Multi-Strain Probiotics Alleviate Alcoholic Liver Disease Via Microbiota-Metabolism Axis: A Randomized Controlled Study.

Tumor necrosis factor alpha-induced receptor 1 signaling in alcoholic liver disease: A gut reaction?

Polyene phosphatidyl choline injection regulates lipid homeostasis via AKT-PDE3-PKA in mice.

Objective To observe the clinical value of doppler ultrasound in evaluation of the treatment outcome of alcoholic liver disease.Methods 212 patients with alcoholic liver disease were selected.Ultrasound and liver function tests were applied before and after treatment,and temperance and medicines were applied for treating.The effects were used to observe the senlitivity of ultrasound applied in evaluation the treatment outcome of alcoholic liver disease.Results Of 212 cases,95 cases were diagnosed as alcoholic fatty liver disease by ultrasound before treatment,and the detection rate before treatment was 96.70％.51 cases were diagnosed as alcoholic hepatitis and 59 cases were alcoholic cirrhosis.After treatment,there were 37 cases had abnormal ultrasound images in 43 patients with alcoholic liver disease,and the detection rate was 86.04％.And 9 cases were diagnosed as alcoholic fatty liver disease by ultrasound,12 cases were diagnosed as alcoholic hepatitis and 16 cases were alcoholic cirrhosis.Conclusion It was noninvasive,cheap,convenient and repeated by using doppler ultrasound,and it was conducive to grasp the change of the condition of the patients for doctors.Ultrasound could be chosen as the preferred method for diagnosis of alcoholic liver disease. Key words: Liver diseases, alcoholic; Ultrasonography, Doppler; Evaluation studies

Alcoholic liver disease (ALD) has a significant impact on human health and is one of the leading causes of liver disease mortality. The early and exact diagnosis of ALD is very important since the early stage of disease progression can be reversible. Although ALD can be evaluated by ultrasound, CT, or MRI, there is still no imaging technique sufficient in the diagnosis of early-stage ALD. Of the current studies, epigenetic modulation plays a significant role in the development and progression of ALD. In this work, we evaluate whether BRDs play a vital role in the early-stage ALD using our new PET imaging probe of BET proteins, [11C]CW22. PET/CT imaging of [11C]CW22 and [18F]FDG was used to identify early-stage lesions of livers and brains in the mice model. We found that the average uptake values of livers and brains in early-stage ALD were significantly increased for [11C]CW22 PET/CT imaging but only slightly changed in [18F]FDG PET/CT imaging. Consistently, we also found that BRD 3, 4 protein expression levels were significantly higher in the liver and brain tissues of early-stage ALD. Furthermore, through Pmod software, we found that [11C]CW22 PET/CT uptakes in the brain stem, cerebellum, and midbrain were significantly up-regulated in the early-stage ALD. In conclusion, BRDs were important mediators of damage in early-stage ALD. [11C]CW22 PET/CT imaging can detect the early-phase alcohol-induced damage of livers and brains, which will likely lead to human trials in the future.

TRPV6 channel mediates alcohol-induced gut barrier dysfunction and systemic response.

To compare the gut microbiota composition among patients with alcoholic fatty liver disease (AFLD), individuals with alcohol use disorder (AUD) without liver damage, and healthy controls, and to investigate correlations between microbial profiles and liver health. A retrospective analysis was conducted on 34 participants: 14 with AFLD, 10 with AUD without liver damage, and 10 healthy controls. Blood biochemical markers, liver function tests, lipid profiles, and gut microbiota composition were assessed. Gut microbiota was analyzed via high-throughput 16S rRNA gene sequencing. Alpha and beta diversity indices were calculated, and group-specific microbial taxa were identified. AFLD patients showed a decreased Firmicutes/Bacteroidetes ratio and an increased abundance of Bacteroidetes, indicating gut dysbiosis compared to the other groups. Biochemical markers, including triglycerides, alanine aminotransferase, gamma-glutamyl transferase, and cholinesterase, were significantly altered in AFLD patients (all P > 0.05). Beta diversity analysis revealed distinct microbial communities in the AFLD group. Notably, taxa such as Megamonas and Selenomonadales were enriched in AFLD, while beneficial genera like Ruminococcus and Faecalibacterium were significantly reduced. AFLD is associated with marked gut microbiota alterations and distinct microbial signatures, which correlate with liver dysfunction and biochemical abnormalities, highlighting the role of dysbiosis in disease pathogenesis.

Background/Objectives: Alcoholic liver disease (ALD) is intricately linked to gut microbiota dysbiosis and metabolic disturbances along the gut–liver axis. Octenyl succinic anhydride (OSA) starch escapes digestion in the small intestine and ferments in the colon, modulating gut microbiota and metabolism. This study explored the protective effects of OSA starch against ALD and elucidated the underlying gut microbiota–metabolite interactions. Methods: A chronic ethanol-fed mouse model was conducted to evaluate the protective effects of OSA starch against ALD, and multi-omics analyses integrating 16S rRNA sequencing, PICRUSt2 functional predictions, and metabolomics were used to reveal potential mechanism. Results: OSA starch supplementation in ALD mice significantly reduced liver fat accumulation, lowered the liver index to 4.11%, and restored serum transaminase levels closer to normal. Multi-omics analyses revealed that OSA starch enriched beneficial gut bacteria such as Faecalibaculum rodentium and Bifidobacterium adolescentis. OSA starch also enhanced microbial metabolic functions, including pyruvate, butanoate, and propanoate metabolism. These shifts were accompanied by regulation of fecal and serum metabolites, including pyruvate, 2-hydroxybutanoic acid, and lactic acid. Structural equation modeling further confirmed that OSA starch ameliorates ALD via coordinated modulation of gut microbiota, microbial functions, metabolites, and serum markers. Conclusions: OSA starch protects against alcoholic liver injury by remodeling the gut–liver metabolic network, presenting a promising dietary strategy for ALD.

Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. In developed countries, ALD is a major cause of end-stage liver disease that requires transplantation. The spectrum of ALD includes simple steatosis, alcoholic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Alcohol abstinence is the most effective therapy for ALD. However, targeted therapies are urgently needed for patients with severe ALD (i.e., alcoholic hepatitis) or those who do not abstain from alcohol. The lack of studies and the availability of animal models that do not reflect all the features of this disease in humans inhibit the development of new drugs for ALD. In ALD-associated fibrosis, hepatic stellate cells are the principal cell type responsible for extracellular matrix production. Although the mechanisms underlying fibrosis in ALD are largely similar to those observed in other chronic liver diseases, oxidative stress, methionine metabolism abnormalities, hepatocyte apoptosis, and endotoxin lipopolysaccharides that activate Kupffer cells may play unique roles in disease-related fibrogenesis. Lipogenesis during the early stages of ALD has recently been implicated as a risk factor for the progression of cirrhosis. Other topics include osteopontin, interleukin-1 signaling, and genetic polymorphism. In this review, we discuss the basic pathogenesis of ALD and focus on liver fibrogenesis.

Alcoholic liver disease (ALD) is a global liver disease which characterized by liver inflammation, fatty liver, alcoholic hepatitis, or liver cirrhosis. Alcohol abuse is one of the main reasons for liver disease. Alcoholic fatty liver (AFL) disease is the early stage of ALD and associated with the excessive lipids accumulation in hepatocytes as well as oxidative stress. MicroRNA-203 (miR-203) is known to suppress the proliferation and metastasis of hepatocellular carcinoma, but the role in the progression of alcoholic liver disease is not clear and is warranted for further investigation. In the present study, we have found the expression of miR-203 is down-regulated in Gao-Binge alcoholic mice model and ethanol-induced AML-12 cell lines in vitro. Furthermore, over-expression of miR-203 decrease the lipids accumulation in liver and ethanol-induced AML-12 cells. Mechanistically, we identified that Lipin1 is a key regulator of hepatic lipid metabolism, and acts as a downstream target for miR-203. In summary, our results suggested that over-expression of miR-203 inhibited the liver lipids accumulation and the progression of AFL by targeting Lipin1.

Lactobacillus rhamnosus GG Treatment Potentiates Intestinal Hypoxia-Inducible Factor, Promotes Intestinal Integrity and Ameliorates Alcohol-Induced Liver Injury

Complete abstinence is the cornerstone of alcohol-related liver disease (ALD) management. However, many patients struggle to achieve or sustain abstinence, prompting growing interest in harm reduction strategies, particularly pharmacological interventions to reduce alcohol intake. Nalmefene, an opioid receptor modulator, has shown efficacy in reducing alcohol consumption among individuals with alcohol dependence. However, its effects on hepatic parameters in ALD have not been well studied in real-world settings. To evaluate the efficacy and safety of nalmefene in patients with ALD, focusing on changes in alcohol consumption, liver function, and hepatic reserve capacity. The present retrospective observational study included 21 patients with ALD who received nalmefene therapy at our institution between September 2019 and December 2023. Data on alcohol intake, liver function tests, hepatic reserve capacity, and alcohol use disorders identification test scores were collected at baseline and after 6months of treatment. Adverse events were also recorded. Within 1month of initiating nalmefene, significant reductions in heavy drinking days and total alcohol consumption were observed. These reductions were accompanied by improvements in liver function parameters. However, no statistically significant changes in hepatic reserve capacity were noted. Most adverse events were mild to moderate (Grade 1 or 2), and no serious adverse events occurred. Nalmefene appears to be a safe and effective pharmacological option for reducing alcohol intake and improving liver function in patients with ALD. These findings support its use as part of a harm reduction approach for those unable to achieve complete abstinence.

Accrued evidence has indicated that epigenetic mechanisms altered by alcohol have been implicated in the progression and development of alcoholic liver disease (ALD). SIRT1 plays an important role in ALD progression and has emerged as a promising therapeutic target for treating ALD. The purpose of this study is to investigate the efficacy of [11C]WL-1 for quantitative imaging of SIRT1 in mouse models of early-stage ALD. Positron emission tomography/computerized tomography (PET/CT) imaging was carried out 60 min following the injection of [11C]WL-1 in mouse models of early-stage ALD and normal control mice. The time-activity curves for ALD mouse livers showed remarkably decreased total uptake of [11C]WL-1 relative to that for control mouse livers. Moreover, compared with the normal control mice, decreased uptake in the cortex, hippocampus, and cerebellum was also observed in early-stage ALD mice, while the uptake of [11C]WL-1 in amygdala showed no significant changes. Western blot analysis confirmed that the protein levels of SIRT1 in the brains of early-stage ALD mice were decreased significantly when compared to the normal control mouse brains. Collectively, PET imaging with [11C]WL-1 would facilitate future clinical studies, aiming to demonstrate the roles of SIRT1 in ALD.

Liver disease secondary to alcohol ranges from alcoholic fatty liver disease to acute hepatitis to cirrhotic liver disease. It is imperative that alcohol be discontinued to allow for any potential improvement in liver function, with most benefit being seen in the early stages of the disease. Alcoholic liver disease has a profound effect on nutrient intake, nutrition status, and metabolism, contributing to a high prevalence of malnutrition in this population. Early intervention with nutrition therapy may improve response to treatment, alleviate symptoms, and improve quality and quantity of life. In this review, nutrition assessment parameters and medical nutrition therapy goals for alcoholic liver disease are discussed.

It has been reported that basement membranes were found around the sinusoidal walls in cirrhotic livers, indicating the development of capillarization of the sinusoids. It has been also emphasized that capillarization of the sinusoids is more prominent in alcoholic liver disease (ALD). In the present study, factor VIII related antigen (VIII-Ag) and UEA-1 were identified immunohistochemically in order to analyze capillarization of the sinusoids in chronic liver diseases. Electron microscopic studies on the endothelial cells and sinusoids were also performed. Electron microscopic studies revealed that the number of fenestra in the endothelial cells decreased and basement membranes were clearly observed in the space of Disse from an early stage of ALD. However, these changes were not observed in the early stage of non-ALD. VIII-Ag or UEA-1 was not stainable in the sinusoidal cells of normal livers or at an early stage of non-ALD. However, in ALD, both VIII-Ag and UEA-1 were clearly demonstrated in the sinusoidal cells from the early stage of fibrosis. These results suggest that the sinusoidal endothelial cells may transform to vascular endothelial cells from an early stage of ALD. The alterations in the sinusoidal endothelium and the basement membrane formation in the Disse space indicate that capillarization of the sinusoid may occur. Capillarization of the sinusoid may cause a disturbance in exchanges of many bioactive substances between the sinusoidal blood and hepatocytes across the Disse space and may thereby contribute to the pathogenesis of ALD.

Functions of hepatic non-parenchymal cells in alcoholic liver disease