Nonalcoholic Controls Research Articles

NAMPT gene rs2058539 variant is a risk factor for nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease is a chronic liver disease and a growing global epidemic. The aim of this study was to investigate the association between a visfatin gene (NAMPT) variant and nonalcoholic fatty liver disease, owing to the connection between this disease and insulin resistance, obesity, inflammation, and oxidative stress, and the role of visfatin in these metabolic disorders. In the present case-control study, we enrolled 312 genetically unrelated individuals, including 154 patients with biopsy-proven nonalcoholic fatty liver disease and 158 controls. The rs2058539 polymorphism of NAMPT gene was genotyped using the PCR-RFLP method. Genotype and allele distributions of NAMPT gene rs2058539 polymorphism conformed to the Hardy-Weinberg equilibrium both in the case and control groups (p>0.05). The distribution of NAMPT rs2058539 genotypes and alleles differed significantly between the cases with nonalcoholic fatty liver disease and controls. The "CC" genotype of the NAMPT rs2058539 compared with "AA" genotype was associated with a 2.5-fold increased risk of nonalcoholic fatty liver disease after adjustment for confounding factors [p=0.034; odds ratio (OR)=2.52, 95% confidence interval (CI)=1.36-4.37]. Moreover, the NAMPT rs2058539 "C" allele was significantly overrepresented in the nonalcoholic fatty liver disease patients than controls (p=0.022; OR=1.77, 95%CI=1.14-2.31). Our findings indicated for the first time that the NAMPT rs2058539 "CC" genotype is a marker of increased nonalcoholic fatty liver disease susceptibility; however, it needs to be supported by further investigations in other populations.

Assessment of cognitive impairment in patients with alcohol dependence – A comparative study

Background: Alcohol intake has long been associated with an increase in disease and mortality. Recent investigations have made a significant contribution to our comprehension of the connection between drinking and particular ailments and have demonstrated that the relationship between alcohol use and its consequences on health is complicated and multifaceted. Aims and Objectives: This study aims to evaluate cognition ability in alcoholics with a prolonged history of alcohol intake. Blinded Montreal Cognitive Assessment (MoCA) was used to analyze cognition ability. Materials and Methods: It is a comparative study between two study groups. The study includes 30 healthy alcoholic males (experimental group) attending the psychiatric hospital outpatient department and 30 healthy appropriate non-alcoholics (control group) within the age group of 18–45 years of age. The total sample size is n = 60. Results: The age of individuals did not show any statistically significant correlation with alcohol consumption (P = 0.7). In our results, alcohol consumption has a significant impact on cognition. Mean blind MoCA score is found to be 12.5 in alcoholics and 18.9 in non-alcoholics (P < 0.001). Conclusion: The proportion of heavy, moderate, and light drinkers was found to be 37%, 40%, and 23%, respectively. Blind MoCA score was found to be higher in the non-alcoholic (control) group compared to the alcoholic (experimental) group.

Exploring heart rate variability in alcohol-dependent subjects using frequency-domain analysis

Background: Alcohol-seeking behavior despite being aware of its adverse effects is defined as alcohol dependence (AD). AD syndrome is a cluster of physiological, behavioral, psychological, and perceptual phenomena that develop subsequent to chronic alcohol ingestion. Ethanol is a potent central nervous system depressant that causes toxic damage to the vasomotor and cardiac autonomic nerve fibers which leads to autonomic imbalance leading to arrhythmias and sudden cardiac deaths. Recording and analyzing the heart rate variability (HRV) using the frequency-domain method delineate the autonomic imbalance in alcoholic individuals which may be due to reduced parasympathetic activity and/or sympathetic hyperactivity. Aims and Objectives: The aim of the study was to assess and compare the cardiac autonomic function between the AD group and the non-alcoholic control group using the frequency domain method of HRV. Materials and Methods: A total of 55 alcohol-dependent individuals in the age group of 20–55 years were selected from the psychiatry outpatient department, based on the International Classification of Diseases-10 (Diagnostic and Statistical Manual -IV) criteria as the study population. Fifty-five age and gender-matched healthy volunteers from the master health check-up scheme from the Department of Community Medicine were selected as the control population. Institutional Ethical Committee clearance was obtained. After obtaining informed written consent from the individuals, the short-term 5 min HRV was recorded in the supine position with eyes closed. The results were analyzed and interpreted. Statistical analysis was done using the software Statistical Package for the Social Sciences version 21.0. Results: The frequency domain parameters high frequency (HF) which is a specific marker of parasympathetic activity was significantly reduced, and low frequency (LF) which is a marker of sympathetic activity was significantly increased in the alcoholic group compared to the non-alcoholic group, respectively. The LF: HF ratio which denotes sympathetic-vagal balance was increased in the alcohol-dependent group. Conclusion: HF was decreased, LF and LF: HF ratio was increased in alcoholic-dependent individuals indicating autonomic imbalance with reduced parasympathetic activity and increased sympathetic activity which suggests that alcohol affects the cardiac autonomic status. This concludes that the frequency domain method of HRV could be used as a short-term non-invasive test to assess cardiac autonomic dysfunction in alcohol-dependent individuals.

Comparison of time domain indices of heart rate variability between alcohol-dependent individuals and non-alcoholic subjects

Background: Alcohol dependence develops because of repeated alcohol intake. Alcohol damages the cardiac autonomic nerve fibers leading to autonomic imbalance, resulting in reduced heart rate variability (HRV). HRV refers to the complex beat-to-beat variation in the heart rate, produced by the interplay of sympathetic and parasympathetic neural activity at the Sino-atrial node. Our body works effectively in parasympathetic activity dominance. The time domain indices of HRV are specific markers of parasympathetic activity. A decrease in the time domain parameters indicates reduced parasympathetic activity in the heart, indicating cardiac autonomic dysfunction with vagal neuropathy. Aims and Objectives: The objectives of the study are as follows: (1) To assess the HRV in alcohol-dependent individuals using time domain indices. (2) To compare the HRV between alcoholic-dependent individuals and non-alcoholic subjects. Materials and Methods: A total of 110 individuals in the age group of 20–55 years were recruited for our study. Among them, 55 were alcohol-dependent individuals selected based on the diagnostic and statistical manual-IV, international classification of diseases-10 criteria, and 55 age and gender-matched volunteers were selected as healthy non-alcoholic controls. Short-term HRV was recorded in a supine posture, and the results were interpreted. Statistical analysis was done using the software SPSS version 21.0. Results: Our results showed a significant reduction in the time-domain parameters of HRV – SDNN, RMSSD, NN50, and pNN50 in the alcohol-dependent individuals compared to the controls, suggesting reduced parasympathetic activity in the heart indicating cardiac autonomic neuropathy. Conclusion: Alcohol affects the cardiac autonomic status leading to sudden death due to arrhythmias. HRV can be used as a non-invasive test to assess cardiac autonomic dysfunction and its biofeedback can help alcohol-dependent individuals to adopt healthy lifestyle measures.

Impaired Executive Functioning Associated with Alcohol-Related Neurocognitive Disorder including Korsakoff's Syndrome.

(1) Background: chronic alcohol use is consistently associated with impaired executive functioning, but its profile across the spectrum from mild to major alcohol-related cognitive impairment is, to date, unclear. This study aims to compare executive performances of patients with alcohol-induced neurocognitive disorder, including Korsakoff's syndrome (KS), by using a computerized assessment battery allowing a fine-grained and precise neuropsychological assessment; (2) Methods: performances of 22 patients with alcohol-related cognitive impairment (ARCI) and 20 patients with KS were compared to those of 22 matched non-alcoholic controls. All participants were diagnosed in accordance with DSM-5-TR criteria and were at least six weeks abstinent from alcohol prior to assessment. Executive function was evaluated using four subtests of Cambridge Neuropsychological Test Automated Battery (CANTAB®); (3) Results: significant differences between groups were found on spatial working memory (updating), sustained attention and inhibitory control, set shifting, and planning. Healthy controls performed significantly better than both patient groups (Games-Howell post hoc; p < 0.05), but no differences in performance were found between the ARCI and KS group; (4) Conclusions: ARCI and KS patients showed significant executive impairments, most prominent in updating, set-shifting and general planning abilities. Findings suggest equivalent levels of executive function in ARCI and KS patients. Our results highlight executive function as a significant hallmark of alcohol-induced neurocognitive disorder and stipulate the importance of early assessment and evaluation of skills to guide treatment.

Novel Microbial Signatures in the Faecal Microbiome Associated with Severe Alcoholic Hepatitis: Bacteroides Finegoldii and Veillonella Dispar

Background: Alcoholic hepatitis is associated with dysbiosis, resulting in compositional changes in the gut microbiome, endotoxin transfer to the portal vein, and activation of inflammatory signalling pathways in the liver. However, the microbiome signature of severe alcoholic hepatitis (AH) patients of Indian origin is unknown. Aim: To investigate the microbiome diversity of Indian AH patients in comparison to non-alcoholic healthy controls (HC). Methods: 16S rRNA amplicon-based metagenomics analysis of faecal samples at the time of AH diagnosis (n=12) was compared with HC (n=6), and correlation with survival status, co-occurrence networking, Linear Discriminant Analysis Effect Size (LEfSe), and the relationship between diet – microbiome were performed. Results: 16S rDNA data showed a significant abundance of the Enterobacteriaceae family belonging to the phylum Proteobacteria and a depletion of the phylum Firmicutes in AH. A species-level classification identified Klebsiella pneumonia, Klebsiella variicola, and Parabacteroides distasonis as having the highest predictive performance value with reference to mortality at 60 days. Apart from this, a unique finding was the abundance of Bacteroides finegoldii and Veillonella dispar in AH patients. Moreover, the co-occurrence networking analysis revealed a higher level of connectivity and complexity within the microbial community of AH patients compared to HC. Thus, indicating the significant positive association (Spearman r &gt; 0.7, p &lt; 0.01) among members of the Firmicutes, Bacteroidetes, and Proteobacteria phyla in AH. Wilcoxon-Rank Sum test (p &lt; 0.01) identified Firmicutes phyla occurrence associated with high carbohydrate intake and Actinobacteria phyla with low protein intake. Conclusion: The findings provide the baseline occurrence profile of the gut microbiome signature of liver damage and the diet-microbiome relationship in patients with severe AH. The study demonstrated an abundance of Proteobacteria phyla, indicating their role in inflammatory conditions, and further identified Bacteroides finegoldii and Veillonella dispar in severe AH patients. Additionally, Klebsiella pneumonia, Klebsiella variicola, and Parabacteroides distasonis were identified as mortality-predictive risk biomarkers.

Impact of prior alcohol use on the subsequent development of cancer cachexia in male and female mice.

Alcohol is a carcinogen and its intake prior to developing cancer and throughout its duration exacerbates cancer cachexia in rodent models. However, the effects on cancer cachexia of stopping alcohol prior to tumor establishment are unknown. Male and female mice consumed either a nonalcohol control liquid diet (CON) or a 20% ethanol (kcal/day) liquid diet (EtOH) for 6 weeks. All mice then consumed a control diet and mice in the cancer groups were inoculated with C26 colon cancer cells. Gastrocnemius muscles were collected and analyzed after ~2 weeks. Skeletal muscle weight and male epididymal and female perigonadal fat mass were reduced more by the combination of cancer and prior EtOH than either exposure alone in both males and females. In males, protein synthesis was reduced by 30% following alcohol exposure, while no reductions were observed in female mice. AMPK Thr172 phosphorylation was increased in both male and female EtOH-Cancer groups, while Akt Thr308 phosphorylation was reduced only among males in EtOH-Cancer mice. Substrates in the mTORC1 pathway were reduced by cancer in both males and females, but prior alcohol intake only reduced phosphorylation of 4E-BP1 Ser65 and rpS6 Ser240/244 to a greater extent in male, but not female, mice. Autophagic and proteasomal signaling were largely unaffected by prior alcohol intake in cancer mice, despite a greater increase in Murf1 mRNA in both sexes. Prior alcohol consumption accelerates or worsens the onset of certain aspects of cancer cachexia in a sex-dependent manner, with males being more sensitive to these exposures, even with abstinence from alcohol prior to tumor initiation.

0166 Effects of Evening Pre-Sleep Alcohol on Next-Day Psychomotor Vigilance (PVT) Performance

Abstract Introduction Few reports have examined how pre-sleep alcohol affects performance on the next day given adequate sleep opportunity on a preferred schedule. Our goal is to identify whether alcohol intake targeting .08g% 1 hr before sleep of ~8 h will affect PVT performance on subsequent days, with the hypothesis that morning performance will be negatively affected. Methods 25 adults (13F; age range 22-57 y) completed the full study, including at-home sleep on a fixed schedule of 8-9 hr and two 3-night in-lab PSG sessions spaced ≥3 days apart. Sessions were counterbalanced for alcoholic or nonalcoholic control beverage administered in 3 drinks over 45 minutes ending 1 hr before bedtime. Alcohol was targeted to .08g%. The 10-min PVT (Ambulatory Monitoring, Inc.) was given each night (PM-Lab) 1.5 hr before drinking and in the morning after a light breakfast (AM-Lab) 50 min after waking. PVT was performed at home/work twice each day within 1.5-h windows starting 3h after waking (AM-Home) and 7.5h after waking (PM-Home). Two reaction time (RT) variables were assessed: RRT (1/RT), FRT (10% fastest RT). Linear mixed effects models were used to account for nesting of assessments within alcohol/control condition and days. Results RRTs showed slowed RT (meanRT±SE) following alcohol: AM-Lab F=7.234, p=.008, alcohol RT=246±9.6 msec, control RT=234±9.6 msec; AM-Home F=17.936, p&amp;lt;.001, alcohol RT=254±9.5 msec, control RT=242±9.6 msec; but not PM-Home or PM-Lab tests. FRT slowed for AM-Lab F=9.391, p=.003, alcohol FRT=195±4.3 msec, control FRT=201±4.3 msec; AM-Home F=17.251, p=.001, alcohol FRT= 202±4.4 msec, control FRT=194±4.4 msec; PM-Home F=3.379, p=.068 (trend), alcohol FR=200±4.8 msec, control FRT=196±4.8 msec, but not for PM-Lab PVTs. PM-Home FRT also had a significant day order effect: F=3.087, p=.0496, Day 1 FRT=197±5.0 msec, Day 2 FRT=202±5.0 msec, Day 3 FRT=195±5.0 msec. Conclusion We found statistically significant slowing of psychomotor vigilance RT on days after pre-sleep alcohol lasting up to 3-4.5h after waking in the morning (with a trend up to 7.5-9h post waking). PVT lapses (not shown) were similarly affected by alcohol. Thus, even with sufficient sleep opportunity, RT is impaired following 3 consecutive nights of alcohol drinking. Support (if any) R01AA025593

Effect of Oral Administration of Syzygium cumini Seed Powder on the Hepatic Function-related Enzymes of the Alcoholic Transport Laborers

Background: Syzygium cumini (locally known as Kalo Jam) seed powder is being used as folk medicine in various diseases since unknown times in Bangladesh. However, data on the systematic studies in human subjects are rare. Objective: To determine the effect of Syzygium cumini seed powder on the hepatic function-related enzymes of the alcoholic transport laborers. Methods: Here, we investigated the effects of oral administration of Syzygium cumini seed powder on hepaticfunction markers that included activities of Gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and renal-function markers such as creatinine and urea along with lipid profile, blood pressure and body mass index (BMI) upon chronic alcoholic human volunteers. Results: The levels of serum ALT, AST and GGT levels decreased, respectively, by 15.0, 8.5 and 23.0% after oral administration of the S. cumini powder in the alcoholic subjects. However, the levels of creatinine and urea were not altered significantly. In contrast, the effects of administration of S. cumini on the hepatic ALT, AST and GGT enzymes in the non-alcoholic control subjects were less prominent than those found in the alcoholic subjects. Blood pressure decreased only by 5-4 mmHg, while BMI was not altered in either the alcoholic or the non-alcoholic groups. Furthermore, there were significant reduction in the levels of TC (by 10%) and LDL-C (by &gt;20%) and elevation of HDL-C (by 11%) in the S. cumini-prescribed alcoholic subjects. TC and LDL-C levels also decreased in the non-alcoholic subjects, but the rate was not statistically significant. Conclusions: Our results suggest that S. cumini seed extract ameliorated GGT, ALT and the atherosclerotic lipid parameters TC and LDL-C without having a significant side effect on the kidney functions, as indicated by the unaltered levels of serum creatinine levels in the alcoholic human subjects without any effect on BP and BMI of the same subjects. Thus, alcohol drinkers can be advised to intake S. cumini seed powder to protect against the oxidative hepatic damage. Bangladesh Medical Res Counc Bull 2022; 48: 97-104

Emergency Department Treatment of Alcohol-Related Seizures: A Retrospective Chart Review (P12-1.008)

<h3>Objective:</h3> To critically analyze the management of alcohol-related seizures including alcohol withdrawal (AW) and alcohol-induced (AI) presentations. <h3>Background:</h3> Although alcohol related seizures are common, there remains considerable difficulty in differentiating seizure etiologies among alcohol users which in turn complicates clinical decision making. <h3>Design/Methods:</h3> Between June and December 2018, 558 ED seizure visits at three urban emergency departments were reviewed to capture all alcohol-related seizures. Data was collected on patient demographics, seizure history, treatments, diagnostics, and discharge information. Data was categorized into three groups: AW (seizure &gt; 24 hours from last drink), AI (alcohol used within 24 hours), and a non-alcohol related seizure control (SC) group. Functional seizure encounters were excluded. Chi square analysis was performed with a significance level of p &lt;0.05. <h3>Results:</h3> We identified 53 AW, 60 AI, and 445 SC encounters with similar racial make-up and median age. The AW group had significantly less home anti-seizure medication (ASM) than the AI and SC groups (p &lt;0.001) and were less likely to be given an ASM in the ED (p &lt;0.001). Less ASMs were prescribed on discharge to the AI (p &lt;0.02) and AW groups (p &lt;0.001) than SC. AW group received more head CTs compared to SC (p &lt;0.02) despite similar rates of head trauma. AW had more benzodiazepines given in the ED (p &lt;0.001), inpatient admissions (p &lt;0.006), and ICU admissions (p &lt;0.001) than SC. AI group returned to the ED with seizures more often compared to SC (p &lt;0.03). <h3>Conclusions:</h3> Despite AI presenting more often with recurrent seizures, they were less likely to receive ASM treatments on discharge. AW seizures were more likely to have a head CT despite no increased history of head trauma. Larger studies are needed to determine risk factors for recurrent alcohol-related seizures to reduce ED visits and determine appropriate treatments. <b>Disclosure:</b> Mr. Hijazi has nothing to disclose. Ms. Sukkarieh has nothing to disclose. Dr. Tetarbe has nothing to disclose. Dr. Aravind has nothing to disclose. Dr. Basha has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Zutshi has nothing to disclose.

Skeletal muscle atrophy is exacerbated by steatotic and fibrotic liver-derived TNF-alpha in senescence-accelerated mice.

Although liver diseases, including non-alcoholic steatohepatitis, are associated with skeletal muscle atrophy, the mechanism behind their association has not been fully elucidated. In this study, the effects of aging and non-alcoholic steatohepatitis on the skeletal muscle and the interaction between the liver and muscle were investigated using a diet-induced non-alcoholic steatohepatitis model in senescence-accelerated mice. A total of four groups of senescence-accelerated mice and the control mice were fed either a non-alcoholic steatohepatitis-inducing or control diet, and their livers and skeletal muscles were removed for examinations. In the senescence-accelerated/non-alcoholic steatohepatitis group, serum level of alanine aminotransferase was markedly elevated and histopathology of non-alcoholic steatohepatitis was significant. Skeletal muscles were also markedly atrophied. The expression of the ubiquitin ligase Murf1 in the muscle was significantly increased with muscle atrophy, while that of Tnfa was not significantly different. In contrast, the hepatic Tnfa expression and serum TNF-α levels were significantly increased in the senescence-accelerated/non-alcoholic steatohepatitis group. These results suggest that liver-derived TNF-α might promote muscle atrophy associated with steatohepatitis and aging through Murf-1. The metabolomic analysis of skeletal muscle indicated higher spermidine and lower tryptophan levels in the steatohepatitis-diet group. The findings of this study revealed an aspect of liver-muscle interaction, which might be important in developing treatments for sarcopenia associated with liver diseases.

A metagenomic study identifies a Prevotella copri enriched microbial profile associated with non-alcoholic steatohepatitis in subjects with obesity.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease. Increasing evidence indicates that the gut microbiota can play an important role in the pathophysiology of NAFLD. Recently, several studies have tested the predictive value of gut microbiome profiles in NAFLD progression; however, comparisons of microbial signatures in NAFLD or non-alcoholic steatohepatitis (NASH) have produced discrepant results, possibly due to ethnic and environmental factors. Thus, we aimed to characterize the gut metagenome composition of patients with fatty liver disease. Gut microbiome of 45 well-characterized patients with obesity and biopsy-proven NAFLD was evaluated using shot-gun sequencing: 11 non-alcoholic fatty liver controls (non-NAFL), 11 with fatty liver, and 23 with NASH. Our study showed that Parabacteroides distasonis and Alistipes putredenis were enriched in fatty liver but not in NASH patients. Notably, in a hierarchical clustering analysis, microbial profiles were differentially distributed among groups, and membership to a Prevotella copri dominant cluster was associated with a greater risk of developing NASH. Functional analyses showed that although no differences in LPS biosynthesis pathways were observed, Prevotella-dominant subjects had higher circulating levels of LPS and a lower abundance of pathways encoding butyrate production. Our findings suggest that a Prevotella copri dominant bacterial community is associated with a greater risk for NAFLD disease progression, probably linked to higher intestinal permeability and lower capacity for butyrate production.

Expression of Integrin β1, Focal Adhesion Kinase, and PDZ-Binding Motif in Human Liver Cirrhosis and Simple Steatosis

Background: Integrins are transmembrane mechanosensitive proteins that negatively contribute to the pathogenesis of different types of chronic liver disease and can activate focal adhesion kinase (FAK). Objectives: This study aimed to determine the hepatic integrin β1 and FAK mRNA as well as the transcriptional coactivator with PDZ-binding motif (TAZ) protein expressions in cirrhotic patients and simple steatosis. Methods: In this case–control study, liver tissues were collected from 30 cirrhotic patients with various etiologies (i.e., nonalcoholic steatohepatitis-, primary sclerosing cholangitis-, alcoholic-, autoimmune hepatitis [AIH]- and hepatitis B virus [HBV]/hepatitis C virus [HCV]-related cirrhosis [six per group]), liver samples with simple steatosis (n=6), and control liver tissues (n=9). Results: Integrin β1 gene expression was significantly up-regulated in all cirrhotic groups compared to control group (P&lt;0.05), with the exception of AIH cirrhosis. However, hepatic FAK gene expression and TAZ protein level in the cirrhotic groups were not significantly different than those in the control group. Furthermore, hepatic integrin β1 and FAK gene expressions as well as TAZ protein level in simple steatosis were significantly lower than those in nonalcoholic steatohepatitis (NASH) cirrhosis and control (P&lt;0.05). Conclusion: Integrin β1 was up-regulated in cirrhotic liver tissues. In addition, FAK, integrin β1, and TAZ were concordantly down-regulated in simple steatosis, and may have been involve in the steatosis development.

Correlation between Serum Steroid Hormones and Gut Microbiota in Patients with Alcohol-Associated Liver Disease.

Alcohol-associated liver disease is a major public health concern globally. Alterations of steroid hormones and gut microbiota were both found in patients with alcohol-associated liver disease. However, their correlation has not been well characterized in these patients. In this study, we measured the level of 30 steroid hormones in serum and fecal samples collected from non-alcoholic controls, patients with alcohol use disorder, and patients with alcohol-associated hepatitis. The profile of serum and fecal steroid hormones was quite different in patients with alcohol-associated hepatitis from that in patients with alcohol use disorder and control subjects. Stronger alterations were observed in male patients than in females. Correlations were found not only between serum steroids and gut bacteria but also between serum steroids and gut fungi. These correlations need to be taken into consideration during the development of treatment strategies for alcohol-associated liver disease.

The effect of acute alcohol intoxication on alcohol cue salience: An event-related brain potential study.

Alcohol cue salience is considered core to the broader understanding of drinking behaviors. In the present research, we sought to build the knowledge of alcohol cue salience by exploring P3 responses to alcohol images among social drinkers within a large-scale alcohol-administration study. Participants (N = 246) were randomly assigned to receive either a moderate dose of alcohol (target BAC = .08%) or a nonalcoholic control beverage. Following beverage administration, participants engaged in image-viewing tasks while EEG was recorded. We examined the impact of alcohol on the amplitude of P3 responses to pictures of alcoholic versus nonalcoholic beverages, exploring both beverage-manipulation and individual-difference moderators of these effects. Results revealed a significant effect of acute alcohol intoxication on P3 responses across stimulus types, with the overall amplitude of P3 being significantly smaller among participants consuming alcohol versus a nonalcoholic beverage. In addition, results revealed a significant main effect of image type, such that P3 amplitude was larger for alcohol images compared to nonalcohol images. No interactions emerged between stimulus type and beverage condition or stimulus type and AUD risk level. With the aim of better understanding the potential influence of the broader context on responses to individual cues, the present study examined the perceived salience of alcohol cues within a drinking setting. Findings provide evidence for alcohol cue salience that is both robust and also widespread across drinkers. More generally, the present study's findings may offer new directions for understanding neurocognitive processes of alcohol cue salience across contexts. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

273-OR: Postprandial Dysfunction in Metabolic Associated Fatty Liver Disease (MAFLD)

Metabolic dysfunction in patients with metabolic fatty liver disease (MAFLD) may increase the risk for diabetes development. The liver is essential for the postprandial control of our metabolism and hormonal response, yet most studies focus on fasting conditions. We therefore studied the fasting and postprandial phase in individuals with biopsy-proven nonalcoholic fatty liver disease (NAFLD, (n = 9, mean age 50 y, mean BMI 35 kg/m2, no/mild fibrosis) , cirrhosis (n = 10, age 62 y, BMI 32 kg/m2, CHILD A/B) and healthy controls (n = 10, age 23, BMI 25 kg/m2) , randomized 1:1 to fasting or Nutridrink (Nutricia, 300 kcal) . None of the postprandial patients had type 2 diabetes (T2D) . In the NAFLD/cirrhosis groups, 17/classified as MAFLD. Peripheral blood samples were collected at 0, 15, 45, 60, 90 and 120 minutes. At time point 60, a transjugular liver biopsy and liver vein blood were taken. Levels of glucose, insulin, C-peptide, glucagon, and fibroblast growth factor 21 (FGF21) were measured in peripheral blood, glucagon and FGF21 also in liver vein blood. Postprandial peak glucose and C-peptide was increased in NAFLD and cirrhosis compared with healthy (mean peak glucose (mM) 7, 10, 6; mean peak C-peptide (pM) 2675, 3340, 1689, respectively) . The postprandial incremental AUC for insulin was significantly increased in patients with NAFLD compared to healthy. Patients with NAFLD and cirrhosis had hyperglucagonemia, a phenotype related to prediabetes. FGF21 was increased in NAFLD and cirrhosis and correlated to age (r= .61, P = .001) and fasting glucose (r = .54, P = .006) . Glucagon levels were higher in liver vein compared to peripheral blood, while FGF21 levels were similar in both compartments. In summary, patients with NAFLD and cirrhosis without T2D showed significant metabolic dysfunction after a standardized meal compared to healthy controls. We found impaired glucose tolerance, hyperinsulinemia and hyperglucagonemia in both NAFLD and cirrhosis, suggesting a condition of prediabetes in patients with MAFLD. Disclosure J. Grandt: None. A.H. Jensen: None. M.P. Werge: None. E.B. Rashu: None. A. Junker: None. L. Hobolth: None. C. Mortensen: None. M. Vyberg: None. R. Serizawa: Consultant; Merck Sharp &amp; Dohme Corp. L. Gluud: Advisory Panel; Novo Nordisk. Consultant; Pfizer Inc. Research Support; Alexion Pharmaceuticals, Inc., Gilead Sciences, Inc., Novo Nordisk, Sobi. N.J. Wewer Albrechtsen: Research Support; Mercodia AB, Novo Nordisk, Regeneron Pharmaceuticals Inc. Speaker's Bureau; Merck &amp; Co., Inc., Mercodia AB. Funding Nicolai J. Wewer Albrechtsen was financed by NNF Excellence Emerging Investigator Grant – Endocrinology and Metabolism (Application No. NNF19OC0055001) , EFSD Future Leader Award (NNF21SA0072746) and DFF Sapere Aude.

Lipidomics for the Prediction of Progressive Liver Disease in Patients with Alcohol Use Disorder.

Alcohol-related liver disease is a public health care burden globally. Only 10–20% of patients with alcohol use disorder have progressive liver disease. This study aimed to identify lipid biomarkers for the early identification of progressive alcohol-related liver disease, which is a key step for early intervention. We performed untargeted lipidomics analysis in serum and fecal samples for a cohort of 49 subjects, including 17 non-alcoholic controls, 16 patients with non-progressive alcohol-related liver disease, and 16 patients with progressive alcohol-related liver disease. The serum and fecal lipidome profiles in the two patient groups were different from that in the controls. Nine lipid biomarkers were identified that were significantly different between patients with progressive liver disease and patients with non-progressive liver disease in both serum and fecal samples. We further built a random forest model to predict progressive alcohol-related liver disease using nine lipid biomarkers. Fecal lipids performed better (Area Under the Curve, AUC = 0.90) than serum lipids (AUC = 0.79). The lipid biomarkers identified are promising candidates for the early identification of progressive alcohol-related liver disease.

Does acute alcohol consumption increase risk-taking while gambling? A systematic review and meta-analysis.

To estimate the effect of acute alcohol consumption on risk-taking while gambling, examine blood alcohol concentration as a moderator and explore possible moderators of this effect. A systematic review and meta-analysis was completed. A Boolean search strategy was used to identify studies that included (a) alcohol consumption as an independent variable; (b) a gambling or risk-taking task; (c) a control or placebo comparison; (d) human participants; and (e) English publications. Descriptive information, sample characteristics and experimental data were extracted from each study. Searched databases included: PsycINFO, Web of Science, Medline, Cochrane Library and ProQuest Dissertations and Theses. Included as participants were experiments that compared the effects of alcohol and non-alcoholic or placebo beverages on risk-taking while gambling. Comprehensive Meta-Analysis version 3.3.070 was used. Standardized mean differences of risk-taking while gambling between the experimental and control conditions were calculated when studies did not report effect sizes. Random-effects models were used for overall effect and meta-regressions while mixed-effects models were used for subgroup analyses. Twenty articles containing 47 alcohol versus control comparisons met inclusion criteria. The overall Hedges'g for the difference between groups consuming alcohol and groups consuming a placebo or non-alcoholic drink control was 0.03, 95% confidence interval (CI) = -0.07, 0.12, p = 0.60, indicating no significant difference. Larger effect sizes were found for studies using non-alcoholic control drinks (Hedges' g = 0.30, 95% CI = 0.01, 0.58) compared to placebo beverages (Hedges' g = -0.03, 95% CI = -0.13, 0.06), Cochran's Q= 4.67, p = 0.03. Finding that acute alcohol consumption had no reliable effect on risk-taking while gambling was consistent with existing animal research. No support was found for the relation between alcohol dose and risk-taking. The significantly larger effect size for experiments using non-alcoholic versus placebo beverages suggests the potential role of expectancy effects.

Is metabolic syndrome a risk factor in hepatectomy? A meta-analysis with subgroup analysis for histologically confirmed hepatic manifestations

BackgroundMetabolic syndrome (MetS) is a risk factor in surgery. MetS can progress to metabolic (dysfunction)-associated fatty liver disease (MAFLD), a vast-growing etiology of primary liver tumors which are major indications for liver surgery. The aim of this meta-analysis was to investigate the impact of MetS on complications and long-term outcomes after hepatectomy.MethodsThe protocol for this meta-analysis was registered at PROSPERO prior to data extraction. MEDLINE, Web of Science, and Cochrane Library were searched for publications on liver resections and MetS. Comparative studies were included. Outcomes encompassed postoperative complications, mortality, and long-term oncologic status. Data were pooled as odds ratio (OR) with a random-effects model. Risk of bias was assessed using the Quality in Prognostic Studies tool (QUIPS), and the certainty of the evidence was evaluated with GRADE. Subgroup analyses for patients with histopathologically confirmed non-alcoholic fatty liver disease (NAFLD) versus controls were performed.ResultsThe meta-analyses included fifteen comparative studies. Patients with MetS suffered significantly more overall complications (OR 1.55; 95% CI [1.05; 2.29]; p=0.03), major complications (OR 1.97 95% CI [1.13; 3.43]; p=0.02; I2=62%), postoperative hemorrhages (OR 1.76; 95% CI [1.23; 2.50]; p=0.01) and infections (OR 1.63; 95% CI [1.03; 2.57]; p=0.04). There were no significant differences in mortality, recurrence, 1- or 5-year overall or recurrence-free survivals. Patients with histologically confirmed NAFLD did not have significantly more overall complications; however, PHLF rates were increased (OR 4.87; 95% CI [1.22; 19.47]; p=0.04). Recurrence and survival outcomes did not differ significantly. The certainty of the evidence for each outcome ranged from low to very low.ConclusionPatients with MetS that undergo liver surgery suffer more complications, such as postoperative hemorrhage and infection but not liver-specific complications—PHLF and biliary leakage. Histologically confirmed NAFLD is associated with significantly higher PHLF rates, yet, survivals of these patients are similar to patients without the MetS. Further studies should focus on identifying the tipping point for increased risk in patients with MetS-associated liver disease, as well as reliable markers of MAFLD stages and early markers of PHLF.Trial registrationPROSPERO Nr: CRD42021253768

Non-Alkolik Yağlı Karaciğer Hastalığı Olan ve Olmayan Obez Çocuklarda Hepatik Vasküler Akım Değişikliklerinin Değerlendirilmesi

Objective: To evaluate hepatic vascular flow alterations using Doppler ultrasound in obese children with and without non-alcoholic fatty liver disease.Material and Methods: Ninety-one obese and 30 healthy lean (control) children were enrolled in this study. Obese children were divided into two groups: children with non-alcoholic fatty liver disease and children without non-alcoholic fatty liver disease; according to hepatic fatty changes on ultrasound, and blood serum alanine aminotransferase levels above 30 IU/L. Portal vein diameter, portal blood flow volume and hepatic artery resistive index were calculated using Doppler ultrasound.Results: Portal vein diameter and portal blood flow volume values in children with non-alcoholic fatty liver disease were found close to the controls. However, the values of portal vein diameter and portal blood flow volume were lower in children without non-alcoholic fatty liver disease group than the other groups (p&amp;lt;0.001). Hepatic artery resistive index was higher in children without non-alcoholic fatty liver disease group than children with non-alcoholic fatty liver disease group (0.64±0.1 and 0.60±0.1, respectively) (p=0.03), whereas hepatic artery resistive index was found to be close in children with non-alcoholic fatty liver disease and controls. These findings were similar to the differences in hepatic vascular changes observed during the development of non-alcoholic fatty liver disease, which were described in physio-pathological studies.Conclusion: Portal vein diameter, portal blood flow volume and hepatic artery resistive index values in obese children show significant differences according to the presence or absence of fatty liver. These differences are consistent with hepatic physio-pathological changes in non-alcoholic fatty liver disease. Therefore, hepatic vascular Doppler indices may be a new tool that can be used to monitor the development and progression of non-alcoholic fatty liver disease in obese children.