Alcoholic Liver Research Articles

Chronic binge drinking-induced susceptibility to colonic inflammation is microbiome-dependent

ABSTRACT Alterations in intestinal permeability and the gut microbiome caused by alcohol abuse are associated with alcoholic liver disease and with worsening of inflammatory bowel diseases (IBD) symptoms. To resolve the direct effects of chronic ethanol consumption on the colon and its microbiome in the absence of acute or chronic alcohol-induced liver disease, we developed a mouse model of chronic binge drinking that uncovers how alcohol may enhance susceptibility to colitis via the microbiota. Employing daily ethanol gavage, we recapitulate key features of binge ethanol consumption. We found that binge ethanol drinking worsens intestinal infection, colonic injury and inflammation, and this effect persists beyond the drinking period. Using gnotobiotics, we showed that alcohol-driven susceptibility to colitis is microbiota-dependent and transferable to ethanol-naïve mice by microbiome transplantation. Allobaculum spp. expanded in binge drinking mice, and administration of Allobaculum fili was sufficient to enhance colitis in non-drinking mice. Our study provides a model to study binge drinking-microbiota interactions and their effects on host disease and reinforces the pathogenic function of Allobaculum spp. as colitogenic bacteria. Our findings illustrate how chronic binge drinking-induced alterations of the microbiome may affect susceptibility to IBD onset or flares.

Causal effects of smoking, alcohol consumption, and coffee intake on hepatobiliary and pancreatic diseases: A Mendelian randomization study

BackgroundHepatobiliary and pancreatic diseases, such as cirrhosis, hepatocellular carcinoma, cholelithiasis, and pancreatitis, are major global health challenges. Lifestyle factors like smoking, alcohol consumption, and coffee intake are commonly studied for their health impacts. However, observational studies often face issues with confounding factors and reverse causality, making it difficult to establish causal relationships. MethodsThis research uses Mendelian randomization (MR) to investigate the causal effects of smoking, alcohol use, and coffee intake on 10 hepatobiliary and pancreatic diseases. Genetic data from the Sequencing Consortium of Alcohol and Nicotine Use (GSCAN) and self-reported GWAS were used to derive instrumental variables (IVs). The outcomes were obtained from the FinnGen and UK Biobank cohorts. Univariable and multivariable MR analyses were conducted to assess the associations. ResultsGenetic predisposition to tobacco use was associated with increased risks of acute pancreatitis, alcoholic hepatitis, chronic pancreatitis, cirrhosis, gallstones, liver cancer, and pancreatic cancer. Alcohol consumption was linked to acute pancreatitis, chronic pancreatitis, alcoholic liver disease, hepatic cancer, and cholangitis. Coffee intake showed minimal associations, with a slight protective effect against non-alcoholic steatohepatitis. ConclusionsThis study confirms the harmful effects of inhaling tobacco and consuming alcohol on hepatobiliary and pancreatic diseases. It highlights the need for public health strategies to reduce tobacco use and heavy alcohol consumption. Coffee intake showed minimal effects, suggesting further research is needed to understand its relationship with hepatobiliary health.

Metabolic characteristics of patients with MetALD: Caveats of a new definition.

Recently, a new entity was introduced, MetALD, which includes patients with metabolic dysfunction-associated steatotic liver disease (MASLD), who consume moderate amounts of alcohol. However, little is known regarding the metabolic and clinical characteristics of these patients. Data from the National Health and Nutrition Examination Surveys 2017-2020 was used. Participants without valid transient elastography (TE) measurements, incomplete alcohol consumption report, or with alternative etiologies of liver steatosis were excluded. A total of 6901 patients were included in the study, of which 106 (1.5%) had MetALD. Overall, MetALD patients showed a metabolic profile that was more similar to patients with alcohol related liver disease (ALD) than MASLD. Specifically, while patients with MetALD showed values in-between MASLD and ALD for body mass index (BMI), aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyltransferase (GGT) and haemoglobin A1c, they had similar high-density lipoprotein cholesterol (HDL-C), blood pressure, prevalence of diabetes and insulin resistance to ALD patients. Increasing alcohol consumption was associated with lower insulin resistance and A1c and higher triglycerides, HDL-C and blood pressure. Moreover, while AST, ALT and GGT increased with alcohol consumption, this did not translate into worse hepatic steatosis or liver fibrosis by TE. MetALD patients share some characteristics with MASLD, but they resemble ALD patients more, especially after adjusting for BMI. Alcohol consumption produces a dissociation between insulin resistance and some cardiometabolic risk factors (blood pressure and HDL-C), which may make the current classification of patients challenging.

Cocaine-derived hippuric acid activates mtDNA-STING signaling in alcoholic liver disease: Implications for alcohol and cocaine co-abuse

The simultaneous abuse of alcohol-cocaine is known to cause stronger and more unpredictable cellular damage in the liver, heart, and brain. However, the mechanistic crosstalk between cocaine and alcohol in liver injury remains unclear. The findings revealed cocaine-induced liver injury and inflammation in both marmosets and mice. Of note, co-administration of cocaine and ethanol in mice causes more severe liver damage than individual treatment. The metabolomic analysis confirmed that hippuric acid (HA) is the most abundant metabolite in marmoset serum after cocaine consumption and that is formed in primary marmoset hepatocytes. HA, a metabolite of cocaine, increases mitochondrial DNA leakage and subsequently increases the production of proinflammatory factors via STING signaling in Kupffer cells (KCs). In addition, conditioned media of cocaine-treated KC induced hepatocellular necrosis via alcohol-induced TNFR1. Finally, disruption of STING signaling in vivo ameliorated co-administration of alcohol- and cocaine-induced liver damage and inflammation. These findings postulate intervention of HA-STING-TNFR1 axis as a novel strategy for treatment of alcohol- and cocaine-induced excessive liver damage.Graphical

A research study on the utility of GGT level and AST/ALT ratio in alcoholic liver diseases

A research study on the utility of GGT level and AST/ALT ratio in alcoholic liver diseases

Elucidating hydroxysafflor yellow A's multi-target mechanisms against alcoholic liver disease through integrative pharmacology

BackgroundAlcoholic liver disease (ALD) significantly contributes to global liver-related morbidity and mortality. Natural products play a crucial role in the prevention and treatment of ALD. Hydroxysafflor yellow A (HSYA), a unique and primary component of Safflower (Carthamus tinctorius l.), exhibits diverse pharmacological activities. However, the impact and mechanism of HSYA on ALD have not been fully elucidated. PurposeThe purpose of this study was to employ an integrative pharmacology approach to assess the multi-targeted mechanism of HSYA against ALD. MethodsNetwork pharmacology and molecular docking techniques were used to analyze the potential therapeutic signaling pathways and targets of HSYA against ALD. An ALD model in zebrafish larvae was established. Larvae were pretreated with HSYA and then exposed to ethanol. Liver injury was measured by fluorescence expression analysis in the liver-specific transgenic zebrafish line Tg (fabp10a:DsRed) and liver tissue H&E staining. Liver steatosis was determined by whole-mount oil red O staining and TG level. Additionally, an ethanol-induced hepatocyte injury model was established in vitro to observe hepatocyte damage (cell viability, ALT level), lipid accumulation (oil red O staining, TC and TG), and oxidative stress (ROS, MDA, GPx and SOD) in HepG2 cells treated with or without HSYA. Finally, qRT-PCR combined with network pharmacology and molecular docking was employed to validate the effects of HSYA on targets. ResultsHSYA exhibited a significant, dose-dependent improvement in ethanol-induced liver injury in zebrafish larvae and HepG2 cells. Network pharmacology analysis revealed that HSYA may exert pharmacological effects against ALD through 341 potential targets. These targets are involved in various signaling pathways, including lipid metabolism and atherosclerosis, PI3K-Akt signaling pathway, MAPK signaling pathway, and ALD itself. Molecular docking studies displayed that HSYA had a strong binding affinity toward the domains of IL1B, IL6, TNF, PPARA, PPARG, HMGCR and ADH5. qRT-PCR assays demonstrated that HSYA effectively reversed the ethanol-induced aberrant gene expression of SREBF1, FASN, ACACA, CPT1A, PPARA, IL1B, IL6, TNFα, ADH5, and ALDH2 in vivo and in vitro. ConclusionThis study offers a comprehensive investigation into the anti-ALD mechanisms of HSYA using an integrative pharmacology approach. The potential targets of HSYA may be implicated in enhancing ethanol catabolism, reducing lipid accumulation, mitigating oxidative stress, and inhibiting inflammatory response.

Cysteine triggered cascade reaction forming coumarin: Visualization of cysteine fluctuation in alcoholic liver disease by a NIR fluorescent probe

Alcoholic liver disease (ALD) is a chronic toxic liver injury caused by long-term heavy drinking. Due to the increasing incidence, ALD is becoming one of important medical tasks. Many studies have shown that the main mechanism of liver damage caused by large amounts of alcohol may be related to antioxidant stress. As an important antioxidant, cysteine (Cys) is involved in maintaining the normal redox balance and detoxifying metabolic function of the liver, which may be closely related to the pathogenesis of ALD. Therefore, it is necessary to develop a simple non-invasive method for rapid monitoring of Cys in liver. Thus, a near-infrared (NIR) fluorescent probe DCI-Ac-Cys which undergoes Cys triggered cascade reaction to form coumarin fluorophore is developed. Using the DCI-Ac-Cys, decreased Cys was observed in the liver of ALD mice. Importantly, different levels of Cys were monitored in the livers of ALD mice taking silybin and curcumin with the antioxidant effects, indicating the excellent therapeutic effect on ALD. This study provides the important references for the accurate diagnosis of ALD and the pharmacodynamic evaluation of silybin and curcumin in the treatment of ALD, and support new ideas for the pathogenesis of ALD.

Unveiling the multifaceted role of adropin in various diseases (Review).

Adropin is a secreted peptide encoded by the energy homeostasis‑associated gene, which also functions as a membrane‑bound protein facilitating intercellular communication. This peptide has been detected in various tissues and body fluids, including the brain, liver, kidney, heart, pancreas, small intestine, endothelial cells and colostrum. Notably, the amino acid sequences of adropin are identical in humans, mice and rats. Previous studies have demonstrated that adropin levels fluctuate under different physiological and pathological conditions. Adropin plays a role in regulating carbohydrate metabolism, lipid metabolism and intercellular molecular signaling pathways, implicating its involvement in the progression of numerous diseases, such as acute myocardial infarction, lung injury, non‑alcoholic fatty liver disease/non‑alcoholic steatohepatitis, kidney disease, polycystic ovary syndrome, obesity, and diabetes, atherosclerosis, systemic sclerosis and cancer. Despite its significance, the precise role and mechanism of this protein remain inadequately understood and studied. To elucidate the function of adropin and its clinical research status, a systematic review of recent studies on adropin across various diseases was conducted. Additionally, several challenges and limitations associated with adropin research in both animal and clinical contexts were identified, aiming to offer valuable insights for future investigation.

Efficacy and safety of palliative treatment in patients with autoimmune liver disease-associated hepatocellular carcinoma

Introduction and ObjectivesAutoimmune liver diseases (AILD) are rare causes hepatocellular carcinoma (HCC), and data on the efficacy and tolerability of anti-tumor therapies are scarce. This pan-European study aimed to assess outcomes in AILD-HCC patients treated with tyrosine kinase inhibitors (TKIs) or transarterial chemoembolization (TACE) compared with patients with more common HCC etiologies, including viral, alcoholic or non-alcoholic fatty liver disease. Materials and Methods107 patients with HCC-AILD (AIH:55; PBC:52) treated at 13 European centres between 1996 and 2020 were included. 65 received TACE and 28 received TKI therapy. 43 (66 %) were female (median age 73 years) with HCC tumor stage BCLC A (34 %), B (46 %), C (9 %) or D (11 %). For each treatment type, propensity score matching was used to match AILD to non-AILD-HCC on a 1:1 basis, yielding in a final cohort of 130 TACE and 56 TKI patients for comparative analyses of median overall survival (mOS) and treatment tolerability. ResultsHCC-AILD patients showed comparable mOS to controls for both TACE (19.5 vs. 22.1 months, p = 0.9) and TKI (15.4 vs. 15.1 months, p = 0.5). Adverse events were less frequent in AILD-HCC patients than controls (33 % % vs. 62 %, p = 0.003). For TKIs, there were no significant differences in adverse events (73% vs. 86%, p = 0.2) or interruption rates (44% vs. 36 %, p = 0.7). ConclusionsIn summary, this study demonstrates comparable mOS for AILD-HCC patients undergoing local and systemic treatments, with better tolerability than HCC of other causes. TKIs remain important therapeutic options for AILD-HCC patients, particularly given their exclusion from recent immunotherapy trials.

Effects of Several Tea-like Plants on Liver Injury Induced by Alcohol via Their Antioxidation, Anti-Inflammation, and Regulation of Gut Microbiota.

Liver injury induced by alcohol is a serious global health problem. Several tea-like plants are widely used as beverages, which are drunk like tea. In this study, the hepatoprotective effects of eight tea-like plant extracts with the intake of 200 mg/kg.bw/day were investigated and compared using a C57BL/6J mouse model of acute alcohol exposure, including sweet tea, vine tea, Rabdosia serra kudo, broadleaf holly leaf, mulberry leaf, bamboo leaf, Camellia nitidissima, and Akebia trifoliata peels. The results showed that the eight tea-like plants had hepatoprotective effects to different degrees against acute alcohol exposure via enhancing the activities of alcoholic metabolism enzymes, ameliorating oxidative stress and inflammation in the liver, as well as regulating gut microbiota. In particular, sweet tea, bamboo leaf, mulberry leaf, and Camellia nitidissima increased the activities of alcohol dehydrogenase or aldehyde dehydrogenase. Among these tea-like plants, sweet tea and Camellia nitidissima had the greatest hepatoprotective effects, and their bioactive compounds were determined by high-performance liquid chromatography. Chlorogenic acid, rutin, and ellagic acid were identified in sweet tea, and epicatechin, rutin, and ellagic acid were identified in Camellia nitidissima, which could contribute to their hepatoprotective action. These tea-like plants could be drunk or developed into functional food against alcoholic liver injury, especially sweet tea and Camellia nitidissima. In the future, the effects of sweet tea and Camellia nitidissima on chronic alcoholic liver diseases should be further investigated.

Diet modifies the association between alcohol consumption and severe alcohol-related liver disease incidence

It is elusive why some heavy drinkers progress to severe alcohol-related liver disease (ALD) while others do not. This study aimed to investigate if the association between alcohol consumption and severe ALD is modified by diet. This prospective study included 303,269 UK Biobank participants. Alcohol consumption and diet were self-reported. The diet score was created from 4 items selected using LASSO. Cox proportional hazard model showed that the diet score was monotonically associated with severe ALD risk, adjusted for sociodemographics, lifestyle factors, and alcohol consumption. Relative excess risk due to interaction analysis indicated that having a higher ALD diet score and a higher alcohol consumption simultaneously confers to 2.44 times (95% CI: 1.06-3.83) higher risk than the sum of excess risk of each factor. In this work, we show that people who have a poor diet might be more susceptible to severe ALD due to alcohol consumption.

Frequency of Peptic Ulcer Disease in Patients with Chronic Liver Disease Presenting with Upper Gastrointestinal Bleeding

Background: Peptic ulcer disease (PUD) is a significant cause of morbidity and mortality worldwide, particularly in patients with chronic liver disease (CLD). The occurrence of upper gastrointestinal bleeding (UGIB) in CLD patients presents a serious complication, often requiring urgent medical intervention. Objective: The main objective of this study was to determine the frequency of peptic ulcer disease in patients with chronic liver disease presenting with upper gastrointestinal bleeding. Methods: This retrospective observational study was conducted at Ayub Teaching Hospital, Abbottabad, from 2021 to 2023. Data were collected from 105 patients diagnosed with chronic liver disease who presented with symptoms of upper gastrointestinal bleeding. The diagnosis of CLD was confirmed through clinical evaluation, biochemical tests, imaging studies, and/or liver biopsy. Patients included were aged 18 years and above and presented with UGIB evidenced by hematemesis, melena, or both. Exclusion criteria were individuals with bleeding disorders unrelated to CLD and those who did not undergo endoscopic evaluation. Data collection involved demographic information, clinical history, duration and etiology of CLD, comorbid conditions, and UGIB presentation. Upper gastrointestinal endoscopy was performed on all patients to identify the source of bleeding. Statistical analysis was performed using SPSS version 25, with a p-value of less than 0.05 considered statistically significant. Results: The study included 105 patients, with a mean age of 55.3±3.27 years; 65 (61.9%) were male, and 40 (38.1%) were female. The etiologies of CLD were viral hepatitis (42.9%), alcoholic liver disease (28.6%), non-alcoholic fatty liver disease (19.0%), and other causes (9.5%). Clinical presentations of UGIB included hematemesis (66.7%), melena (23.8%), and both (9.5%). Endoscopic findings revealed that 35 patients (33.3%) had peptic ulcer disease, with 20 (57.1%) having duodenal ulcers and 15 (42.9%) having gastric ulcers. Other sources of UGIB included esophageal varices (38.1%), gastric varices (14.3%), erosive gastritis (9.5%), and malignancies (4.8%). Associated risk factors for PUD included NSAID use (42.9%), smoking (28.6%), and coexisting portal hypertension (71.4%). The mean size of ulcers was 10.2 mm. Endoscopic therapy was utilized in 71.4% of cases, with pharmacological treatment primarily including proton pump inhibitors (85.7%). Complications included rebleeding within 7 days (14.3%) and the need for surgical intervention (5.7%). The mean hospital stay was 7.8 days, and in-hospital mortality was observed in 8.6% of patients. Conclusion: Peptic ulcer disease represents a substantial yet manageable complication in patients with chronic liver disease presenting with upper gastrointestinal bleeding. Prompt recognition and targeted therapeutic interventions are crucial for optimizing outcomes in this high-risk population.

Therapeutic Potential of Lactiplantibacillus plantarum FB091 in Alleviating Alcohol-Induced Liver Disease through Gut-Liver Axis.

Alcoholic liver disease (ALD) poses a significant global health burden, often requiring liver transplantation and resulting in fatalities. Current treatments, like corticosteroids, effectively reduce inflammation but carry significant immunosuppressive risks. This study evaluates Lactiplantibacillus plantarum FB091, a newly isolated probiotic strain, as a safer alternative for ALD treatment. Using an in vivo mouse model, we assessed the effects of L. plantarum FB091 on alcohol-induced liver damage and gut microbiota composition. Alcohol and probiotics administration did not significantly impact water/feed intake or body weight. Histopathological analysis showed that L. plantarum FB091 reduced hepatocellular ballooning and inflammatory cell infiltration in liver tissues and mitigated structural damage in colon tissues, demonstrating protective effects against alcohol-induced damage. Biomarker analysis indicated that L. plantarum FB091 decreased aspartate aminotransferase levels, suggesting reduced liver damage, and increased alcohol dehydrogenase activity, indicating enhanced alcohol metabolism. Additionally, cytokine assays revealed a reduction in pro-inflammatory TNF-α and an increase in anti-inflammatory IL-10 levels in colon tissues of the L. plantarum FB091 group, suggesting an anti-inflammatory effect. Gut microbiota analysis showed changes in the L. plantarum FB091 group, including a reduction in Cyanobacteria and an increase in beneficial bacteria such as Akkermansia and Lactobacillus. These changes correlated with the recovery and protection of liver and colon health. Overall, L. plantarum FB091 shows potential as a therapeutic probiotic for managing ALD through its protective effects on liver and colon tissues, enhancement of alcohol metabolism, and beneficial modulation of gut microbiota. Further clinical studies are warranted to confirm these findings in humans.

Outcome of patients admitted with alcohol-related liver disease- a single centre study

Outcome of patients admitted with alcohol-related liver disease- a single centre study

A study of metabolic profile among non obese and obese subjects with non alcoholic fatty liver disease (NAFLD) and assessing the underlying liver steatosis and fibrosis using fibroscan

A study of metabolic profile among non obese and obese subjects with non alcoholic fatty liver disease (NAFLD) and assessing the underlying liver steatosis and fibrosis using fibroscan

Haptoglobin genotypes and their association with metabolic risk factors and liver stiffness among non alcoholic fatty liver disease (NAFLD): a population nested case control study

Haptoglobin genotypes and their association with metabolic risk factors and liver stiffness among non alcoholic fatty liver disease (NAFLD): a population nested case control study

Beyond the usual suspects: an unusual cause of upper gastrointestinal bleeding in alcohol-related liver disease

Beyond the usual suspects: an unusual cause of upper gastrointestinal bleeding in alcohol-related liver disease

Metabolic syndrome: a stealthy complication in alcoholic liver disease

Metabolic syndrome: a stealthy complication in alcoholic liver disease

Liver Transplantation for Alcohol related liver disease in the era of Acute on chronic liver fai

Liver Transplantation for Alcohol related liver disease in the era of Acute on chronic liver fai

Effects of protein source variation on fecal microbiota transplant outcomes in a mouse model of alcohol-related liver disease

Effects of protein source variation on fecal microbiota transplant outcomes in a mouse model of alcohol-related liver disease