Utility of gamma-glutamyl transpeptidase and mean corpuscular volume in alcoholic liver disease

The present study was designed to establish the role of Gamma-glutamyl transpeptidase (gamma-GT) and mean corpuscular volume (MCV) in alcoholic liver disease (ALD). Serum gamma-GT, total and direct bilirubin, albumin, total protein, AST, ALT and ALP were assayed by standard methods in a clinical chemistry autoanalyser. MCV, Hb, PCV and RBC were measured by an automated cell counter. Activity of gamma-GT and MCV levels were significantly higher in the patients with ALD compared to controls. A gamma-GT level of > or = 25 U/l was found to be significantly associated with ALD. MCV level > or = 100 fl/l showed a significant association with ALD. An AST to ALT ratio > 1 was found in 92% of the patients. None of the patients showed an ALT level > or = 300 IU/l. The degree of AST elevation in the patients with ALD was higher (3.7 times) then ALT (3.2 times). A gamma-GT level > or = 25 IU/L and an MCV level > or = 100 fl/l stand as markers of heavy alcohol consumption in this study. An AST to ALT ratio > 1 was present in most of the patients with ALD. The degree of elevation of AST was higher than ALT in the patients with ALD.     

酒精摄入量与肝功能、平均红细胞体积的关系

目的 探讨肝功能和平均红细胞体积(MCV)等指标在饮酒者中的临床价值.方法 随机抽取我院体检中心体检人员624名,研究饮酒与谷氨酰转肽酶(GGT)、丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)及MCV异常的关系.结果 受试者中日摄人乙醇超过20g者占24.05%,日摄人乙醇超过40 g者占15.2%,日摄人乙醇超过80g者占6.6%.随着日饮酒量增多,饮酒者的MCV逐渐增高.饮酒可引起GGT、ALT和AST异常,并与饮酒量成正比,其中以GGT为著,AST次之.结论 GGT、ALT和AST的检测有助于饮酒者肝损害的诊断,MCV的检测可作为危险饮酒的监测指标.     

Association between erythrocyte mean corpuscular volume and peripheral arterial disease in male subjects: a case control study

Elevated serum total homocysteine, an established risk factor for peripheral arterial disease, is influenced by the vitamin B12 and folate status. Since these vitamins are inversely correlated with erythrocyte mean corpuscular volume, an investigation of whether mean corpuscular volume is higher in patients with symptomatic peripheral arterial disease than in healthy subjects was performed. Furthermore, a determination of predictors of increased mean corpuscular volume levels in this population free of symptomatic coronary artery disease, cerebrovascular disease, and diabetes mellitus was carried out. From 469 consecutive patients with symptomatic peripheral arterial disease, 100 fulfilled study inclusion criteria. Peripheral arterial disease was confirmed by angiography. One hundred age-matched subjects without peripheral arterial disease as verified by ankle-brachial index measurements >0.9 served as control subjects. Patients with PAD displayed a significantly higher mean corpuscular volume level (94.5 fl) than control subjects (90.9 fl, p<0.001). Logistic regression analysis showed that current smoking status (p<0.001) and mean corpuscular volume (p=0.009), but not total homocysteine or lipid parameters discriminated case control status. In addition, logistic regression analysis revealed a relationship of mean corpuscular volume with smoking (p=0.001), gamma-glutamyltransferase (p<0.001), and total homocysteine (p=0.012). This model predicted mean corpuscular volume values with an accuracy of 83%. Elevated mean corpuscular volume is a predictor of symptomatic peripheral arterial disease in the sample studied. A deficiency of folate and/or vitamin B12 may be responsible for this observation, as indicated by the correlation of mean corpuscular volume with total homocysteine. Due to the additional association of mean corpuscular volume with smoking and gamma-glutamyltransferase, an unhealthy lifestyle with low vitamin intake may cause elevated mean corpuscular volume values in patients with PAD.     

Study of erythrocyte mean corpuscular volume during cytotoxic therapy as a predictive parameter of the risk of secondary leukemia in Hodgkin's disease

Erythrocyte mean corpuscular volume (MCV) evolution was studied during cytotoxic therapy in 12 patients with Hodgkin's disease who developed secondary acute leukemia and in 83 patients with Hodgkin's disease without secondary leukemia as control group. Significant differences were observed in the maximum MCV and in the MCV maximum increase during therapy between the two groups of patients. These differences remained significant between the patients treated with chemotherapy alone and those treated with chemotherapy and radiotherapy. MCV maximum increase greater than 23.9 fl was observed in all patients with secondary leukemia and in only 20% of those without secondary leukemia; it was reached 46.3 months before the first sign of preleukemia. Its value in predicting the leukemic risk in Hodgkin's disease is discussed.     

The negative correlation between mean corpuscular volume and erythrocyte count in anemic and non-anemic children

Summary A significant negative correlation was observed between mean corpuscular volume and erythrocyte count in school children 6 to 14 years of age. Slopes of regression lines of MCV/RBC were significantly higher in anemics than in non-anemics, but no significant difference was observed between boys and girls.     

Hangover susceptibility in relation to aldehyde dehydrogenase-2 genotype, alcohol flushing, and mean corpuscular volume in Japanese workers

BACKGROUND: A study of Asian-American students suggested a positive association between inactive ALDH2*2 and susceptibility to hangover. A biomarker for moderate-to-heavy drinking in persons with inactive aldehyde dehydrogenase-2 (ALDH2) is increased mean corpuscular volume (MCV). METHODS: Associations between hangover and ALDH2 genotype, alcohol flushing, and MCV were examined for 251 Japanese workers (139 men, 112 women). RESULTS: Inactive ALDH2*1/2*2 heterozygotes drank less alcohol than active ALDH2*1/2*1 homozygotes (p < 0.0001), but the frequency of hangover did not significantly differ between the two groups for either gender. The amount of drinking reported to lead to hangover was significantly less for male and female ALDH2*1/2*2 heterozygotes than for their ALDH2*1/2*1 homozygous counterparts (p < 0.005). The proportion of men who had hangover three times or more during the past year increased significantly with increased daily alcohol consumption in men with the ALDH2*1/2*2 genotype (p = 0.0002) but not in those with the ALDH2*1/2*1 genotype. For men who usually consumed <44 g of ethanol/day, the median amount of drinking before hangover was significantly lower for ALDH2*1/2*2 men than for ALDH2*1/2*1 men reporting the same level of consumption. Hangover occurred with consistently high frequency among ALDH2*1/2*1 men, regardless of their daily consumption. Similar findings were observed in a comparison of men who never flushed and those who reported current or former flushing, a surrogate marker of inactive ALDH2. Assessment of hangover risk by quartiles of MCV showed that men with MCV of > or =96 had a significantly higher risk of hangover than did men with MCV of <91 (odds ratio = 5.56; 95% confidence interval = 1.69-18.25). CONCLUSIONS: Inactive heterozygous ALDH2, alcohol flushing, and increased MCV were positively associated with hangover susceptibility in Japanese workers, suggesting that acetaldehyde is etiologically linked to the development of hangover.     

Combined use of erythrocyte zinc protoporphyrin and mean corpuscular volume in differentiation of thalassemia from iron deficiency anemia

Abstract: In a retrospective study the diagnostic value of erythrocyte zinc protoporphyrin (ZPP) measurement as a means of distinguishing iron deficiency anemia from thalassemia syndromes in patients with microcytosis was explored. ZPP values were increased in all patients with iron deficiency and in part of the patients with thalassemia. The combined measurement of erythrocyte mean corpuscular volume (MCV) and ZPP resulted in a correct classification of patients with iron deficiency and with thalassemia in more than 95%. The predictive value of this method is better than the results obtained by using formulae derived from red cell indices. In population screening programs for thalassemia syndromes, in which MCV determination is used as the initial test, the ZPP test is recommended as a second test, in order to discriminate between patients with microcytosis due to iron deficiency and patients with microcytosis due to thalassemia syndromes.     

丙氨酸转氨酶和天冬氨酸转氨酶是反映HBeAg阴性慢性乙型肝炎肝组织炎性分级的敏感指标

目的 分析HBeAg阴性慢性乙型肝炎(CHB)自然病程中血清ALT和AST水平,以及由相同肝实质细胞体积分摊的血清ALT和AST水平与肝组织炎症活动度分级的关系.方法 检测HBeAg阴性CHB患者肝组织病理学不同炎症活动度分级患者血清ALT和AST水平,以及相同肝实质细胞体积分摊的血清ALT和AST水平.数据经ANOVA检验.结果 145例CHB肝组织炎症活动度分级G1～G4级患者血清ALT水平分别为(35.3±29.1)、(91.6±120.4)、(111.6±116.1)和(118.0±122.1)U/L,用相同肝脏实质细胞体积分摊后的血清ALT水平分别为(54.0±45.1)、(144.2±184.9)、(191.3±204.8)和(215.1±226.5)U/L,G1级分别与G2～G4两两比较,差异有统计学意义(P＜0.05);G1～G4的AST水平分别为(35.5±29.0)、(64.9±71.7)、(96.0±81.9)和(102.8±77.0)U/L,相同肝脏实质细胞体积分摊后的血清AST水平分别为(54.3±44.6)、(102.3±107.9)、(165.2±148.7)和(189.4±145.4)U/L,G1与G3、G1与G4、G2与G3、G2与G4比较,差异有统计学意义(P＜0.05).结论 HBeAg阴性CHB自然病程中,ALT和AST均是反映肝组织炎症活动度分级严重性的较为敏感的指标.

Abstract：

Objective To investigate the relationship between serum levels of alanine aminotransferase (ALT)or aspartate aminotransferase (AST)apportioned by the same hepatic parenchyma cell volume and liver histological necroinflammation grades in HBeAg-negative chronic hepatitis B (CHB)patients.Methods A total of 145 CHB patients were divided into four groups:Gl,G2,G3 and G4 based on the liver histological necroinflammation grade.The serum ALT and AST levels were determined by automatic biochemical instrument in these four groups.Furthermore,serum ALT and AST levels were then apportioned by the same hepatic parenchyma cell volume.The data were analyzed by ANOVA.Results Mean serum ALT levels in G1,G2,G3 and G4 groups were (35.3±29.1),(91.6±120.4),(111.6± 116.1)and (118.0±122.1)U/L,respectively,and the serum ALT levels apportioned by same hepatic parenchyma cell volume were ( 54.0 ± 45.1 ),( 144.2 ± 184.9 ),(191.3± 204.8)and (215.1 ± 226.5)U/L,respectively.The pairwise comparison between G1 and other three groups all showed statistically significant difference (P＜0.05).Meanwhile,AST levels in G1 to G4 groups were (35.5± 29.0),(64.9±71.7),(96.0±81.9)and (102.8±77.0)U/L,respectively and the serum AST levels apportioned by the same hepatic parenchyma cell volume were (54.3±44.6),(102.3± 107.9),(165.2±148.7)and (189.4±145.4)U/L,respectively.The pairwise comparison between G1 and G3,G1 and G4,G2 and G3,G2 and G4 all showed statistically significant difference (P＜0.05).Conclusion Both AST and ALT levels are sensitive indicators for liver inflammation grading in HBeAg-negative CHB patients during the natural history of the disease.     

Erythrocyte mean corpuscular volume associated with the anatomical distribution in peripheral arterial disease

BACKGROUND: Elevated erythrocyte mean corpuscular volume (MCV) has been suggested to be a risk factor for peripheral arterial disease (PAD). The aim of the present study was to evaluate whether MCV was associated with a distinct pattern of severe atherosclerosis (lumen reductions > or = 75%) in patients with symptomatic PAD, as measured by angiography. PATIENTS AND METHODS: 100 consecutively admitted male PAD patients with iliac, femoral-popliteal and crural disease manifestation were compared with 100 male age-matched control subjects without PAD on the basis of angiographically determined lumen reductions > or = 75%. RESULTS: The pattern of severe atherosclerosis was as follows: 41 PAD patients displayed stenoses/occlusions in the iliac segment, 68 in the femoral-popliteal and 15 in the crural segment. When comparing the PAD patients with the controls by multivariate conditional logistic regression analysis, MCV was an independent predictor of severe atherosclerosis in the iliac (OR = 2.72 for an increment of 5 fl, 95% CI = 1.15-6.40) and the femoral-popliteal segment (OR = 3.13 for an increment of 5 fl, 95% CI = 1.51-6.49) but not in the crural site. This pattern was similar to the impact of smoking. CONCLUSION: Higher MCV values contributed to lumen reductions > or = 75% of the proximal segments in patients with symptomatic PAD. This observation could be clinically important since revascularisation procedures are done predominantly in these segments. As a consequence, observance of elevated MCV values should be considered in PAD patients.     

Validity of carbohydrate-deficient transferrin (%CDT), gamma-glutamyltransferase (gamma-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

AIM: 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. DESIGN: 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. FINDINGS: 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). CONCLUSION: %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.     

Dupuytren's contracture, alcohol consumption, and chronic liver disease

This prospective study was undertaken to assess the prevalence of Dupuytren's contracture (DC) and its relationship with possible causes, especially alcohol consumption and chronic liver disease. Four hundred thirty-two consecutively hospitalized patients were examined for evidence of DC. They were divided into five groups based on the following clinical, biologic, and histologic criteria: alcoholic cirrhosis (89 patients), noncirrhotic alcoholic liver disease (55 patients), chronic alcoholism without liver disease (46 patients), nonalcoholic chronic liver disease (68 patients), and a control group (174 patients). The prevalence of DC in these five groups of patients was 32.5%, 22%, 28%, 6%, and 12%, respectively; the prevalence of DC was higher in patients with cirrhotic or noncirrhotic alcoholic liver disease (25.5%) than it was in patients with nonalcoholic liver disease (6%), but it was not significantly different in alcoholic patients with or without liver disease. The relationship between DC and age, sex, manual labor, previous hand injuries, diabetes mellitus, alcohol consumption, and cigarette smoking was assessed by univariate and logistic regression methods. Nine variables were significantly different in patients with or without DC: age, sex, manual labor, previous hand injuries, diabetes mellitus, daily alcohol consumption, duration of alcohol consumption, total alcohol consumption, and duration of cigarette smoking. In our patients, variables that could explain DC were, in decreasing order, age, total alcohol consumption, sex (male), and previous hand injuries. In alcoholic patients, these variables were age and previous hand injuries; in nonalcoholic patients, these variables were age and cigarette smoking. These results emphasize the high prevalence of DC in alcoholic patients and the absence of a correlation between DC and chronic liver disease. Age and alcohol consumption are the best explanatory variables of DC in hospitalized patients.     

Sex differences of carbohydrate-deficient transferrin, gamma-glutamyltransferase, and mean corpuscular volume in alcohol-dependent patients

BACKGROUND: Biological markers like carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT), and mean corpuscular volume (MCV) are used widely to screen for alcoholism. Most research has focused on male alcoholics, and there are few studies on female patients. The results are inconsistent; in general, they show lower sensitivities for all markers for women. METHODS: We compared the diagnostic value of CDT, GGT, and MCV in 126 alcohol-dependent patients (91 men, 35 women) who entered an inpatient treatment program. For the receiver operating characteristic (ROC) analyses, we investigated a control group of 112 patients (64 men, 38 women) from the Department of Psychiatry at the University of Tübingen with no diagnosis of substance abuse or substance dependency. RESULTS: Mean levels of CDT and MCV were significantly different in male and female patients. CDT showed higher test results in men (4.4% vs. 2.8%, p < 0.05), whereas mean levels of MCV were higher in women (99.7 fl vs. 96.4 fl,p < 0.01). The sensitivities of CDT and GGT were higher in men than in women (CDT: 76% vs. 54%,p < 0.1; GGT: 68% vs. 43%,p < 0.05), and the sensitivity of MCV was significantly higher in women (71% vs. 41%,p < 0.01). The superiority of MCV in women also was supported by ROC analyses (p < 0.01). The combined use of markers showed satisfactory sensitivity rates of > or = 80% not only in men but also in women. Yet, the specificity rates were partly below the recommended 90% for identifying alcohol abuse; therefore, these markers must be combined with caution. CONCLUSIONS: If combined, the biological markers CDT and GGT are useful diagnostic instruments for both alcohol-dependent men and women. According to our results, the "forgotten" marker MCV is superior in women and is a marker of second choice in men. The combination GGT and MCV is the most cost-effective choice for men and women.     

Isoenzymes of aspartate aminotransferase in chronic liver diseases

The total activity and activity of the cytoplasmic and mitochondrial isoenzyme of aspartate aminotransferase was examined in blood plasma of 56 patients with chronic liver diseases (chronic hepatitis in 27, liver cirrhosis in 23, secondary neoplastic effection of the liver in 6). All the patients with biochemically active forms of liver disease manifested increased the total as well as cytoplasmic enzyme activity, as compared with control group, 57% of the patients manifested simultaneously also increased activity of the mitochondrial isoenzyme. In 13% of the patients with stabilised forms of liver diseases manifested isolated increase of the mitochondrial isoenzyme activity. This might be of importance for the evaluation of the course of the disease. In patients with tumorous metastases in the liver a strikingly high share and activity of mitochondrial isoenzyme was shown.     

Elevated mean corpuscular volume as a predictor of hematologic toxicity due to methotrexate therapy

Retrospective analysis of 23 rheumatoid arthritis patients receiving low-dose methotrexate (MTX) demonstrated an association between the mean corpuscular volume (MCV) and hematologic toxicity. All 6 patients who developed hematologic toxicity were folate deficient, and 4 of 6 had marked macrocytosis. Furthermore, the mean MCV of the patients who developed toxicity was significantly higher than that of the controls without toxicity (P less than 0.02). This difference in MCV was associated with an increased probability of developing toxicity with time (P less than 0.005). These results suggest that sustained elevation in the MCV may be a predictor of impending hematologic toxicity due to folate depletion.