Erythrocyte Mean Corpuscular Volume Research Articles

Immunovirological Efficacy of Once-Daily Maraviroc Plus Ritonavir-Boosted Atazanavir After 48 Weeks in Naive HIV-Infected Patients.

Toxicities related to the use of nucleoside analogues have increased the interest in developing nucleoside-sparing regimens, mainly combining protease inhibitors with raltegravir. However, data regarding the use of CCR5-antagonists in this setting and in the naive scenario are scarce. The main objective was to analyze the immunovirological efficacy and tolerability of a low-dose, once-daily, maraviroc (MVC)-containing, nucleoside reverse transcriptase inhibitor-sparing dual therapy compared with standard triple therapy after 48 weeks for naive HIV-infected patients in the routine clinical practice setting. All naive HIV-infected patients with stable clinical condition that started antiretroviral treatment since February 1, 2008 to May 30,h 2012 were included. MVC clinical test was used to select candidate subjects to MVC therapy. Thirty-two subjects with MVC + atazanavir/ritonavir (ATV/r) and 66 with standard triple therapy were analyzed. A comparable virological efficacy between groups was found after 48 weeks (87.5% vs. 80.3% of HIV undetectability, p = 0.37, MVC + ATV/r and triple therapy groups, respectively). The CD4 recovery after 48 weeks was similar and more than 200 cells/mm3 in both groups. No need of therapy changes or treatment discontinuations was observed in the MVC + ATV/r group. Effect on lipid profile, high-sensitivity C reactive protein, and β2-microglobulin was similar for both groups. Noteworthy, a significant increase of erythrocyte mean corpuscular volume was observed only in the triple therapy group. A nucleoside-sparing MVC-containing dual therapy showed similar immunovirological efficacy and tolerability than standard triple therapy in naive HIV-infected patients.

Cross-sectional study on N,N-dimethylformamide (DMF); effects on liver and alcohol intolerance.

There are still concerns regarding occupational exposure to hepatotoxic DMF. This study was designed to evaluate possible liver damaging effects of DMF under current workplace conditions in synthetic fibres industries. Among other laboratory parameters, liver function parameters (alkaline phosphatase (ALP), aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase), the mean corpuscular erythrocyte volume (MCV) and carbohydrate-deficient transferrin (CDT) of the workforce of two companies present at the days of study were investigated. Internal exposure to DMF was assessed via three different biomarkers [sum of N-methylformamide and N-hydroxymethyl-N-methylformamide, N-acetyl-S-(N-carbamoyl)cysteine (AMCC) and 3-methyl-5-isopropylhydantoin (MIH)]. Alcohol consumption was assessed by means of direct ethanol metabolites (ethylglucuronide and ethylsulfate). None of the tested liver enzyme activities showed a positive association with any of the three exposure markers, nor did CDT and MCV. CDT was negatively associated with AMCC and the ALP activity negatively with all three exposure markers. Changes in liver function are seen mainly in conjunction with ethanol consumption but also with increasing body weight and age. MCV was associated with smoking. Almost half of the workers stated to experience alcohol flush reaction. The present study indicates that long-term exposure to DMF, which was specified by median urinary AMCC levels of 4.84mg/g creatinine and DMF haemoglobin adduct levels of 60.5nmol/MIH/g globin, respectively, does not result in any adverse liver effects. In contrast, these DMF exposure levels still elicit certain alcohol intolerance reactions.

D43 - Capecitabine and Regorafenib-related increased mean corpuscular volume of red blood cell may be a predictive marker of treatment response and survival in patients with metastatic colorectal cancer

Background: Erythrocyte mean corpuscular volume (MCV) increase has been described in patients treated with capecitabine. Moreover, tyrosine kinase inhibitors have been shown to induce macrocytosis in patients with renal cancer cell and gastrointestinal stromal tumors, presumably via the inhibition of erythroid progenitor cells of the bone marrow. Therefore, the aim of our study was to evaluate the potential association of the erythrocyte MCV increase with tumor response and survival in patients with metastatic colorectal cancer (mCRC) treated with capecitabine and regorafenib. Patients and methods: A retrospective review of 30 patients with mCRC who were treated with capecitabine or regorafenib for at least 3 months at the Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy. Complete blood count (CBC) including red blood cell indices were recorded at baseline and after 4, 8 and 12 weeks from capecitabine or regorafenib treatment. Results: Baseline MCV levels and MCV levels after 4, 8 and 12 weeks were registered for each patient treated with capecitabine or regorafenib. Median ΔMCV [(post-treatment MCV values after 12 weeks) - (baseline MCV values)] was calculated. Patients were grouped according to ΔMCV into two groups in order to carry out survival analysis and correlation with tumor response. Moreover, univariate and multivariate analysis was performed to investigate if MCV increase was independently associated with favorable survival outcomes. Conclusions: Erythrocyte MCV increase may be used as a predictive marker for treatment response, PFS and OS in patients with mCRC treated with capecitabine or regorafenib. In the future, response to TAS-102 (trifluridine-tipiracil) and MCV increase will be also evaluated.

Effects of nanocrystalline PbSe on hematopoietic system and bone marrow micronucleus rate of rats.

To investigate the effect of lead selenide nanocrystals on hematopoietic system and bone marrow micronucleus rate of rats. Specific pathogen free SD rats were randomly divided into 4 groups (8 rats in each group), and injected with of 0 (control group), 10 (low dose group), 20 (middle dose group), 30 mg/kg (high dose group) nanocrystalline PbSe, respectively. Seven weeks after injection, the blood was taken from rats for routine index detection; the number of micronucleus cells per 1000 polychromatic erythrocyte from bone marrow was counted. White blood cell (WBC), lymphocyte (LYM) count in low dose group rats, and WBC, LYM, granulocyte (GRN), monocytes (MOD) counts in high dose group significantly increased compared to those of control group. LYM% ratio decreased while GRN% ratio increased along with the increase of exposure dosage. Compared with those of the control group, levels of erythrocyte mean corpuscular volume (MCV) in low dose group, hemoglobin (HGB), red blood cell specific volume (HCT), MCV in middle dose group and red blood cell (RBC), HGB, HCT, MCV in high dose group, were markedly decreased. Red blood cell distribution width (RDW), blood platelet (PLT) levels in three exposure groups of were higher than those in control group. Marrow micronucleus test results showed that, the micronucleus rate rise in mid dose and high dose group compared with the control group, suggesting that nanocrystalline PbSe has genetic toxicity on rats. Nano PbSe can lead to changes in blood routine index and bone marrow micronucleus rate, and its toxicity was positively related to the dosage.

Hypo- and hypernatremia results in inaccurate erythrocyte mean corpuscular volume measurement in vitro, when using Sysmex XE 2100

Introduction. Automated hematology analyzers dilute patient erythrocytes with an isoosmotic diluent before quantitating the erythrocyte mean cell volume (MCV). However, if patient plasma osmolality differs from the diluent, water will cross the erythrocytes membrane and establish a new equilibrium across the membrane. Since the new equilibrium is reached before the measurement of the MCV, the measured MCV may not reflect the true MCV in vivo. Aim. Calculation of the theoretical change in MCV at changed P-Sodium/P-Osmolality and to investigate if the automated blood cell counter Sysmex XE 2100 measures MCV correctly in hypo- and hyperosmolality and hypo-and hypernatremia. In addition, to examine whether the theoretically calculated change in MCV corresponds with the experimentally determined MCV change. Method. Theoretical calculation of the MCV inaccuracy at hypo- and hypernatremia, as well as at hypo- and hyperosmolality. Experimental studies with comparison of MCV measured at Sysmex XE 2100 to MCV found by using the manual measured packed cell volume method. Results and conclusion. Measurement of MCV in hypo- and hypernatremia patients using the automated blood cell counter Sysmex XE 2100 resulted in inaccurate MCV. The experimental results also revealed a strong correlation between P-Osmolality/P-Sodium and MCV inaccuracy (R2 = 0.70/0.85) similar to the theoretically calculated MCV inaccuracy. We suggest using mean cellular Hb (MCH) instead of MCV, mean corpuscular Hb concentration (MCHC) and B-Erythrocyte volume fraction (EVF). Alternatively, we suggest standardizing the measured MCV to a normal P-Sodium e.g. 140 mmol/L to estimate the in vivo MCV.

Is plasma soluble CD36 associated with cardiovascular risk factors in early onset coronary artery disease patients?

Background and purpose. This is the first study to investigate the relationship between plasma concentration of soluble CD36 (sCD36) and CD36 gene polymorphisms as well as clinical and echocardiographic parameters in patients with early onset coronary artery disease (CAD). Methods. sCD36 concentrations were measured by the ELISA kits. CD36 sequence alterations detected by the DHPLC technique comprised single nucleotide substitutions: rs3173798, rs3211892, rs5956 and rs141680676. Results. There were significant negative correlations between sCD36 and red blood cell count, hemoglobin, hematocrit and glucose concentration, ApoB/ApoA1 ratio, patients’ weight and waist circumference, BMI, WHR, systolic blood pressure, MAP values, left ventricular end-diastolic diameter and volume, left atrium diameter, right ventricular end-diastolic diameter. There were significant positive correlations between sCD36 and patients’ age, mean corpuscular volume of erythrocytes, HDL-cholesterol, ApoA1 concentrations. Significantly higher CD36 plasma levels were found in female subgroup. There was no association between CD36 genotypes and sCD36 concentrations. Multiple linear regression analysis revealed that significant independent predictors of higher plasma sCD36 level were female gender, older age, lower serum glucose and lower RBC. Conclusion. The presented data suggest possible protective effects of higher sCD36 concentration in relation to metabolic syndrome components in CAD patients. Higher sCD36 concentration is also associated with lower risk of left ventricular hypertrophy, but on the other hand is a potential risk factor of impaired left ventricle diastolic function.

Predictive role of erythrocyte macrocytosis during treatment with pemetrexed in advanced non-small cell lung cancer patients.

Pemetrexed has been approved for the treatment of advanced non-small cell lung cancer (NSCLC) non-squamous histology, both as first- and second-line therapy. Pemetrexed is an antimetabolite drug, that inhibits enzymes involved in nucleotides bio-synthesis arresting cancer cells cycle. The aim of this study was the evaluation of the impact of pemetrexed on erythrocyte mean corpuscular volume (MCV) change and its possible correlation with disease control rate (DCR), progression free (PFS) and overall survival (OS) in NSCLC patients. A retrospective collection of clinical and laboratory data (including basal MCV and maximum MCV occurred during therapy) in advanced NSCLC patients treated with pemetrexed at seven Italian centers was performed. Nonparametric tests, univariate and multivariate analysis were used to assess correlation between variables and to identify predictors of outcomes. 191 patients were enrolled: median age 62, 60% male, 61% performance status (PS) 0, 91% stage IV, 88% adenocarcinoma histotype, 25% never smoker, 62% received pemetrexed as first-line. Mean MCV significantly increased from basal (89fL) to during treatment (94fL), with mean ΔMCV=4fL. The median time from therapy start to maximum MCV was 2.2 months. Median PFS was 7 [CI95% 6-8] and 3 [CI95% 2-4] months [P=0.0016], and median survival was 17 [CI95% 12-23] and 10 [CI95% 8-12] months [P=0.02], in patients with ΔMCV>5fL (n=80) and ΔMCV≤5fL (n=111), respectively. Multivariate analysis identified age ≥62, PS 0, adenocarcinoma histology and ΔMCV>5fL as independent predictors of longer PFS. A ΔMCV>5fL significantly correlates with DCR. Pemetrexed induces macrocytosis. ΔMCV>5fL on pemetrexed therapy correlated with better DCR, PFS and OS. These results deserve further validation in prospective studies.

Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia.

Some familial platelet disorders are associated with predisposition to leukemia, myelodysplastic syndrome (MDS) or dyserythropoietic anemia.1,2 We identified a family with autosomal dominant thrombocytopenia, high erythrocyte mean corpuscular volume (MCV) and two occurrences of B-cell precursor acute lymphoblastic leukemia (ALL). Whole exome sequencing identified a heterozygous single nucleotide change in ETV6 (Ets Variant Gene 6), c.641C>T, encoding a p.Pro214Leu substitution in the central domain, segregating with thrombocytopenia and elevated MCV. A screen of 23 families with similar phenotype found two with ETV6 mutations. One family had the p.Pro214Leu mutation and one individual with ALL. The other family had a c.1252A>G transition producing a p.Arg418Gly substitution in the DNA binding domain, with alternative splicing and exon-skipping. Functional characterization of these mutations showed aberrant cellular localization of mutant and endogenous ETV6, decreased transcriptional repression and altered megakaryocyte maturation. Our findings underscore a key role for ETV6 in platelet formation and leukemia predisposition.

Iron-refractory iron deficiency anemia.

Iron is essential for life because it is indispensable for several biological reactions, such as oxygen transport, DNA synthesis, and cell proliferation. Over the past few years, our understanding of iron metabolism and its regulation has changed dramatically. New disorders of iron metabolism have emerged, and the role of iron as a cofactor in other disorders has begun to be recognized. The study of genetic conditions such as hemochromatosis and iron-refractory iron deficiency anemia (IRIDA) has provided crucial insights into the molecular mechanisms controlling iron homeostasis. In the future, these advances may be exploited to improve treatment of both genetic and acquired iron disorders. IRIDA is caused by mutations in TMPRSS6, the gene encoding matriptase-2, which downregulates hepcidin expression under conditions of iron deficiency. The typical features of this disorder are hypochromic, microcytic anemia with a very low mean corpuscular volume of erythrocytes, low transferrin saturation, no (or inadequate) response to oral iron, and only a partial response to parenteral iron. In contrast to classic iron deficiency anemia, serum ferritin levels are usually low-normal, and serum or urinary hepcidin levels are inappropriately high for the degree of anemia. Although the number of cases reported thus far in the literature does not exceed 100, this disorder is considered the most common of the “atypical” microcytic anemias. The aim of this review is to share the current knowledge on IRIDA and increase awareness in this field.

Change in erythrocyte mean corpuscular volume during combination therapy with azathioprine and infliximab is associated with mucosal healing: a post hoc analysis from SONIC.

The adequacy of exposure of purine analogs as measured by 6-thioguanine nucleotides concentrations in the setting of combination therapy remains poorly understood. The aim of this study was to investigate the relationship between the mean corpuscular volume (MCV) value (as a surrogate marker of 6-thioguanine nucleotides concentration) and Crohn's disease outcomes in the setting of combination therapy with infliximab. The SONIC trial was a randomized controlled trial comparing infliximab to azathioprine and to infliximab plus azathioprine in 508 Crohn's disease patients. An increase of at least 7 femtoliter (fL) of the MCV (ΔMCV) was used for statistical analysis. At week 26, the mean increase of MCV was similar among patients treated with azathioprine alone (mean of 7.9 fL) or in combination with infliximab (mean of 8.5 fL). In the azathioprine group, 63.6% of patients with ΔMCV >7 were in steroid-free clinical remission at week 26 as compared with 33.3% of patients without ΔMCV >7 (P = 0.0046). In the combination therapy group, ΔMCV above 7 was associated with mucosal healing (75.0% for ΔMCV >7 versus 47.1% for ΔMCV <7, P = 0.0172) but not with steroid-free clinical remission. Patients with a ΔMCV above 7 were more likely to have infliximab trough level above 3 μg/mL at week 30 (68.4% versus 38.8% for ΔMCV <7, P = 0.0032). These results suggest that ΔMCV above 7 (which is a surrogate for a higher 6-thioguanine nucleotides concentration) leads to improved Crohn's disease outcomes, even when combined with infliximab. It also suggests the possibility that a lower azathioprine exposure might be less effective in combination therapy.

YKL-40 and alcoholic liver and pancreas damage and disease in 86,258 individuals from the general population: cohort and mendelian randomization studies.

We tested the hypothesis that observationally and genetically increased YKL-40 concentrations are associated with alcoholic liver and pancreas damage and disease. We performed cohort and mendelian randomization in 86,258 individuals from the Danish general population, with measured concentrations of plasma YKL-40 (n = 21 646) and CHI3L1 rs4950928 genotype (n = 84 738). Increased YKL-40 was associated with increased alanine aminotransferase, bilirubin, alkaline phosphatase, γ-glutamyl transferase, erythrocyte mean corpuscular volume, C-reactive protein, and fibrinogen and with decreased albumin; coagulation factors II, VII, and X; and pancreatic amylase. The multifactorially adjusted hazard ratio for alcoholic liver cirrhosis comparing the 96%-100% vs 0%-33% YKL-40 percentile categories was 41 (95% CI 14-118). Corresponding ratios were 7.9 (5.1-12) for any alcoholic liver disease, 4.1 (1.7-10) for alcoholic pancreatitis, and 3.4 (1.9-6.1) for any pancreatitis. CHI3L1 rs4950928 genotype explained 14% of the variation in plasma YKL-40 concentrations but was not associated with alcoholic liver and pancreas damage or disease. A doubling in YKL-40 concentrations was associated with a multifactorially adjusted observational hazard ratio of 2.8 (2.4-3.3) for alcoholic liver cirrhosis and a corresponding genetic odds ratio of 1.1 (0.7-1.5). Corresponding risk estimates were 2.0 (1.8-2.2) observationally and 1.0 (0.8-1.1) genetically for any alcoholic liver disease, 1.4 (1.1-1.9) observationally and 1.1 (0.8-1.5) genetically for alcoholic pancreatitis, and 1.3 (1.1-1.6) observationally and 1.0 (0.8-1.3) genetically for any pancreatitis. Excessive alcohol consumption combined with YKL-40 concentrations in the top 5% was associated with 10-year risk of alcoholic liver cirrhosis of up to 7% in ever-smokers and 2% in never-smokers. YKL-40 concentration within the top 5% was a marker for alcoholic liver cirrhosis, with no evidence to support a causal relationship.

Hematology and serum biochemistry of captive gharial (Gavialis gangeticus) in India

Aim: To study the hematological and serum biochemical parameters of the critically endangered gharial (Gavialis gangeticus). Materials and Methods: Blood samples for hemato-biochemical analyses were collected from the ventral median coccygeal vein of six juvenile and six sub adult gharials of Dewari Gharial Rearing Centre of National Chambal Sanctuary, Madhya Pradesh, India. Hematological examination was performed manually. Differential leukocyte count was performed on the blood smears stained with Giemsa’s stain. The analysis of serum was conducted by eppendorf ECOM-F 6124 semi auto biochemical analyzer using standard ERBA biochemical reagent kits. Results: Peripheral blood cells of gharial showed erythrocytes with an oval outline and centrally located prominent round to oval nucleus. Erythrocyte count in sub adult gharials was significantly greater than juveniles. Whereas erythrocyte mean corpuscular volume and erythrocyte size in juveniles was significantly larger than sub adults. The average most abundant leukocyte type in gharial was lymphocytes (53%), followed by heterophils (27%), eosinophils (10%), monocytes (7%) and basophils (3%). Aspartate aminotransferase, alkaline phosphatase, blood urea nitrogen, triglycerides and albumin concentrations in sub adult gharials were significantly higher than juveniles. No significant differences were determined in other hemato-biochemical parameters between juvenile and sub adult gharials under study. Conclusion: A preliminary database on hematology and blood biochemistry of gharial was established. The data will be useful in routine health evaluations, especially in relation to determining potential effects associated with factors such as pollution and infectious diseases.

JAK2V617F somatic mutation in the general population: myeloproliferative neoplasm development and progression rate

Clinical significance of the JAK2V617F mutation in patients with a myeloproliferative neoplasm has been the target of intensive research in recent years. However, there is considerably uncertainty about prognosis in JAK2V617F positive individuals without overt signs of myeloproliferative disease. In this study, we tested the hypothesis that increased JAK2V617F somatic mutation burden is associated with myeloproliferative neoplasm progression rate in the general population. Among 49,488 individuals from the Copenhagen General Population Study, 63 (0.1%) tested positive for the JAK2V617F mutation in the time period 2003-2008. Of these, 48 were available for re-examination in 2012. Level of JAK2V617F mutation burden was associated with myeloproliferative neoplasm progression rate, consistent with a biological continuum of increasing JAK2V617F mutation burden across increasing severity of myeloproliferative neoplasm from no disease (n=8 at re-examination) through essential thrombocythemia (n=20) and polycythemia vera (n=13) to primary myelofibrosis (n=7). Among those diagnosed with a myeloproliferative neoplasm only at re-examination in 2012, in the preceding years JAK2V617F mutation burden increased by 0.55% per year, erythrocyte volume fraction increased by 1.19% per year, and erythrocyte mean corpuscular volume increased by 1.25% per year, while there was no change in platelet count or erythropoietin levels. Furthermore, we established a JAK2V617F mutation burden cut-off point of 2% indicative of disease versus no disease; however, individuals with a mutation burden below 2% may suffer from a latent form of myeloproliferative disease revealed by a slightly larger spleen and/or slightly higher lactic acid dehydrogenase concentration compared to controls. Of all 63 JAK2V617F positive individuals, 48 were eventually diagnosed with a myeloproliferative neoplasm.

Biochemical Markers of Acute and Chronic Ethanol Use: Forensic and Clinical Applications

Background: The analysis of ethanol in bio-samples is an important method for determination of acute alcohol use/abuse both in clinical and forensic toxicology. In forensic cases, it is known that micro-organisms involved in the postmortem putrefaction process can produce alcohol and when the body has been traumatized. In clinical setting, post-ingestion time has a critical role for determination of alcohol level in biological fluids and the ethanol has been decreased during post-ingestion period, especially in chronic alcohol abusers. From this view, new biomarkers have been studied for evaluation of acute and chronic ethanol use/abuse in clinical and forensic cases. In this article, the role of each biomarker in determination of alcohol use/abuse was reviewed.Methods: We searched the PubMed and Google Scholar databases for articles about biomarkers of ethanol use/abuse with words “Alcohol”, “Ethanol”, “Biomarker”, “Abuse”, “Forensic” and “Clinical” from 1975-2014. Results: In postmortem cases, alcohol concentrations in blood, urine and vitreous depending on the status of the body. Urine and vitreous analysis may also be helpful, particularly in conjunction with blood. If none of these specimens is available, resort can be made to other organ and tissue samples but there are difficulties in both methodology and interpretation of results relating any alcohol present to ingested ethanol. Ethanol in gastric contents generally indicates recent ingestion, but the rapid absorption of ethanol and postmortem diffusion from the stomach may limit the usefulness of analysis of gastric contents. It is possible to measure parameters which are associated with or indicate ethanol consumption. Recently, ethyl glucuronide (EtG), 5-hydroxytryptophol (5-HTOL), gamma- glutamyltransferase (GGT), mean corpuscular volume (MCV) of erythrocytes and aminotransferases were found to have some applications in the clinical and medico-legal settings for determination of alcohol use/abuse history in acute and chronic states. Conclusion: 5-HPTOL and EtG can be considered as new biomarkers for determination of alcohol use/abuse in clinical and medico-legal settings.

Etiologies and diagnostic work‐up of extreme macrocytosis defined by an erythrocyte mean corpuscular volume over 130°fL: A study of 109 patients

Etiologies and diagnostic work‐up of extreme macrocytosis defined by an erythrocyte mean corpuscular volume over 130°fL: A study of 109 patients

In vitro increase of mean corpuscular volume difference (dMCV) as a marker for serum hypertonicity in dogs

Spurious increase in erythrocyte mean corpuscular volume (MCV) on automated cell analyzers is a well-characterized lab error in hypertonic patients. A difference between automated and manual MCV (dMCV) greater than 2 fl has been shown to predict hypertonicity in humans. The purpose of this study was to investigate dMCV as a marker for serum hypertonicity in dogs and to examine the relationship between dMCV and three methods of estimating serum tonicity: measured (OsMM), calculated (OsMC), and calculated effective (OsMCE) osmolalities. OsMC, OsMCE, and dMCV were calculated from routine blood values and OsMM was directly measured in 121 dogs. The dMCV of hypertonic dogs was significantly larger than that of normotonic dogs for all three osmolality methods. dMCV predicted hypertonicity as estimated by OsMM better than it predicted hypertonicity as estimated by OsMC and OsMCE. A cutoff of 2.96 fl yielded the best sensitivity (76%) and specificity (71%) for hypertonicity estimated by OsMM.

Tayanç-Prasad Sendromu

The Tayanc-Prasad Syndrome is characterized by growth retardation, hypogonadism hepatosplenomegaly, iron and zinc deficiency anemia, geophagia and alterations in the small intestine mucosa. A fifteen- year- old girl presented with fatigue, short stature, delayed puberty, geophagia, growth retardation and hepatosplenomegaly. It was learnt that she didn’t demonstrate any adolescent characteristics, consumed inadequate amounts of animal foods, and had pica syndrome. On her physical examination her height, and weight were under the 3. percentile relative to her age-, and gender-matched peers, and she had splenohepatomegaly. Laboratory findings showed low haemoglobin (4.9 g/dl), haematocrit (17.6 %), erythrocyte mean corpuscular volume (56.8 fL), serum ferritin (&lt;1.2 ng/dl) and increased of erythrocyte distribution width (21.9 %). The patient with profound iron deficiency was diagnosed as Tayanc-Prasad Syndrome with low levels of zinc in hair. In conclusion, zinc deficiency should be kept in mind in patients with severe iron deficiency anemia.

Mean Corpuscular Volume (MCV) Values Reflect Therapeutic Effectiveness in Zidovudine‐Receiving HIV Patients

An increase of the mean corpuscular volume (MCV) of erythrocytes and alterations in the lipid profiles have been described in HIV-infected patients under combination of anti-retroviral treatment (cART), particularly zidovudine (AZT). In 687 sera from 179 HIV-positive patients, MCV levels were correlated with the clinical outcome or therapeutic effectiveness. The sera were classified into three groups according to AZT treatment; cART with AZT (n = 317), cART without AZT (n = 262), and no anti-retroviral therapy (n = 108). The MCV and lipid profile values were increased after cART. The AZT-based cART group had higher MCV levels (111.6 ± 7.0 vs. 97.8 ± 7.0 fl, P < 0.001) and a higher incidence of macrocytosis (>99 fl; 95.3% vs. 38.2%, P < 0.001) than the non-AZT-based cART group. The receiver operating characteristic curve analysis showed that the area under the curve was 0.835 and the cut-off of MCV (>102 fl) had a sensitivity of 96.1% and specificity of 66.7% for detecting HIV-RNA (-) sera in AZT-based cART group. In the multivariate regression analysis, HIV-viral load and HDL-cholesterol were the only significant correlates to the MCV values in the AZT-base cART group (P < 0.05). The MCV values could be used as a surrogate marker to monitor the clinical outcome of HIV-infected patients receiving AZT-based cART.

Su1722 Kupffer Cell-Specific Calcium Signaling Drives Inflammation in Alcoholic Liver Disease (ALD) in Mice

[Background] A simple method for discriminating alcoholic liver disease (ALD) from nonalcoholic fatty liver disease (NAFLD) could be helpful in the management of fatty liver disease. Although ALD/NAFLD index is known to be useful in Caucasian subjects (Dunn et al. Gastroenterology 2006;131:1057-1063), no corresponding indices for Asian subjects have been reported yet. In this study, we aimed to develop a discrimination index for Japanese subjects using readily available clinical parameters. [Materials and Methods] Between 2009 and 2010, we conducted a nationwide survey for Japanese subjects to evaluate the status of fatty liver disease and collected data from 695 subjects with biopsy-proven ALD (n = 147) or NAFLD (n = 548). The index was developed on the basis of clinical parameters that were significant on multiple logistic regression analysis. [Results] This multivariate analysis identified the following significant parameters: gender, body mass index (BMI), aspartate aminotransferase level/alanine aminotransferase level, γ-glutamyl transpeptidase level, and mean corpuscular erythrocyte volume. Discrimination index greater than 0 was suggestive of ALD and that less than 0 was suggestive of NAFLD. The index had an area under the receiver operating characteristic (ROC) curve of 0.936 (95% confidence interval, 0.910-0.962). For diagnosing ALD, following were the suggested values for assessment: sensitivity, 66.7%; specificity, 96.7%; positive predictive value, 84.5%; and negative predictive value, 91.5%. On the other hand, for diagnosing NAFLD, following were the suggested values for assessment: sensitivity, 96.7%; specificity, 66.7%; positive predictive value, 91.5%; and negative predictive value, 84.5%. The index was validated for use in subgroups classified according to histological findings or BMI. In the simple steatosis group, the sensitivity and specificity for diagnosing ALD were 42.3% and 93.5%, respectively; in the fibrosis group, the sensitivity and specificity for diagnosing ALD were 80.0% and 97.5%, respectively. In the group with BMI ,25 kg/m2, the sensitivity and specificity for diagnosing ALD were 77.2% and 92.2%, respectively; in the group with BMI ≥25 kg/m2, the sensitivity and specificity for diagnosing ALD were 43.5% and 98.7%, respectively. [Conclusions] This index is excellent for differentiating ALD from NAFLD: it is particularly helpful for ruling in ALD and ruling out NAFLD. Thus, we believe that this index should be validated in other Asian populations.

Su1720 Differentiation of Alcoholic Liver Disease From Nonalcoholic Fatty Liver Disease Using a Logistic Regression Model Based on Clinical Parameters

[Background] A simple method for discriminating alcoholic liver disease (ALD) from nonalcoholic fatty liver disease (NAFLD) could be helpful in the management of fatty liver disease. Although ALD/NAFLD index is known to be useful in Caucasian subjects (Dunn et al. Gastroenterology 2006;131:1057-1063), no corresponding indices for Asian subjects have been reported yet. In this study, we aimed to develop a discrimination index for Japanese subjects using readily available clinical parameters. [Materials and Methods] Between 2009 and 2010, we conducted a nationwide survey for Japanese subjects to evaluate the status of fatty liver disease and collected data from 695 subjects with biopsy-proven ALD (n = 147) or NAFLD (n = 548). The index was developed on the basis of clinical parameters that were significant on multiple logistic regression analysis. [Results] This multivariate analysis identified the following significant parameters: gender, body mass index (BMI), aspartate aminotransferase level/alanine aminotransferase level, γ-glutamyl transpeptidase level, and mean corpuscular erythrocyte volume. Discrimination index greater than 0 was suggestive of ALD and that less than 0 was suggestive of NAFLD. The index had an area under the receiver operating characteristic (ROC) curve of 0.936 (95% confidence interval, 0.910-0.962). For diagnosing ALD, following were the suggested values for assessment: sensitivity, 66.7%; specificity, 96.7%; positive predictive value, 84.5%; and negative predictive value, 91.5%. On the other hand, for diagnosing NAFLD, following were the suggested values for assessment: sensitivity, 96.7%; specificity, 66.7%; positive predictive value, 91.5%; and negative predictive value, 84.5%. The index was validated for use in subgroups classified according to histological findings or BMI. In the simple steatosis group, the sensitivity and specificity for diagnosing ALD were 42.3% and 93.5%, respectively; in the fibrosis group, the sensitivity and specificity for diagnosing ALD were 80.0% and 97.5%, respectively. In the group with BMI ,25 kg/m2, the sensitivity and specificity for diagnosing ALD were 77.2% and 92.2%, respectively; in the group with BMI ≥25 kg/m2, the sensitivity and specificity for diagnosing ALD were 43.5% and 98.7%, respectively. [Conclusions] This index is excellent for differentiating ALD from NAFLD: it is particularly helpful for ruling in ALD and ruling out NAFLD. Thus, we believe that this index should be validated in other Asian populations.