Relationships between blood levels of fat soluble vitamins and disease etiology and severity in adults awaiting liver transplantation.

BACKGROUND AND AIMS: Although malnutrition is common in liver disease, there are limited data on fat soluble vitamins in various diseases. The aims of this study were to: (i) determine fat soluble vitamin levels in patients assessed for liver transplantation; (ii) compare levels between different disease etiologies (hepatocellular and cholestatic) and between subgroups of hepatocellular disease; and (iii) assess the multivariate contribution to vitamin levels of etiology and various indicators of disease severity. METHODS: This was a cross-sectional study of 107 inpatients awaiting liver transplantation, mean age 47 years. Biochemical parameters included plasma retinol, 25-hydroxycholecalciferol, and vitamin E. Biochemical (albumin, bilirubin and zinc) and clinical indicators (Child-Pugh and Model of End Stage Liver Disease [MELD] scores) of disease severity were determined. RESULTS: Deficiencies of retinol (< 1.0 µmol/L), 25-hydroxycholecalciferol (< 50 nmol/L) and vitamin E (< 11 µmol/L) were present in 75%, 66% and 3%, respectively, of patients. Concentrations of retinol and vitamin E were lower in hepatocellular than cholestatic disease but 25-hydroxycholecalciferol concentrations were similar. Child-Pugh score was higher in hepatocellular than cholestatic disease. Concentrations of retinol were lower in alcoholic liver disease (ALD) than hepatitis and Child-Pugh score was higher in ALD. For the whole group, levels of retinol, 25-hydroxycholecalciferol and vitamin E were negatively related to Child-Pugh score, MELD score and bilirubin, and positively related to albumin. When Child-Pugh scores were controlled for, retinol was lower in the hepatocellular group. CONCLUSIONS: There was a high prevalence of fat soluble vitamin deficiencies with vitamin levels being related to disease severity. Retinol was lower in the hepatocellular group.

Dark adaptation in vitamin A-deficient adults awaiting liver transplantation: improvement with intramuscular vitamin A treatment.

BACKGROUND/AIMS: Although vitamin A deficiency is common in chronic liver disease, limited data exist on impairment of dark adaptation and response to therapy. The aims were (1) to assess dark adaptation in patients, (2) to assess the relationship between dark adaptation and vitamin A status, zinc and Child-Pugh score, (3) to compare perceived and measured dark adaptation and (4) to assess the dark adaptation response to intramuscular vitamin A. METHODS: This was a prospective study of 20 patients (alcoholic liver disease 10, other parenchymal diseases six, cholestatic diseases four) awaiting liver transplantation. Selection was based on low serum retinol. There were 15 age-matched controls. Dark adaptation was measured with a SST-1 dark adaptometer and perception by questionnaire. Eight patients received 50, 000 IU of retinyl palmitate, and dark adaptation was repeated at 1 month. RESULTS: Forty per cent of patients had impaired dark adaptation. Patients with alcoholic liver disease were more impaired than those with other parenchymal diseases (p=0.015). No relationship was found between dark adaptation and the biochemical indicators or Child-Pugh score. Seventy-five per cent of patients with impairment did not perceive a problem. After intervention, light of half the previous intensity could be seen (p=0.05). CONCLUSIONS: Dark-adaptation impairment was common, was worse in alcoholic liver disease, was largely not appreciated by the patients and improved with vitamin A treatment.

Clinical utility of serum soluble transferrin receptor levels and comparison with bone marrow iron stores as an index for iron-deficient erythropoiesis in a heterogeneous group of patients.

AIM: To evaluate the correlation between raised soluble transferrin receptor (sTfR) and stainable marrow iron, and to define the utility of sTfR in discriminating between the presence or absence of iron-deficient erythropoiesis in patients with anaemia of chronic disease. METHODS: Seventy-six consecutive adult patients without accelerated erythropoiesis who had undergone bone marrow (BM) aspiration/trephine for various clinical reasons during 2003-2006 were studied. All patients had serum iron studies (iron, transferrin and ferritin) and sTfR performed within 1 week of BM aspiration/trephine. These 76 patients were assigned to three groups based on the iron status of the BM and sTfR level: patients with normal sTfR and normal BM iron stores (n = 49), patients with an elevated sTfR and normal BM iron stores (n = 13) and patients reduced or absent BM iron stores (n = 14). Means (95% confidence interval) for mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC), red blood cell haemoglobin (RBC Hb) content and median (5th and 95th percentiles) for haemoglobin were then calculated. RESULTS: All patients with absent BM iron stores had an elevated sTfR level. Patients with normal BM iron stores and elevated sTfR levels had significantly lower Hb, MCV, MCHC and RBC Hb content than patients with normal BM iron stores and normal sTfR levels. CONCLUSION: sTfR is the most sensitive serum biochemical marker for the identification of iron-deficient erythropoiesis. Normal BM iron stores can coexist with elevated sTfR and decreased MCV and MCHC. sTfR levels correlate better than BM iron stores with decreased MCV and MCHC. Therefore, sTfR is a useful marker of iron-deficient erythropoiesis, due to both absent iron stores, and restricted iron supply due to anaemia of chronic disease. As a single investigation, however, sTfR does not discriminate between these two causes of iron-deficient erythropoiesis.

Correction and reporting of potassium results in haemolysed samples.

BACKGROUND: Potassium is usually the most important analyte affected by in vitro haemolysis and the result obtained may falsely indicate or disguise a life-threatening abnormality and so give rise to inappropriate treatment. The purpose of the study was to provide a solution to the problem of reporting potassium on haemolysed samples, taking into account both clinical needs and analytical concerns (inter-individual and inter-sample variability). METHODS: Using a new procedure that mimics the collection process in an actual clinical setting, haemolysed samples were prepared from 41 volunteers with a range of inter-individual factors - haemoglobin 80-173 g/L, red blood cells 2.42-6.77 x 10(12)/L, leucocytes 3.0-306 x 10(9) /L and platelets 31-710 x 10(9)/L - in order to develop a more accurate correction equation using a haemolytic index (HI) corresponding to g Hb/L in plasma. RESULTS: The mean (range) potassium increase was 0.0036 mmol/L (0.0029-0.0053 mmol/L) per unit HI. The following equation was developed to estimate potassium increase per HI, in order to compensate approximately for potassium leakage in haemolysed samples: Corrected K+ = Measured K+ -(HI x 0.004). CONCLUSION: The balanced solution is this: instead of reporting the post-haemolysis corrected potassium result a qualitative comment is given, indicating the likely range of the potassium concentration. If the potassium result is in a critically low or high range, it is communicated promptly to the requesting clinician.

Neonatal biochemical screening for disease.

BACKGROUND: The practice of screening the neonatal population for certain diseases by biochemical testing of a dried blood spot is an established public health initiative in many countries. The diseases for which screening is done vary from region to region, based on ethnic, financial and political considerations. Criteria have been established to identify diseases suitable for neonatal screening. DISEASES SCREENED: In Western countries, screening for phenylketonuria (PKU) and congenital hypothyroidism (CH) has been introduced throughout. Subsequently, cost-benefit analysis has confirmed the existence of a financial benefit. Other diseases screened for in some regions include galactosemia, aminoacidemias and organic acidemias, cystic fibrosis, congenital adrenal hyperplasia, biotinidase deficiency, hemoglobinopathies, glucose-6-phosphate dehydrogenase deficiency, and Duchenne muscular dystrophy, although in no case has a clear financial benefit been established. CONCLUSIONS: Since the introduction of neonatal screening over 40 years ago, new methods have resulted in an increase in the number of diseases amenable to screening, better automation and greater specificity. Methods currently used include growth of an inhibited bacterial auxotroph (the original phenylalanine (phe) method of Dr. Robert Guthrie), spectrophotometry, fluorometry, immunoassay, and tandem mass spectrometry with electrospray ionization.