BACKGROUND Various prognostic scores have been developed to predict mortality and response to steroids in alcoholic hepatitis(AH).We aimed to further validate and compare these scores,particularly pre-day 7 Lille scor...BACKGROUND Various prognostic scores have been developed to predict mortality and response to steroids in alcoholic hepatitis(AH).We aimed to further validate and compare these scores,particularly pre-day 7 Lille scores,in addition to identifying reliable predictors of complications and mortality such as renal dysfunction and nutritional status.AIM To identify predictors of complications and mortality in AH,particularly focusing on demographics,renal involvement,underlying liver disease,and nutrition.METHODS This is a retrospective analysis of patients admitted to a large urban tertiary care center with AH from 2020 to 2022.Receiver operating characteristics(ROC)curve analysis was conducted to compare established prognostic scores with Lille scores from day 3 to day 7(LM3-7).Logistic regression equations were conducted to identify predictor variables.RESULTS Severe AH(SAH)as defined by Maddrey’s discriminant function≥32 was diagnosed in 150 out of 425 patients with AH.LM3-7 had 28-day mortality rates in the responder group of 7%-11%,while in the non-responder group,mortality rates were approximately 38%-42%.LM3-7 had 90-day mortality rates in the responder group of 12%to 17%,while in the non-responder group,mortality rates were 48%-53%.Furthermore,all LM3-7 scores showed comparable efficacy in predicting mortality using ROC curve analysis;Area under ROC ranged from 0.771 to 0.802 for 28-day mortality and 0.743 to 0.809 for 90-day mortality.Regarding complications and mortality in AH,significant predictors included poor nutritional status,underlying cirrhosis,and acute renal dysfunction.CONCLUSION LM3-6 is as accurate as LM7 in predicting corticosteroid efficacy for 28-day and 90-day mortality in patients with SAH.Holding glucocorticoids early during the disease course can prevent unnecessary complications.展开更多
BACKGROUND Severe alcoholic hepatitis(SAH)carries a 90-day mortality rate approaching 50%.Management includes corticosteroids,nutritional support,and early liver transplantation in selected cases.However,the mid-term ...BACKGROUND Severe alcoholic hepatitis(SAH)carries a 90-day mortality rate approaching 50%.Management includes corticosteroids,nutritional support,and early liver transplantation in selected cases.However,the mid-term impact of available therapies remains unclear.This systematic review provides a critical evaluation of treatments for SAH,specifically focusing on survival or mortality at 90 days as an essential window that captures short-and mid-term outcomes.The 90-day window is clinically significant,as it reflects the remission of systemic inflam-mation,early liver recovery,and minimizes confounding long-term behaviors such as alcohol relapse.AIM To review the effect of different treatments for SAH on survival and mortality at 90 days.METHODS A systematic search of PubMed and EMBASE(last updated March 2025)was performed without language restrictions,focusing on studies published in the last decade.Study selection and data extraction were performed independently by at least two reviewers.Risk of bias was assessed using RoB 2.0 and Risk-of Bias in Non-Randomized Studies of Interventions tools.Due to heterogeneity in study designs and interventions,a meta-analysis was not feasible.A qualitative synthesis was conducted using narrative summaries and evidence tables.RESULTS Searches in the databases yielded 645 citations in PubMed and 1516 in EMBASE.Of these 2161 studies,618 were duplicates and therefore removed.A total of eight studies were included in qualitative synthesis.Among the included publications,six were randomized control trials(RCT)and two were retrospective cohort studies.These studies evaluated 90-day mortality or survival in SAH patients treated with corticosteroids(n=2),pentoxifylline(n=1),anakinra plus zinc(n=2),granulocyte colony-stimulating factor(n=1),amoxicillin-clavulanate(n=1),fecal microbiota transplantation(n=1)or extracorporeal liver assist device(n=1).While most studies were conducted in Western countries,two had a global scope.CONCLUSION Steroids remain the first-line therapy for SAH despite reports of them not having any 90-day survival benefit.These results highlight the need for multicenter,biomarker-guided RCTs evaluating emerging treatments to improve mid-term survival in SAH.展开更多
BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver diseases.This study aims to specifically investigate the rol...BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver diseases.This study aims to specifically investigate the role of MLKL’s adenosine triphosphate(ATP)-binding pocket in facilitating necroptosis-independent pathways that may contribute to liver disease progression.By focusing on this mechanism,we seek to identify potential therapeutic targets that can modulate MLKL activity,offering new strategies for the prevention and treatment of liver-related pathologies.AIM To investigate the possibility of using the ATP-binding pocket-associated,necro-ptosis-independent MLKL pathway as a target for liver diseases.METHODS Cell death following necroptosis stimuli was evaluated using cell proliferation assays,flow cytometry,and electron microscopy in various cells.The human liver organoid system was used to evaluate whether the MLKL ATP pocket-binding inhibitor could attenuate inflammation.Additionally,alcoholic and non-alcoholic fatty liver diseases animal models were used to determine whether MLKL ATP pocket inhibitors could attenuate liver injury.RESULTS While an MLKL ATP pocket-binding inhibitor did not prevent necroptosis-induced cell death in RAW 264.7 cells,it did reduce the necroptosis-led expression of CXCL2,ICAM,and VCAM.Notably,MLKL ATP pocket inhibitor diminishes the expression of CXCL2,ICAM,and VCAM by inhibiting the IκB kinase and nuclear factor kappa-B pathways without inducing necroptosis-induced cell death in two-dimensional cell culture as well as the human-derived liver organoid system.Although MLKL ATP-binding inhibitor was ineffective in non-alcoholic fatty liver disease animal models,MLKL ATP-binding inhibitor attenuated hepatic inflammation in the alcoholic liver disease model.CONCLUSION MLKL ATP pocket-binding inhibitor exerted anti-inflammatory effects through the necroptosis-independent MLKL pathway in an animal model of alcoholic liver disease.展开更多
Objective:To investigate the protective effects of the combined concentrated liquid extract of Pueraria lobata(Willd.)Ohwi root(P.lobata,Ge Gen)and Hovenia dulcis Thunb.(H.dulcis,Zhi Ju Zi)against ethanol-induced live...Objective:To investigate the protective effects of the combined concentrated liquid extract of Pueraria lobata(Willd.)Ohwi root(P.lobata,Ge Gen)and Hovenia dulcis Thunb.(H.dulcis,Zhi Ju Zi)against ethanol-induced liver damage in vitro,using a human hepatoma cell line G2(HepG2)cell model.Methods:HepG2 cells were cultured in medium containing 4%ethanol to establish a model of alcoholic liver damage.The cells were then treated with the combined extract obtained via cryogenic extraction.Biochemical assays and Western blot analyses were performed to assess the levels of oxidative stress markers,antioxidant enzymes,and inflammatory cytokines.In addition,activation of the phosphoinositide 3-kinase/protein kinase B(PI3K/AKT)pathway was examined to elucidate the mechanisms underlying the effects of the extract.Results:Treatment with the extract contributed to a significant reduction in the release of nitric oxide and reactive oxygen species in the ethanol-treated HepG2 cells;promoted the elevated expression of superoxide dismutase,catalase,and glutathione,indicating enhanced antioxidant defenses;and showed strong free radical-scavenging activity against 1,1-diphenyl-2-picrylhydrazyl radicals.In addition,by activating the PI3K/AKT pathway,treatment promoted increases in the expression of nuclear factor erythroid 2-related factor 2 and its downstream targets,subsequently inhibiting apoptosis.Moreover.inflammatory responses were mitigated,as indicated by reductions in the expression of tumor necrosis factor-alpha and interleukin-6,and we detected reduction in the levels of alanine aminotransferase and aspartate aminotransferase,thereby indicating hepatoprotective effects.Conclusion:The combined P.lobata root and H.dulcis extract was established to have notable antioxidative and anti-inflammatory properties,effectively alleviating ethanol-induced liver damage in vitro.These findings highlight the potential applicability of this extract as a candidate for treating alcoholic liver disease.展开更多
BACKGROUND Focal nodular hyperplasia(FNH)-like lesions are hyperplastic formations in patients with micronodular cirrhosis and a history of alcohol abuse.Although pathologically similar to hepatocellular carcinoma(HCC...BACKGROUND Focal nodular hyperplasia(FNH)-like lesions are hyperplastic formations in patients with micronodular cirrhosis and a history of alcohol abuse.Although pathologically similar to hepatocellular carcinoma(HCC)lesions,they are benign.As such,it is important to develop methods to distinguish between FNH-like lesions and HCC.AIM To evaluate diagnostically differential radiological findings between FNH-like lesions and HCC.METHODS We studied pathologically confirmed FNH-like lesions in 13 patients with alco-holic cirrhosis[10 men and 3 women;mean age:54.5±12.5(33-72)years]who were negative for hepatitis-B surface antigen and hepatitis-C virus antibody and underwent dynamic computed tomography(CT)and magnetic resonance imaging(MRI),including superparamagnetic iron oxide(SPIO)and/or gadoxetic acid-enhanced MRI.Seven patients also underwent angiography-assisted CT.RESULTS The evaluated lesion features included arterial enhancement pattern,washout appearance(low density compared with that of surrounding liver parenchyma),signal intensity on T1-weighted image(T1WI)and T2-weighted image(T2WI),central scar presence,chemical shift on in-and out-of-phase images,and uptake pattern on gadoxetic acid-enhanced MRI hepatobiliary phase and SPIO-enhanced MRI.Eleven patients had multiple small lesions(<1.5 cm).Radiological features of FNH-like lesions included hypervascularity despite small lesions,lack of“corona-like”enhancement in the late phase on CT during hepatic angiography(CTHA),high-intensity on T1WI,slightly high-or iso-intensity on T2WI,no signal decrease in out-of-phase images,and complete SPIO uptake or incomplete/partial uptake of gadoxetic acid.Pathologically,similar to HCC,FNH-like lesions showed many unpaired arteries and sinusoidal capillarization.CONCLUSION Overall,the present study showed that FNH-like lesions have unique radiological findings useful for differential diagnosis.Specifically,SPIO-and/or gadoxetic acid-enhanced MRI and CTHA features might facilitate differential diagnosis of FNH-like lesions and HCC.展开更多
Rape bee pollen has attracted increasing interests for its excellent protective effect against chemicalinduced liver injury owing to its abundant polyphenols.This study aims to analyze the types and contents of phenol...Rape bee pollen has attracted increasing interests for its excellent protective effect against chemicalinduced liver injury owing to its abundant polyphenols.This study aims to analyze the types and contents of phenolamides(seldom concerned)in rape bee pollen and their protective mechanism on alcoholic liver disease(ALD).Different from the previous finding that flavonoids are dominant polyphenols in bee pollen polyphenolic extract,our results demonstrated that there are only three flavonoids but 24 phenolamides in the as-prepared rape bee pollen phenolic extract(PPE).In addition,PPE was found to significantly improve the viability(from 54.9%to 84.1%,89.2%,and 94.0%)of alcohol-induced AML12 cells and alleviate alcoholinduced cell apoptosis(from 28.5%to 22.89%,22.0%,and 17.4%).To dissect the underlying mechanism for the protective effect of PPE against ALD,the molecular pathway was identified by RNA-Seq analysis.Transcriptome data revealed that PPE may protect against ALD by decreasing inflammation,cholesterol,and fatty acid synthesis(P<0.05).The National Institute on Alcohol Abuse and Alcoholism(NIAAA)model was used to further evaluate the hepatoprotective effect of PPE in vivo,and the results validated that PPE could alleviate liver injury and hepatic steatosis(from 22.7%to 11.5%and 10.9%)induced by alcohol.As the dominant polyphenols in PPE,phenolamides can be a class of valuable polyphenolic compounds in bee pollen with the potential to alleviate ALD.展开更多
Alcoholic liver disease(ALD),which includes a range of diseases,ranging from alcoholic steatosis,hepatitis,and fibrosis to cirrhosis and hepatocarcinoma,is a process of epigenetic remodeling involving multiple genes a...Alcoholic liver disease(ALD),which includes a range of diseases,ranging from alcoholic steatosis,hepatitis,and fibrosis to cirrhosis and hepatocarcinoma,is a process of epigenetic remodeling involving multiple genes and metabolic pathways.ALD is involved in various transcriptional regulatory mechanisms,including lipid metabolism disorders,inflammatory responses,autophagy,fibrogenesis,oxidative stress,fatty acid metabolism,iron metabolism,and endoplasmic reticulum stress.In the occurrence of ALD and its response to the microenvironment,various transcription factors(TFs)play important roles.Targeted therapy involving these TFs may pave a novel avenue for the treatment of ALD.Here,we summarize the molecular characteristics of TFs and their involvement in the biological and pathological processes of ALD.We further discuss the current pharmaceutical treatments targeting these TFs and their mediators.This study provides detailed and accurate regulation maps of TFs for the targeted therapy of ALD.展开更多
Alcoholic liver disease(ALD)is one of the major global public health problems.Yeast extract(YE),a product prepared from yeast,has been proven to have antioxidant and anti-inflammatory properties.However,the potential ...Alcoholic liver disease(ALD)is one of the major global public health problems.Yeast extract(YE),a product prepared from yeast,has been proven to have antioxidant and anti-inflammatory properties.However,the potential role of YE in the prevention of ALD remains unclear.The present study aimed to investigate the protective effects of YE on ALD and explore the underlying mechanism based on gut microbiota.The result showed that YE supplementation significantly ameliorated chronic alcohol exposure-induced liver injury in mice.In addition,YE counteracted alcohol-induced gut dysbiosis,intestinal barrier dysfunction,lipopolysaccharide(LPS)leakage-induced inflammatory response in the liver.Moreover,microbiota depletion by a broad-spectrum antibiotic was sufficient to block the protective effect of YE on ALD,indicating the contribution of gut dysbiosis modulation to the hepatoprotective role of YE.Furthermore,we demonstrated the causal relationship between gut microbiota and hepatoprotective effects of YE with the fecal microbiota transplantation(FMT)experiment.Compared with the ALD-FMT mice,gut dysbiosis,intestinal barrier dysfunction,LPS/TLR4 signaling pathway activation,and liver inflammatory response were significantly improved in the YE-FMT mice.Together,our findings highlight that dietary YE protects against ALD through gut dysbiosis correction.展开更多
BACKGROUND Studies investigating diagnostic delays and their effects on patients with alcoholic cirrhosis.AIM To investigate the current status and associated factors influencing diagnostic delays in 401 patients with...BACKGROUND Studies investigating diagnostic delays and their effects on patients with alcoholic cirrhosis.AIM To investigate the current status and associated factors influencing diagnostic delays in 401 patients with alcoholic cirrhosis.METHODS A cross-sectional analysis was conducted at a tertiary hospital in China from June 2020 to December 2023.Data were collected through telephone follow-ups and questionnaires.The Wilcoxon and Kruskal-Wallis H tests were used to compare diagnostic delays across various characteristics.Multivariate linear regression was employed to identify factors associated with diagnostic delays.RESULTS The median diagnostic delay was 5 months,with an interquartile range of 2-11 months.The proportions of patients with alcoholic cirrhosis who initially visited tertiary,secondary,and primary hospitals were 38.9%,37.91%,and 23.19%,respectively.Furthermore,the rates of patients undergoing liver computed tomography(CT)during their first visit at tertiary,secondary,and primary hospitals were 92.95%,13.82%,and 1.08%,respectively(P<0.001).Significant differences were observed in diagnostic delay-related characteristics,including residence,resident type,initial diagnosis,medical insurance,liver CT,and liver ultrasound during the first visit,age,years of education,family size,marital status,annual family income,years of drinking,daily alcohol consumption,and type of alcohol consumed(P<0.01).Furthermore,diagnostic delays were variably associated with daily alcohol consumption and other characteristics(i.e.residence,years of drinking,medical insurance,years of education,annual family income,liver CT and ultrasound during the first visit).Significant predictors of diagnostic delay identified on multivariate linear regression analysis included years of education,daily alcohol consumption,annual family income and blood ammonia levels(P<0.01).Patients with alcoholic cirrhosis experience varying degrees of diagnostic delays,necessitating interventions targeting potential contributing factors.CONCLUSION Our study indicates that patients with alcoholic cirrhosis may experience varying degrees of diagnostic delay.Interventions targeting potential factors contributing to diagnostic delay are necessary.展开更多
In this article,we discuss the recently published article by Yang et al.This retrospective analysis,which was conducted at a large urban tertiary care center,focused on comparing Lille model scores at days 3 and 7 wit...In this article,we discuss the recently published article by Yang et al.This retrospective analysis,which was conducted at a large urban tertiary care center,focused on comparing Lille model scores at days 3 and 7 with established scoring systems and identifying critical clinical predictors,such as renal dysfunction,nutritional status,and underlying cirrhosis.Alcoholic hepatitis(AH),a severe manifestation of alcohol-related liver disease,is associated with high morbidity and mortality,necessitating accurate prognostic tools and comprehensive clinical assessments.Prognostic tools are invaluable for early risk stratification,but they must be contextualized within the multifactorial nature of AH.Acute renal dysfunction and poor nutritional status,for example,are not just complications but pivotal markers of disease severity and systemic impact.Addressing these factors requires a holistic approach that extends beyond scoring systems to include targeted interventions and comprehensive patient care.This editorial emphasizes the need for a paradigm shift in AH management,where prognostic models are complemented by a deeper understanding of patient-specific factors.Such an approach can guide clinicians in tailoring therapies and improving outcomes for this high-risk population.展开更多
Severe alcoholic hepatitis remains one of hepatology’s most urgent challenges,with rapid clinical deterioration and high early mortality.This manuscript comments on and contextualizes the recent systematic review by ...Severe alcoholic hepatitis remains one of hepatology’s most urgent challenges,with rapid clinical deterioration and high early mortality.This manuscript comments on and contextualizes the recent systematic review by Quiñones-Calvo et al,which redirects attention from short-term endpoints toward 90-day survival,integrating evidence from associated clinical studies.For decades,corticosteroids have been the mainstay of treatment,reducing 28-day mortality but offering limited benefit for three months.The review emphasizes that the most critical threats to recovery,late infections,renal decline,and relapse,often emerge after the first month.By synthesizing recent studies,it highlights promising interventions such as fecal microbiota transplantation(FMT),which improved 90-day survival in a small randomized trial,and granulocyte colony-stimulating factor(G-CSF),which showed a robust survival benefit in a large retrospective cohort,alongside emerging strategies like plasma exchange and targeted biologics.These findings support a shift toward a two-phase care model:Early stabilization followed by recovery consolidation.For clinicians,such a model may help guide treatment decisions,with therapies like FMT or G-CSF warranting consideration in corticosteroid non-responders,pending further validation in larger randomized controlled trials.Adoption of 90-day survival as a central metric could bridge the gap between initial rescue and sustained remission,providing a more realistic measure of therapeutic success in one of hepatology’s most unforgiving conditions.展开更多
The present study aimed to analyze the potential mechanism of action of Chaihu-Astragalus in treating alcoholic liver fibrosis using network pharmacology and molecular docking techniques.We initially screened the acti...The present study aimed to analyze the potential mechanism of action of Chaihu-Astragalus in treating alcoholic liver fibrosis using network pharmacology and molecular docking techniques.We initially screened the active ingredients and targets of Chaihu-Astragalus through the TCMSP database.Additionally,we identified disease-related targets associated with alcoholic liver fibrosis via the GeneCards database,subsequently obtaining the intersection targets of Chaihu-Astragalus for treating alcoholic liver fibrosis.Using Cytoscape software,we constructed a“drug-active ingredient-intersection target”network and evaluated the network’s major active ingredients.The intersection targets were then subjected to protein-protein interaction network analysis using the STRING database to identify possible core targets.GO functional and KEGG pathway enrichment analyses were conducted using the DAVID platform.Molecular docking verification of key active ingredients and core targets was performed using Schrödinger software and the Maestro platform.We identified 26 active ingredients and 180 potential targets(intersection targets).Key active compounds,such as quercetin,kaempferol,prickly mangosteen,isorhamnetin,and Areapillin,were highlighted.Core targets were also identified,including AKT1,TP53,JUN,TNF,and IL-6.Enrichment analyses revealed that potential targets were mainly associated with PI3K-Akt,TNF,MAPK,and other signaling pathways.Chaihu-Astragalus acted on multiple targets such as AKT1,TP53,and JUN primarily through various active ingredients like quercetin and kaempferol.Thus,it affected treating alcoholic liver fibrosis through multiple signaling pathways,such as PI3K-Akt,TNF,and MAPK.It demonstrated characteristics of being multi-component,multi-target,and multi-pathway in its approach.展开更多
The development of rodent models that accurately reflect the pathogenesis of alcoholic liver disease(ALD)in humans is crucial for evaluating the nutritional intervention of food bioactive ingredients in ALD.Although v...The development of rodent models that accurately reflect the pathogenesis of alcoholic liver disease(ALD)in humans is crucial for evaluating the nutritional intervention of food bioactive ingredients in ALD.Although various models have been employed to establish ALD models over the past few decades,most successful cases are associated with high mortality rates,operational difficulties,and incompatibility formation mechanism compared to human ALD.However,the ALD models established by oral administration that simulate human drinking behavior often fail to induce significant liver damage.Therefore,it is imperative to explore simple and effective modes of oral administration for establishing ALD models consistent with the pathophysiological process of human ALD.Herein,we summarized the pathogenesis of ALD and discussed several issues related to construct ALD models with rodents(mainly mice and rats)by oral administration,including animal selection,animal feeding,alcohol intervention,and evaluation criteria.The purpose of this review is to provide a standardized and efficient formula for ALD modeling,so as to facilitate efficacy evaluation and mechanism analysis of food bioactive ingredients in ALD.展开更多
Severe alcoholic hepatitis(SAH)is associated with high short-term mortality.The SAH population exhibits extreme heterogeneity in disease severity,clinical presentation,decompensations,and outcomes.Nonetheless,improvin...Severe alcoholic hepatitis(SAH)is associated with high short-term mortality.The SAH population exhibits extreme heterogeneity in disease severity,clinical presentation,decompensations,and outcomes.Nonetheless,improving outcomes and preventing adverse events is a major challenge when selecting an appropriate treatment for alcoholic hepatitis.Currently,steroids are the standard of care for SAH with Maddrey’s discriminant function>32 and model for end stage liver disease>20;however,they have limited usage due to ineligibility in approx-imately two-third of such patients.Approximately 25%of patients do not respond to steroids and require alternative therapies.An array of evolving therapies,such as granulocyte colony-stimulating factors,plasma exchange,fecal microbiota transplantation,antibiotics,anti-cytokine therapies,and N-acetylcysteine,showing variable success,are emerging.Hence,it is also crucial to select appro-priate therapy.The present review discusses the standard of care,the existing therapies,risk stratification for outcomes,and the selection of appropriate therapy to improve survival in SAH patients.展开更多
Although mixed lineage kinase domain-like protein(MLKL)is widely recognized as a critical effector in the necroptotic signaling pathway,MLKL plays broader regulatory roles beyond programmed necroptosis.Notably,Xuan Yu...Although mixed lineage kinase domain-like protein(MLKL)is widely recognized as a critical effector in the necroptotic signaling pathway,MLKL plays broader regulatory roles beyond programmed necroptosis.Notably,Xuan Yuan et al demonstrated that CPD4,an ATP-binding pocket inhibitor of MLKL,significantly reduces liver inflammation and improves liver function by inhibiting NF-κB signaling,suggesting its use as a potential therapeutic candidate for alcoholic liver disease.However,the pharmacokinetic properties and long-term toxicity of CPD4 require further evaluation.Moreover,a single therapeutic strategy targeting MLKL may not be sufficient.Future studies should focus on the precise regulation of MLKL and develop combination therapies to achieve dual intervention of inflammatory and cell death pathways.This paper provides an important theoretical foundation for translational research on MLKL-targeted therapy.However,its clinical translation requires overcoming existing limitations and further elucidating the regulatory network of MLKL in complex microenvironments.展开更多
The aim of this project is to explore the mechanism of the treatment of alcoholic liver by means of network pharmacology and molecular docking.In this study,the chemical components of the extract of Callistephus chine...The aim of this project is to explore the mechanism of the treatment of alcoholic liver by means of network pharmacology and molecular docking.In this study,the chemical components of the extract of Callistephus chinensis(L.)Nees.were characterized by LC-MS/MS,identifying 6 compounds by positive and negative total ion flow maps.The target of chrysanthemum was derived from SwissTargetPrediction database,and the target related to alcoholic liver was derived from GeneCards and OMIM database.Add the target to the String database to build the protein interaction platform Microbiology software was used for GO bioprocess enrichment analysis and KEGG pathway enrichment analysis,and the target pathway network was constructed.In Discovery Studio 2016 Client software verified molecular docking,China aster flavonoids compounds and the adhesion strength of the key targets.Five potential active components were screened from the flavonoid monomer compounds of the chrysanthemum Cupressus.546 Bioprocess(BP),75 cell composition(CC)and 185·molecular function(MF)were obtained by GO enrichment analysis.KEGG enrichment analysis for each cross target involved a pathway.Network analysis showed that it was the main active component of flavonoids in the treatment of alcoholic liver,and other related signals were related to the treatment of alcoholic liver.This study showed that the flavonoids of Callistephus chinensis(L.)Nees were involved in the treatment of alcoholic liver by regulating multi-target and multi-pathway.展开更多
Alcohol consumption poses an escalating public health challenge.However,the impact of alcoholic liver disease(ALD)on post-transplant hepatitis B virus(HBV)reactivation and surgical outcomes remains inadequately charac...Alcohol consumption poses an escalating public health challenge.However,the impact of alcoholic liver disease(ALD)on post-transplant hepatitis B virus(HBV)reactivation and surgical outcomes remains inadequately characterized.Herein,we retrospectively analyzed our cohort(NCT06114251)comprising 453 patients with an HBV background.Propensity score matching(PSM)and sensitivity analyses were employed to assess the influence of ALD on surgical outcomes.Benchmark analysis compared the predictive performance of 21 models for post-transplant HBV reactivation.The Shapley additive explanation(SHAP)algorithm facilitated feature ranking and model interpretation.Patients were stratified into three subgroups based on the alcohol-modified HBV reactivation index(AMBRI).Among the cohort,113 patients(24.9%)had concurrent pre-transplant diagnoses of ALD and HBV infection,while 340(75.1%)had HBV infection alone.The presence of ALD was associated with an elevated risk of HBV reactivation and liver metastasis.PSM and sensitivity analyses revealed significantly lower five-year HBV reactivation-free survival(74.9%vs 85.4%),overall survival(OS,56.2%vs 70.5%),and tumor recurrence-free survival(RFS,47.8%vs 63.3%)in the ALD cohort.In recipients without HBV reactivation,hepatocellular carcinomas(HCCs)arising from both ALD and HBV exhibited inferior RFS(log-rank P=0.026)and OS beyond one year(landmark P=0.032)compared to HBV-related HCC alone.Benchmark analysis identified the surv.cforest model as the optimal predictor,achieving an area under the receiver operating characteristic(AUC)curve of 0.914 in internal validation and 0.884 in external validation,outperforming the published Cox model(AUC=0.78).AMBRI-based stratification delineated three distinct risk subgroups,with the intermediate-and high-risk groups exhibiting significantly worse OS and RFS than the low-risk group.In this study,stratification by AMBRI identified intermediate-and high-risk groups with poorer post-transplant outcomes,underscoring the necessity for intensified surveillance and enhanced HBV treatment regimens,particularly in recipients with pre-transplant ALD.展开更多
This study investigated the preventive effects of soybean meal peptides(SPs)and their purification peptides(GTYW)on acute alcoholic liver injury.We combined the gut microbiota,metabolites,liver inflammation,and oxidat...This study investigated the preventive effects of soybean meal peptides(SPs)and their purification peptides(GTYW)on acute alcoholic liver injury.We combined the gut microbiota,metabolites,liver inflammation,and oxidative stress indicators to explore the prevention mechanism of SPs and GTYW.Results showed that SPs,GTYW effectively improved the hepatic oxidative stress and inflammatory.Additionally,SPs and GTYW reversed the effects of alcohol on the gut microbiota,which were evident in the increased abundance of Alloprevotella,Parasutterella in the GTYW group and norank_f__Muribaculaceae in the SPs group.Nontargeted metabolomic analysis showed that SPs ameliorated metabolic disorders by regulating phenylalanine,tyrosine and tryptophan biosynthesis,while GTYW regulated metabolites throughα-linolenic acid metabolism and phenylalanine metabolism.Furthermore,significant correlations were observed between gut microbiota,metabolites and liver indicators.These findings confirmed that SPs and GTYW can prevent acute alcoholic liver injury.展开更多
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 histopath...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.展开更多
Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic ...Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ≥ 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and portopulmonary hypertension. Alcoholic cirrhotics have increased risk of developing hepatomas. Liver transplantation is the ultimate therapy for severe ALD, but generally requires 6 mo of proven abstinence for eligibility. Alcoholic cirrhotics who maintain abstinence generally have a relatively favorable prognosis after liver transplantation.展开更多
文摘BACKGROUND Various prognostic scores have been developed to predict mortality and response to steroids in alcoholic hepatitis(AH).We aimed to further validate and compare these scores,particularly pre-day 7 Lille scores,in addition to identifying reliable predictors of complications and mortality such as renal dysfunction and nutritional status.AIM To identify predictors of complications and mortality in AH,particularly focusing on demographics,renal involvement,underlying liver disease,and nutrition.METHODS This is a retrospective analysis of patients admitted to a large urban tertiary care center with AH from 2020 to 2022.Receiver operating characteristics(ROC)curve analysis was conducted to compare established prognostic scores with Lille scores from day 3 to day 7(LM3-7).Logistic regression equations were conducted to identify predictor variables.RESULTS Severe AH(SAH)as defined by Maddrey’s discriminant function≥32 was diagnosed in 150 out of 425 patients with AH.LM3-7 had 28-day mortality rates in the responder group of 7%-11%,while in the non-responder group,mortality rates were approximately 38%-42%.LM3-7 had 90-day mortality rates in the responder group of 12%to 17%,while in the non-responder group,mortality rates were 48%-53%.Furthermore,all LM3-7 scores showed comparable efficacy in predicting mortality using ROC curve analysis;Area under ROC ranged from 0.771 to 0.802 for 28-day mortality and 0.743 to 0.809 for 90-day mortality.Regarding complications and mortality in AH,significant predictors included poor nutritional status,underlying cirrhosis,and acute renal dysfunction.CONCLUSION LM3-6 is as accurate as LM7 in predicting corticosteroid efficacy for 28-day and 90-day mortality in patients with SAH.Holding glucocorticoids early during the disease course can prevent unnecessary complications.
基金Supported by Hepatology Training Grant from the Spanish Association for The Study of Liver(AEEH-Asociación Española para el Estudio del Hígado)in 2023,No.G28551570(to Quiñones-Calvo M).
文摘BACKGROUND Severe alcoholic hepatitis(SAH)carries a 90-day mortality rate approaching 50%.Management includes corticosteroids,nutritional support,and early liver transplantation in selected cases.However,the mid-term impact of available therapies remains unclear.This systematic review provides a critical evaluation of treatments for SAH,specifically focusing on survival or mortality at 90 days as an essential window that captures short-and mid-term outcomes.The 90-day window is clinically significant,as it reflects the remission of systemic inflam-mation,early liver recovery,and minimizes confounding long-term behaviors such as alcohol relapse.AIM To review the effect of different treatments for SAH on survival and mortality at 90 days.METHODS A systematic search of PubMed and EMBASE(last updated March 2025)was performed without language restrictions,focusing on studies published in the last decade.Study selection and data extraction were performed independently by at least two reviewers.Risk of bias was assessed using RoB 2.0 and Risk-of Bias in Non-Randomized Studies of Interventions tools.Due to heterogeneity in study designs and interventions,a meta-analysis was not feasible.A qualitative synthesis was conducted using narrative summaries and evidence tables.RESULTS Searches in the databases yielded 645 citations in PubMed and 1516 in EMBASE.Of these 2161 studies,618 were duplicates and therefore removed.A total of eight studies were included in qualitative synthesis.Among the included publications,six were randomized control trials(RCT)and two were retrospective cohort studies.These studies evaluated 90-day mortality or survival in SAH patients treated with corticosteroids(n=2),pentoxifylline(n=1),anakinra plus zinc(n=2),granulocyte colony-stimulating factor(n=1),amoxicillin-clavulanate(n=1),fecal microbiota transplantation(n=1)or extracorporeal liver assist device(n=1).While most studies were conducted in Western countries,two had a global scope.CONCLUSION Steroids remain the first-line therapy for SAH despite reports of them not having any 90-day survival benefit.These results highlight the need for multicenter,biomarker-guided RCTs evaluating emerging treatments to improve mid-term survival in SAH.
基金Supported by the National Research Foundation of Korea Grant Funded by the Korea Government,No.RS-2024-00440477the Korea Institute of Science and Technology Institutional Program,No.2E33111-24-042.
文摘BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver diseases.This study aims to specifically investigate the role of MLKL’s adenosine triphosphate(ATP)-binding pocket in facilitating necroptosis-independent pathways that may contribute to liver disease progression.By focusing on this mechanism,we seek to identify potential therapeutic targets that can modulate MLKL activity,offering new strategies for the prevention and treatment of liver-related pathologies.AIM To investigate the possibility of using the ATP-binding pocket-associated,necro-ptosis-independent MLKL pathway as a target for liver diseases.METHODS Cell death following necroptosis stimuli was evaluated using cell proliferation assays,flow cytometry,and electron microscopy in various cells.The human liver organoid system was used to evaluate whether the MLKL ATP pocket-binding inhibitor could attenuate inflammation.Additionally,alcoholic and non-alcoholic fatty liver diseases animal models were used to determine whether MLKL ATP pocket inhibitors could attenuate liver injury.RESULTS While an MLKL ATP pocket-binding inhibitor did not prevent necroptosis-induced cell death in RAW 264.7 cells,it did reduce the necroptosis-led expression of CXCL2,ICAM,and VCAM.Notably,MLKL ATP pocket inhibitor diminishes the expression of CXCL2,ICAM,and VCAM by inhibiting the IκB kinase and nuclear factor kappa-B pathways without inducing necroptosis-induced cell death in two-dimensional cell culture as well as the human-derived liver organoid system.Although MLKL ATP-binding inhibitor was ineffective in non-alcoholic fatty liver disease animal models,MLKL ATP-binding inhibitor attenuated hepatic inflammation in the alcoholic liver disease model.CONCLUSION MLKL ATP pocket-binding inhibitor exerted anti-inflammatory effects through the necroptosis-independent MLKL pathway in an animal model of alcoholic liver disease.
基金supported by the National Natural Science Foundation of China(82004027)the Fundamental Research Funds for the Central Universities(JUSRP11961).
文摘Objective:To investigate the protective effects of the combined concentrated liquid extract of Pueraria lobata(Willd.)Ohwi root(P.lobata,Ge Gen)and Hovenia dulcis Thunb.(H.dulcis,Zhi Ju Zi)against ethanol-induced liver damage in vitro,using a human hepatoma cell line G2(HepG2)cell model.Methods:HepG2 cells were cultured in medium containing 4%ethanol to establish a model of alcoholic liver damage.The cells were then treated with the combined extract obtained via cryogenic extraction.Biochemical assays and Western blot analyses were performed to assess the levels of oxidative stress markers,antioxidant enzymes,and inflammatory cytokines.In addition,activation of the phosphoinositide 3-kinase/protein kinase B(PI3K/AKT)pathway was examined to elucidate the mechanisms underlying the effects of the extract.Results:Treatment with the extract contributed to a significant reduction in the release of nitric oxide and reactive oxygen species in the ethanol-treated HepG2 cells;promoted the elevated expression of superoxide dismutase,catalase,and glutathione,indicating enhanced antioxidant defenses;and showed strong free radical-scavenging activity against 1,1-diphenyl-2-picrylhydrazyl radicals.In addition,by activating the PI3K/AKT pathway,treatment promoted increases in the expression of nuclear factor erythroid 2-related factor 2 and its downstream targets,subsequently inhibiting apoptosis.Moreover.inflammatory responses were mitigated,as indicated by reductions in the expression of tumor necrosis factor-alpha and interleukin-6,and we detected reduction in the levels of alanine aminotransferase and aspartate aminotransferase,thereby indicating hepatoprotective effects.Conclusion:The combined P.lobata root and H.dulcis extract was established to have notable antioxidative and anti-inflammatory properties,effectively alleviating ethanol-induced liver damage in vitro.These findings highlight the potential applicability of this extract as a candidate for treating alcoholic liver disease.
文摘BACKGROUND Focal nodular hyperplasia(FNH)-like lesions are hyperplastic formations in patients with micronodular cirrhosis and a history of alcohol abuse.Although pathologically similar to hepatocellular carcinoma(HCC)lesions,they are benign.As such,it is important to develop methods to distinguish between FNH-like lesions and HCC.AIM To evaluate diagnostically differential radiological findings between FNH-like lesions and HCC.METHODS We studied pathologically confirmed FNH-like lesions in 13 patients with alco-holic cirrhosis[10 men and 3 women;mean age:54.5±12.5(33-72)years]who were negative for hepatitis-B surface antigen and hepatitis-C virus antibody and underwent dynamic computed tomography(CT)and magnetic resonance imaging(MRI),including superparamagnetic iron oxide(SPIO)and/or gadoxetic acid-enhanced MRI.Seven patients also underwent angiography-assisted CT.RESULTS The evaluated lesion features included arterial enhancement pattern,washout appearance(low density compared with that of surrounding liver parenchyma),signal intensity on T1-weighted image(T1WI)and T2-weighted image(T2WI),central scar presence,chemical shift on in-and out-of-phase images,and uptake pattern on gadoxetic acid-enhanced MRI hepatobiliary phase and SPIO-enhanced MRI.Eleven patients had multiple small lesions(<1.5 cm).Radiological features of FNH-like lesions included hypervascularity despite small lesions,lack of“corona-like”enhancement in the late phase on CT during hepatic angiography(CTHA),high-intensity on T1WI,slightly high-or iso-intensity on T2WI,no signal decrease in out-of-phase images,and complete SPIO uptake or incomplete/partial uptake of gadoxetic acid.Pathologically,similar to HCC,FNH-like lesions showed many unpaired arteries and sinusoidal capillarization.CONCLUSION Overall,the present study showed that FNH-like lesions have unique radiological findings useful for differential diagnosis.Specifically,SPIO-and/or gadoxetic acid-enhanced MRI and CTHA features might facilitate differential diagnosis of FNH-like lesions and HCC.
基金supported by Key Research and Development Program of Hubei Province(2022BBA0072)Applied Fundamental Frontier Project of Wuhan Science and Technology Bureau(2020020601012271)。
文摘Rape bee pollen has attracted increasing interests for its excellent protective effect against chemicalinduced liver injury owing to its abundant polyphenols.This study aims to analyze the types and contents of phenolamides(seldom concerned)in rape bee pollen and their protective mechanism on alcoholic liver disease(ALD).Different from the previous finding that flavonoids are dominant polyphenols in bee pollen polyphenolic extract,our results demonstrated that there are only three flavonoids but 24 phenolamides in the as-prepared rape bee pollen phenolic extract(PPE).In addition,PPE was found to significantly improve the viability(from 54.9%to 84.1%,89.2%,and 94.0%)of alcohol-induced AML12 cells and alleviate alcoholinduced cell apoptosis(from 28.5%to 22.89%,22.0%,and 17.4%).To dissect the underlying mechanism for the protective effect of PPE against ALD,the molecular pathway was identified by RNA-Seq analysis.Transcriptome data revealed that PPE may protect against ALD by decreasing inflammation,cholesterol,and fatty acid synthesis(P<0.05).The National Institute on Alcohol Abuse and Alcoholism(NIAAA)model was used to further evaluate the hepatoprotective effect of PPE in vivo,and the results validated that PPE could alleviate liver injury and hepatic steatosis(from 22.7%to 11.5%and 10.9%)induced by alcohol.As the dominant polyphenols in PPE,phenolamides can be a class of valuable polyphenolic compounds in bee pollen with the potential to alleviate ALD.
基金supported by the National Natural Science Foundation of China(No.82160818)the Innovative Research Group Project of the National Natural Science Foundation of China(No.22JR5RA622).
文摘Alcoholic liver disease(ALD),which includes a range of diseases,ranging from alcoholic steatosis,hepatitis,and fibrosis to cirrhosis and hepatocarcinoma,is a process of epigenetic remodeling involving multiple genes and metabolic pathways.ALD is involved in various transcriptional regulatory mechanisms,including lipid metabolism disorders,inflammatory responses,autophagy,fibrogenesis,oxidative stress,fatty acid metabolism,iron metabolism,and endoplasmic reticulum stress.In the occurrence of ALD and its response to the microenvironment,various transcription factors(TFs)play important roles.Targeted therapy involving these TFs may pave a novel avenue for the treatment of ALD.Here,we summarize the molecular characteristics of TFs and their involvement in the biological and pathological processes of ALD.We further discuss the current pharmaceutical treatments targeting these TFs and their mediators.This study provides detailed and accurate regulation maps of TFs for the targeted therapy of ALD.
基金supported by Angel Nutritech Nutrition Fund(AF2021003)。
文摘Alcoholic liver disease(ALD)is one of the major global public health problems.Yeast extract(YE),a product prepared from yeast,has been proven to have antioxidant and anti-inflammatory properties.However,the potential role of YE in the prevention of ALD remains unclear.The present study aimed to investigate the protective effects of YE on ALD and explore the underlying mechanism based on gut microbiota.The result showed that YE supplementation significantly ameliorated chronic alcohol exposure-induced liver injury in mice.In addition,YE counteracted alcohol-induced gut dysbiosis,intestinal barrier dysfunction,lipopolysaccharide(LPS)leakage-induced inflammatory response in the liver.Moreover,microbiota depletion by a broad-spectrum antibiotic was sufficient to block the protective effect of YE on ALD,indicating the contribution of gut dysbiosis modulation to the hepatoprotective role of YE.Furthermore,we demonstrated the causal relationship between gut microbiota and hepatoprotective effects of YE with the fecal microbiota transplantation(FMT)experiment.Compared with the ALD-FMT mice,gut dysbiosis,intestinal barrier dysfunction,LPS/TLR4 signaling pathway activation,and liver inflammatory response were significantly improved in the YE-FMT mice.Together,our findings highlight that dietary YE protects against ALD through gut dysbiosis correction.
基金Supported by National Key Research and Development Program of China,No.2019YFE0190800.
文摘BACKGROUND Studies investigating diagnostic delays and their effects on patients with alcoholic cirrhosis.AIM To investigate the current status and associated factors influencing diagnostic delays in 401 patients with alcoholic cirrhosis.METHODS A cross-sectional analysis was conducted at a tertiary hospital in China from June 2020 to December 2023.Data were collected through telephone follow-ups and questionnaires.The Wilcoxon and Kruskal-Wallis H tests were used to compare diagnostic delays across various characteristics.Multivariate linear regression was employed to identify factors associated with diagnostic delays.RESULTS The median diagnostic delay was 5 months,with an interquartile range of 2-11 months.The proportions of patients with alcoholic cirrhosis who initially visited tertiary,secondary,and primary hospitals were 38.9%,37.91%,and 23.19%,respectively.Furthermore,the rates of patients undergoing liver computed tomography(CT)during their first visit at tertiary,secondary,and primary hospitals were 92.95%,13.82%,and 1.08%,respectively(P<0.001).Significant differences were observed in diagnostic delay-related characteristics,including residence,resident type,initial diagnosis,medical insurance,liver CT,and liver ultrasound during the first visit,age,years of education,family size,marital status,annual family income,years of drinking,daily alcohol consumption,and type of alcohol consumed(P<0.01).Furthermore,diagnostic delays were variably associated with daily alcohol consumption and other characteristics(i.e.residence,years of drinking,medical insurance,years of education,annual family income,liver CT and ultrasound during the first visit).Significant predictors of diagnostic delay identified on multivariate linear regression analysis included years of education,daily alcohol consumption,annual family income and blood ammonia levels(P<0.01).Patients with alcoholic cirrhosis experience varying degrees of diagnostic delays,necessitating interventions targeting potential contributing factors.CONCLUSION Our study indicates that patients with alcoholic cirrhosis may experience varying degrees of diagnostic delay.Interventions targeting potential factors contributing to diagnostic delay are necessary.
文摘In this article,we discuss the recently published article by Yang et al.This retrospective analysis,which was conducted at a large urban tertiary care center,focused on comparing Lille model scores at days 3 and 7 with established scoring systems and identifying critical clinical predictors,such as renal dysfunction,nutritional status,and underlying cirrhosis.Alcoholic hepatitis(AH),a severe manifestation of alcohol-related liver disease,is associated with high morbidity and mortality,necessitating accurate prognostic tools and comprehensive clinical assessments.Prognostic tools are invaluable for early risk stratification,but they must be contextualized within the multifactorial nature of AH.Acute renal dysfunction and poor nutritional status,for example,are not just complications but pivotal markers of disease severity and systemic impact.Addressing these factors requires a holistic approach that extends beyond scoring systems to include targeted interventions and comprehensive patient care.This editorial emphasizes the need for a paradigm shift in AH management,where prognostic models are complemented by a deeper understanding of patient-specific factors.Such an approach can guide clinicians in tailoring therapies and improving outcomes for this high-risk population.
文摘Severe alcoholic hepatitis remains one of hepatology’s most urgent challenges,with rapid clinical deterioration and high early mortality.This manuscript comments on and contextualizes the recent systematic review by Quiñones-Calvo et al,which redirects attention from short-term endpoints toward 90-day survival,integrating evidence from associated clinical studies.For decades,corticosteroids have been the mainstay of treatment,reducing 28-day mortality but offering limited benefit for three months.The review emphasizes that the most critical threats to recovery,late infections,renal decline,and relapse,often emerge after the first month.By synthesizing recent studies,it highlights promising interventions such as fecal microbiota transplantation(FMT),which improved 90-day survival in a small randomized trial,and granulocyte colony-stimulating factor(G-CSF),which showed a robust survival benefit in a large retrospective cohort,alongside emerging strategies like plasma exchange and targeted biologics.These findings support a shift toward a two-phase care model:Early stabilization followed by recovery consolidation.For clinicians,such a model may help guide treatment decisions,with therapies like FMT or G-CSF warranting consideration in corticosteroid non-responders,pending further validation in larger randomized controlled trials.Adoption of 90-day survival as a central metric could bridge the gap between initial rescue and sustained remission,providing a more realistic measure of therapeutic success in one of hepatology’s most unforgiving conditions.
基金National Natural Science Foundation of China(Grant No.81573969).
文摘The present study aimed to analyze the potential mechanism of action of Chaihu-Astragalus in treating alcoholic liver fibrosis using network pharmacology and molecular docking techniques.We initially screened the active ingredients and targets of Chaihu-Astragalus through the TCMSP database.Additionally,we identified disease-related targets associated with alcoholic liver fibrosis via the GeneCards database,subsequently obtaining the intersection targets of Chaihu-Astragalus for treating alcoholic liver fibrosis.Using Cytoscape software,we constructed a“drug-active ingredient-intersection target”network and evaluated the network’s major active ingredients.The intersection targets were then subjected to protein-protein interaction network analysis using the STRING database to identify possible core targets.GO functional and KEGG pathway enrichment analyses were conducted using the DAVID platform.Molecular docking verification of key active ingredients and core targets was performed using Schrödinger software and the Maestro platform.We identified 26 active ingredients and 180 potential targets(intersection targets).Key active compounds,such as quercetin,kaempferol,prickly mangosteen,isorhamnetin,and Areapillin,were highlighted.Core targets were also identified,including AKT1,TP53,JUN,TNF,and IL-6.Enrichment analyses revealed that potential targets were mainly associated with PI3K-Akt,TNF,MAPK,and other signaling pathways.Chaihu-Astragalus acted on multiple targets such as AKT1,TP53,and JUN primarily through various active ingredients like quercetin and kaempferol.Thus,it affected treating alcoholic liver fibrosis through multiple signaling pathways,such as PI3K-Akt,TNF,and MAPK.It demonstrated characteristics of being multi-component,multi-target,and multi-pathway in its approach.
基金supported by the National Natural Science Foundation of China(32430083).
文摘The development of rodent models that accurately reflect the pathogenesis of alcoholic liver disease(ALD)in humans is crucial for evaluating the nutritional intervention of food bioactive ingredients in ALD.Although various models have been employed to establish ALD models over the past few decades,most successful cases are associated with high mortality rates,operational difficulties,and incompatibility formation mechanism compared to human ALD.However,the ALD models established by oral administration that simulate human drinking behavior often fail to induce significant liver damage.Therefore,it is imperative to explore simple and effective modes of oral administration for establishing ALD models consistent with the pathophysiological process of human ALD.Herein,we summarized the pathogenesis of ALD and discussed several issues related to construct ALD models with rodents(mainly mice and rats)by oral administration,including animal selection,animal feeding,alcohol intervention,and evaluation criteria.The purpose of this review is to provide a standardized and efficient formula for ALD modeling,so as to facilitate efficacy evaluation and mechanism analysis of food bioactive ingredients in ALD.
文摘Severe alcoholic hepatitis(SAH)is associated with high short-term mortality.The SAH population exhibits extreme heterogeneity in disease severity,clinical presentation,decompensations,and outcomes.Nonetheless,improving outcomes and preventing adverse events is a major challenge when selecting an appropriate treatment for alcoholic hepatitis.Currently,steroids are the standard of care for SAH with Maddrey’s discriminant function>32 and model for end stage liver disease>20;however,they have limited usage due to ineligibility in approx-imately two-third of such patients.Approximately 25%of patients do not respond to steroids and require alternative therapies.An array of evolving therapies,such as granulocyte colony-stimulating factors,plasma exchange,fecal microbiota transplantation,antibiotics,anti-cytokine therapies,and N-acetylcysteine,showing variable success,are emerging.Hence,it is also crucial to select appro-priate therapy.The present review discusses the standard of care,the existing therapies,risk stratification for outcomes,and the selection of appropriate therapy to improve survival in SAH patients.
文摘Although mixed lineage kinase domain-like protein(MLKL)is widely recognized as a critical effector in the necroptotic signaling pathway,MLKL plays broader regulatory roles beyond programmed necroptosis.Notably,Xuan Yuan et al demonstrated that CPD4,an ATP-binding pocket inhibitor of MLKL,significantly reduces liver inflammation and improves liver function by inhibiting NF-κB signaling,suggesting its use as a potential therapeutic candidate for alcoholic liver disease.However,the pharmacokinetic properties and long-term toxicity of CPD4 require further evaluation.Moreover,a single therapeutic strategy targeting MLKL may not be sufficient.Future studies should focus on the precise regulation of MLKL and develop combination therapies to achieve dual intervention of inflammatory and cell death pathways.This paper provides an important theoretical foundation for translational research on MLKL-targeted therapy.However,its clinical translation requires overcoming existing limitations and further elucidating the regulatory network of MLKL in complex microenvironments.
文摘The aim of this project is to explore the mechanism of the treatment of alcoholic liver by means of network pharmacology and molecular docking.In this study,the chemical components of the extract of Callistephus chinensis(L.)Nees.were characterized by LC-MS/MS,identifying 6 compounds by positive and negative total ion flow maps.The target of chrysanthemum was derived from SwissTargetPrediction database,and the target related to alcoholic liver was derived from GeneCards and OMIM database.Add the target to the String database to build the protein interaction platform Microbiology software was used for GO bioprocess enrichment analysis and KEGG pathway enrichment analysis,and the target pathway network was constructed.In Discovery Studio 2016 Client software verified molecular docking,China aster flavonoids compounds and the adhesion strength of the key targets.Five potential active components were screened from the flavonoid monomer compounds of the chrysanthemum Cupressus.546 Bioprocess(BP),75 cell composition(CC)and 185·molecular function(MF)were obtained by GO enrichment analysis.KEGG enrichment analysis for each cross target involved a pathway.Network analysis showed that it was the main active component of flavonoids in the treatment of alcoholic liver,and other related signals were related to the treatment of alcoholic liver.This study showed that the flavonoids of Callistephus chinensis(L.)Nees were involved in the treatment of alcoholic liver by regulating multi-target and multi-pathway.
基金supported by the National Natural Science Foun-dation of China(92159202)the National Science and Technology Major Project of China(2017ZX10203205)+4 种基金the Fundamental Research Funds for the Central Universities(2022ZFJH003)the Major Research Plan of Key Research and Development Project of Zhejiang Province(2024C03149 and 2023C03046)the National Key Research and Development Program of China(2021YFF1200404 and 2021YFA1201200)the Zhejiang Provincial Natural Science Foundation of China(LQ24C050005 and LQ22H160052)the Medical and Health Technology Program Project of Zhejiang Province(2021434810).
文摘Alcohol consumption poses an escalating public health challenge.However,the impact of alcoholic liver disease(ALD)on post-transplant hepatitis B virus(HBV)reactivation and surgical outcomes remains inadequately characterized.Herein,we retrospectively analyzed our cohort(NCT06114251)comprising 453 patients with an HBV background.Propensity score matching(PSM)and sensitivity analyses were employed to assess the influence of ALD on surgical outcomes.Benchmark analysis compared the predictive performance of 21 models for post-transplant HBV reactivation.The Shapley additive explanation(SHAP)algorithm facilitated feature ranking and model interpretation.Patients were stratified into three subgroups based on the alcohol-modified HBV reactivation index(AMBRI).Among the cohort,113 patients(24.9%)had concurrent pre-transplant diagnoses of ALD and HBV infection,while 340(75.1%)had HBV infection alone.The presence of ALD was associated with an elevated risk of HBV reactivation and liver metastasis.PSM and sensitivity analyses revealed significantly lower five-year HBV reactivation-free survival(74.9%vs 85.4%),overall survival(OS,56.2%vs 70.5%),and tumor recurrence-free survival(RFS,47.8%vs 63.3%)in the ALD cohort.In recipients without HBV reactivation,hepatocellular carcinomas(HCCs)arising from both ALD and HBV exhibited inferior RFS(log-rank P=0.026)and OS beyond one year(landmark P=0.032)compared to HBV-related HCC alone.Benchmark analysis identified the surv.cforest model as the optimal predictor,achieving an area under the receiver operating characteristic(AUC)curve of 0.914 in internal validation and 0.884 in external validation,outperforming the published Cox model(AUC=0.78).AMBRI-based stratification delineated three distinct risk subgroups,with the intermediate-and high-risk groups exhibiting significantly worse OS and RFS than the low-risk group.In this study,stratification by AMBRI identified intermediate-and high-risk groups with poorer post-transplant outcomes,underscoring the necessity for intensified surveillance and enhanced HBV treatment regimens,particularly in recipients with pre-transplant ALD.
基金funded by the National Key R&D Program of China(2022YFD2101002)Jilin Province Science and Technology Youth Talent Support Project(QT202021)Fundamental Research Funds for the Central Universities。
文摘This study investigated the preventive effects of soybean meal peptides(SPs)and their purification peptides(GTYW)on acute alcoholic liver injury.We combined the gut microbiota,metabolites,liver inflammation,and oxidative stress indicators to explore the prevention mechanism of SPs and GTYW.Results showed that SPs,GTYW effectively improved the hepatic oxidative stress and inflammatory.Additionally,SPs and GTYW reversed the effects of alcohol on the gut microbiota,which were evident in the increased abundance of Alloprevotella,Parasutterella in the GTYW group and norank_f__Muribaculaceae in the SPs group.Nontargeted metabolomic analysis showed that SPs ameliorated metabolic disorders by regulating phenylalanine,tyrosine and tryptophan biosynthesis,while GTYW regulated metabolites throughα-linolenic acid metabolism and phenylalanine metabolism.Furthermore,significant correlations were observed between gut microbiota,metabolites and liver indicators.These findings confirmed that SPs and GTYW can prevent acute alcoholic liver injury.
基金The current project is funded by Shandong Provincial Natural Science Foundation,China(ZR2020MH370)Major Science and Technology Innovation in Shandong Province(2017CXGC1307)Ji’nan Science and Technology Project(201303055)。
文摘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.
文摘Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ≥ 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and portopulmonary hypertension. Alcoholic cirrhotics have increased risk of developing hepatomas. Liver transplantation is the ultimate therapy for severe ALD, but generally requires 6 mo of proven abstinence for eligibility. Alcoholic cirrhotics who maintain abstinence generally have a relatively favorable prognosis after liver transplantation.
