Has mortality related to alcohol decreased in Sweden?

In Sweden sales of alcohol dropped 17% from 1976 to 1982. Similarly, comparison of data from 1979 and 1982 shows that the mortality from cirrhosis of the liver declined appreciably, by 28% in men and 29% in women. During 1979-82 mortality from pancreatitis also declined noticeably, by 30% in men and 36% in women. By contrast, no decrease occurred in mortality from alcoholic psychosis, alcoholism, or alcohol intoxication. The decrease in mortality from cirrhosis of the liver and pancreatitis is probably explained by a decrease in the consumption of alcohol among an important subgroup of high consumers of alcohol. The lack of a decrease in mortality from alcoholic psychosis, alcoholism, and alcohol intoxication may be because such diagnoses are often made in socially deteriorated, more dependent alcoholic subjects who have not been able to reduce their consumption.     

Importance of markers of hepatitis B virus in alcoholic liver disease.

To determine the importance of the presence of serological markers of hepatitis B virus infection in patients with alcohol related liver disease we compared cumulative alcohol intake and clinical and histological features in patients with markers of hepatitis B virus infection and in those without. Hepatitis B surface antigen (HBsAg) was detected in five (2%) out of 285 patients studied and antibody to HBsAg (anti-HBs) in 41 (14%); one patient had antibody to hepatitis B core antigen alone. The combined prevalence of markers of hepatitis B virus infection was similar in patients with alcoholic cirrhosis (18%) and precirrhotic liver disease (13%). Two patients positive for HBsAg had histological features of both alcoholic liver disease and chronic active hepatitis, with stainable HBsAg. Patients with anti-HBs were, however, histologically indistinguishable from patients without markers, and the mean cumulative alcohol intake of patients with anti-HBs was similar to or even higher than that of patients with liver disease of comparable severity who had no evidence of previous infection. The presence of markers of hepatitis B virus infection was related to former residence in countries with a high prevalence of the infection and to previous parenteral treatment and blood transfusions. Infection with hepatitis B virus does not enhance the development of chronic liver disease in heavy drinkers, except in the small number who remain positive for HBsAg.     

彩超与GGT联合检测对酒精依赖患者酒精肝的诊断价值

目的:研究分析彩超和谷氨酰转肽酶(GGT)联合检测对酒精依赖患者酒精性脂肪肝诊断的临床意义。方法:对2013年5月-2014年4月于我院住院并诊断为酒精依赖的患者39例(研究组)行肝脏彩超及GGT检测,另选取同期来源于本院职工、进修医护人员40例为对照组,对其结果进行分析。结果:研究组血清GGT为(189.95±226.52)U/L,显著高于对照组的(26.85±18.94)U/L,差异有统计学意义(t=4.54,P0.001);研究组中彩超诊断为脂肪肝者的GGT水平与非脂肪肝者有明显差异(P0.05),且高于对照组中的脂肪肝者,差异有统计学意义(P0.05)。结论:对于酒精依赖患者,血清GGT是敏感性较高的检测指标,GGT的检测有利于酒精性疾病的早期发现。彩超与GGT联合检测能提高临床对酒精性脂肪肝的检出率。     

Innate immunity in alcoholic liver disease

Excessive alcohol consumption is a leading cause of chronic liver disease in the Western world. Alcohol-induced hepatotoxicity and oxidative stress are important mechanisms contributing to the pathogenesis of alcoholic liver disease. However, emerging evidence suggests that activation of innate immunity involving TLR4 and complement also plays an important role in initiating alcoholic steatohepatitis and fibrosis, but the role of adaptive immunity in the pathogenesis of alcoholic liver disease remains obscure. Activation of a TLR4-mediated MyD88-independent (TRIF/IRF-3) signaling pathway in Kupffer cells contributes to alcoholic steatohepatitis, whereas activation of TLR4 signaling in hepatic stellate cells promotes liver fibrosis. Alcohol consumption activates the complement system in the liver by yet unidentified mechanisms, leading to alcoholic steatohepatitis. In contrast to activation of TLR4 and complement, alcohol consumption can inhibit natural killer cells, another important innate immunity component, contributing to alcohol-mediated acceleration of viral infection and liver fibrosis in patients with chronic viral hepatitis. Understanding of the role of innate immunity in the pathogenesis of alcoholic liver disease may help us identify novel therapeutic targets to treat this disease.     

Psychiatric morbidity in patients with alcoholic liver disease.

Seventy one patients with alcoholic liver disease and an equal number with non-alcoholic liver disease were interviewed using the schedule for affective disorders and schizophrenia. Forty seven (66%) of the group with alcoholic liver disease had or had had psychiatric illnesses compared with 23 (32%) of the control group (p less than 0.001). Affective disorder, particularly major depression, neurotic disorders, and antisocial personality, were all more common among the patients with alcoholic liver disease than the controls. No patient had schizophrenia or other forms of psychosis. Among the patients with alcoholic liver disease 11 men (24%) and 14 women (54%) had an affective or a neurotic disorder that had antedated their heavy drinking, and 30 (77%) of those who had had such a problem at any time had symptoms at the time of interview. Abstinence from alcohol is essential for patients with severe alcoholic liver disease. In view of the high prevalence of psychiatric disorders in these patients psychiatric assessment is important to increase the patients'' likelihood of complying with such advice.     

Clinical utility of red cell distribution width in alcoholic and non-alcoholic liver cirrhosis

Red blood cell distribution width (RDW) is a measure of the variation of red blood cell width that is reported as apart of standard complete blood count. Red blood cell distribution width results are often used together with mean corpuscular volume (MCV) results to figure out mixed anemia. The aim of our study was to compare the values of RDW in alcoholic and non-alcoholic liver cirrhosis and to determine if RDW follows the severity of disease according to Child-Pugh score. We retrospectively analyzed 241 patients (176 men and 65 women) with liver cirrhosis and anemia, defined as a hemoglobin value < 130 g/L in men and < 120 g/L in women, which were hospitalized in our Division in a period between 2006 and 2008. Patients were divided in two groups; in first were patients with alcoholic liver cirrhosis, and in second with non-alcoholic cirrhosis. Severity of disease was determined according to Child-Pugh score. Red blood cells distribution width Normal reference range is 11-15%. Alcoholic liver cirrhosis had 204 patients (85%) while non-alcoholic cirrhosis had 37 patients (15%). In group of alcoholic cirrhosis the average RDW was 16.8%. In relation to severity of disease the average RDW for Child-Pugh A was 16.80%, for Child-Pugh B was 16.92%, for Child-Pugh C was 17.10%. In the group of non-alcoholic cirrhosis the average RDW was 16.73% and in relation to severity of disease for Child-Pugh A was 16.25%, for Child-Pugh B 17.01% and for Child-Pugh C was 16.87%. We didn't find statistically significant difference of RDW between alcoholic and non alcoholic cirrhosis (p > 0.05) and we didn't proved any statistically significant increase of RDW in relation to severity of disease in group of alcoholic cirrhosis (p = 0.915) nor in group of patients with non-alcoholic cirrhosis (p = 0.697). Our study showed that RDW had not any clinical value in differentiation of anemia neither in alcoholic and non-alcoholic liver cirrhosis nor in severity of liver disease.     

Serum selenium levels and oxidative balance as differential markers in hepatic damage caused by alcohol

Aims

Antioxidant system abnormalities have been associated with ethanol consumption. This study examines the effects of chronic ethanol consumption on oxidative balance, including selenium (Se) levels in alcoholic patients with or without liver disease, and if these measurements could be indicative of liver disease.

Main methods

Serum Se levels, antioxidant enzymes' activities, malondialdehyde (MDA) and protein carbonyl (PC) were determined in three groups of patients: alcoholics without liver disease, alcoholics with liver disease, and non-alcoholics with liver disease; and in healthy volunteers.

Key findings

Serum Se levels were lower in alcoholic patients and in patients affected by liver disease and especially lower in the alcoholic liver disease group. These values were correlated with the activity of glutathione peroxidase (GPx), the antioxidant selenoprotein. The antioxidant activities of the glutathione reductase (GR) and superoxide dismutase (SOD) were also lower in the three non-healthy groups. However, GR activity decreased and SOD activity increased in the non-alcoholic liver disease group versus alcoholic groups. Higher concentrations of PC in serum were found in non-healthy groups and were higher in alcoholic patients who also showed higher MDA levels. The highest MDA and PC levels were found in the alcoholic liver disease group.

Significance

We conclude that serum Se levels are drastically decreased in alcoholic liver disease patients, showing that this element has a direct correlation with GPx activity, and lipid oxidation, suggesting that the serum Se/MDA ratio could be an indicator of hepatic damage caused by alcohol consumption, and pointing to Se as a possible antioxidant therapy.     

Changing pattern of alcoholic liver disease in Great Britain: relation to sex and signs of autoimmunity.

A survey of 293 patients with alcoholic liver disease showed that women, particularly those aged under 45, had a significantly higher incidence of alcoholic hepatitis, with or without superimposed cirrhosis, than men. The long-term prognosis for both women who continued to drink and those who stopped drinking was worse than that for men. Autoantibodies were more common in women, which suggested that immune mechanisms may play a part in the pathogenesis and progression of alcoholic liver disease in women.     

Altered hepatic retinyl ester concentration and acyl composition in response to alcohol consumption

Retinoids (vitamin A and its metabolites) are essential micronutrients that regulate many cellular processes. Greater than 70% of the body's retinoid reserves are stored in the liver as retinyl ester (RE). Chronic alcohol consumption induces depletion of hepatic retinoid stores, and the extent of this has been correlated with advancing stages of alcoholic liver disease. The goal of this study was to analyze the mechanisms responsible for depletion of hepatic RE stores by alcohol consumption. A change in the fatty-acyl composition of RE in alcohol-fed mice was observed within two weeks after the start of alcohol consumption. Specifically, alcohol-feeding was associated with a significant decline in hepatic retinyl palmitate levels; however, total RE levels were maintained by a compensatory increase in levels of usually minor RE species, particularly retinyl oleate. Our data suggests that alcohol feeding initially stimulates a futile cycle of RE hydrolysis and synthesis, and that the change in RE acyl composition is associated with a change in the acyl composition of hepatic phosphatidylcholine. The alcohol-induced change in RE acyl composition was specific to the liver, and was not seen in lung or white adipose tissue. This shift in hepatic RE fatty acyl composition is a sensitive indicator of alcohol consumption and may be an early biomarker for events associated with the development of alcoholic liver disease.     

Moderation in Australia-policy and achievements

Alcohol has been consumed in Australia since European settlement in 1788. In 1998, approximately 60% of Australians consumed an alcoholic beverage at least once per week. The effects of alcohol on the human body are dose dependent, where the harmful effects of alcohol are generally observed only when alcohol consumption exceeds moderate consumption levels of 30 to 40 g of alcohol per day. The discovery that a J-shaped curve described the relationship between level of alcohol consumption and risk of cardiovascular disease was, however, only made in 1990-cardiovascular disease is the leading cause of death in the western world. Thus prior to 1990, Australian public health policy focused primarily on the harmful effects of alcohol consumption and the health benefits of a moderate level of alcohol consumption have only recently been recognized in public policy. This paper chronicles changes in Australian Federal government policy on alcohol since the initial draft National health policy on alcohol in Australia was presented to the Ministerial Council on Drug Strategy in 1987 to the National Drug Strategic plan for action 2001 to 2003-2004 which was launched in July last year.     

Liver transplantation in patients with alcoholic cirrhosis: selection criteria and rates of survival and relapse.

OBJECTIVE--To evaluate the outcome of liver transplantation in patients with alcoholic cirrhosis with respect to selection criteria, survival, and evidence suggesting a return to harmful drinking. DESIGN--Nine year retrospective study. SETTING--Cambridge and King''s College Hospital liver transplant programme. SUBJECTS--24 Patients (three women, 21 men) with alcoholic cirrhosis. MAIN OUTCOME MEASURES--Survival, rehabilitation, and clinical and laboratory evidence of a return to harmful drinking after transplantation. RESULTS--15 Patients were selected for transplantation because of repeated admission to hospital for the complications of advanced portal hypertension despite abstinence, and six because they had a hepatocellular carcinoma superimposed on alcoholic cirrhosis. Three patients who were not abstinent received transplants. The one year survival rate was 66%, and of the 18 patients surviving at least three months, 17 had been rehabilitated. In three patients laboratory variables and histological examination of the liver suggested a return to drinking, though they did not admit to taking alcohol. These patients represented the only cases in the series that were not abstinent before transplantation. CONCLUSIONS--The survival and rehabilitation of patients who received transplants for alcoholic cirrhosis compared favourably with those of patients who received transplants for cirrhosis of other aetiology. The criteria for selection for liver transplantation in patients with alcoholic cirrhosis should include recurrent complications related to severe portal hypertension despite maximum medical treatment in addition to a minimum period of six months of abstinence before transplantation.     

Circulating Lipids Are Associated with Alcoholic Liver Cirrhosis and Represent Potential Biomarkers for Risk Assessment

Liver disease is the greatest cause of death related to alcohol and a major public health problem. While excessive alcohol intake results in hepatosteatosis in most individuals, this can progress in some to more severe forms of liver disease including fibrosis and cirrhosis. An ongoing challenge in the management of alcoholic liver disease is the identification of liver injury early in the disease process such that intervention strategies can prevent serious long term outcomes. Given that excessive alcohol consumption results in dysregulation of lipid metabolism we applied lipid profiling technology to characterise and compare serum lipid profiles from excessive chronic drinkers with no liver disease to those with advanced alcoholic cirrhosis. In a cohort of 59 excessive drinkers (31 with liver cirrhosis and 28 with no evidence of liver disease) we used electrospray ionisation tandem mass spectrometry to measure over 300 individual lipid species in serum, including species of the major phospholipid, sphingolipid, glycerolipid and sterol classes. Six of the 25 lipid classes and subclasses were significantly associated with alcoholic liver cirrhosis; these included dihexosylceramide, trihexosylceramide, alkylphosphatidylcholine, lysoalkylphosphatidylcholine, phosphatidylinositol and free cholesterol. Multivariate classification models created with only clinical characteristics gave an optimal model with an AUC of 0.847 and an accuracy of 79.7%. The addition of lipid measurements to the clinical characteristics resulted in models of improved performance with an AUC of 0.892 and accuracy of 81.8%. The gain in AUC and accuracy of the combined models highlight the potential of serum lipids as markers of liver injury in alcoholic liver disease.     

Alcohol consumption and the risk of alcohol related cirrhosis in women.

The risks in women of cirrhosis with a likely primary alcohol aetiology were estimated for various levels of alcohol consumption in a case-control study. Data were obtained from 41 women with a first diagnosis of cirrhosis who had no evidence of non-alcohol-related cirrhosis; three matched controls were interviewed for each case. Significant increases in the risk of cirrhosis were detected at levels of consumption between 41 and 60 g daily; above this level a dose-response relation was observed. The risk of cirrhosis did not appear to be influenced by other nutritional factors or history of liver disease or use of hepatotoxic drugs. One per cent of Australian women consume more than 40 g alcohol daily, yet more than 90% of women identified with cirrhosis consumed alcohol at this level. Preventive interventions to reduce alcohol consumption in the small group of women who consume more than 40 g daily have the potential to reduce substantially the incidence of alcohol related cirrhosis.     

Acetaldehyde adducts in blood and bone marrow of patients with ethanol-induced erythrocyte abnormalities

BACKGROUND: Although alcohol abuse is known to cause a wide array of adverse effects on blood cell formation, the molecular mechanisms by which alcohol exerts its toxic actions remain poorly defined. We examine here the formation of acetaldehyde-derived protein modifications in erythrocytes and in their bone marrow precursors using antibodies specifically recognizing acetaldehyde-modified epitopes in proteins independently of the nature of the carrier protein. MATERIALS AND METHODS: We studied 138 consecutive adult patients undergoing bone marrow aspiration due to macrocytosis (MCV values above 99 fL). Assessment included complete blood counts, morphologic review, assessment of alcohol consumption, and biochemical and immunocytochemical assays for acetaldehyde adducts. RESULTS: There were 68 patients (49%) with a history of excessive alcohol consumption, 28 (20%) of whom were patients with severe dependence. The blood smears prepared from the alcoholic patients with macrocytosis also contained stomatocytes and knizocytes. Bone marrow aspirates from 12 alcoholic patients showed vacuolization of pronormoblasts and the presence of ring sideroblasts was noted in 8 cases. In immunocytochemical analyses of the peripheral blood erythrocytes, acetaldehyde-derived epitopes were found to occur both on the cell membrane and inside the erythrocytes. Bone marrow aspirates also showed positive staining for acetaldehyde adducts in the erythropoietic cells in 8 of 11 (73%) consecutive alcoholic patients. Separation of the erythrocyte proteins from the samples of alcoholics on HPLC-chromatography revealed the formation of fast-eluting hemoglobin fractions, which also reacted with antibodies against acetaldehyde adducts. CONCLUSIONS: Current data suggest that acetaldehyde-erythrocyte adducts are formed in vivo in blood and bone marrow of patients with excessive alcohol consumption. This may contribute to the generation of the erythrocyte abnormalities, which are frequently observed in alcoholic patients.     

Cue Reactivity Is Associated with Duration and Severity of Alcohol Dependence: An fMRI Study

Introduction

With the progression of substance dependence, drug cue-related brain activation is thought to shift from motivational towards habit pathways. However, a direct association between cue-induced brain activation and dependence duration has not yet been shown. We therefore examined the relationship between alcohol cue-reactivity in the brain, cue-induced subjective craving and alcohol dependence duration and severity. Since alcohol dependence is highly comorbid with depression/anxiety, which may modulate brain responses to alcohol cues, we also examined the relation between comorbid depression/anxiety and cue-reactivity.

Methods

We compared 30 alcohol dependent patients with 15 healthy controls and 15 depression/anxiety patients during a visual alcohol cue-reactivity task using functional magnetic resonance imaging blood oxygenated level-dependent responses and subjective craving as outcomes. Within the alcohol dependent group we correlated cue-reactivity with alcohol dependence severity and duration, with cue-induced craving and with depression/anxiety levels.

Results

Alcohol dependent patients showed greater cue-reactivity in motivational brain pathways and stronger subjective craving than depression/anxiety patients and healthy controls. Depression/anxiety was not associated with cue-reactivity, but depression severity in alcohol dependent patients was positively associated with craving. Within alcohol dependence, longer duration of alcohol dependence was associated with stronger cue-related activation of the posterior putamen, a structure involved in habits, whereas higher alcohol dependence severity was associated with lower cue-reactivity in the anterior putamen, an area implicated in goal-directed behavior preceding habit formation.

Conclusion

Cue-reactivity in alcohol dependence is not modulated by comorbid depression or anxiety. More importantly, the current data confirm the hypothesis of a ventral to dorsal striatal shift of learning processes with longer dependence duration, which could underlie increasingly habitual substance use with progressing substance dependence.     

Carbohydrate deficient transferrin: a marker for alcohol abuse.

OBJECTIVE--To assess the value of serum carbohydrate deficient transferrin as detected by isoelectric focusing on agarose as an indicator of alcohol abuse. DESIGN--Coded analysis of serum samples taken from patients with carefully defined alcohol intake both with and without liver disease. Comparison of carbohydrate deficient transferrin with standard laboratory tests for alcohol abuse. SETTING--A teaching hospital unit with an interest in general medicine and liver disease. PATIENTS--22 "Self confessed" alcoholics admitting to a daily alcohol intake of at least 80 g for a minimum of three weeks; 15 of the 22 self confessed alcoholics admitted to hospital for alcohol withdrawal; 68 patients with alcoholic liver disease confirmed by biopsy attending outpatient clinics and claiming to be drinking less than 50 g alcohol daily; 47 patients with non-alcoholic liver disorders confirmed by biopsy; and 38 patients with disorders other than of the liver and no evidence of excessive alcohol consumption. INTERVENTION--Serial studies performed on the 15 patients undergoing alcohol withdrawal in hospital. MAIN OUTCOME measure--Determination of relative value of techniques for detecting alcohol abuse. RESULTS--Carbohydrate deficient transferrin was detected in 19 of the 22 (86%) self confessed alcohol abusers, none of the 47 patients with non-alcoholic liver disease, and one of the 38 (3%) controls. Withdrawal of alcohol led to the disappearance of carbohydrate deficient transferrin at a variable rate, though in some subjects it remained detectable for up to 15 days. Carbohydrate deficient transferrin was considerably superior to the currently available conventional markers for alcohol abuse. CONCLUSION--As the technique is fairly simple, sensitive, and inexpensive we suggest that it may be valuable in detecting alcohol abuse.     

Discovery of serum biomarkers of alcoholic fatty liver in a rodent model: C-reactive protein

Background  

Excessive consumption of alcohol contributes to alcoholic liver disease. Fatty liver is the early stage of alcohol-related liver disease. The aim of this study was to search for specific serological biomarkers of alcoholic fatty liver (AFL) compared to healthy controls, non-alcoholic fatty liver (NAFL) and liver fibrosis in a rodent model.     

Failure of Electron Paramagnetic Resonance Spectroscopy Studies to Detect Elevated Free Radical Signals in Liver Biopsy Specimens from Patients with Alcoholic Liver Disease

Electron paramagnetic resonance spectroscopy (EPR) was used to study free radicals and transition metal complexes in liver tissue taken from patients with liver disease. Samples were frozen to 77K directly following biopsy to prevent deterioration. Our major aim was to compare signals from patients suffering from alcohol abuse with those from patients having liver damage not induced by alcohol. Samples were obtained from 19 chronic alcohol abusers and 7 non-alcoholic liver disease patients. Of the 19 alcoholic patients, 18 had an increased fat content, 6 had Mallory's hyaline, 12 had an acute inflammatory response, 9 had increased stainable iron and 4 had evidence of fibrosis. A signal derived from free radicals with a spectroscopic splitting factor of g = 2.0045 was found in all samples. This signal in the alcoholic patients had a mean amplitude of 2.96 cm (± 1.42 SD), and in patients with non-alcoholic liver disease 2.12cm (±0.82) (p = 0.10NS), measured under identical instrument settings.

The molar proportion of diene conjugated linoleic acid (DCLA), a free radical marker, in the sera of alcoholic patients was 2.68% (±1.93), but did not correlate with the free radical signals obtained by EPR spectroscopy. Also, there was no correlation between the free radical derived EPR signal and fat content, Mallory's hyaline, inflammatory infiltrate, iron or fibrosis in the liver biopsy specimens. Similarly the concentrations of aspartate transaminase, albumin, and gamma-glutamyl transferase in serum samples showed no correlations with free radical concentrations.

The absence of any significant increase in the stable free radical signal in the presence of alcohol induced liver disease and the lack of correlation between the signal and either histological or serological evidence of liver damage, suggests that alcohol derived free radicals may not be involved in the pathogenesis of alcoholic liver disease.

Unusually large sextet features characteristic of MN(II) complexes were observed for all liver samples. Such signals are very rare in human tissue, showing that there is a strong accumulation of Mn (II) in the liver. However, no systematic trends were observed. In some samples signals characteristic of iron-sulphur cluster units were detected, but again no correlations could be discovered.     

Use of a questionnaire in general practice to increase the recognition of patients with excessive alcohol consumption.

A self administered questionnaire, the health survey questionnaire, was designed to detect excessive alcohol consumption and mailed to patients who were registered with two general practices. Replies were received from 2572(75%) of 3452 patients. Excessive consumption was taken as 42 units of alcohol per week or more for men and 21 units per week or more for women: 1 unit = approximately 10 g ethanol and is equivalent to a half pint of beer, one glass of wine, or one standard measure of spirits. One hundred and twenty men (11%) and 68 women (5%) were identified by their responses to the questionnaire as excessive drinkers. According to their responses, roughly half of these expressed some concern about their drinking. In the practice where a disease register was kept 18 patients had been recorded as heavy drinkers before the study, and an additional 74 were detected by the questionnaire. Within 12 months after the questionnaire survey three groups of respondents were reviewed: (a) the excessive drinkers, (b) those who indicated concern about drinking but did not exceed the limits for excessive consumption, and (c) a random sample of those who were in neither of these two categories. Patients in these three groups were interviewed in a standard fashion to determine their alcohol consumption. Breath alcohol measurement was also carried out and a blood sample taken for the estimation of mean cell volume, gamma glutamyltranspeptidase activity, and serum aspartate transaminase activity. There were highly significant correlations between estimates of consumption obtained by the questionnaire and those obtained at interview except among the women who were excessive consumers, whose responses to the questionnaire indicated levels of consumption that were much higher than those to which they admitted at interview. Stated weekly consumption at interview that was above the limits set for the study was used as the standard measure for comparing the questionnaire with the other indicators of excessive drinking. The questionnaire had a considerably greater estimated sensitivity in detecting male excessive consumers than any of the blood tests. Among the women it apparently performed less well, although the numbers stating excessive consumption at interview were small. Breath alcohol measurement was positive in only a few of the excessive drinkers. The use of this simple and inexpensive instrument is likely to prove widely acceptable to patients in general practice and should result in a considerable increase in the recognition by general practitioners of patients with excessive alcohol consumption.     

Blood thiamine and thiamine phosphate ester concentrations in alcoholic and non-alcoholic liver diseases.

Thiamine state was investigated in patients with alcoholic liver disease, patients with various non-alcoholic liver diseases, and controls using a direct technique (thiochrome assay) to measure thiamine, thiamine monophospate, and the active coenzyme thiamine pyrophosphate in whole blood after isolating the fractions by ion exchange chromatography. Overall nutrition was similar in all groups as assessed by anthropometry, and no patient had clinical evidence of thiamine deficiency. There was no significant difference among the groups in mean concentration of any form of thiamine. The scatter was much greater in patients with alcoholic liver disease but only 8.7% had biochemical thiamine deficiency (defined as a blood concentration of the active coenzyme greater than 2 SD below the mean control value). An unexpected finding was of abnormally high total thiamine concentrations (greater than 2 SD above the mean control value) in 17.4% of patients with alcoholic liver disease, the highest concentrations being found in two patients with severe alcoholic hepatitis and cirrhosis. The ratio of phosphorylated to unphosphorylated thiamine was calculated as an index of phosphorylation and, although the mean did not differ significantly among the groups, the range was greatest in alcoholic liver disease. The lowest ratios occurred in the two patients with severe alcoholic hepatitis, but neither had evidence of thiamine pyrophosphate deficiency. Contrary to studies using indirect assay techniques, these results suggest that thiamine deficiency is unusual in well nourished patients with alcoholic liver disease. The new finding of unexpectedly high thiamine concentrations in some patients may be due to abnormalities of hepatic storage or release in liver disease, particularly in severe alcoholic hepatitis. There was no convincing evidence of impaired thiamine phosphorylation in any patients with liver disease. Conclusions from studies using indirect assays on the prevalence and mechanisms of thiamine deficiency in liver diseases may not be valid.