Erythrocyte Mean Corpuscular Volume Research Articles

Impaired Erythrocyte Filterability of Spontaneously Hypertensive Rats: Investigation by Nickel Mesh Filtration Technique

Deformability of erythrocytes plays a key role in the impairment of the microcirculation in hypertension. However, erythrocyte deformability in spontaneously hypertensive rats (SHR) during development of hypertension has not been fully investigated so far. Erythrocyte filterability (whole cell deformability) was investigated in relation to blood pressure measured by the tail-cuff method in SHR and age-matched Wistar-Kyoto rats (WKY), using a highly sensitive and reproducible nickel mesh filtration technique. Impaired erythrocyte filterability was marked (37.0+/-17.5%) in prehypertensive young SHR (7 weeks of age) and sustained (51.6+/-13.3%) in hypertensive mature SHR (18 weeks of age), when compared with that of age-matched WKY (62.1+/-7.2% in 7 weeks of age, P<0.005, and 71.1+/-3.9% in 18 weeks of age, P<0.005, respectively). This impairment in SHR could not be explained by the mean corpuscular volume or mean corpuscular hemoglobin concentration of erythrocytes, but the erythrocyte count was significantly (P<0.005) greater in SHR than in the age-matched WKY. Although the precise mechanisms remain to be elucidated, markedly impaired erythrocyte filterability in SHR is considered to contribute to the development and maintenance of genetic hypertension. (Circ J 2010; 74: 129 - 136).

Use of epoetin beta during combination therapy of infection with hepatitis c virus with ribavirin improves a sustained viral response

The aim of the study was to evaluate the effects of epoetin-beta on anemia and sustained viral response in patients with chronic hepatitis C receiving treatment with pegylated interferon and ribavirin. Forty-two Caucasian patients with chronic hepatitis C infection, treated with pegylated interferon alpha-2a or alpha-2b plus ribavirin, who experienced at least a 2 log decline in HCV-RNA in the first month of therapy and a > or =2.5 g/dl hemoglobin drop from baseline, were recruited. They were divided into two groups: 22 patients received epoetin-beta 30,000 U administered s.c. q.w. (group A) and 20 patients received a reduced ribavirin dose of 600 mg daily (group B). The end-of-treatment response was 95.4% (21/22) in group A and 80% (16/20) (P = 0.2) in group B. Sustained viral response in group A was 81.8% (18/22), statistically higher than in group B (45%, 9/20) (P = 0.03). Mean corpuscular volume of erythrocytes was statistically lower in group A than in group B 4 weeks after starting epoetin-beta or reduced ribavirin dose (P < 0.001), end-of-treatment (P < 0.001) and after 6 months follow-up (P < 0.001). A negative correlation between the levels of ferritin serum was found in group A at the baseline and mean corpuscular volume value after 1 month of combination antiviral therapy (r = -0.45; P = 0.35), 4 weeks after starting epoetin-beta (r = -0.43; P = 0.04) and after 6 months follow-up (r = -0.45; P = 0.03). Administration of epoetin-beta increases sustained viral response rates among patients developing anemia, because the standard dose of ribavirin is maintained, thereby reducing the side-effects of antiviral treatment.

Effect of Dialysis on Erythropoietin and some Hematological Parameters in Patients with Chronic Renal Failure

Background and objective: A prospective study was carried out for estimation the concentration of the erythropoietin hormone and its effects on some hematological parameters in chronic renal failure patients despite medical treatment. The object of the study was to evaluate the available evidences which support the relationship between anemia and adverse outcomes in chronic renal failure patients, to estimate the erythropoietin concentration of plasma in chronic renal failure patients and to examine the relationship between the anemia and erythropoietin concentration in patients with chronic kidney disease. Methods: One hundred and eleven (111) patients with CRF on dialysis in the Dialysis and Kidney Disease Center in Hawler Teaching Hospital and (40) control groups were studied. Haematological parameters: were performed by conventional manual methods. The quantitative measurement of erythropoietin concentration in serum was done by using the Erythropoietin ELISA kit (IBL Immuno Biological Laboratories Hamburg Erythropoietin Kit, German). Results: Hemoglobin, red blood cells, packed cell volume, and mean corpuscular hemoglobin were significantly decreased (P&lt;0.001) in all age groups of Chronic renal failure patients, while, erythrocyte sedimentation rate and mean corpuscular volume (MCV) were increased significantly (P&lt;0.001). Total white blood cells were decreased significantly (P&lt;0.01) at the ages (40-60, &gt;60) years groups, while not significantly decreased at the ages (&lt;20, 20-40) years. Plasma erythropoietin was decreased significantly at the level (P&lt;0.001) in chronic renal failure patients. Conclusion: Anemia is a common and often an early complication of chronic renal diseases and decreased renal production of erythropoietin is the major cause of anemia in these patients.

Safety and tolerability of sirolimus treatment in patients with autosomal dominant polycystic kidney disease

We initiated a randomized controlled clinical trial to assess the effect of sirolimus on disease progression in patients affected by autosomal dominant polycystic kidney disease (ADPKD). Here we report the preliminary safety results of the first 6 months of treatment. A total of 25 patients were randomized to sirolimus 2 mg/day and 25 patients to no treatment except standard care. Treatment adherence was monitored electronically. At baseline and at Month 6, laboratory parameters were analysed and the urinary protein profile in 24-h urine collections was determined. Both treatment groups were well balanced for age, sex and renal function. In 94.1 +/- 11.4% of the study days, patients in the sirolimus group were exposed to the drug when assuming a therapeutic efficacy duration of 30 h. At Month 6, the mean sirolimus dose and trough level were 1.28 +/- 0.71 mg/day and 3.8 +/- 1.9 microg/l, respectively. Glomerular (albumin, transferrin, IgG) and tubular (retinol-binding protein, alpha(1)-microglobulin) protein excretion remained unchanged. Glomerular filtration rate also did not change significantly. Haematological parameters were similar in both groups, except for a mild reduction of the mean corpuscular volume of erythrocytes in patients receiving sirolimus. Lipid levels were similar in both groups. Adverse events were transient and mild, and no grade 3 or 4 events occurred. The incidence of infections was similar in the sirolimus group (80%) and the standard group (88%). The most common gastrointestinal adverse events were mucositis (72% in the sirolimus group versus 16% in the standard group, P = 0.0001) and diarrhoea (36% in the sirolimus versus 20% in the standard group, P = 0.345). Treatment of ADPKD patients with sirolimus with a dose of 1-2 mg/day is safe and does not cause proteinuria or impairment of GFR. Treatment adherence was excellent. (ClinicalTrials.gov number, NCT00346918.).

Increased Red Cell Corpuscular Volume and Hepatic Mitochondrial Function in NRTI-Treated HIV Infected Patients

An increase of the mean corpuscular volume of the red blood cells has been repeatedly described in antiretroviral treated patients. Most commonly macrocytosis was associated with the use of certain nucleoside reverse transcriptase inhibitors. The aim of this study was to analyse if macrocytosis might be a marker of mitochondrial toxicity in antiretrovirally treated HIV-infected patients. Using the (13)C-methionine breath test we analysed the hepatic mitochondrial function in vivo in antiretrovirally treated HIV-infected patients with macrocytosis. MCV was significantly negatively correlated to the breath test results. For the first time we could show a significant association between an increase of the mean corpuscular erythrocyte volume by treatment with nucleoside reverse transcriptase inhibitors (NRTI) and the hepatic mitochondrial function in vivo.

The presence of α‐thalassaemia trait blunts the response to hydroxycarbamide in patients with sickle cell disease

Hydroxycarbamide (HC), although a key drug therapy in sickle cell disease (SCD), does not result in a clinical response in all patients. Increases in fetal haemoglobin (HbF) and mean corpuscular volume of erythrocytes are standard clinical measures of HC efficacy in SCD. Genetic studies have determined that the majority of HbF regulation occurs outside the beta-globin locus. Approximately 30% of SCD patients have co-inherited alpha-thalassaemia resulting in hypochromic and microcytic erythrocytes. We provide data from 30 SCD patients (10 with alpha-thalassaemia) demonstrating that co-existing alpha-thalassaemia significantly affects several standard measures of HC efficacy in SCD.

The Association of ADH and ALDH Gene Variants With Alcohol Drinking Habits and Cardiovascular Disease Risk Factors

Genetic variation in ethanol metabolism may have an influence on both alcohol drinking habits and the susceptibility to health effects of alcohol drinking. Such influences are likely to bias exposure-disease associations in epidemiologic studies of health effects of alcohol drinking. In a Caucasian population, we examined the association of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genetic variants with alcohol drinking habits, biomarkers of alcohol exposure, and risk factors for cardiovascular disease. The study population consisted of 1,216 Danish men and women aged 15-77 years participating in a health examination in 1998. The health examination included a self-administered questionnaire (alcohol drinking habits), a physical examination (blood pressure), and various blood tests [alanine aminotransferase (ALAT), erythrocyte mean corpuscular volume (E-MCV), and lipids]. ADH and ALDH gene variants were determined by standard techniques. Data were analyzed by regression analyses adjusted for relevant confounders. Self-reported alcohol drinking was significantly associated with increasing levels of ALAT, E-MCV, high-density lipoprotein cholesterol, and blood pressure. The ALDH1b ala69val variant was associated with nondrinking and total alcohol intake. The ALDH2 promoter variant was associated with binge-drinking, and the ALDH1b1 ala69val polymorphism was associated with diastolic blood pressure. We did not find any statistically significant interactions between any of the gene variants and alcohol consumption in relation to the various outcomes. In this Caucasian population sample, we found evidence to support that genetic variation in ethanol metabolism may influence drinking habits, but no statistically significant gene-environment interactions. More large-scale epidemiologic studies are needed to confirm theses results and to further investigate genetic susceptibility to the effects of alcohol drinking.

Assessment of Hemorheological Deformability of Human Red Cells Exposed totert-Butyl Hydroperoxide, Verapamil and Ascorbate by Ektacytometer

Normal erythrocyte is deformable and this facilitates blood flow in the capillaries. Oxidative stress reduces the deformability of erythrocytes, and influences on blood flow in microcirculation. The objective of this study was to investigate the deformability of erythrocytes exposed to oxidative stress, the protective effects of verapamil and ascorbic acid against oxidative damages in erythrocytes, and the value of the microfluidic ektacytometer, RheoScan-D (RheoMeditech, Korea) in clinical application. Effects of oxidative stress on erythrocytes were investigated using tert-butyl hydroperoxide (tBHP). Before exposure to tBHP, the erythrocytes were pretreated with verapamil and ascorbic acid to examine their protective effect against oxidative damages. The deformability of erythrocytes was measured by the microfluidic ektacytometer, RheoScan-D. When treated with tBHP, the deformability of erythrocytes was decreased (P<0.01) and methemoglobin (metHb) formation and mean corpuscular volume (MCV) of erythrocytes were increased (P<0.01, P<0.05) compared to those of the untreated control cells. Compared to the tBHP treated cells, pretreatment with verapamil increased the deformability of erythrocytes (P<0.01) and decreased metHb formation (P<0.01) and MCV (P<0.05). Likewise, pretreatment with ascorbic acid increased the deformability of erythrocytes (P<0.01) and decreased metHb formation (P<0.01). Oxidative stress reduces the deformability of erythrocytes and the deformability could be one of markers for oxidative damage. Verapamil and ascorbic acid have protective role against tBHP induced oxidative stress. The ektacytometer, RheoScan-D used in this study is convenient for clinical measurement and could be used in various fields of clinical medicine.

In vitro studies of amikacin-loaded human carrier erythrocytes

Erythrocyte-encapsulated antibiotics have the potential to provide an effective therapy against intracellular pathogens. The advantages over the administration of free antibiotics include a lower systemic dose, decreased toxicity, a sustained delivery of the antibiotic at higher concentrations to the intracellular site of pathogen replication, and increased efficacy. In this study, the encapsulation of amikacin by human carrier erythrocytes prepared using a hypo-osmotic dialysis was investigated. The effects of the initial amikacin dialysis concentration and hypo-osmotic dialysis time on the encapsulation efficiency of amikacin were determined, and the osmotic fragility and hematologic parameters of amikacin-loaded carrier erythrocytes were measured. The efficiency of amikacin entrapment by carrier erythrocytes was dependent on the initial dialysis concentration of the drug. Statistically significant differences in the osmotic fragility profiles between control and carrier erythrocytes were observed, which were dependent on the hypo-osmotic dialysis time and on the dialysis concentration of amikacin. Mean hematologic parameters were evaluated and compared with unloaded, native erythrocytes; the mean corpuscular volume (MCV) of amikacin-loaded carrier erythrocytes was statistically significant smaller. Amikacin demonstrated a sustained release from loaded erythrocytes over a 48-h period, which suggests a potential use of the erythrocyte as a slow systemic-release system for antibiotics.

Measurement of direct ethanol metabolites in a case of a former driving under the influence (DUI) of alcohol offender, now claiming abstinence

A 37-year-old female subject had been convicted of driving under the influence of alcohol, and 19 months later, claimed abstinence after supervised disulfiram treatment. Our aim was to elucidate the value of direct ethanol metabolites as measures of abstinence. Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEE) in hair, phosphatidylethanol in whole blood and EtG and ethyl sulphate in urine were measured. The results were compared with self-report of alcohol consumption and traditional blood biomarkers for chronically elevated alcohol consumption as carbohydrate deficient transferrin (CDT), gamma glutamyl transpeptidase, mean corpuscular erythrocyte volume, aspartate aminotransferase and alanine aminotransferase. EtG was found in distal parts of hair only, whereas the proximal parts were negative. Furthermore, FAEE concentrations were found in the typical distribution over the hair length and showed values typical for either moderate social drinking or abstinence. CDT was above cut-off in 9 out of 16 analyses with a decreasing tendency and the lowest values in the last 2 months before the end of sampling. The data suggest that in addition to traditional markers, a combination of direct ethanol metabolites can be useful in the expert assessment of judging driving ability. A careful individual interpretation of the results for the different markers, however, is an absolute necessity.

Beverage-specific effects of ethanol consumption on its biological markers

Serum gamma-glutamyltransferase (GGT) and erythrocyte mean corpuscular volume (MCV) are well-known biological markers of excessive ethanol consumption. The beverage-specific effects of ethanol consumption on GGT level and MCV value were analyzed cross-sectionally and retrospectively among middle-aged Japanese men who underwent a retirement health checkup (n = 974). Both the consumption of distilled alcohol and that of fermented alcohol positively correlated with the logarithm of GGT [standard regression coefficient (beta) 0.261 and 0.174, respectively]. The prevalence rate of elevated GGT levels > or = 70 IU/L) was higher among heavy drinkers of distilled alcohol than among heavy drinkers of fermented alcohol (38.8% vs. 27.6%, p = 0.013). The MCV value correlated with distilled alcohol consumption (beta: 0.212, p < 0.0001) but not with fermented alcohol consumption (beta: 0.043, not significant). The prevalence rate of an elevated MCV (> or = 97 fL) was higher among heavy drinkers of distilled alcohol than among heavy drinkers of fermented alcohol (35.3% vs. 16.8%, p < 0.001). These results suggest that MCV is less sensitive for detecting heavy consumption of fermented alcohol than for detecting that of distilled alcohol in apparently healthy middle-aged men.

The erythrocyte mean corpuscular volume is associated with serum levels of thyroid stimulating hormone in women

The erythrocyte mean corpuscular volume is associated with serum levels of thyroid stimulating hormone in women

Macrocytosis and Cobalamin Deficiency in Patients Treated with Sunitinib

To the Editor: Sunitinib malate is a multitargeted tyrosine kinase inhibitor approved for the treatment of advanced renal-cell carcinoma. We report on an asymptomatic increase in the mean corpuscular volume of erythrocytes and cobalamin deficiency in six patients with metastatic renal-cell carcinoma who were treated for more than 5 months with sunitinib as part of a clinical trial evaluating the efficacy and safety of continuous daily administration of the drug. The starting dose of sunitinib was 37.5 mg daily; three patients required a dose reduction to 25 mg, and one patient had a dose escalation to 50 mg daily. An . . .

Higher prevalence of anemia among pregnant immigrant women compared to pregnant ethnic Danish women

The aim of the study was to investigate whether the well-known high anemia prevalence in pregnant women from the eastern Mediterranean and Asian regions decreased when the women immigrated to a low-frequency region (Denmark). During 70 months, 1,741 pregnant immigrant women referred from primary care to an obligatory hemoglobinopathy screening were eligible for the study, as their screening was negative. To compare this group with a cohort of 205 pregnant ethnic Danish women, the groups were matched by gestational age, and a total of 406 immigrant women were included. Hemoglobin (Hb) and iron status parameters were examined in the two groups. The prevalence of anemia was higher in the immigrant group (20.0%) compared to the Danish women (4.9%) (P < 0.0001). Blood Hb concentration was 119 +/- 12 g/l (mean +/- SD) in the immigrant group compared to 122 +/- 9 g/l in the Danish group (P = 0.01). Erythrocyte mean corpuscular volume (MCV) was also lower in the immigrant group (87 +/- 7 fl vs 96 +/- 4 fl) (P < 0.0001). A total of 13.1% of the immigrant women had an MCV <80 fl (the lower reference limit) compared to 0.0% in the Danish group, and plasma iron, ferritin, and transferrin saturation values indicated iron deficiency. Conclusively, the pregnant immigrant women had significantly higher prevalence of anemia compared to pregnant women of Danish origin. It indicates the need for an alternative routine screening procedure for this population group, which should also include nutritional counselling.

Combinations of carbohydrate-deficient transferrin, mean corpuscular erythrocyte volume, gamma-glutamyltransferase, homocysteine and folate increase the significance of biological markers in alcohol dependent patients

Aims The traditionally used biological markers for alcoholism include a wide range of sensitivity and specificity as single tests. This study focuses on the combination of established laboratory parameters with new meaningful biomarkers to advance the significance regarding alcohol dependence. Design We analyzed blood samples from alcohol-dependent patients ( n = 177) compared with a control group ( n = 181). In the statistical calculation we included carbohydrate-deficient transferrin (CDT), mean corpuscular erythrocyte volume (MCV), gamma-glutamyltransferase (GGT), total plasma homocysteine, and folate. Results None of the examined biomarkers reached sensitivity above 90% while all markers showed a good specificity. Combinations of different markers led to a significant elevation in sensitivity. Best values for men were achieved by using a combination of MCV, CDT, GGT, homocysteine and folate in different weightings (sensitivity: 98.6%, specificity: 86.4%). For women, similar results were yielded by combining MCV and CDT (sensitivity: 94.1%, specificity: 96%). The addition of homocysteine and folate in different weightings did not result in further enhancement. Conclusions Gender-specific clusters including MCV, CDT, GGT, homocysteine and folate led to an increase in sensitivity compared to single laboratory markers. This is a reliable help to identify patients with regular heavy drinking in clinical practice which might prevent further complications.

Biochemical markers of alcoholism

Alcohol and alcohol-related diseases have become a major cause of death in Western countries. The most sensitive and specific of the commonly used biomarkers of alcohol intake are carbohydrate-deficient transferrin (CDT), and the combination of gamma-glutamyltransferase (GGT) and CDT. Other widely used laboratory markers are GGT, mean corpuscular volume of erythrocytes and the ratio of aspartate aminotransferase to alanine aminotransferase. Blood ethanol levels reveal recent alcohol use. However, more specific and sensitive biomarkers to improve the detection of excessive alcohol use at an early stage are needed. New biomarkers, not yet used in routine clinical work, include phosphatidylethanol, fatty acid ethyl esters, ethyl glucuronide, sialic acid, and acetaldehyde adducts.

Antibacterial activities and toxicological potentials of crude ethanolic extracts of Euphorbia hirta

Leaves of Euphorbia hirta used in traditional medicine for the treatments of boils, wounds and control of diarrhoea and dysentery were extracted by maceration in ethanol. The agar diffusion method was used to determine the antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi and Bacillus subtilis at different concentrations while toxicological studies was carried out through intraperitoneal injection of albino rat with varying concentrations of the extract. Antibacterial sensitivity test indicated that the extract inhibited the growth of S. aureus, E. coli, B. subtilis and P. aeruginosa to varying degrees while S. typhi was not affected. Minimum inhibitory concentration (MIC), of the extract against E. coli, S aureus, P. aeruginosa and B. subtilis were 58.09, 22.55, 57.64 and 74.61 mg/ml respectively. Hematological analyses revealed that there was no significant difference (p = 0.05) between the total red blood cells (RBC), white blood cells (WBC), hemoglobin (Hb) and mean corpuscular hemoglobin concentration (MCHC) values of the rats used as control and those treated with the different concentrations of the extract. Also, the erythrocyte sedimentation rate (ESR) and mean corpuscular volume (MCV) values were significantly different at certain concentrations of the extract administered which indicates that the plant extract is heamatologically not toxic to rats. The plant extract was found to contain tannins, alkaloids and flavonoids which may be responsible for its antimicrobial properties. The results justify the traditional use of the plant in the treatment of sores, boils, wounds and control of dysentery and diarrhoea.

Clinical manifestations of hematologic and oncologic disorders in patients with Down syndrome

Hematologic abnormalities are common in individuals with Down syndrome (DS). Increased erythrocyte mean corpuscular volume (MCV) is frequently found among DS infants and remains elevated throughout life in two-thirds of patients, making interpretation of red cell indices for diagnosis of nutritional anemias or bone marrow failure disorders more challenging. Transient myeloproliferative disorder (TMD) associated with pancytopenia, hepatosplenomegaly, and circulating immature WBCs, is found almost exclusively in DS infants with an incidence of approximately 10%. In most cases, TMD regresses spontaneously within the first 3 months of life, but in some children, it can be life threatening or even fatal. Despite the high rate of spontaneous regression, TMD can be a preleukemic disorder in 20-30% of children with DS. The types of malignancy, response to therapy, and clinical outcome in children with DS are also unique. There is an increased risk of leukemia with an equal incidence of lymphoid and myeloid leukemia. Acute megakaryocytic leukemia (AMKL) subtype is the most common form of acute myeloid leukemia (AML) in this setting, and is uncommon in children without DS. Somatic mutations of the gene encoding the hematopoetic growth factor GATA1 have been shown to be specific for TMD and AMKL in children with DS. Myelodysplastic syndrome can precede AML. Children with DS and leukemia are more sensitive to some chemotherapeutic agents such as methotrexate than other children which requires careful monitoring for toxicity. Although the risk for leukemia is higher in individuals with DS, these patients have a lower risk of developing solid tumors, with the exception of germ cell tumors, and perhaps retinoblastoma and lymphoma.

Altered Distribution of Transferrin Isoforms According to Serum Storage Conditions

Measurements of carbohydrate-deficient transferrin (CDT) are used to detect alcohol abuse (1)(2)(3)(4)(5)(6). Various patient factors(7)(8)(9)(10)(11) and comigration of analytes with transferrin (Tf) isoforms(12)(13) can affect the results of the measurements. Recent studies have questioned the influence of serum and blood storage conditions on CDT and yielded varying (and sometimes contradictory) findings(14)(15)(16)(17). Moreover, the stability of CDT may vary among serum samples(14)(16). We studied CDT and Tf isoforms in serum specimens stored at 25 °C, 4 °C, and −20 °C. We used 100 discarded serum samples; 8 were from alcohol abusers in treatment (4 with increased disialo-Tf and the presence of asialo-Tf; 4 with increased disialo-Tf but without asialo-Tf), and 6 were from moderate drinkers (CDT within reference values). For sera from alcohol abusers, the alcohol abuse diagnosis was based on psychological evaluation; CDT, γ-glutamyltransferase, and transaminase (aspartate aminotransferase and alanine aminotransferase) concentrations; and erythrocyte mean corpuscular volume. Each of the 14 specimens was divided into 3 samples and stored in glass vials (4 mL; Supelco 27137) at room temperature (25 °C in the dark), in a refrigerator (4 °C), or in a freezer (−20 °C). Samples were then analyzed periodically for 28–81 days [mean (SD), 51.6 (14.7) days]. The main reason for discontinuing follow-up was the appearance of solid particles in the serum. For frozen samples (−20 °C), the time between thawing and refreezing was <5 min. Serum Tf was analyzed (13) by use of capillary electrophoresis (P/ACE 5500) and a reagent set (CEofix; ANALIS). Electropherograms displayed all major Tf isoforms: asialo-Tf (when present), disialo-Tf, trisialo-Tf, tetrasialo-Tf, pentasialo-Tf, and hexasialo-Tf. The signal was integrated in the valley-to-valley …

Validity of carbohydrate‐deficient transferrin (%CDT), γ‐glutamyltransferase (γ‐GT) and mean corpuscular erythrocyte volume (MCV) as biomarkers for chronic alcohol abuse: a study in patients with alcohol dependence and liver disorders of non‐alcoholic and alcoholic origin

To test the clinical performance of carbohydrate-deficient transferrin (%CDT), gamma-glutamyltransferase (gamma-GT) and mean corpuscular erythrocyte volume (MCV) as biomarkers for alcoholism with a special focus on patients suffering from liver diseases. Well-characterized collectives of alcohol-dependent patients with current consumption (ALC patients, n = 101), and relevant control groups (115 social drinkers, 46 patients with unspecifically increased gamma-GT, 51 hepatitis patients and 20/31 patients with non-alcohol/alcohol-dependent liver cirrhosis) were included into the study. The Positive Alcohol Use Disorders Test (AUDIT) score, International Classification of Diseases version 10 (ICD-10)/Diagnostic and Statistical Manual version IV (DSM-IV) criteria and blood drawn within 4 days of last drinking were inclusion criteria for subjects with regular heavy drinking. %CDT was determined using an automated assay which recently had been completely modified. Median AUDIT scores of patients without/with regular heavy drinking were 1-3/27. The following medians/95th percentiles were obtained for %CDT: social drinkers 2.2/3.0, patients with unspecifically increased gamma-GT 2.1/3.0, hepatitis 2.0/4.4, non-alcohol-dependent liver cirrhosis 2.4/4.8, alcohol-dependent liver cirrhosis 3.0/5.9, ALC patients 3.9/14.9. Differences between patients without and with alcohol abuse were highly significant (P < 0.001). No differences in CDT values were found between males and females. There was no correlation between %CDT values, gamma-GT, MCV and the amount of alcohol consumed in ALC patients; 3.0%CDT (95th percentile social drinkers) is proposed as cut-off for the test used (Tina-quant %CDT 2nd-generation). At this cut-off, the sensitivity for ALC patients was 73.3%, whereas gamma-GT/MCV had a sensitivity of 71.3%/64.4%. Multivariate analysis performed at 95% specificity resulted in an improvement of the sensitivity by combining %CDT with gamma-GT (83.2%). A further enhancement of the sensitivity to 88.1% was obtained by combination of %CDT, gamma-GT and MCV. The diagnostic specificity of %CDT calculated at the cut-off of 3% was 93.5% in patients with unspecifically increased gamma-GT, 88.2% in hepatitis patients and 70.0% in patients with non-alcohol-dependent liver cirrhosis. %CDT was more specific in these patient collectives than MCV, and especially more than gamma-GT (specificity in hepatitis 52.9%, and 35.0% in non-alcohol-dependent liver cirrhosis). %CDT is of high diagnostic value to support diagnosis of alcohol-use disorders. The specificity of this marker in patient groups with liver disorders is superior to the biomarkers gamma-GT and MCV.