-loaded Hfe-null (Hfe(-/-) ) mice were fed chow (CC), a AIN-93G standard control (SC), or a corn oil-modified, AIN-93G-based (CO) diet with or without the addition of 20% ethanol (EtOH) in the drinking water for 8 weeks and assessed for liver injury.

Comparison of the diagnostic accuracy of measured and calculated free cortisol in acutely ill patients using the Coolens equation.

Objective: To investigate the agreement between two methods of measurement of plasma free cortisol in acutely ill patients; an indirect method using the Coolens equation, and direct measurement using high-performance liquid chromatography-tandem mass spectrometry, which is the gold standard.

Design, Participants And Setting: Prospective observational study among patients with septic shock in a tertiary intensive care unit and patients with liver failure attending a hospital outpatient clinic while awaiting transplantation. Paired values of free cortisol levels obtained from direct measurement and from calculation were analysed to provide estimates of bias and precision for the two methods.

The serum hepcidin:ferritin ratio is a potential biomarker for cirrhosis.

Background: Serum hepcidin concentration is potentially affected by inflammation and iron stores in chronic liver disease (CLD), but little is known about the relationship between hepcidin and the degree of hepatic fibrosis. We investigated the potential role of serum hepcidin as a biomarker of advanced liver disease.

Methods: Serum hepcidin was measured in 332 adults with CLD of varying aetiologies, 45 healthy and 50 non-liver disease patient controls.

Serial changes in plasma total cortisol, plasma free cortisol, and tissue cortisol activity in patients with septic shock: an observational study.

Published data on adrenocortical function in septic shock have enrolled patients at various stages of critical illness and predominantly used plasma total cortisol, with minimal information on serial changes. Moreover, plasma free cortisol and tissue corticosteroid activity may not be strongly associated; however, few published data exist. The aim of this prospective observational study was to investigate serial changes in plasma total and free cortisol and tissue cortisol activity in septic shock.

Altered lipid metabolism in Hfe-knockout mice promotes severe NAFLD and early fibrosis.

The HFE protein plays a crucial role in the control of cellular iron homeostasis. Steatosis is commonly observed in HFE-related iron-overload disorders, and current evidence suggests a causal link between iron and steatosis. Here, we investigated the potential contribution of HFE mutations to hepatic lipid metabolism and its role in the pathogenesis of nonalcoholic fatty liver disease.

Characterising adrenal function using directly measured plasma free cortisol in stable severe liver disease.

Background & Aims: Adrenal insufficiency (AI) has been reported in patients with advanced liver disease. Diagnosing AI is problematic owing to controversies in using total serum cortisol as a measure of adrenal function. No published data exist on directly measured plasma free cortisol (PFC) in patients with liver disease.

Use of mycophenolate mofetil in inflammatory bowel disease.

Aim: To assess the efficacy and safety of mycophenolate mofetil (MMF) prospectively in inflammatory bowel disease (IBD) patients intolerant or refractory to conventional medical therapy.

Methods: Crohn's disease (CD) or ulcerative colitis/IBD unclassified (UC/IBDU) patients intolerant or refractory to conventional medical therapy received MMF (500-2000 mg bid). Clinical response was assessed by the Harvey Bradshaw index (HBI) or colitis activity index (CAI) after 2, 6 and 12 mo of therapy, as were steroid usage and adverse effects.

Predicting iron overload in hyperferritinemia.

Background & Aims: Hyperferritinemia is a common abnormality. This study determined the prevalence of hepatic iron overload in subjects of northern European origin with hyperferritinemia.

Methods: Fifty-two consecutive subjects referred for evaluation of suspected iron overload (serum ferritin level >350 microg/L) were divided into 3 groups: group 1, increased transferrin saturation and no significant hemochromatosis gene product (HFE) mutations (N = 17); group 2, increased transferrin saturation and C282Y homozygosity or C282Y/H63D compound heterozygosity (N = 22); and group 3, normal transferrin saturation and no significant HFE mutations (N = 13).