Alcoholic Liver Research Articles

Pueraria Extract Ameliorates Alcoholic Liver Disease via the Liver-Gut-Brain Axis: Focus on Restoring the Intestinal Barrier and Inhibiting Alcohol Metabolism.

Alcoholic liver disease (ALD) is one of the causes of hepatocellular carcinoma, accompanied by intestinal leakage and microbial changes. Pueraria has protective effects on liver injury. The aim of this study was to investigate the mechanism of pueraria in the treatment of ALD. UPLC-Q/TOF-MS was used to analyze the composition of the pueraria extract (PUE). Acute and chronic ALD models were established to evaluate the antialcoholic and hepatoprotective effects of PUE. As a result, PUE treatment reduced the serum levels of ALT, AST, TC, and TG and inflammatory factors and alleviated liver inflammation and drunk state. PUE decreased the gene expression of ADH1 and the serum level of acetaldehyde (ACH) to inhibit the generation of ACH from ethanol metabolism, increased the gene level of ALDH2 to accelerate the decomposition of ACH, and thereby alleviated liver inflammation and intestinal barrier damage. Meanwhile, 16 S rDNA revealed that PUE altered the microbiota composition, reduced the amount of Proteobacteria and Desulfobacterota, and thus inhibited the generation of lipopolysaccharide and its downstream-like TLR4/MyD88/NF-κB pathway. PUE also increased the abundance of Bacteroides, Ruminococcus, and Prevotella and producted short-chain fatty acids to protect the intestinal wall. Treatment with fecal microbiota transplantation further confirmed that PUE gut microbiota dependently alleviated ALD. Therefore, PUE regulated gut microbiota and inhibited ethanol metabolism to alleviate ALD through the liver-gut-brain axis. It has good prospects in the future.

Cirrhosis in primary practice: many patients remain potentially undiagnosed and are not receiving liver cancer surveillance.

Most patients with cirrhosis have compensated disease and are cared for in primary care; however, the exact epidemiology within Australia remains largely unknown. The aim of this study was to assess cirrhosis care in an Australian primary care setting by evaluating rates of cirrhosis diagnosis, appropriate hepatocellular carcinoma (HCC) surveillance and specialist communication. Electronic medical records in consenting general practices were reviewed using the "Liver Toolkit" to identify patients with an existing cirrhosis diagnosis. Individual cases were reviewed to identify outcomes of interest. One hundred seventy-one patients with confirmed cirrhosis across nine general practices were identified (74% male, mean age: 61.2years). There was significant variation in the rate of cirrhosis diagnosis between practices (range 31.7-637.9 per 100 000 patients, P<0.0001). Patients with cirrhosis had predominately compensated disease (75% Child-Pugh A) and common etiologies of cirrhosis were alcohol (49%), hepatitis C (47%), and metabolic dysfunction-associated steatotic liver disease (29%). Forty-two patients (25%) had received appropriate HCC surveillance. Predictors of inadequate HCC surveillance were time from last specialist correspondence (odds ratio [OR]=1.06 per month increase, 95% confidence interval [CI]: 1.02-1.10, P=0.002) and hepatitis B (OR=0.24, 95% CI: 0.06-0.98, P=0.047). Specialist correspondence with primary care was older than 2years or absent in 37% of cases. There was a 20-fold difference in the rate of cirrhosis diagnosis between general practices within Sydney, suggesting a large proportion of patients remain undiagnosed. Three quarters of patients with diagnosed cirrhosis are not receiving appropriate HCC surveillance.

Adverse health outcomes in offspring of parents with alcohol-related liver disease: Nationwide Danish cohort study.

Parental drinking can cause harm to the offspring. A parent's diagnosis of alcohol-related liver disease (ALD) might be an opportunity to reach offspring with preventive interventions. We investigated offspring risk of adverse health outcomes throughout life, their association with their parent's educational level and diagnosis of ALD. We used nationwide health registries to identify offspring of parents diagnosed with ALD in Denmark 1996 to 2018 and age- and sex-matched comparators (20:1). We estimated the incidence rate ratios (IRRs) of hospital contacts with adverse health outcomes, overall and in socioeconomic strata. We used a self-controlled design to examine whether health outcomes were more likely to occur during the first year after the parent's ALD diagnosis. The 60,804 offspring of parents with ALD had a higher incidence rate of hospital contacts from age 15 to 60 years for psychiatric disease, poisoning, fracture or injury, alcohol-specific diagnoses, other substance abuse, and of death than comparators. Associations were stronger for offspring with low compared to high socioeconomic position: The IRR for admission due to poisoning was 2.2 versus 1.0 for offspring of an ALD parent with a primary level versus a highly educated ALD parent. Offspring had an increased risk for admission with psychiatric disease and poisoning in the year after their parent's ALD diagnosis. For example, among offspring whose first hospital contact with psychiatric disease was at age 13 to 25 years, the IRR in the first year after their parent's ALD diagnosis versus at another time was 1.29 (95% CI 1.13, 1.47). Main limitation was inability to include adverse health outcomes not involving hospital contact. Offspring of parents with ALD had a long-lasting higher rate of health outcomes associated with poor mental health and self-harm that increased shortly after their parent's diagnosis of ALD. Offspring of parents of low educational level were particularly vulnerable. This study highlights an opportunity to reach out to offspring in connection with their parent's hospitalization with ALD.

Phospholipase D2 drives cellular lipotoxicity and tissue inflammation in alcohol-associated liver disease

AimsExcessive alcohol consumption leads to alcoholic liver disease (ALD), a major contributing factor to cirrhosis and hepatocellular carcinoma. In the present study we investigated the involvement of phospholipase D2 (PLD2) in the pathogenesis of ALD. Methods and materialsALD was induced in mice by chronic and binge ethanol feeding (the NIAAA model). Cellular transcriptome was examined by RNA-seq. Key findingsAnalysis of RNA-seq datasets indicated that PLD2 expression was up-regulated in liver tissues and in hepatocytes during ALD pathogenesis. Exposure of hepatocytes to ethanol treatment led to an increase in PLD2 expression. Similarly, ethanol feeding in mice stimulated PLD2 expression in the liver. On the contrary, PLD2 knockdown in hepatocytes down-regulated expression of pro-inflammatory and pro-lipogenic genes and dampened lipid accumulation. Consistently, PLD2 knockdown in mice significantly ameliorated ALD pathogenesis as evidenced by reduced steatosis and hepatic inflamamation. RNA-seq identified several metabolic pathways that were influenced by PLD2 deficiency. SignificanceOur data demonstrate that PLD2 is a novel regulator of ALD and suggest that small-molecule PLD2 inhibitors can be considered as a reasonable strategy for ALD treatment.

Causal relationships between the gut microbiota, inflammatory cytokines, and alcoholic liver disease: a Mendelian randomization analysis.

Previous studies have suggested a potential association between gut microbiota and the development of alcohol-related liver disease (ALD). However, the causal relationship between gut microbiota and ALD, as well as the role of inflammatory cytokines as mediators, remains unclear. This study aims to explore the causal relationship between gut microbiota and ALD using Mendelian randomization (MR) methods, and to analyze the mediating role of inflammatory cytokines. Gut microbiota, 91 inflammatory cytokines, and ALD were identified from summary data of large-scale genome-wide association studies (GWAS). MR was employed to investigate the causal relationship between gut microbiota, cytokines, and ALD, with the inverse variance-weighted method (IVW) as the primary statistical approach. Additionally, we examined whether inflammatory cytokines act as mediating factors in the pathway from gut microbiota to ALD. The IVW results confirmed two positive and one negative causal effect between genetic liability in the gut microbiota and ALD. Escherichia coli (P= 0.003) was identified as a protective factor for ALD, while Roseburia hominis (P=0.023) and Family Porphyromonadaceae (P=0.038) were identified as risk factors for ALD. Furthermore, there were five positive and two negative causal effects between inflammatory cytokines and ALD, with CUB domain-containing protein 1 (P= 0.035), Macrophage colony-stimulating factor 1 (P=0.047), Cystatin D (P = 0.035), Fractalkine (P=0.000000038), Monocyte chemoattractant protein-1 (P=0.004) positively associated with ALD onset. CD40L receptor (P= 0.044) and Leukemia inhibitory factor (P = 0.024) exhibited protective effects against ALD. Mediation MR analysis indicated that CUB domain-containing protein 1 (mediation proportion=1.6%, P=0.035), Cystatin D (mediation proportion=1.5%, P=0.012), and Monocyte chemoattractant protein-1 (mediation proportion=3.3%, P=0.005) mediated the causal effect of Roseburia hominis on ALD. In conclusion, our study supports a causal relationship among gut microbiota, inflammatory cytokines and ALD, with inflammatory cytokines potentially acting as mediating factors in the pathway from gut microbiota to ALD.

The Multifaceted Role of Bilirubin in Liver Disease: A Literature Review.

Bilirubin, the primary breakdown product of hemoproteins, particularly hemoglobin, plays a key role in the diagnosis, prognosis, and monitoring of liver diseases. In acute liver diseases, such as acute liver failure, drug-induced liver injury, and viral hepatitis, bilirubin serves as a biomarker reflecting the extent of hepatocyte loss and liver damage. Chronic liver diseases, including alcohol-related liver disease, chronic hepatitis C virus infection, metabolic dysfunction-associated fatty liver disease, and autoimmune liver diseases, are marked by persistent liver injury and inflammation. Bilirubin levels in chronic liver diseases provide insight into liver function, disease severity, and prognosis. As a versatile biomarker, bilirubin offers valuable information on the pathophysiology of liver diseases and aids in guiding clinical decision-making regarding the treatment of liver diseases and their complications. This review aimed to explore the multifunctional role of bilirubin in liver diseases by analyzing its biological functions beyond its role as a biomarker of liver damage.

Higher Adherence to the Mediterranean Diet Is Associated with a Lower Risk of Steatotic, Alcohol-Related, and Metabolic Dysfunction-Associated Steatotic Liver Disease: A Retrospective Analysis

Background and Aims: Metabolic liver disease is associated with obesity, insulin resistance, cardiovascular disease, and metabolic disorders. A Mediterranean diet (MD), known for its anti-inflammatory and antioxidant properties, is effective in managing various chronic diseases, including liver diseases. This study aimed to explore the influence of adherence to the MD on the risk of chronic metabolic diseases, including steatotic liver disease (SLD), metabolic dysfunction-associated steatotic liver disease (MASLD), and alcohol-related liver diseases (ALDs). Methods: This retrospective cohort study analyzed 5395 individuals from a single center between 2020 and 2022, grouped by adherence to the MD using the Korean Mediterranean Diet Adherence Score (K-MEDAS). MASLD score, ALD, and cardiovascular risk factors were also assessed. Statistical analyses were performed using 1:1 exact matching and multiple regression to compare the less adherent (K-MEDAS 0–7) and highly adherent (K-MEDAS 8–13) groups. Results: Adjusting for confounding variables, high adherence to the MD was significantly associated with lower rates of SLD (odds ratio [OR] 0.818, 95% confidence interval [CI] 0.700–0.957, p = 0.012), MASLD (OR 0.839, 95% CI 0.714–0.986, p = 0.033), and ALD (OR 0.677, 95% CI 0.671–0.683, p &lt; 0.001). Post-propensity score matching analysis revealed that the highly adherent group exhibited significantly lower triglyceride levels, triglyceride and glucose index, atherogenic Index of Plasma, and Framingham risk scores than the less adherent group. Conclusions: Good adherence to the MD considerably reduces the risk of SLD, MASLD, and ALD, underscoring its protective effects and potential to prevent metabolic liver diseases and their complications.

Oral supplementation of choline attenuates the development of alcohol-related liver disease (ALD)

BackgroundChronic alcohol intake is associated with alterations of choline metabolism in various tissues. Here, we assessed if an oral choline supplementation attenuated the development of alcohol-related liver disease (ALD) in mice.MethodsFemale C57BL/6 J mice (n = 8/group) were either pair-fed a liquid control diet, or a Lieber DeCarli liquid diet (5% ethanol) ± 2.7 g choline/kg diet for 29 days. Liver damage, markers of intestinal permeability and intestinal microbiota composition were determined. Moreover, the effects of choline on ethanol-induced intestinal permeability were assessed in an ex vivo model.ResultsALD development as determined by liver histology and assessing markers of inflammation (e.g., nitric oxide, interleukin 6 and 4-hydroxynonenal protein adducts) was attenuated by the supplementation of choline. Intestinal permeability in small intestine being significantly higher in ethanol-fed mice was at the level of controls in ethanol-fed mice receiving choline. In contrast, no effects of the choline supplementation were found on intestinal microbiota composition. Choline also significantly attenuated the ethanol-induced intestinal barrier dysfunction in small intestinal tissue ex vivo, an effect almost entirely abolished by the choline oxidase inhibitor dimbunol.ConclusionOur results suggest that an oral choline supplementation attenuates the development of ALD in mice and is related to a protection from intestinal barrier dysfunction.

Association of Liver Disease and Chronic Pruritus: A Case-Control Study.

Through the identification of 22 803 cases of chronic pruritus, with a control group comprising 91 212 participants from a national database, we performed a comparative analysis revealing that patients with chronic pruritus had a significantly higher prevalence of liver disease compared to controls. Upon reverse analysis, we similarly found patients with liver disease had a significantly higher prevalence of chronic pruritus. Subsequent multivariate logistic regression highlighted increased odds for several liver diseases in the pruritus cohort, including metabolic dysfunction-associated steatotic liver disease (aOR 1.65, 95% CI 1.53-1.78) and alcohol-related liver disease (aOR 1.69, 95% CI 1.43-1.98). The increased odds were most pronounced for hepatitis B (aOR 2.01, 95% CI 1.67-2.42) and cholangitis + primary sclerosing cholangitis + primary biliary cholangitis (aOR 1.81, 95% CI 1.65-1.99). Our results reveal a strong correlation between pruritus in hepatic pathologies different than commonly reported cholestatic diseases.

Osteopontin Promotes Cholangiocyte Secretion of Chemokines to Support Macrophage Recruitment and Fibrosis in MASH.

Osteopontin (OPN) promotes the ductular reaction and is a major driver of chronic liver disease (CLD) progression. Although CLD is characterised by the accumulation of inflammatory cells including macrophages around the peri-portal regions, the influence of OPN on recruitment is unclear. We investigated the role of OPN in cholangiocyte chemokine production and macrophage recruitment by combining invivo, invitro, and in silico approaches. The effects of OPN on cholangiocyte chemokine production and macrophage migration were assessed in culture, alongside RNA-sequencing to identify genes and pathways affected by OPN depletion. Murine liver injury models were used to assess liver chemokine expression and liver macrophage/monocyte recruitment. OPN and chemokine expression were analysed in liver tissue and plasma from biopsy-proven metabolic dysfunction-associated alcoholic steatohepatitis (MASH) patients. OPN-knockdown in cholangiocytes reduced chemokine secretion. RNA-sequencing showed OPN-related effects clustered around immunity, chemotaxis and chemokine production. Macrophage exposure to cholangiocyte-conditioned media showed OPN-supported migration via chemokines chemokine (C-C motif) ligand (CCL)2, CCL5 and chemokine (C-X-C motif) ligand (CXCL)1. These effects were related to NF-κB signalling. Murine liver fibrosis was accompanied by upregulated liver OPN, CCL2, CCL5 and CXCL1 mRNA, and accumulation of liver cluster of differentiation (CD)11b/F4/80+CC chemokine receptors (CCR2)high macrophages but treatment with OPN-specific neutralising aptamers reduced fibrosis, chemokine mRNAs and accumulation of liver CD11b/F4/80+CCR2high/lymphocyte antigen 6 complexhigh inflammatory monocytes. In human MASH, liver OPN correlated with chemokines CCL2 and IL8 in association with portal injury and fibrosis. Plasma OPN, serum CCL2 and IL8 also increased with fibrosis stage. OPN promotes cholangiocyte chemokine secretion and the accumulation of pro-inflammatory monocytes. These data support neutralisation of OPN as an anti-inflammatory and anti-fibrotic strategy.

Diagnostic models for differentiating fatty liver disease of alcohol and non-alcoholic genesis

Introduction. Fatty liver disease is the largest contributor to the burden of chronic liver disease worldwide. Current approaches do not allow sufficient differentiation between alcoholic and non-alcoholic etiology of the process.Aim. Create diagnostic panels including electrical and viscoelastic parameters of erythrocytes to differentiate fatty liver disease of alcoholic and non-alcoholic genesis.Materials and methods. The study included 38 men (47.5 ± 2.9 years) with NAFLD; 31 men with alcoholic fatty liver disease (AFLD) (45.1 ± 3.1 years) according to ultrasound of the abdominal organs, the degree of fibrosis did not exceed F1 (FibroScan® 502). Electrical and viscoelastic parameters of erythrocytes were studied by dielectrophoresis using an electro-optical cell detection system. To determine the parameters of erythrocytes – biomarkers for distinguishing between AFLD and NAFLD, a system of machine learning methods – Random Forest was used.Results. Electrical, viscoelastic parameters of erythrocytes, which are biomarkers for distinguishing between AFLD and NAFLD, were established: cell membrane capacity (p = 1.21E-11), the degree of change in the deformation amplitude at a frequency of 5 x 105 Hz (p = 2.38E-08), cell polarizability at a frequency of 106 Hz (p = 9.38E-08), the speed of erythrocyte movement to the electrodes (p = 4.32E-06), the magnitude of the dipole moment (p = 1.66E-05), relative polarizability (p = 2.35E-05), the index of erythrocyte destruction at a frequency of 5 x 105 Hz (p = 0.016), the position of the crossover frequency (p = 2.13E- 06). The diagnostic model, including five parameters – the position of the crossover frequency, cell polarizability at a frequency of 106 Hz, cell electrical conductivity, membrane capacity, the degree of change in the deformation amplitude at a frequency of 5 x 105 Hz, provided the highest diagnostic accuracy with an AUC of 0.975, a sensitivity of 96.3%, and a specificity of 91.8% in differentiating between AFLD and NAFLD.Conclusion. Thus, systematic exposure to alcohol modifies the structure of erythrocyte membranes, leading to a decrease in the surface charge, the barrier function of membranes, reducing the resistance of cells, their ability to deform, which determines the key role of the identified electrical, viscoelastic parameters of erythrocytes in differentiating between AFLD and NAFLD.

Epidemiology of liver diseases: global disease burden and forecasted research trends.

We assessed the global incidence, mortality, and disability-adjusted life years (DALYs) associated with various liver diseases, including alcohol-related liver disease (ALD), hepatitis B/C virus infections (HBV or HCV), liver cancer, metabolic dysfunction-associated steatotic liver disease (MASLD), and other chronic liver diseases, from the 2019 Global Burden of Disease study. Additionally, we analyzed the global trends in hepatology research and drug development. From 2000 to 2019, prevalence rates increased for ALD, MASLD and other liver diseases, while they decreased for HBV, HCV, and liver cancer. Countries with a high socio-demographic index (SDI) exhibited the lowest mortality rates and DALYs. The burden of liver diseases varied due to factors like sex and region. In nine representative countries, MASLD, along with hepatobiliary cancer, showed highest increase in funding in hepatology research. Globally, the major research categories in hepatology papers from 2000 to 2019 were cancer, pathobiology, and MASLD. The United States (U.S.) was at the forefront of hepatology research, with China gradually increasing its influence over time. Hepatologists worldwide are increasingly focusing on studying the communication between the liver and other organs, while underestimating the research on ALD. Cancer, HCV, and MASLD were the primary diseases targeted for therapeutic development in clinical trials. However, the proportion of new drugs approved for the treatment of liver diseases was relatively low among all newly approved drugs in the U.S., China, Japan, and the European Union. Notably, there were no approved drug for the treatment of ALD in the world.

Rice Protein Peptides Alleviate Alcoholic Liver Disease via the PPARγ Signaling Pathway: Through Liver Metabolomics and Gut Microbiota Analysis.

Alcoholic liver disease (ALD) is the predominant type of liver disease worldwide, resulting in significant mortality and a high disease burden. ALD damages multiple organs, including the liver, gut, and brain, causing inflammation, oxidative stress, and fat deposition. In this study, we investigated the effects of rice protein peptides (RPP) on ALD in mice with a primary focus on the gut microbiota and liver metabolites. The results showed that administration of RPP significantly alleviated the symptoms of ALD in mice including adiposity, oxidative stress, and inflammation. The KEGG pathway shows that RPP downregulates the liver metabolite of capric acid and the metabolism of fatty acid biosynthesis compared with the MOD group. Mechanistically, RPP downregulated the PPARγ signaling pathway and suppressed the expression of fatty acid biosynthesis genes (FASN, ACC1, ACSL1, and ACSL3). Furthermore, two active peptides (YLPTKQ and PKLPR) with potential therapeutic functions for ALD were screened by Caco-2 cell modeling and molecular docking techniques. In addition, RPP treatment alleviates gut microbiota dysbiosis by reversing the F/B ratio, increasing the relative abundance of Alloprevotella and Alistipes, and upregulating the level of short-chain fatty acids. In conclusion, RPP alleviates ALD steatosis through the PPARγ signaling pathway by YLPTKQ and PKLPR and regulates gut microbiota.

African American Females are More Vulnerable to Develop Biliary Injury in NAFLD (Nonalcoholic fatty liver disease) Patients – A Single Institute Experience

Abstract Introduction/Objective Chronic alcohol exposure alone may take decades to induce severe liver disease, yet when combined with elements such as the Western diet, liver pathogenesis accelerates, resulting in earlier symptoms. Identifying the specific contributions of alcohol, diet, and other factors to liver disease is challenging, despite the availability of diagnostic tools like patient histories, liver enzyme tests, imaging, and biopsies. Methods/Case Report This study seeks to detail the liver disease profile of patients who underwent liver biopsies in 2022. Comprehensive profiles were created by retrieving liver biopsy specimens and associated diagnostic data from electronic medical records. Two independent pathologists analyzed the biopsy slides, looking for liver damage associated with alcohol consumption and Western diet influences. We employed enhanced staining techniques to better associate specific types of liver damage with demographic variables. The data analysis was conducted using GraphPad Prism 9 for robust statistical evaluation. Results (if a Case Study enter NA) The research included 88 participants—41 males and 47 females, with average ages of 56 and 62 respectively. The predominant diagnosis was fatty liver disease, with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) accounting for 26% of cases, and alcoholic liver disease (ALD) making up 10%. The NAFLD/NASH group (n=23) consisted mainly of African Americans (n=15) and Caucasians (n=8). Among these, African Americans showed a significantly greater ductular reaction and portal inflammation (p&amp;lt;0.05). Conversely, no notable differences in portal fibrosis and bile stasis were observed between these groups. Notably, African American females (n=11) demonstrated more severe pathological features compared to Caucasian females (n=6), including elevated levels of ductular reaction, fibrosis, portal inflammation, and bile stasis (p&amp;lt;0.05), suggesting a higher vulnerability to biliary injuries. Conclusion The study highlights the complex interplay between lifestyle factors and liver disease development and emphasizes the need for precise diagnostic strategies that consider these multifactorial influences. Additionally, it reveals ethnic disparities in the pathology of NAFLD, advocating for further research into their causes and implications for clinical management. Future investigations should focus on race and gender-specific factors and adapt local healthcare strategies to effectively manage the escalating burden of liver disease.

Free radical detection in precision-cut mouse liver slices with diamond-based quantum sensing

Free radical generation plays a key role in many biological processes including cell communication, maturation, and aging. In addition, free radical generation is usually elevated in cells under stress as is the case for many different pathological conditions. In liver tissue, cells produce radicals when exposed to toxic substances but also, for instance, in cancer, alcoholic liver disease and liver cirrhosis. However, free radicals are small, short-lived, and occur in low abundance making them challenging to detect and especially to time resolve, leading to a lack of nanoscale information. Recently, our group has demonstrated that diamond-based quantum sensing offers a solution to measure free radical generation in single living cells. The method is based on defects in diamonds, the so-called nitrogen-vacancy centers, which change their optical properties based on their magnetic surrounding. As a result, this technique reveals magnetic resonance signals by optical means offering high sensitivity. However, compared to cells, there are several challenges that we resolved here: Tissues are more fragile, have a higher background fluorescence, have less particle uptake, and do not adhere to microscopy slides. Here, we overcame those challenges and adapted the method to perform measurements in living tissues. More specifically, we used precision-cut liver slices and were able to detect free radical generation during a stress response to ethanol, as well as the reduction in the radical load after adding an antioxidant.

Selenium Attenuates Ethanol-induced Hepatocellular Injury by Regulating Ferroptosis and Apoptosis.

Ferroptosis is a newly identified type of cell death which is strongly linked to the development of several diseases. Whereas, the role of ferroptosis in the improvement of ethanol-induced hepatocytes injury by selenium has not been confirmed. In this study, an in vitro cell damage model was established using half inhibition concentration of ethanol to induce NCTC clone 1469. Cell activity, lipid peroxidation, apoptosis and the expression of markers related to ferroptosis pathway was determined. A mouse model of alcoholic liver disease (ALD) was constructed and the effectiveness of selenium and ferrostatin-1 in treating ALD in vivo was assessed by serum liver function tests, tissue staining and immunohistochemistry for ferroptosis related proteins. Pretreatment with selenomethionine and ebselen significantly improved ethanol-induced reduction in hepatocyte viability, elevated GSH levels and SOD enzyme activity, reduced MDA and iron content, while improving ethanol-induced changes in apoptosis levels and ferroptosis markers GPX4, SLC7A11, and ACSL4, with the effect of Selenomethionine being more significant. In vivo results also indicated that intervention with selenium or ferroptosis inhibitors significantly improved ethanol-induced liver tissue damage, significantly reduced serum ALT and AST levels, upregulated GPX4 and SLC7A11, but reduced ACSL4 protein levels in liver tissue. The process of ethanol damage to hepatocytes is regulated by the ferroptosis pathway. Selenium may exert a beneficial role in ethanol-induced hepatocyte injury by antagonizing oxidative stress and regulating apoptosis and ferroptosis pathways.

Enhancing the Management of Alcohol-Related Liver Disease: Addressing Socioeconomic Disparities and the Role of Social Work in Intervention Strategies

Enhancing the Management of Alcohol-Related Liver Disease: Addressing Socioeconomic Disparities and the Role of Social Work in Intervention Strategies

Assessing Alcohol Genes Targets in Mouse Liver

Background: Alcohol is a risk factor for liver diseases. There is a correlation between alcohol consumption and fatty liver disease. Experiences have shown gene expression alteration in the liver following alcohol consumption. Since the molecular mechanism of connection between alcohol consumption and fatty liver disease needs a clear perspective, this study aims to explore the significant genes that are targeted by alcohol in the liver of mice.Methods: Gene expression profiles of mice livers fed with alcohol were retrieved from the Gene Expression Omnibus (GEO) database and compared with the control samples. Data are pre-evaluated with the GEO2R program, and the significant differentially expressed genes (DEGs) are analyzed via gene expression evaluations and regulatory network assessment. Results: Among the 25619 dysregulated genes, 78 significant DEGs were pointed out. Gene expression analysis showed that most extremely dysregulated genes are up-regulated and belong to the cytochrome P450 genes family. Finally, cytochrome P450 and glutathione S-transferase genes family, as well as hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 4, were introduced as the critical targeted genes.Conclusion: In conclusion, detoxification of xenobiotics, cellular metabolism and homeostasis, the pathogenesis of some liver diseases, synthesis of several prostaglandins and steroid hormones, and inflammation fibrosis in the liver are possibly associated with alcohol consumption.

Therapeutic effects of fecal microbial transplantation on alcoholic liver injury in rat models

ObjectiveDisruption of gut microbiota is closely related to the progression of alcoholic liver disease (ALD). This study aimed to explore the therapeutic effect of fecal microbiota transplantation (FMT) in ALD rats using a combination of microbiological and metabolomic techniques. MethodsThree liver injury rat models were constructed using alcohol, CCL4, and alcohol combined with CCL4, and administered an FMT treatment comprising the fecal microbiota of healthy rats via the gastric route for 12 consecutive weeks. We measured the therapeutic effect of FMT treatment on liver inflammation, intestinal mucosal barrier, and bacterial translocation in ALD rats using 16S rRNA and UPLC-Q/TOF-MS technology to detect the effects of FMT on the intestinal microbiota and metabolic patterns of ALD rats. ResultsFMT treatment effectively improved liver function, prolonged survival time, improved the intestinal mucosal barrier, reduced bacterial translocation, alleviated liver inflammation, and delayed the progression of liver fibrosis in three types of liver injury models. The microbiome and metabolomic results showed that FMT can effectively improve gut microbiota disorder in ALD rats and improve metabolic patterns by regulating metabolic pathways such as the arachidonic acid and retinol pathways. ConclusionFMT treatment could reverse alcohol induced liver injury by improving gut microbiota and metabolic patterns in ALD rats, and oral FMT could be an effective therapeutic approach for ALD.

SIRS criteria versus qSOFA score in patients with severe alcohol-related hepatitis.

Severe alcohol-related hepatitis (sAH) is a potentially life-threatening complication of alcohol-related liver disease. SIRS criteria have been related to disease severity and may be a prognostic factor. Recently, qSOFA has been shown to be more prognostically accurate than SIRS in other inflammatory conditions. To determine whether qSOFA is a better prognostic score than SIRS criteria in sAH. We included 62 consecutive patients admitted for sAH, defined by modified Maddrey DF ≥32. MELD-Na, SIRS criteria and qSOFA score were calculated. Survival at 180 days was assessed. Twenty-four patients (38.7%) died after 180days. Three or more SIRS criteria and two or more qSOFA criteria were associated with 180-day mortality (LR=12.09, p=0.001; LR=4.81, p=0.028, respectively). Patients with MELD-Na >30 points died during follow-up more frequently (LR=5.997; p=0.014). SIRS respiratory criterion (B=5.113; p=0.023) and qSOFA respiratory criterion (B=5.985; p=0.05), bilirubin (>10mg/dL; LR=5.43, p=0.006), creatinine (>1mg/dL; B=5.885, p=0.015) and hyponatraemia (LR=5.75, p=0.018) were associated with mortality. Cox Regression model revealed that only SIRS and MELD-Na were independent prognostic factors. SIRS criteria seem to be more useful for patients with sAH, as well as MELD-Na. In contrast, qSOFA has no independent prognostic value in patients with sAH.