Guideline Review: European Association for the Study of Liver (EASL) Clinical Practice Guidelines on Haemochromatosis.

The European Association for the Study of the Liver (EASL) has recently (June 2022) produced new clinical practice guidelines for the investigation and management of haemochromatosis, to replace the previous document published in 2010. Here, we provide an overview of the principal changes recommended for the investigation and management of haemochromatosis arising from these guidelines and highlight particular areas where evidence is lacking and where future focus on specific research would improve patient treatment and outcomes. The guideline provides several important new recommendations that will have a meaningful impact on patient management.

Recommended reference intervals for copper and zinc in serum using the US National Health and Nutrition Examination surveys (NHANES) data.

Background And Aims: In view of the wide variations in reference intervals (RIs) for copper and zinc concentrations in serum, this study was designed to derive appropriate RIs that could be routinely adopted in other laboratories, so allowing better interpretation of results. A secondary aim was to assess the effects of several variables on serum concentrations of copper and zinc.

Materials And Methods: Data from over 21,000 individuals were downloaded from four National Health and Nutrition Examination Surveys conducted by the US Centers for Disease Control and Prevention.

Gadolinium Concentrations in Biological Matrices From Patients Exposed to Gadolinium-Based Contrast Agents.

Objectives: There is increasing evidence that Gd may be retained within the skin, bones, and solid organs in patients with normal renal function after exposure to Gd-based contrast agents (GBCAs). Here we present clinical data from 19 patients who requested referral to our clinical toxicology service for assessment of potential "Gd toxicity."

Materials And Methods: Patients had undergone a median of 2 (interquartile range [IQR], 1-5) exposures to GBCAs and were reviewed at a median of 5 months (IQR, 2-8 months) after the last GBCA exposure.

Establishing Reference Intervals for Gadolinium Concentrations in Blood, Plasma, and Urine in Individuals Not Previously Exposed to Gadolinium-Based Contrast Agents.

Objectives: Over the recent years, there have been increasing concerns that exposure to gadolinium-based contrast agents (GBCAs) may be associated with retention of Gd within the skin, bones, and solid organs in patients with normal renal function, although the clinical implications of this deposition remain to be established. There are no published data available to guide the development of reference intervals for Gd concentrations in biological samples from healthy people. The aims of this study were to (1) determine whether healthy individuals who have not received GBCAs have detectable concentrations of Gd in their blood and urine, and (2) to develop a reference range for Gd concentrations in blood and spot urine samples for healthy individuals.

Clinical relevance of trace element measurement in patients on initiation of parenteral nutrition.

Background and Aims Serum zinc, copper and selenium are measured in patients prior to commencing on parenteral nutrition; however, their interpretation can be difficult due to acute phase reactions. We assessed (i) the relationship of raised C-reactive protein with trace elements and albumin (ii) benefits of measuring trace elements when C-reactive protein is raised in patients requiring short-term parenteral nutrition. Methods Samples were collected for zinc, copper, selenium and albumin at baseline and then every two weeks and correlated with C-reactive protein results in patients on parenteral nutrition.

A healthy volunteer study to investigate trace element contamination of blood samples by stainless steel venepuncture needles.

Context: The trace elements cobalt (Co), chromium (Cr), manganese (Mn) and nickel (Ni) are normally present at low concentrations in blood. There has been a concern that stainless steel venepuncture needles typically used for collection of blood samples may contaminate these samples, leading to the masking of deficiency states or causing potential clinical confusion as to whether an individual has a "toxic" concentration.

Objective: To determine whether there is any difference between the concentrations of the trace elements obtained by different methods of blood sampling.

Fetal iron levels are regulated by maternal and fetal Hfe genotype and dietary iron.

Background: Iron metabolism during pregnancy maintains fetal iron levels at the expense of the mother. The mechanism behind this regulation is still not clear despite recent advances. Here we examine the role of maternal and fetal Hfe, its downstream signaling molecule, hepcidin and dietary iron in the regulation of placental iron transfer.

Use of a clinically approved iron oxide MRI contrast agent to label human hepatocytes.

Reliable noninvasive methods are needed to monitor cell engraftment and graft survival after hepatocyte transplantation. Superparamagnetic iron oxide nanoparticles (SPIOs) have been shown to accumulate in various types of cells, and are currently the labeling agent of choice for cellular magnetic resonance imaging (MRI). However, for successful clinical translation to hepatocyte transplantation, it is important that hepatocytes maintain their viability and synthetic function after labeling.

Factitiously elevated blood chromium.

Context: Chromium toxicity is rare in individuals who do not have a history of occupational or deliberate exposure to chromium or chromium-containing compounds.

Case Report: A 39-year-old female with confirmed bile acid malabsorption had an elevated whole blood chromium concentration of 76.3 nmol/L (normal < 40 nmol/L).

Identification of a Steap3 endosomal targeting motif essential for normal iron metabolism.

Hereditary forms of iron-deficiency anemia, including animal models, have taught us much about the normal physiologic control of iron metabolism. However, the discovery of new informative mutants is limited by the natural mutation frequency. To address this limitation, we have developed a screen for heritable abnormalities of red blood cell morphology in mice with single-nucleotide changes induced by the chemical mutagen ethylnitrosourea (ENU).

Iron and cadmium uptake by duodenum of hypotransferrinaemic mice.

Absorption from food is an important route for entry of the toxic metal, cadmium, into the body. Both cadmium and iron are believed to be taken up by duodenal enterocytes via the iron regulated, proton-coupled transporter, DMT1. This means that cadmium uptake could be enhanced in conditions where iron absorption is increased.

Effect of areca nut on salivary copper concentration in chronic chewers.

The chewing of areca nut is associated with the development of oral submucous fibrosis (OSF), a condition predominantly encountered in Asians indulging in the habit. The pathogenesis of this condition is however, unclear, though several mechanisms have been proposed. Copper has previously been implicated as a possible aetiological factor.

Role of interleukin-6 in hypoxic regulation of intestinal iron absorption.

The regulation of intestinal iron absorption is not fully understood. Hepcidin, a liver-produced peptide, has recently been identified as a negative regulator of iron absorption in various conditions associated with altered iron metabolism (e.g.

The effects of inhibition of haem biosynthesis by griseofulvin on intestinal iron absorption.

The relationship between haem biosynthesis and intestinal iron absorption in mice was investigated by ascertaining the effect of the haem synthesis inhibitor, griseofulvin, on duodenal iron absorption using both in vivo and in vitro measurements. Urinary 5-aminolaevulinic acid levels were increased within 24 hr of feeding mice with griseofulvin diet (2.5% w/w), with more marked increases seen after 3-7 days.

Effect of Tin-mesoporphyrin, an inhibitor of haem catabolism, on intestinal iron absorption.

Haem biosynthesis is the most important destination for absorbed iron, hence it can be hypothesized that iron absorption regulation should be integrated with haem metabolism. As an initial step to test this hypothesis, the effect on iron absorption of Tin-mesoporphyrin (SnMP), inhibitor of haem oxygenase, altering haem and its biosynthetic intermediates, was studied. Mice injected with SnMP (5-25 micro mol/kg daily for up to 3 d) showed dose-dependent increases in intestinal iron absorption measured in vivo and in vitro.

Iron absorption: biochemical and molecular insights into the importance of iron species for intestinal uptake.

Recent advances in cloning of proteins involved in intestinal iron absorption can inform design and understanding of therapeutic iron preparations. Redox chemistry of iron is particularly important in iron metabolism, both as a potential source of toxic intermediates and as an essential requirement for efficient iron transport. The initial step in iron absorption (uptake from lumen to mucosa) is particularly important and several pathways involving Fe(III) reduction or transport and Fe(II) transport have been identified.