The Utility of Carbohydrate-Deficient Transferrin in Identifying Chronic Alcohol Users in the Injured Patient: Expanding the Toolkit.

BACKGROUND: Alcohol use remains abundant in patients with traumatic injury. Previous studies have suggested that serum carbohydrate-deficient transferrin (%dCDT) levels, relative to blood alcohol levels (BALs), may better differentiate episodic binge drinkers from sustained heavy consumers in admitted patients with traumatic injury. We characterized %dCDT levels and BAL levels to differentiate binge drinkers from sustained heavy consumers in admitted trauma patients and their associations with outcomes. METHODS: This prospective, cross-sectional, observational study assessed %dCDT and BAL levels in admitted male and female patients with traumatic injury (≥18 y) at an American College of Surgeons Committee on Trauma level-1 center from July 2014 to June 2016. We designated patients with %dCDT levels ≥1.7% (CDT+) as chronic alcohol users and dichotomized acutely intoxicated patients using three different BAL-level thresholds. Primary outcomes included in-hospital complications, along with prolonged ventilation and intensive care unit length of stay, both defined as the top decile. Secondary outcomes included rates of drug or alcohol withdrawal and all-cause mortality. Analyses were adjusted for clinical factors. RESULTS: We studied 715 patients (77.5% men, 60.6% ≤ 40 y of age, median Injury Severity Score: 14, 41.7% motor vehicle crashes, 17.9% gunshot wounds, 11.1% falls). While 31.0% were CDT+, 48.7% were BAL>0. After adjusting for CDT levels, BAL levels >0, >100, or >200 were not associated with adverse outcomes. However, CDT+ relative to patients with CDT were associated with complications (adjusted odds ratio: 1.96 [1.24-3.09]), prolonged ventilation days (3.23 [1.08-9.65]), and prolonged intensive care unit stays (2.83 [1.20-6.68]). CONCLUSIONS: In this 2-year prospective, cross-sectional, and observational study, we found that %dCDT levels, relative to BAL levels, may better stratify admitted patients with traumatic injury into acute versus chronic alcohol users, identifying those at higher risk for in-hospital complications.

Moderate alcohol consumption is associated with impaired insulin secretion and fasting glucose in non-obese non-diabetic men.

AIMS/INTRODUCTION: A low insulin secretion capacity has been implicated in the high prevalence of non-obese diabetes in East Asians. As alcohol consumption alters insulin and glucose metabolism, we tested the hypothesis that alcohol consumption contributes to impaired insulin secretion and glucose intolerance in lean/normal-weight non-diabetic Japanese men. MATERIALS AND METHODS: This cross-sectional study was undertaken among the residents of Shika town, Japan, between 2011 and 2017. A total of 402 non-diabetic men, including participants with normal fasting plasma glucose (FPG) and impaired FPG (FPG 5.6-6.9 mmol/L), and aged ≥40 years, were examined. FPG, the homeostasis model assessment of insulin secretion capacity (HOMA-B) and alcohol consumption were evaluated and compared between the body mass index (BMI) <25 and BMI ≥25 groups. RESULTS: HOMA-B levels were lower in the BMI <25 group than in the BMI ≥25 group. Alcohol consumption correlated with a low HOMA-B level regardless of BMI, and, thus, the HOMA-B levels of alcohol drinkers were significantly lower in the BMI <25 group. A multivariable logistic regression analysis showed that alcohol consumption, even light-to-moderate consumption (1-25 g/day), was associated with significantly low levels of HOMA-B and impaired FPG in the BMI <25 group. Among participants with impaired FPG, a low level of HOMA-B was observed in alcohol drinkers, but not in non-drinkers. In contrast, light-to-moderate alcohol consumption was not related to HOMA-B or FPG in the BMI ≥25-group. CONCLUSION: Alcohol consumption, even a small amount, might contribute to reductions in HOMA-B levels and impaired FPG in lean/normal-weight Japanese men.

Changes in Circulating Metabolome Precede Alcohol-Related Diseases in Middle-Aged Men: A Prospective Population-Based Study With a 30-Year Follow-Up.

BACKGROUND: Heavy alcohol use has been associated with altered circulating metabolome. We investigated whether changes in the circulating metabolome precede incident diagnoses of alcohol-related diseases. METHODS: This is a prospective population-based cohort study where the participants were 42- to 60-year-old males at baseline (years 1984 to 1989). Subjects who received a diagnosis for an alcohol-related disease during the follow-up were defined as cases (n = 92, mean follow-up of 13.6 years before diagnosis). Diagnoses were obtained through linkage with national health registries. We used 2 control groups: controls who self-reported similar levels of alcohol use as compared to cases at baseline (alcohol-controls, n = 92), and controls who self-reported only light drinking at baseline (control-controls, n = 90). A nontargeted metabolomics analysis of baseline serum samples was performed. RESULTS: There were significant differences between the study groups in the baseline serum levels of 64 metabolites: in amino acids (e.g., glutamine [FDR-corrected q-value = 0.0012]), glycerophospholipids (e.g., lysophosphatidylcholine 16:1 [q = 0.0008]), steroids (e.g., cortisone [q = 0.00001]), and fatty acids (e.g., palmitoleic acid [q = 0.0031]). The main finding was that after controlling for baseline levels of self-reported alcohol use and the biomarker of alcohol use, gamma-glutamyl transferase, and when compared to both alcohol-control and control-control group, the alcohol-case group had lower serum levels of asparagine (Cohen's d = -0.48 [95% CI -0.78 to -0.19] and d = -0.49 [-0.78 to -0.19], respectively) and serotonin (d = -0.45 [-0.74 to -0.15], and d = -0.46 [-0.75 to -0.16], respectively), with no difference between the two control groups (asparagine d = 0.00 [-0.29 to 0.29] and serotonin d = -0.01 [-0.30 to 0.29]). CONCLUSIONS: Changes in the circulating metabolome, especially lower serum levels of asparagine and serotonin, are associated with later diagnoses of alcohol-related diseases, even after adjustment for the baseline level of alcohol use.

Liver stiffness correlates with serum osteopontin and TAZ expression in human liver cirrhosis.

The pivotal role of the extracellular matrix (ECM) as both a cause and consequence of liver fibrosis is striking. However, mechanotransducer molecules and profibrogenic factors induced by liver stiffness are still unclear. The current study aimed to investigate liver stiffness and its correlation with the expression of the transcriptional coactivator with PDZ-binding motif (TAZ) and serum osteopontin (OPN) in human cirrhosis. In this case-control study, liver tissue stiffness was determined using atomic force microscopy in cirrhotic livers (n = 38) of different etiologies and in controls (n = 10). Immunohistochemical and qRT-PCR analyses were performed to analyze TAZ expression. Besides, western blotting and ELISA were performed to assess liver Indian hedgehog and serum OPN levels, respectively. Liver stiffness, TAZ expression, and hepatic gene expression and serum protein levels of OPN were significantly increased in patients with cirrhosis compared with the control groups (all P < 0.001), specifically in autoimmune- and alcohol-related cirrhosis. In cirrhotic patients, liver stiffness was significantly associated with the expression of nuclear TAZ and OPN. The correlation between matrix stiffness as a mechanical property, TAZ as a potential mechanotransducer, and OPN as a matricellular factor suggests possible effects of mechanical features of the ECM on the expression of the aforementioned profibrogenic markers, which is predominant in autoimmune- and alcohol-related cirrhosis.

Long-Chain ω-3 Levels Are Associated With Increased Alcohol Sensitivity in a Population-Based Sample of Adolescents.

BACKGROUND: The levels of the ω-3 long-chain polyunsaturated fatty acids (ω-3 LC-PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been associated with alcohol sensitivity in vertebrate and invertebrate model systems, but prior studies have not examined this association in human samples despite evidence of associations between ω-3 LC-PUFA levels and alcohol-related phenotypes. Both alcohol sensitivity and ω-3 LC-PUFA levels are impacted by genetic factors, and these influences may contribute to observed associations between phenotypes. Given the potential for using EPA and DHA supplementation in adjuvant care for alcohol misuse and other outcomes, it is important to clarify how ω-3 LC-PUFA levels relate to alcohol sensitivity. METHODS: Analyses were conducted using data from the Avon Longitudinal Study of Parents and Children. Plasma ω-3 LC-PUFA levels were measured at ages 15.5 and 17.5. Participants reported on their initial alcohol sensitivity using the early drinking Self-Rating of the Effects of Alcohol (SRE-5) scale, for which more drinks needed for effects indicates lower levels of response per drink, at ages 15.5, 16.5, and 17.5. Polygenic liability for alcohol consumption, alcohol problems, EPA levels, and DHA levels was derived using summary statistics from large, publicly available datasets. Linear regressions were used to examine the cross-sectional and longitudinal associations between ω-3 LC-PUFA levels and SRE scores. RESULTS: Age 15.5 ω-3 LC-PUFA levels were negatively associated with contemporaneous SRE scores and with age 17.5 SRE scores. One modest association (p = 0.02) between polygenic liability and SRE scores was observed, between alcohol problems-based polygenic risk scores (PRS) and age 16.5 SRE scores. Tests of moderation by genetic liability were not warranted. CONCLUSIONS: Plasma ω-3 LC-PUFA levels may be related to initial sensitivity to alcohol during adolescence. These data indicate that diet-related factors have the potential to impact humans' earliest responses to alcohol exposure.

Sex difference in IgE sensitization associated with alcohol consumption in the general population.

The association of alcohol consumption and immunoglobulin E (IgE) sensitization is debated. Few population-based studies have investigated whether such associations differ by sex. We explored the association of alcohol consumption with IgE sensitization in the general population, stratified by sex. We analyzed data for 1,723 adults from the 2010 Korean National Health and Nutrition Examination Survey. We divided subjects into three groups according to their self-reported alcohol consumption or serum level of gamma-glutamyltransferase (GGT), an objective marker of alcohol consumption. After adjustments, the odds ratios (ORs) of male high-risk drinkers were 2.09 (95% confidence interval [CI], 1.34-3.28) for total IgE and 1.71 (95% CI, 1.03-2.83) for Dermatophagoides farinae (DF)-specific IgE compared with male low-risk drinkers. In females, the dog-specific IgE level was associated with high-risk drinking (OR, 11.74; 95% CI, 2.04-67.24). The ORs of males in the high-serum-GGT group were 2.73 (95% CI, 1.72-4.33) for total IgE and 2.17 (95% CI, 1.35-3.47) for DF-specific IgE compared with those in the low-serum-GGT group. This study suggests a possible link between alcohol consumption and IgE sensitization, moreover, the risk of IgE sensitization was significantly higher in male high-risk drinkers. Therefore, clinicians should consider the risk of IgE sensitization possibly afflicting male high-risk drinkers.

Breath/Blood Alcohol Concentration as an Indicator of Alcohol Use Problems.

INTRODUCTION: The Federal Aviation Administration Office of Aerospace Medicine (AAM) is required by law to identify pilots who have driving under the influence (DUI) convictions. It is the responsibility of AAM to determine, based on the DUI, if the pilot has a drinking problem and needs follow-up treatment. Pilots with alcohol problems are at risk to themselves and the public and need to have treatment to reduce the extent of the risk. It has been suggested by some that a blood alcohol concentration (BAC) of 0.15 g · dL-1 is evidence of tolerance and the pilot should be placed in an alcohol treatment program.METHOD: The National Institute on Alcohol Abuse and Alcoholism (NIAAA) Clinician's Guide considers a person at risk for a drinking problem when a man drinks 5 or more drinks or a woman drinks 4 or more drinks in a day and reaches a 0.08 g · dL-1 of ethanol in the blood. It is possible to estimate from a BAC or breath alcohol concentration (BrAC) the number of drinks consumed using the volume of distribution for ethanol and the weight of the individual. A spread sheet tool was developed to estimate the number of drinks consumed.RESULTS: It was determined that DUI/DWI concentrations could be used to determine the minimum number of drinks consumed. Overweight people reach binge drinking levels and higher Hingson levels at lower DUI/DWI concentrations than people with an average weight or lower.DISCUSSION: Using this tool there is a high probability (99.7%) of identifying a true binge drinker.Canfield DV, Forster EM, Cheong Z-I, Cowan JM. Breath/blood alcohol concentration as an indicator of alcohol use problems. Aerosp Med Hum Perform. 2019; 90(5):488-491.

Decreased plasma concentrations of BDNF and IGF-1 in abstinent patients with alcohol use disorders.

The identification of growth factors as potential biomarkers in alcohol addiction may help to understand underlying mechanisms associated with the pathogenesis of alcohol use disorders (AUDs). Previous studies have linked growth factors to neural plasticity in neurocognitive impairment and mental disorders. In order to further clarify the impact of chronic alcohol consumption on circulating growth factors, a cross-sectional study was performed in abstinent AUD patients (alcohol group, N = 91) and healthy control subjects (control group, N = 55) to examine plasma concentrations of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1) and IGF-1 binding protein-3 (IGFBP-3). The association of these plasma peptides with relevant AUD-related variables and psychiatric comorbidity was explored. The alcohol group was diagnosed with severe AUD and showed an average of 13 years of problematic use and 10 months of abstinence at the moment of participating in the study. Regarding common medical conditions associated with AUD, we observed an elevated incidence of alcohol-induced liver and pancreas diseases (18.7%) and psychiatric comorbidity (76.9%). Thus, AUD patients displayed a high prevalence of dual diagnosis (39.3%) [mainly depression (19.9%)] and comorbid substance use disorders (40.7%). Plasma BDNF and IGF-1 concentrations were significantly lower in the alcohol group than in the control group (p<0.001). Remarkably, there was a negative association between IGF-1 concentrations and age in the control group (r = -0.52, p<0.001) that was not found in the alcohol group. Concerning AUD-related variables, AUD patients with liver and pancreas diseases showed even lower concentrations of BDNF (p<0.05). In contrast, the changes in plasma concentrations of these peptides were not associated with abstinence, problematic use, AUD severity or lifetime psychiatric comorbidity. These results suggest that further research is necessary to elucidate the role of BDNF in alcohol-induced toxicity and the biological significance of the lack of correlation between age and plasma IGF-1 levels in abstinent AUD patients.

Biomarkers of the alcohol hangover state: Ethyl glucuronide (EtG) and ethyl sulfate (EtS).

INTRODUCTION: The aim of this study was to investigate the usefulness of ethyl glucuronide (EtG) and ethyl sulfate (EtS) as biomarkers of the hangover state. METHODS: Thirty-sixhealthy social drinkers participated in this study, being of naturalistic design. Eighteen participants experience regular hangovers (the hangover group), whereas the other 18 claim to not experience a hangover (the hangover-immune group). On a control day (alcohol-free) day and a post-alcohol day, urine EtG and EtS concentrations were determined and hangover severity assessed. RESULTS: Urinary EtG and EtS concentrations were significantly increased on post-alcohol day compared to the control day (p = .0001). Both EtG and EtS concentrations did not significantly correlate with the overall hangover score, nor with the estimated peak blood alcohol concentrations and number of alcoholic drinks. EtG correlated significantly only with the individual hangover symptom "headache" (p = .033; r = .403). No significant correlations were found with the EtG to EtS ratio. EtG and EtS concentrations significantly correlated with urine ethanol concentrations. CONCLUSIONS: Although urine EtG and EtS concentration did not significantly correlate to estimated peak blood alcohol concentrations or the number of alcoholic drinks consumed, a significant correlation was found with urine ethanol concentration. However, urine EtG and EtS concentrations did not significantly correlate with overall hangover severity.

Blood homocysteine concentration and mood disorders with mixed features among patients with alcohol use disorder.

BACKGROUND: Blood homocysteine concentration (BHC) is higher in patients with alcohol use disorder (AUD). Previous studies have found a relationship between depressive symptoms severity and BHC in AUD patients and recently some authors have found high BHC among patients with bipolar disorder, both during manic and depressive episodes and in euthymic state. However, BHC in patients with mixed mood episode has not yet been investigated. The aim of this study was to evaluate the BHC of patients with AUD and mixed mood episode. METHODS: A sample of AUD outpatients was assessed by Mini-International Neuropsychiatric Interview (MINI Plus): those with a DSM-IV-TR mood disorder with mixed features were included in the MIXED group (n = 45), whereas those without mood episode were gathered in the NO MOOD group (n = 23). Two subgroups, MIXMANIA and MIXDEPRESSION, were formed according to the prevalence of manic or depressive symptoms, assessed by Young Mania Rating Scale (YMRS), and Hamilton Rating Scale for Depression (HDRS). The Alcohol Use Disorder Identification Test (AUDIT) was used to appraise the AUD. BHC was determined by High-Performance Liquid Chromatography. RESULTS: The MIXED group showed greater severity of both depressive (26.35 ± 9.96 vs. 4.77 ± 0.92; p < 0.001) and manic (22.35 ± 3.30 vs. 6.14 ± 1.12; p < 0.001) symptoms, and higher BHC (28.80 ± 11.47 vs. 10.83 ± 2.81; p < 0.001), than the NO MOOD group. BHC was strongly correlated to the HDRS, YMRS and AUDIT scores, just as HDRS was to YMRS, and AUDIT was to both HDRS and YMRS, in the MIXED group only (p < 0.001). The MIXDEPRESSION subgroup showed higher BHC than the MIXMANIA subgroup (Mdn = 42.96, IQR = 10.44 vs. Mdn = 19.77, IQR = 5.93; p < 0.001). A linear regression model conducted on the MIXED group found a significant predictive value for BHC of both HDRS (ß = 0.560, t = 2.43, p = 0.026) and AUDIT (ß = 0.348, t = 2.17, p = 0.044). CONCLUSIONS: Depressive symptoms seem to be mainly implicated in the BHC elevation among patients with both mixed features mood disorder and AUD.

SmartStart: Results of a large point of entry study into preloading alcohol and associated behaviours.

BACKGROUND: There is a growing trend of preloading with alcohol before entering entertainment districts. It is claimed that this occurs to save money and that preloading may be a good indicator of harmful drinking and risk taking behaviours more generally. No study has collected data from a large sample as the participants entered entertainment districts and measured blood alcohol concentration (BAC) levels and self-reported drinking and risk taking behaviours in a systematic way. METHODS: In this research, police and academics worked together to gauge the breadth and depth of preloading behaviours. In all, 3039 people completed a questionnaire and were breathalysed as they entered entertainment districts in Queensland, Australia. Of those, 2751 represented people from Brisbane and this data, collected every Thursday night to Sunday morning during the warm months, was analysed. RESULTS: More than 79% of people reported to preload and 71% returned a BAC greater than zero, both with little difference between the genders. Of preloaders, the mean BAC was 0.071, with 'to socialise with friends' being the primary reason given for preloading. Increasing preloading BAC was related to increasing risk taking and antisocial behaviours, as well as alcohol abuse and dependence. Older people entering entertainment districts had more accurate estimates of their BAC, yet 20% of our sample did not understand how the BAC system worked. Conducting the research was associated with a higher access rate to police and a lower arrest rate in the areas of data collection in comparison to the same nights 1year earlier. CONCLUSION: Preloading is widespread and involves moderate to heavy drinking in the Australian population visiting entertainment districts. Any interventions to curb drinking behaviours and reduce violence in night time entertainment districts need to involve approaches aimed at cultural phenomena, such as preloading behaviours.

Validating Harmful Alcohol Use as a Phenotype for Genetic Discovery Using Phosphatidylethanol and a Polymorphism in ADH1B.

BACKGROUND: Although alcohol risk is heritable, few genetic risk variants have been identified. Longitudinal electronic health record (EHR) data offer a largely untapped source of phenotypic information for genetic studies, but EHR-derived phenotypes for harmful alcohol exposure have yet to be validated. Using a variant of known effect, we used EHR data to develop and validate a phenotype for harmful alcohol exposure that can be used to identify unknown genetic variants in large samples. Herein, we consider the validity of 3 approaches using the 3-item Alcohol Use Disorders Identification Test consumption measure (AUDIT-C) as a phenotype for harmful alcohol exposure. METHODS: First, using longitudinal AUDIT-C data from the Veterans Aging Cohort Biomarker Study Cohort (VACS-BC), we compared 3 metrics of AUDIT-C using correlation coefficients: (i) AUDIT-C closest to blood sampling (closest AUDIT-C), (ii) the highest value (highest AUDIT-C), (iii) and longitudinal trajectories generated using joint trajectory modeling (AUDIT-C trajectory). Second, we compared the associations of the 3 AUDIT-C metrics with phosphatidylethanol (PEth), a direct, quantitative biomarker for alcohol in the overall sample using chi-square tests for trend. Last, in the subsample of African Americans (AAs; n = 1,503), we compared the associations of the 3 AUDIT-C metrics with rs2066702 a common missense (Arg369Cys) polymorphism of the ADH1B gene, which encodes an alcohol dehydrogenase isozyme. RESULTS: The sample (n = 1,851, 94.5% male, 65% HIV+, mean age 52 years) had a median of 7 AUDIT-C scores over a median of 6.1 years. Highest AUDIT-C and AUDIT-C trajectory were correlated r = 0.86. The closest AUDIT-C was obtained a median of 2.26 years after the VACS-BC blood draw. Overall and among AAs, all 3 AUDIT-C metrics were associated with PEth (all p < 0.05), but the gradient was steepest with AUDIT-C trajectory. Among AAs (36% with the protective ADH1B allele), the association of rs2066702 with AUDIT-C trajectory and highest AUDIT-C was statistically significant (p < 0.05), and the gradient was steeper for the AUDIT-C trajectory than for the highest AUDIT-C. The closest AUDIT-C was not statistically significantly associated with rs2066702. CONCLUSIONS: EHR data can be used to identify complex phenotypes such as harmful alcohol use. The validity of the phenotype may be enhanced through the use of longitudinal trajectories.

How Should Remote Clinical Monitoring Be Used to Treat Alcohol Use Disorders?: Initial Findings From an Expert Round Table Discussion.

Scientific evidence combined with new health insurance coverage now enable a chronic illness management approach to the treatment of alcohol use disorders (AUDs), including regular monitoring of blood alcohol content (BAC), as a useful indicator of disease control. Recent technical advances now permit many different types of remote, real-time monitoring of BAC. However, there is no body of research to empirically guide clinicians in how to maximize the clinical potential of remote BAC monitoring.As an initial step in guiding and supporting such research, the manufacturer of one remote BAC monitoring system sponsored a group of experienced clinicians and clinical researchers to discuss 8 issues that generally affect remote, clinical BAC monitoring of "adults in outpatient AUD treatment."The expert panel unanimously agreed that remote BAC monitoring for at least 12 months during and after the outpatient treatment of AUD was a clinically viable deterrent to relapse. There was also consensus that positive test results (ie, recent alcohol use) should lead to intensified care and monitoring. However, there was no agreement on specific types of clinical intensification after a positive test. The panel agreed that sharing positive and negative test results with members of the patient support group was helpful in reinforcing abstinence, yet they noted many practical issues regarding information sharing that remain concerning. Significant differences within the panel on several important clinical issues underline the need for more clinical and implementation research to produce empirically-supported guidelines for the use of remote BAC monitoring in AUD treatment.

Vitamin D and alcohol: A review of the current literature.

Vitamin D is associated with bone mineral density, and its deficiency is a global health problem. In psychiatry, low vitamin D levels have been associated with schizophrenia, depression, psychotic symptoms, and, more recently, alcohol use disorders. Alcohol use disorders are among the most prevalent mental disorders worldwide. Therefore, our aim was to evaluate the association between alcohol use and vitamin D serum levels. The PubMed, SCIELO, and Lilacs databases were searched for this systematic review. We assessed all articles published from 1976 to December 2015, and we examined the associated reference lists to retrieve articles that appeared to fulfill our criteria. Of 932 articles, 49 met our inclusion criteria. The majority of the papers (71.4%) were cross-sectional studies. Alcohol intake was found to be positively associated with vitamin D status in 15 articles and negatively associated with vitamin D in 18 articles; no association was found in 16 articles. Heterogeneous results were found in our review, with a similar number of papers indicating a positive association, a negative association or the absence of any association between alcohol use and vitamin D levels. Nevertheless, it is important to note that the studies in which a positive association was found were more recent papers that involved considerably larger sample sizes than those in other studies. The older studies compared vitamin D levels in alcoholic and non-alcoholic patients, in contrast to more recent studies, which focused on more specific populations. In addition, most of the selected papers were from high latitude countries, where exposure to sunlight tends to be lower than in tropical countries. The data concerning vitamin D levels in patients with alcohol use disorders remain controversial. Additional research using a standardized methodology is necessary to demonstrate the real impact of alcohol consumption on vitamin D serum levels as well as on the health status of alcohol users.

Recurrent purpura due to alcohol-related Schamberg's disease and its association with serum immunoglobulins: a longitudinal observation of a heavy drinker.

BACKGROUND: It is unusual for purpura to emerge as a result of drinking alcohol. Such a peculiarity was observed in a 55-year-old man with a 30-year history of heavy alcohol use. CASE PRESENTATION: The Caucasian patient was studied for 11 years during several detoxification treatments. During the last 2 years of that period, purpuric rashes were newly observed. The asymptomatic purpura was limited to both lower limbs, self-limiting with abstinence, and reoccurring swiftly with alcohol relapse. This sequence was observed six times, suggesting a causative role of alcohol or its metabolites. A skin biopsy revealed histological features of purpura pigmentosa progressiva (termed Schamberg's disease). Additionally, alcoholic fatty liver disease markedly elevated serum immunoglobulins (immunoglobulin A and immunoglobulin E), activated T-lymphocytes, and increased C-reactive protein. In addition, moderate combined (cellular and humoral) immunodeficiency was found. Unlike the patient's immunoglobulin A level, his serum immunoglobulin E level fell in the first days of abstinence, which corresponded to the time of purpura decline. Systemic vasculitis and clotting disorders were excluded. The benign character of the purpura was supported by missing circulating immune complexes or complement activation. An alcohol provocation test with vinegar was followed by the development of fresh "cayenne pepper" spots characteristic of Schamberg's disease. CONCLUSIONS: This case report demonstrates that Schamberg's disease can be strongly related to alcohol intake, in our patient most likely as a late complication of severe alcoholism with alcoholic liver disease. Immunologic disturbances thereby acquired could have constituted a basis for a hypersensitivity-like reaction after ingestion of alcohol. Schamberg's disease induction by vinegar may point to an involvement of acetate, a metabolite of ethanol.

Biomarker-Based Approaches for Assessing Alcohol Use Disorders.

Although alcohol use disorders rank among the leading public health problems worldwide, hazardous drinking practices and associated morbidity continue to remain underdiagnosed. It is postulated here that a more systematic use of biomarkers improves the detection of the specific role of alcohol abuse behind poor health. Interventions should be initiated by obtaining information on the actual amounts of recent alcohol consumption through questionnaires and measurements of ethanol and its specific metabolites, such as ethyl glucuronide. Carbohydrate-deficient transferrin is a valuable tool for assessing chronic heavy drinking. Activities of common liver enzymes can be used for screening ethanol-induced liver dysfunction and to provide information on the risk of co-morbidities including insulin resistance, metabolic syndrome and vascular diseases. Conventional biomarkers supplemented with indices of immune activation and fibrogenesis can help to assess the severity and prognosis of ethanol-induced tissue damage. Many ethanol-sensitive biomarkers respond to the status of oxidative stress, and their levels are modulated by factors of life style, including weight gain, physical exercise or coffee consumption in an age- and gender-dependent manner. Therefore, further attention should be paid to defining safe limits of ethanol intake in various demographic categories and establishing common reference intervals for biomarkers of alcohol use disorders.

Impact of Flushing Response on the Relationship between Alcohol Consumption and Gamma-glutamyl Transpeptidase: the KOBE study.

Individuals with an inactive acetaldehyde dehydrogenase 2 have an. elevated level of serum acetaldehyde after drinking alcohol, and this may cause an alcohol flushing response with symptoms such as facial flushing, tachycardia, headache, and nausea. Recent studies have suggested that the flushing response influences the association between alcohol consumption and various health-related outcomes. In the present study, we investigated the impact of the flushing response on the relationship between alcohol consumption and serum y -GTP levels in Japanese drinkers. We conducted a cross-sectional study of 521 Japanese drinkers (260 men and 261 'vomen) to examine the impact of the alcohol flushing response on the relationship between alcohol consumption and serum y -GTP levels. The subjects were divided into three groups according to the amount .of daily alcohol consumption. (low, <20 g; moderate, 20-39 g;. and high, >40 g). Multiple adjustments were performed with linear regression models to examine the association between daily alcohol consumption and serum y-GTP levels, adjusting for potential con- founders including the flushing response. We found that the proportion of flushers was significantly lower in the high alcohol consumption group than in the low consumption group. The results of a multivariable analysis showed that,serum y -GTP levels were significantly higher in the moderate and high consumption groups than in the low consumption group after. adjusting for all potential confounders other than the flushing response. In addition, the association between serum y -GTP levels and alcohol consumption was unchanged after adjusting for the presence of the flushing response. In conclusion, serum y -GTP levels increased with increasing alcohol-consumption regardless of the flushing response. Screening for heavy drinkers using serum y-GTP levels was very important to prevent alcohol-related diseases or health problems in health examination.

Elevated baseline serum glutamate as a pharmacometabolomic biomarker for acamprosate treatment outcome in alcohol-dependent subjects.

Acamprosate has been widely used since the Food and Drug Administration approved the medication for treatment of alcohol use disorders (AUDs) in 2004. Although the detailed molecular mechanism of acamprosate remains unclear, it has been largely known that acamprosate inhibits glutamate action in the brain. However, AUD is a complex and heterogeneous disorder. Thus, biomarkers are required to prescribe this medication to patients who will have the highest likelihood of responding positively. To identify pharmacometabolomic biomarkers of acamprosate response, we utilized serum samples from 120 alcohol-dependent subjects, including 71 responders (maintained continuous abstinence) and 49 non-responders (any alcohol use) during 12 weeks of acamprosate treatment. Notably, baseline serum glutamate levels were significantly higher in responders compared with non-responders. Importantly, serum glutamate levels of responders are normalized after acamprosate treatment, whereas there was no significant glutamate change in non-responders. Subsequent functional studies in animal models revealed that, in the absence of alcohol, acamprosate activates glutamine synthetase, which synthesizes glutamine from glutamate and ammonia. These results suggest that acamprosate reduces serum glutamate levels for those who have elevated baseline serum glutamate levels among responders. Taken together, our findings demonstrate that elevated baseline serum glutamate levels are a potential biomarker associated with positive acamprosate response, which is an important step towards development of a personalized approach to treatment for AUD.

Effect of H. pylori Infection on Cytokine Profiles and Oxidative Balance in Subjects with Chronic Alcohol Ingestion.

Different amounts of ingested alcohol can have distinct effects on the human body. However, there is limited research on chronic alcohol consumption with Helicobacter pylori infection. We sought to investigate the relationship between the cytokine profile, oxidative balance and H. pylori infection in subjects with chronic alcohol consumption. A total of 142 subjects were divided into three groups: 59 subjects with chronic alcohol ingestion and H. pylori infection (group A); 53 subjects with chronic alcohol ingestion without H. pylori infection (group B); and 30 control subjects (group C). The serum levels of CagA, interleukin (IL)-10, E-selectin, TNF-α, malondialdehyde (MDA) and superoxide dismutase (SOD) activity were measured by enzyme-linked immunosorbent assay (ELISA). We found that the ages and serum H. pylori CagA levels among the three groups, as well as both the mean drinking age and the mean daily alcohol consumption between groups A and B, were matched and comparable. Comparing the BMIs among the three groups, the BMI differences were found to be statistically significant (F=3.921, P<0.05). Compared with group C, the BMIs in groups A and B were significantly higher (P<0.001 and P<0.01, respectively); however, the BMI differences between group A and group B were not statistically significant (P>0.05). Additionally, no differences in the serum CagA levels were found in comparisons among the groups (all P>0.05). The serum IL-10 and E-selectin levels in group A were significantly lower than those in group B (serum IL-10: P<0.05; E-selectin: P<0.05). The serum IL-10 in group A was significantly higher than that in group C (P<0.01); the serum E-selectin levels in group A did not significantly differ compared with those in group C (P>0.05). Furthermore, the serum IL-10 and E-selectin levels in group B were significantly higher than those in group C (serum IL-10: P<0.001; E-selectin: P<0.05); however, the serum TNF-α levels did not differ among groups (all P>0.05). Although the serum levels of MDA and SOD in groups A and B were slightly lower than those in group C, there were no significant differences among groups (all P>0.05). In conclusion, we believe that H. pylori infection might cause a significant inhibition of certain cytokine profiles in subjects with chronic alcohol ingestion. Moreover, chronically ingested alcohol may exert an adjusted inflammatory effect, but there was no association between H. pylori infection, chronic alcohol consumption and oxidative balance.