Alcoholic Liver Disease Group Research Articles

Increased Intestinal Permeability and Decreased Resiliency of the Intestinal Barrier in Alcoholic Liver Disease.

Only 20%-30% of individuals with alcohol use disorder (AUD) develop alcoholic liver disease (ALD). While the development of gut-derived endotoxemia is understood to be a required cofactor, increased intestinal permeability in ALD is not completely understood. We recruited 178 subjects-58 healthy controls (HCs), 32 with ALD, 53 with AUD but no liver disease (ALC), and 35 with metabolic dysfunction-associated steatotic liver disease (MASLD). Intestinal permeability was assessed by a sugar cocktail as a percentage of oral dose. The permeability test was repeated after an aspirin challenge in a subset. Five-hour urinary lactulose/mannitol ratio (primarily representing small intestinal permeability) was not statistically different in HC, ALC, ALD, and MASLD groups ( P = 0.40). Twenty-four-hour urinary sucralose (representing whole gut permeability) was increased in ALD ( F = 5.3, P < 0.01) and distinguished ALD from ALC; 24-hour sucralose/lactulose ratio (primarily representing colon permeability) separated the ALD group ( F = 10.2, P < 0.01) from the MASLD group. After aspirin challenge, intestinal permeability increased in all groups and ALD had the largest increase. In a group of patients, we confirmed that (i) the ALD group has increased intestinal permeability compared with the HC, ALC, or MASLD group. In addition, because small bowel permeability (lactulose/mannitol ratio) is normal, the disruption of intestinal barrier seems to be primarily in the large intestine; (ii) decreased resiliency of intestinal barrier to injurious agents (such as NSAID) might be the mechanism for gut leak in subset of AUD who develop ALD.

COMPARISON OF GUT MICROBIOTA IN ALCOHOLIC AND METABOLIC-DYSFUNCION ASSOCIATED STEATOTIC LIVER DISEASE IN ANIMAL MODELS.

Alcoholic liver disease (ALD) and metabolic-dysfunction associated steatotic liver disease (MASLD) are common, and gut microbiota (GM) is involved with both. Here we compared GM composition in animal models of MASLD and ALD to assess whether there are specific patterns for each disease. MASLD model- adult male Sprague Dawley rats, randomized into two groups: MASLD-control (n=10) fed a standard diet; MASLD-group (n=10) fed a high-fat-choline-deficient diet for 16 weeks. ALD model- adult male Wistar rats randomized: ALD-control (n=8) fed a standard diet and water+0.05% saccharin, ALD groups fed with sunflower seed and 10% ethanol+0.05% saccharin for 4 or 8 weeks (ALC4, n=8; ALC8, n=8). ALC4/8 on the last day received alcoholic binge (5g/kg of ethanol). Afterwards, animals were euthanized, and feces were collected for GM analysis. Both experimental models induced typical histopathological features of the diseases. Alpha diversity was lower in MASLD compared with ALD (p<0.001), and structural pattern was different between them (P<0.001). Bacteroidetes (55.7%), Firmicutes (40.6%), and Proteobacteria (1.4%) were the most prevalent phyla in all samples, although differentially abundant among groups. ALC8 had a greater abundance of the phyla Cyanobacteria (5.3%) and Verrucomicrobiota (3.2%) in relation to the others. Differential abundance analysis identified Lactobacillaceae_unclassified, Lachnospiraceae_NK4A136_group, and Turicibacter associated with ALC4 and the Clostridia_UCG_014_ge and Gastranaerophilales_ge genera to ALC8. In this study, we demonstrated that the structural pattern of the GM differs significantly between MASLD and ALD models. Studies are needed to characterize the microbiota and metabolome in both clinical conditions to find new therapeutic strategies. •Changes in the composition of the intestinal microbiota are related to the development of alcoholic liver disease and metabolic-dysfunction associated steatotic liver disease. •The diversity of the intestinal microbiota was lower in animals with MASLD compared to ALD. •The structural pattern of the intestinal microbiota was significantly different among the experimental groups. •Studies are needed to characterize the composition of the intestinal microbiota and metabolome to find new therapeutic strategies.

Non-alcoholic fatty liver disease associated with greater herpes zoster risk than alcoholic fatty liver disease

BackgroundDisease-related stress can trigger the occurrence of herpes zoster (HZ). Fatty liver disease (FLD) can have adverse effects on the human body and may induce stress in affected individuals. In this study, we investigated whether FLD is associated with an elevated risk of HZ.MethodsFor this study, we utilized data from the National Health Insurance Research Database, patients with FLD from 2000 to 2017 were observed (follow-up until 2018). Patients were considered to have FLD if they had at least two outpatient visits or at least one admission record with a diagnostic code of FLD. Patients with FLD were matched 1:1 by age, sex, comorbidities, and index year with control patients. Additionally, the FLD was further categorized into non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) groups. Multivariable Cox proportional hazards model was used to calculate the incidence rate and adjusted hazard ratio (aHR) of HZ for FLD and AFLD and for various age groups, sex and comorbidities. Cumulative incidence curve for HZ was plotted through the Kaplan–Meier method, and p-value was calculated using the log-rank test.ResultsAfter 1:1 propensity-score matching, each cohort comprised 62,418 patients. The FLD cohort was further divided into NAFLD and AFLD groups, which respectively comprised 55,709 and 6709 patients. The FLD cohort had a risk of HZ significantly higher than that of the control cohort (aHR = 1.06; p < 0.001). Additionally, the NAFLD group exhibited a significantly higher risk of HZ than did the AFLD group (aHR = 1.22; p < 0.001). Among patients without any comorbidities, those with FLD had a higher risk of HZ than did those without FLD (aHR = 1.14; p < 0.001).ConclusionPatients with FLD are at an increased risk of HZ development. Additionally, NAFLD is associated with a higher risk of HZ than AFLD. Therefore, patients with NAFLD should be informed of their increased risk of HZ.

Protective mechanism of Coprinus comatus polysaccharide on acute alcoholic liver injury in mice, the metabolomics and gut microbiota investigation

Coprinus comatus polysaccharide (CCP) has significant hepatoprotective effect. To explore hepatoprotective mechanism of CCP, the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopathological examination and biochemical analysis. Simultaneously, hepatoprotective mechanism was also analyzed in conjunction with metabolomics and proliferation of gut microbiota. The results showed that CCP significantly decreased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglyceride (TG) levels in serum of alcoholic liver disease (ALD) mice. Histopathological examination showed that CCP can significantly improve liver damage. Metabolomics results showed that there were significant differences in the level of metabolites in liver tissue of control group, ALD group and CCP group, including taurine, xanthosine, fumaric acid and arachidonic acid, among others. Metabolites pathways analysis showed that hepatoprotective effect of CCP was related to energy metabolism, biosynthesis of unsaturated fatty acids, amino acids metabolism and lipid metabolism. Additionally, CCP inhibited an increase in the number of Clostridium perfringens, Enterobacteriaceae and Enterococcus, and a decrease in the number of Lactobacillus and Bifidobacterium in the gut of ALD mice. All these findings suggested that CCP treatment reversed the phenotype of ethanol-induced liver injury and the associated metabolites pathways.

#6962 INCIDENCE AND PROGNOSIS OF HYPONATREMIA IN HOSPITALIZED PATIENTS WITH ALCOHOLIC LIVER DISEASE

Abstract Background and Aims Hyponatremia is a common electrolyte disorder in hospitalized patients and has a poor prognosis leading to an increased risk of poor quality of life, morbidity, and mortality. Although the prevalence and prognosis of hyponatremia in advanced liver disease such as liver cirrhosis are well known, no previous studies have been conducted on the prevalence of hyponatremia in early liver disease or alcoholic liver disease (ALD). Therefore, the purpose of this study was to investigate the prevalence and prognosis of hyponatremia in ALD group. Method We performed a retrospective, single centre study of patients admitted to the hepatology department from March 2016 to December 2022. Adults aged 18 years or older were included, and patients with liver cirrhosis, one of the common causes of hyponatremia, were excluded from the study. Based on the electronic medical records, the study was conducted by dividing the ALD group including alcoholic hepatitis and heavy alcoholics into a control group. Results A total of 830 patients were included, hyponatremia (under 135 mmol/L) occurred in 32.2%, and the ALD group showed a significantly higher prevalence than the control group (53.8% vs. 28.6, p&amp;lt;0.001). In addition, the ALD group was statistically significantly higher than the control group in mortality at hospitalization (8.4% vs. 3.9%, p = 0.031) and all-cause mortality (22.7% vs. 12.1%, p = 0.002). The length of hospital stay was significantly longer (13.5±10.9 vs. 10.5±9.1, p = 0.006), and the readmission rate was also higher in the ALD group (39.5% vs. 22.5%, p &amp;lt; 0.001). Kaplan-Meier analysis revealed significantly higher overall survival in the control group than the ALD group (87.9% vs. 77.3% p = 0.002). Conclusion Our study shows that ALD has a higher incidence rate of hyponatremia, which is followed by a poor prognosis, such as an increase in readmission rates, length of hospitalization, and mortality. Therefore, clinicians should realize the importance of electrolyte imbalance in ALD patients and strive to improve prognosis through early and appropriate treatment.

Quantitative analysis of lipid metabolism-related differential proteins in patients with alcoholic liver disease

Objective: To screen and identify differential proteins, analyze lipid metabolism-related proteins and pathways, and explore their functions and biological processes in liver tissue of patients with alcoholic liver disease using tandem mass tag (TMT) labeling technology. Methods: Liver tissues that met the inclusion criteria were collected. Eight samples from patients with alcoholic cirrhosis and three samples from the normal control group were screened out. The TMT technique was used to screen differential proteins, perform signaling pathway enrichment analysis, and analyze protein interaction networks to explore the biological processes involved in them. Results: Proteomic analysis identified 2 741 kinds of differentially expressed proteins in the two groups of data with statistical significance (P < 0.05). The standard criteria of P < 0.05 and |log2(foldchange)| > 1 had screened out 106 kinds of differentially expressed proteins. Compared with the control group, the alcoholic liver disease group had 12 kinds of up-regulated proteins and 94 kinds of down-regulated proteins. Among them, there were 2 kinds of up-regulated differential proteins related to lipid metabolism and 14 kinds of down-regulated differential proteins. The results of bioinformatics analysis showed that these proteins were primarily involved in biological processes such as lipid transport, regulation of lipase activity, fatty acid binding, and cholesterol metabolism in lipid metabolism and also had a close link to signal pathways related to lipid metabolism such as peroxisome proliferator-activated receptor signaling pathways, cholesterol metabolism, triglyceride metabolism, and regulation of lipolysis in adipocytes. Conclusion: The 16 kinds of lipid metabolism-related differential proteins may be the key proteins in the pathogenesis of alcoholic liver disease.

Roles and correlations of TIM-3 and LAG-3 with cytokines and chemokines in alcoholic liver disease

BackgroundDysregulation of immune checkpoint regulators has been reported in alcoholic liver disease (ALD). This study was designed to assess the serum levels of cytokines and chemokines associated with ALD and uncover the possible disease correlations with the soluble TIM-3 and LAG-3. MethodsThe soluble TIM-3 and LAG-3 levels were measured by enzyme-linked immunoassay, and 14 cytokines and chemokines were measured using Luminex-based multiplex assay in 111 male ALD patients and 45 healthy controls (HCs). ResultsOur results showed that soluble TIM-3 was significantly increased (p < 0.001) while soluble LAG-3 was significantly decreased (p < 0.001) in ALD group compared to HCs. Among the 14 cytokines and chemokines assessed, granulocyte-colony stimulating factor (G-CSF) (p = 0.003) and interferon γ-induced protein (IP)-10 (p < 0.001) were significantly increased, while interleukin (IL)-4 (p = 0.005) and IL-12 (p40) (p = 0.001) were significantly decreased in the ALD group. Kaplan-Meier analysis showed that overall survival decreased in higher TIM-3 level individuals. ConclusionsOur results showed that TIM-3, LAG-3, and IP-10 appear to be important for clinical diagnosis of ALD and ALD severity and may represent potential therapeutic targets in ALD.

Microbiome Alterations in Alcohol Use Disorder and Alcoholic Liver Disease.

Microbiome alterations are emerging as one of the most important factors that influence the course of alcohol use disorder (AUD). Recent advances in bioinformatics enable more robust and accurate characterization of changes in the composition of the microbiome. In this study, our objective was to provide the most comprehensive and up-to-date evaluation of microbiome alterations associated with AUD and alcoholic liver disease (ALD). To achieve it, we have applied consistent, state of art bioinformatic workflow to raw reads from multiple 16S rRNA sequencing datasets. The study population consisted of 122 patients with AUD, 75 with ALD, 54 with non-alcoholic liver diseases, and 260 healthy controls. We have found several microbiome alterations that were consistent across multiple datasets. The most consistent changes included a significantly lower abundance of multiple butyrate-producing families, including Ruminococcaceae, Lachnospiraceae, and Oscillospiraceae in AUD compared to HC and further reduction of these families in ALD compared with AUD. Other important results include an increase in endotoxin-producing Proteobacteria in AUD, with the ALD group having the largest increase. All of these alterations can potentially contribute to increased intestinal permeability and inflammation associated with AUD and ALD.

Alcoholic liver disease in relation to cancer incidence and mortality: Findings from a large, matched cohort study in South Korea.

To estimate the risk of cancer incidence and mortality among patients with alcoholic liver disease in South Korea. A matched cohort study was conducted, including 1,042,185 men (alcoholic liver disease cases: 208,437; controls: 833,748) and 100,400 women (alcoholic liver disease cases: 20,080; controls: 80,320), matched for sex, age, smoking, alcohol consumption, and body mass index at a 1:4 ratio. The risk of cancer incidence and mortality in the alcoholic liver disease group was assessed using Cox proportional hazards regression models. Both men and women with alcoholic liver disease had an elevated risk of all-cancer and liver cancer incidence and mortality in comparison with the control group. In men, alcoholic liver disease was associated with a significantly higher risk of development of 10 cancer types, including lip, oral cavity, and pharynx; esophagus; liver; gallbladder and biliary tract; pancreas; larynx; lung; kidney; thyroid gland; and leukemia. Subgroup analysis by hepatitis B and C infection showed increased hazard ratios of all cancer incidences and mortality in the alcoholic liver disease group, regardless of hepatitis B or C infection status. In both sexes, a higher number and more years of hospital or clinic visits for alcoholic liver disease were associated with an increased risk of incidence and mortality from all cancers and liver cancer. A more profound dose-response relationship between alcoholic liver disease and alcohol consumption was observed in women than in men. Our findings emphasize the need for a clinical surveillance program and the early detection of cancer in patients with alcoholic liver disease.

Low Serum Testosterone Level and Its Relationship with Hypogonadism in Patients with Chronic Liver Disease

Objective: Loss of libido, low serum testosterone levels, and other symptoms of hypogonadism like subfertility, gynecomastia, and immature testes, is a prevalent medical condition amongst males with advanced chronic liver disease. The purpose of this investigation was to evaluate the low serum testosterone levels association with hypogonadism in people with chronic liver disease. Study Duration: This study was carried out at Outpatient Department (OPD) of Medicine Ayub Teaching Hospital, Abbottabad from 1st January 2022 to 30th June 2022. Material and Methods: The retrospective study was completed on two hundred confirmed patients of hypogonadism with liver cirrhosis. In the repository, the available data was divided into two groups. The first group of chronic liver disease patients was diagnosed due to non-alcoholic fatty liver disease (NAFLD) and second patient group due to alcoholic liver disease (ALD). The patient in NAFLD group were in the age group between 15-30 years whereas the patients from ALD group were 30-60 years of age. The diagnostic values of total testosterone and Sex hormone binding globulin (SHBG) were collected from patient’s record. The independent t test was used for statistical analysis by using SPSS version 22. The frequency distribution of testosterone was also calculated between two types of chronic liver disease patients. Results: The retrospective research was performed. The data were dispersed across two age groups. The youth had no alcohol-related data, while the elderly had. According to hospital data, distribution was based on age between 15 and 30 years (NAFLD) and between 30 and 60 years (ALD). When T-test was applied it showed that there was no statistically significant difference found in means of SHBG between two age groups amongst chronic liver disease patients. In the case of serum testosterone, there was a statistically significant (p 0.05) difference between age groups (Table 1). Figures 1 and 2 illustrate the frequency distribution of total testosterone and its comparison within the liver cirrhosis group, respectively. Practical Implication: Our study predicted that low testosterone can raise the risk of mortality, the necessity for liver transplantation, and the likelihood of severe infection in men with cirrhosis given the mechanisms of action of testosterone. Conclusion: On the basis of two groups of liver cirrhosis, there is a significant age-related change in total serum testosterone, its control by the pituitary and it’s binding to SHBG in males over the age of forty. However, no substantial data was discovered in sex hormone binding globulin. Low testosterone levels are associated with hypogonadism in patients with cirrhosis of the liver. The effect of testosterone replacement treatment on increasing muscle quality in male cirrhotic patients remains to be determined. Safety and effectiveness of the treatment requires additional prospective research. Keywords: Sex Hormone Binding Globulin, Serum Testosterone, Hypogonadism, Chronic Liver Disease

Exercise Affects the Formation and Recovery of Alcoholic Liver Disease through the IL-6-p47phox Oxidative-Stress Axis.

(1) Background: To explore the effect of exercise on the formation and recovery of alcoholic liver disease (ALD) and whether the IL-6–p47phox oxidative–stress axis is involved in that process. (2) Methods: Firstly, 23 six-week-old male C57BL/6J mice were randomly divided into the Con group, ALD group, ALD + NOXI group, ALD + Ex group, and ALD + Ex + NOXI group. The Liber–DeCarli alcoholic liquid diet was used for 6 weeks to establish the ALD mice model, and the Con group was given the TP4030C control diet. The remaining groups were fed with the TP4030B alcoholic diet, and exercise intervention was started after the ALD model establishment and lasted for another 6 weeks, with or without administration of the NOX inhibitor apocynin by intraperitoneal injection on every exercise training day. Secondly, 28 mice were randomly divided into the Sed group, Eth group, Eth + Ex group and Eth + Ex + NOXI group. The Sed group was given the TP4030C control diet. The remaining groups were fed with the TP4030B alcoholic diet and exercise intervention was started synchronously combined with or without administration of intraperitoneal apocynin injections on every exercise training day for 5 weeks. After each individual experiment was accomplished, physiological assessment and biochemical analysis of blood and tissue samples were examined. (3) Results: The levels of TG in serum and IL-6 protein content in liver tissue in the ALD group were significantly increased compared to the Con group (p < 0.05); compared with ALD, p47phox expression in muscle was increased significantly in the ALD + NOXI group (p < 0.05), and TG in serum decreased in the ALD + Ex group (p < 0.05). TG in serum, AST/ALT ratio, and IL-6 content in both liver and muscle decreased (p < 0.05) in the ALD + Ex + NOXI group with MDA in muscle significantly increased (p < 0.01). The AST/ALT ratio, TG in serum, SOD in liver, and p47phox in both liver and muscle in the ALD + Ex + NOXI group were significantly decreased compared with the ALD + NOXI group (p < 0.01). Compared with the ALD + Ex group, the liver index and HDL-C levels in serum were decreased (p < 0.05) in the ALD + Ex + NOXI group. The degree of hepatocyte steatosis and inflammatory infiltration were ameliorated after exercise intervention. In the Eth group, the relative epididymal fat content, HDL-C level, and AST/ALT ratio were significantly decreased, and TG and gp91phox in liver were significantly higher than in the Sed group (p < 0.05, p < 0.01). Compared with the Eth group, the AST/ALT ratio, MDA in the liver, and NOX4 and p47phox protein expression in the liver were significantly increased, and body weight decreased significantly in the Eth + Ex group (p < 0.05, p < 0.01), as did TG in the liver and MDA in muscle. In the th + Ex + NOXI group, gp91phox expression in the liver and body weight were significantly decreased (p < 0.05, p < 0.01). In the Eth + Ex + NOXI group, the ratio of AST/ALT and MDA in muscle were increased when compared with the Eth + Ex group, and the protein expression of gp91phox and p47phox were much lower (p < 0.01). (4) Conclusions: 6 weeks of exercise intervention during the recovery phase of ALD ameliorates hepatocyte damage and dyslipidemia through the IL-6–p47phox oxidative–stress axis, and applying a NOX inhibitor in combination could optimize this. However, drinking alcohol during exercise exacerbates dyslipidemia and oxidative stress, with hepatocyte IL-6–p47phox downregulated.

The useful predictors of zinc deficiency for the management of chronic liver disease.

Zinc deficiency is likely to occur in chronic liver disease. The aim of this study was to determine the prevalence of zinc deficiency in different types of chronic liver disease and to identify the factors that predicted low serum zinc levels. The study was an observational single-center design. We obtained the medical records of 666 patients with chronic liver disease whose serum zinc levels had been measured. The cutoff value for zinc deficiency was a serum level < 70µg/dL. Serum zinc levels in the alcoholic liver disease (ALD) group were significantly lower than in the other groups (hepatitis C virus [HCV], hepatitis B virus [HBV], and other cause) (P < 0.01). The CONUT and ALBI score (r = 0.527, P < 0.01), serum zinc level and ALBI score (r = -0.607, P < 0.01), and serum zinc level and CONUT score (r = -0.465, P < 0.01) correlated with each other. The prevalence of zinc deficiency were 44.8%, 63.2%, 86.7%, 97.1%, and 100% in the mALBI grade 1-CONUT normal, CONUT undernutrition, and mALBI grade 2a, 2b, and 3 groups, respectively. Multivariate analysis identified ALD, CONUT score, aspartate aminotransferase, and hemoglobin as significant, independent predictors of zinc deficiency (P < 0.05). This study identified ALD, CONUT score, aspartate aminotransferase, and hemoglobin as predictors of zinc deficiency in chronic liver disease. The rate of zinc deficiency is high even in patients classified as mALBI grade 1, especially in ALD, while caution may be required in those classified as mALBI grade 1-CONUT undernutrition.

Demonstration of Gut-Barrier Dysfunction in Early Stages of Non-alcoholic Fatty Liver Disease: A Proof-Of-Concept Study

Gut-barrier dysfunction is well recognized in pathogenesis of both non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). However, comparison of components of this dysfunction between the two etiologies remains unexplored especially in early stages of NAFLD. Components of gut-barrier dysfunction like alterations in intestinal permeability (IP) by lactulose mannitol ratio (LMR) in urine, systemic endotoxemia (IgG and IgM anti-endotoxin antibodies), systemic inflammation (serum tumor necrosis factor alpha [TNF-α] and interleukin-1 [IL-1] levels), tight junction (TJ) proteins expression in duodenal biopsy and stool microbiota composition using Oxford Nanopore MinION device were prospectively evaluated in patients with NAFLD (n= 34) with no cirrhosis, ALD (n= 28) and were compared with disease free controls (n= 20). Patients with ALD had more advanced disease than those with NAFLD (median liver stiffness -NAFLD:7.1kPa [5.9-8.9] vs. ALD:14.3kPa [9.6-24], P < 0.001]. Median LMR was significantly higher in NAFLD and ALD group when compared to controls (NAFLD 0.054 [0.037-0.17] vs. controls 0.027 [0.021-0.045] (P= 0.001)) and ALD 0.043 [0.03-0.068] vs. controls 0.027 [0.021-0.045] (P= 0.019)]. Anti-endotoxin antibody titer (IgM) (MMU/mL) was lowest in NAFLD 72.9 [3.2-1089.5] compared to ALD 120.6 [20.1-728]) (P= 0.042) and controls 155.3 [23.8-442.9]) (P= 0.021). Median TNF-α (pg/mL) levels were elevated in patients with NAFLD (53.3 [24.5-115]) compared to controls (16.1 [10.8-33.3]) (P < 0.001) and ALD (12.3 [10.1-42.7]) (P < 0.001). Expression of zonulin-1 and claudin-3 in duodenal mucosa was lowest in NAFLD. On principal co-ordinate analysis (PCoA), the global bacterial composition was significantly different across the three groups (PERMANOVA test, P < 0.001). While remaining activated in both etiologies, gut-barrier dysfunction abnormalities were more pronounced in NAFLD at early stages compared to ALD despite more advanced disease in the latter.

Alcoholic Liver Disease Among Patients with Wernicke Encephalopathy: A Multicenter Observational Study

Backgrounddata regarding the association between Wernicke encephalopathy (WE) and alcoholic liver disease (ALD) are scarce in spite of alcohol consumption being the main risk factor for WE. Aimsto describe the frequency of ALD in a cohort of patients diagnosed with WE and alcohol use disorders (AUDs) and to compare the characteristics of WE patients with and without ALD. Methodswe conducted an observational study in 21 centers through a nationwide registry of the Spanish Society of Internal Medicine. WE Caine criteria were applied and demographic, clinical, and outcome variables were analyzed. Results434 patients were included in the study, of which 372 were men (85.7%), and the mean age was 55 ± 11.8 years. ALD was present in 162 (37.3%) patients and we found a higher percentage of cases with tremor, flapping and hallucinations in the ALD group. A total of 22 patients (5.0%) died during admission (7.4% with ALD vs 3.7% without ALD; P = 0.087). Among the ALD patients, a relationship between mortality and the presence of anemia (Odds ratio [OR]=4.6 Confidence interval [CI]95% 1.1–18.8; P = 0.034), low level of consciousness (OR=4.9 CI95% 1.1–21.2; P = 0.031) and previous diagnosis of cancer (OR=10.3 CI95% 1.8–59.5; P = 0.009) was detected. Complete recovery was achieved by 27 patients with ALD (17.8%) and 71 (27.8%) without ALD (P = 0.030). Conclusionthe association of WE and ALD in patients with AUDs is frequent and potentially linked to differences in clinical presentation and to poorer prognosis, as compared to alcoholic patients with WE without ALD.

Serum Vitamin D in Patients with Non Alcoholic Fatty Liver Disease

Background and study aim. Non alcoholic fatty liver disease has an increasing prevelance worldwide.It is closely assosciated with metabolic syndrome. The aim of this study is to assess the assosciation between non alcoholic fatty liver disease and serum level of Vitamin D. Patients and Methods: This cross sectional study was conducted on 95 subjects devided into 2 groups (1st group 45 patients with sonographically proven Non alcoholic fatty liver disease and 2nd group 50 healthy subjects). All the patients were evaluated by thorough full history taking, clinical examination, routine laboratory investigations, lipid profile,abdominal ultrasound,serum Vitamin D by ELISA.Results.Mean weight, Body mass index and waist circumference were significantly higher in patients with severe steatosis (P value 0.001,0.000,0.002 respectively).Incidence of Diabetes mellitus, hypertension and cardiovascular diseases were significantly higher in patients with non alcoholic fatty liver disease than those without (P value 0.001,0.003 and 0.009 respectively)and they significantly increased with increasing grades of fatty liver.Serum level of Vitamin D was significantly lower in Non Alcoholic Fatty Liver Disease patients than those without ( P value

Mechano-structural alteration in proximal femora of individuals with alcoholic liver disease: Implications for increased bone fragility.

Although increased hip fracture risk is noted in patients with alcoholic liver disease (ALD), their femoral microstructural and mechanical properties were not investigated previously. The present study aimed to analyze the associations between subregional deteriorations in femoral mechano-structural properties and clinical imaging findings to explain increased femoral fracture risk among ALD patients. This study analyzed proximal femora of 33 male cadaveric donors, divided into ALD (n=13, 57±13years) and age-matched control group (n=20, 54±13years). After pathohistological verification of ALD stage, DXA and HSA measurements of the proximal femora were performed, followed by micro-CT and Vickers microindentation of the superolateral neck, inferomedial neck, and intertrochanteric region. Bone mineral density and cross sectional area of the femoral neck were deteriorated in ALD donors, compared with healthy controls (p<0.05). Significant ALD-induced degradation of trabecular and cortical microstructure and Vickers microhardness reduction were noted in the analyzed femoral regions (p<0.05). Still, the most prominent ALD-induced mechano-structural deterioration was noted in intertrochanteric region. Additionally, more severe bone alterations were observed in individuals with an irreversible stage of ALD, alcoholic liver cirrhosis (ALC), than in those with an initial ALD stage, fatty liver disease. Observed osteodensitometric and mechano-structural changes illuminate the basis for increased femoral fracture risk in ALD patients. Additionally, our data suggest bone strength reduction that may result in increased susceptibility to intertrochanteric femoral fracture in men with ALD. Thus, femoral fracture risk assessment should be advised for all ALD patients, especially in those with ALC.

Alcoholic liver disease and autoimmune hepatitis: Sometimes a closer look under the surface is needed

AimsDifferential diagnosis of autoimmune hepatitis (AIH) incorporates various liver diseases, including alcoholic liver disease (ALD). We report on clinical, laboratory and outcome characteristics of AIH patients who were initially referred as ALD based on increased alcohol consumption (AIH/ALD). MethodsFrom 2000-2019, we retrospectively identified 12 AIH/ALD patients [9 males, age: 61 (30-73) years] in our prospective data base of 317 AIH patients. ResultsAIH diagnosis was based on aminotransferases elevation in 10 patients, high IgG in 8, compatible autoantibody profile in all and typical/compatible histology in all 9 with available biopsy. There were no significant differences of baseline demographics, presentation, cirrhosis at diagnosis, response to treatment and simplified score compared to 45 age- and sex-matched AIH patients without alcohol consumption and 44 age- and sex-matched ALD patients. However, the AIH/ALD cohort was characterized by more frequent progression to cirrhosis, higher liver-related deaths and overall mortality compared to AIH, though similar to the ALD group. AST/ALT ratio>1 seems to bear a good positive (0.84) and negative predictive value (0.88) for ALD and AIH diagnosis, respectively, but cannot help in discriminating the AIH/ALD variant. ConclusionsAIH should not be forgotten in patients with alcohol use when clinical and laboratory features hint towards the diagnosis of AIH/ALD variant as this group seems to have worse outcome compared to those with AIH alone suggesting the need for closer follow-up and surveillance. Reliable autoantibody testing and cautious interpretation of liver histology appear mandatory for AIH diagnosis in these difficult to diagnose cases.

Association between oral health and alcoholic liver disease - A cross-sectional analytical study

Background: Alcoholic liver disease (ALD) is a condition with compromised immunity and dental foci can act as a potential source of infection. Aims and Objectives: This study was conducted to assess and compare the oral health among patients with alcoholic liver disease with healthy individuals and to determine an association between oral health and alcoholic liver disease.Materials and Methods: A cross-sectional analytical study assessed 100 participants with ALD and 100 age and gender matched subjects. Demographic details, laboratory investigation results, medical, dental & family history, oral hygiene practices, information about tobacco and alcohol habits were collected. Caries, periodontal disease, oral mucosal lesions and intervention urgency were assessed using WHO (2013) criteria. Descriptive and inferential statistics were used. A p <0.05 was considered as significant.Results: Mean age of participants in ALD and control groups were 43.71 ± 6.79 and 42.82 ± 6.23 years respectively. Caries experience (DMFT) was higher in ALD group (11.55±12.29) than comparison group (8.2±8.89) (p=0.001) giving an association with age of onset of alcohol abuse. Periodontal health was poor among ALD group with more teeth with gingival bleeding, shallow or deep pockets and loss of attachment giving an association between age of onset, duration of disease since diagnosed and MELD score. Among ALD group 7% had leukoplakia. Association was found between oral mucosal lesion and duration of disease since diagnosed and MELD score.Conclusion: Oral health was poor among ALD group than comparison group. Dental caries was associated with alcohol abuse and oral mucosal lesion was associated with alcoholic liver disease whereas periodontal disease was associated with alcohol abuse and alcoholic liver disease.

Особливості перебігу алкогольної хвороби печінки на стадії цирозу у поєднанні з неалкогольною жировою хворобою печінки

SummaryThe purpose was to study the features of clinical and laboratory manifestations ofalcoholic liver disease at the cirrhosis stage associated with non-alcoholic fatty liverdisease.Material and methods. Clinical, laboratory and instrumental examinations wereperformed for 204 patients with hepatic cirrhosis. 78 persons had alcoholic liver disease(Group I) and 126 persons had a combination of alcoholic liver disease with nonalcoholic fatty liver disease (Group II). Group I included 24 women and 54 men(53.2±7.6) years old; 22 women and 104 men (47.8±6.4) years old belonged to GroupII. Patients of Groups I and II were allocated to subgroups according to the classes ofhepatic cirrhosis compensation according to the Child-Pugh criteria: IA (17 patients),IB (38 patients), IC (23 patients); IIA (44 patients), ІІВ (48 patients), ІІС (34 patients).Results and discussion. It was found that the signs of astheno-vegetative, pain,dyspeptic, hepatorenal, hepatopulmonary syndromes, jaundice, medically uncontrolledascites, and manifestations of hepatic encephalopathy were shown more often amongpatients in combination with non-alcoholic fatty liver disease. Somatometric indicessignificantly differed among all patients depending on the degree of compensation. Thethickness of the skin and fat fold are reliable indicators that reflect the state of the fatdepot of the body; the circumference of shoulder muscles is a reliable indicator of thereduction of the somatic protein pool, accompanied by a decrease in the syntheticfunction of the liver and a decrease in the somatic protein pool, especially amongpatients associated with non-alcoholic fatty liver disease.Conclusions. During examining patients with liver cirrhosis, the study of the trophicstatus, synthetic function, and functional state of the liver are recommended for timelycorrection of the revealed disorders.

Effects of alcohol consumption on multiple hepatocarcinogenesis in patients with fatty liver disease.

The number of patients with fatty liver disease (FLD) is increasing globally. Ethanol consumption in FLD is known to be associated with an increased risk of hepatocellular carcinoma (HCC), but the effects of alcohol consumption on the occurrence of multiple HCCs remain unclear. We explored the relationship between the daily ethanol intake and the HCC number. This single-center retrospective study enrolled 114 patients without viral or immune hepatitis undergoing first-line HCC treatment who had been diagnosed with FLD by abdominal ultrasonography or a liver biopsy at the same time as or before HCC detection. We categorized patients into four groups according to the daily alcohol consumption (<20g: non-alcoholic fatty liver disease, n = 45; 20-39g: low-intermediate ethanol intake with FLD, n = 13; 40-69g: high-intermediate ethanol intake with FLD, n = 31; ≥70g: alcoholic fatty liver disease, n = 25). The relationship between the daily ethanol consumption and the number of HCCs (single or multiple) was examined. The risk of multiple HCCs was significantly higher in the high-intermediate ethanol intake with FLD (HR 2.89, 95% CI 1.04-8.02, P = 0.042) and alcoholic fatty liver disease (HR 3.14, 95% CI 1.07-9.22, P = 0.037) groups than in the others. A multivariate analysis showed that a daily ethanol intake ≥40g was associated with a significantly increased risk of multiple HCCs (HR 2.82, 95% CI 1.16-6.88, P = 0.023). Our findings suggest that a high daily ethanol intake might lead to multiple hepatocarcinogenesis in patients with FLD.