BACKGROUND Alterations in plasma and intestinal metabolites contribute to the pathogenesis and progression of alcohol-related liver cirrhosis(ALC).AIM To explore the common and different metabolites in the plasma and ...BACKGROUND Alterations in plasma and intestinal metabolites contribute to the pathogenesis and progression of alcohol-related liver cirrhosis(ALC).AIM To explore the common and different metabolites in the plasma and feces of patients with ALC and evaluate their clinical implications.METHODS According to the inclusion and exclusion criteria,27 patients with ALC and 24 healthy controls(HCs)were selected,and plasma and feces samples were collected.Liver function,blood routine,and other indicators were detected with automatic biochemical and blood routine analyzers.Liquid chromatography-mass spectrometry was used to detect the plasma and feces metabolites of the two groups and the metabolomics of plasma and feces.Also,the correlation between metabolites and clinical features was analyzed.RESULTS More than 300 common metabolites were identified in the plasma and feces of patients with ALC.Pathway analysis showed that these metabolites are enriched in bile acid and amino acid metabolic pathways.Compared to HCs,patients with ALC had a higher level of glycocholic acid(GCA)and taurocholic acid(TCA)in plasma and a lower level of deoxycholic acid(DCA)in the feces,while L-threonine,L-phenylalanine,and L-tyrosine increased simultaneously in plasma and feces.GCA,TCA,L-methionine,L-phenylalanine,and L-tyrosine in plasma were positively correlated with total bilirubin(TBil),prothrombin time(PT),and maddrey discriminant function score(MDF)and negatively correlated with cholinesterase(CHE)and albumin(ALB).The DCA in feces was negatively correlated with TBil,MDF,and PT and positively correlated with CHE and ALB.Moreover,we established a P/S BA ratio of plasma primary bile acid(GCA and TCA)to fecal secondary bile acid(DCA),which was relevant to TBil,PT,and MDF score.CONCLUSION The enrichment of GCA,TCA,L-phenylalanine,L-tyrosine,and L-methionine in the plasma of patients with ALC and the reduction of DCA in feces were related to the severity of ALC.These metabolites may be used as indicators to evaluate the progression of alcohol-related liver cirrhosis.展开更多
Alcohol consumption is one of the leading causes of the global burden of disease and results in high healthcare and economic costs.Heavy alcohol misuse leads to alcohol-related liver disease,which is responsible for a...Alcohol consumption is one of the leading causes of the global burden of disease and results in high healthcare and economic costs.Heavy alcohol misuse leads to alcohol-related liver disease,which is responsible for a significant proportion of alcohol-attributable deaths globally.Other than reducing alcohol consumption,there are currently no effective treatments for alcohol-related liver disease.Oxidative stress refers to an imbalance in the production and elimination of reactive oxygen species and antioxidants.It plays important roles in several aspects of alcohol-related liver disease pathogenesis.Here,we review how chronic alcohol use results in oxidative stress through increased metabolism via the cytochrome P4502E1 system producing reactive oxygen species,acetaldehyde and protein and DNA adducts.These trigger inflammatory signaling pathways within the liver leading to expression of pro-inflammatory mediators causing hepatocyte apoptosis and necrosis.Reactive oxygen species exposure also results in mitochondrial stress within hepatocytes causing structural and functional dysregulation of mitochondria and upregulating apoptotic signaling.There is also evidence that oxidative stress as well as the direct effect of alcohol influences epigenetic regulation.Increased global histone methylation and acetylation and specific histone acetylation inhibits antioxidant responses and promotes expression of key pro-inflammatory genes.This review highlights aspects of the role of oxidative stress in disease pathogenesis that warrant further study including mitochondrial stress and epigenetic regulation.Improved understanding of these processes may identify novel targets for therapy.展开更多
BACKGROUND Looking for undiscovered blood markers of liver fibrosis and steatosis still remains an issue worth exploring.There are still plenty of unresolved issues related to the actual role of hematological indices ...BACKGROUND Looking for undiscovered blood markers of liver fibrosis and steatosis still remains an issue worth exploring.There are still plenty of unresolved issues related to the actual role of hematological indices as potential markers of liver function.AIM To study red blood cell distribution width(RDW),RDW-to-platelet ratio(RPR)and RDW-to-lymphocyte ratio(RLR) in alcohol-related liver cirrhosis(ALC) and metabolic-associated fatty liver disease(MAFLD).METHODS The study group was composed of 302 people:142 patients with ALC and 92 with MAFLD;68 persons were included as controls.RDW,RPR and RLR were measured in each person.Indirect and direct parameters of liver fibrosis were also assessed [aspartate transaminase to alkaline transaminase ratio,aspartate transaminase to platelet ratio index(APRI),fibrosis-4(FIB-4),gamma-glutamyl transpeptidase to platelet ratio(GPR),procollagen I carboxyterminal propeptide,procollagen Ⅲ aminoterminal propeptide,transforming growth factor-α,plateletderived growth factor AB,laminin].MELD score in ALC patients and nonalcoholic fatty liver disease(NAFLD) fibrosis score together with BARD score were obtained in the MAFLD group.The achieved results were compared to controls.Then a correlation between assessed markers was done.Diagnostic value of each investigated parameter and its suggested cut-off in the research group RESULTS RDW,RPR and RLR values turned out to be significantly higher in ALC and MAFLD groups compared to controls(ALC:P<0.0001;NAFLD:P<0.05,P<0.0001 and P<0.0001,respectively).RPR correlated positively with MELD score(P<0.01) and indirect indices of liver fibrosis(FIB-4 and GPR;P<0.0001) in ALC patients;negative correlations were found between PDGF-AB and both:RDW and RPR(P<0.01 and P<0.0001,respectively).RPR correlated positively with NAFLD fibrosis score and APRI(P<0.0001) in the MAFLD group;a positive relationship was observed between RDW and FIB-4,too(P<0.05).AUC values and suggested cut-offs for RDW,RPR and RLR in ALC patients were:0.912(>14.2%),0.965(>0.075) and 0.914(>8.684),respectively.AUC values and suggested cut-offs for RDW,RPR and RLR in MAFLD patients were:0.606(>12.8%),0.724(>0.047) and 0.691(>6.25),respectively.CONCLUSION RDW with its derivatives appear to be valuable diagnostic markers in patients with ALC.They can also be associated with a deterioration of liver function in this group.展开更多
Malnutrition encompassing both macro-and micro-nutrient deficiency,remains one of the most frequent complications of alcohol-related liver disease(ArLD).Protein-energy malnutrition can cause significant complications ...Malnutrition encompassing both macro-and micro-nutrient deficiency,remains one of the most frequent complications of alcohol-related liver disease(ArLD).Protein-energy malnutrition can cause significant complications including sarcopenia,frailty and immunodepression in cirrhotic patients.Malnutrition reduces patient’s survival and negatively affects the quality of life of individuals with ArLD.Moreover,nutritional deficit increases the likelihood of hepatic decompensation in cirrhosis.Prompt recognition of at-risk individuals,early diagnosis and treatment of malnutrition remains a key component of ArLD management.In this review,we describe the pathophysiology of malnutrition in ArLD,review the screening tools available for nutritional assessment and discuss nutritional management strategies relevant to the different stages of ArLD,ranging from acute alcoholic hepatitis through to decompensated end stage liver disease.展开更多
BACKGROUND Alcohol-related liver disease(ALD) is a leading cause of liver failure and indication for liver transplantation that arises in the setting of alcohol use disorder(AUD). Previous reviews of transplantation f...BACKGROUND Alcohol-related liver disease(ALD) is a leading cause of liver failure and indication for liver transplantation that arises in the setting of alcohol use disorder(AUD). Previous reviews of transplantation for ALD are limited in scope of outcomes and type of ALD studied. A comprehensive systematic review could improve use of transplantation in ALD and improve future research. We hypothesize that while transplanting ALD may improve mortality and relapse,findings will be limited by pre-specified causes of heterogeneity-assessment and treatment of AUD, definition of ALD, spectrum of ALD studied, assessment and rates of relapse, and study quality and bias.AIM To optimize liver transplantation for ALD, understanding existing research to guide future research, we conducted a systematic review with meta-analysis.METHODS We conducted a systematic review, comparing liver transplant to no-transplant in patients with ALD, with a primary outcome of both short-and long-term mortality and relapse. We performed a comprehensive search of MEDLINE,EMBASE, Web of Science, and The Cochrane Library databases for peer-reviewed journal articles comparing use of liver transplant in ALD to no-transplant. Two reviewers independently conducted screening, full text review, and data extraction according to the PRISMA guidelines. We report the quality of the evidence according to the GRADE criteria.RESULTS We analyzed data from 10 studies. Of 1332 participants, 34.2%(456/1332) had undergone liver transplantation, while 65.8%(876/1332) had not. While random effects meta-analysis suggested transplant in comparison to no-transplant had an association of reduced mortality that did not reach statistical significance, relative risk(RR) = 0.51(0.25-1.05), but not relapse risk, RR = 0.52(0.18-1.53), significant heterogeneity limited these findings. When restricted to prospective data,transplant compared to no-transplant significantly reduced mortality, RR = 0.25(0.13-0.46, P < 0.01), and relapse, RR = 0.25(0.14-0.45, P < 0.01), with insignificant heterogeneity but persistent small-study effects. The overall quality of the evidence was Very Low. Heterogeneity analysis suggested that AUD assessment and treatment was often not reported while ALD, relapse assessment and rate,and data collection were institutionally rather than standardly defined.CONCLUSION Systematic review of liver transplantation for ALD suggests reduced mortality and relapse in heterogeneous, institution-specific populations with inherent bias.To understand efficacy of transplanting ALD, our research approach must change.展开更多
BACKGROUND The United Kingdom government introduced lockdown restrictions for the first time on 23 March 2020 due to coronavirus disease 2019(COVID-19)pandemic.These were partially lifted on 15 June and further eased ...BACKGROUND The United Kingdom government introduced lockdown restrictions for the first time on 23 March 2020 due to coronavirus disease 2019(COVID-19)pandemic.These were partially lifted on 15 June and further eased on 4 July.Changes in social behaviour,including increased alcohol consumption were described at the time.However,there were no data available to consider the impact of these changes on the number of alcohol-related disease admissions,specifically alcoholrelated acute pancreatitis(AP).This study evaluated the trend of alcohol-related AP admissions at a single centre during the initial COVID-19 lockdown.AIM To evaluate the trend in alcohol-related AP admissions at a single centre during the initial COVID-19 lockdown in the United Kingdom.METHODS All patients admitted with alcohol-related AP from March to September 2016 to 2020 were considered in this study.Patient demographics,their initial presentation with AP,any recurrent admissions,disease severity and length of stay,were evaluated using ANOVA andχ^(2)and Kruskal–Wallis tests.RESULTS One hundred and thirty-six patients were included in the study.The highest total number of AP admissions was seen in March–September 2019 and the highest single-month period was in March–May 2020.Admissions for first-time presentations of AP were highest in 2020 compared to other year groups and were significantly higher compared to previous years,for example,2016(P<0.05).Furthermore,the rate of admissions decreased by 38.89%between March–May 2020 and June–September 2020(P<0.05),coinciding with the easing of lockdown restrictions.This significant decrease was not observed in the previous year groups during those same time periods.Admissions for recurrent AP were highest in 2019.The median length of hospital stay did not differ between patients from each of the year groups.CONCLUSION An increased number of admissions for alcohol-related AP were observed during months when lockdown restrictions were enforced;a fall in figures was noted when restrictions were eased.展开更多
Alcohol-related liver disease(ALD)became an important health issue worldwide.Following chronic alcohol consumption,the development of ALD might be caused by metabolic and immunologic factors,such as reactive oxygen sp...Alcohol-related liver disease(ALD)became an important health issue worldwide.Following chronic alcohol consumption,the development of ALD might be caused by metabolic and immunologic factors,such as reactive oxygen species(ROS)and pro-inflammatory cytokines.For example,hepatic cytochrome P4502E1 enzyme increases ROS production and stimulates de novo lipogenesis after alcohol exposure.In addition,damage-and pathogen-associated molecular patterns stimulate their specific receptors in nonparenchymal cells,including Kupffer cells,hepatic stellate cells(HSCs),and lymphocytes,which result in hepatocyte death and infiltration of pro-inflammatory cells(e.g.,neutrophils and macrophages)in the liver.Moreover,our studies have suggested the novel involvement of neurologic signaling pathways(e.g.,endocannabinoid and glutamate)through the metabolic synapse between hepatocytes and HSCs in the development of alcohol-related hepatic steatosis.Additionally,agouti-related protein and beta2-adrenergic receptors aggravate hepatic steatosis.Furthermore,organ-crosstalk has emerged as a critical issue in ALD.Chronic alcohol consumption induces dysbiosis and barrier disruption in the gut,leading to endotoxin leakage into the portal circulation,or lipolysis-mediated transport of triglycerides from the adipose tissue to the liver.In summary,this review addresses multiple pathogeneses of ALD,provides novel neurologic signaling pathways,and emphasizes the importance of organ-crosstalk in the development of ALD.展开更多
Louvet et al.recently published the French Association for the Study of the Liver(AFEF)and the French Alcohol Society clinical guidelines(1).The AFEF guidelines are the first specific to the screening and care of alco...Louvet et al.recently published the French Association for the Study of the Liver(AFEF)and the French Alcohol Society clinical guidelines(1).The AFEF guidelines are the first specific to the screening and care of alcohol-related liver disease(ALD)in France.We compared these to the guidelines of American Association for the Study of Liver Diseases[AASLD,2020;(2)]and European Association for the Study of Liver[EASL,2018(3)];some noticeable differences and similarities emerge(Table 1).展开更多
Alcohol-related liver disease(ALD),which is caused by excessive alcohol consumption,is one of the most common types of liver disease and a primary cause of hepatic injury,with a disease spectrum that in-cludes steatos...Alcohol-related liver disease(ALD),which is caused by excessive alcohol consumption,is one of the most common types of liver disease and a primary cause of hepatic injury,with a disease spectrum that in-cludes steatosis,steatohepatitis,fibrosis,cirrhosis,and hepatocellular carcinoma.Various lines of evi-dence have indicated that immune cells play a significant role in the inflammatory processes of ALD.On the one hand,the liver contains various resident immune cells that have been proven to perform different functions in ALD.For example,in the progression of the disease,Kupffer cells(KCs)are activated by lipopolysaccharide-Toll-like receptor 4 signaling and release various proinflammatory cytokines.Moreover,alcohol intake has been shown to depress the function of natural killer cells.Additionally,two types of unconventional T cells(natural killer T cells and mucosal-associated invariant T cells)are involved in the development of ALD.On the other hand,alcohol and many different cytokines stimulate the recruitment and infiltration of circulating immune cells(neutrophils,T cells,macrophages,and mast cells)into the liver.The neutrophils can produce proinflammatory mediators and cause the dysfunction of anti-infection processes.Additionally,alcohol intake can change the phenotype of T cells,resulting in their increased production of interleukin-17.Aside from KCs,infiltrating macrophages have also been observed in patients with ALD,but the roles of all of these cells in the progression of the disease have shown both similarities and differences.Additionally,the activated mast cells are also associated with the development of ALD.Herein,we review the diverse roles of the various immune cells in the progression of ALD.展开更多
Hepatocellular carcinoma(HCC)is the most common primary liver malignancy,with increasing incidence worldwide.Alcohol-related cirrhosis(AC)accounts for 30%of the global incidence of HCC and HCC-related deaths.With the ...Hepatocellular carcinoma(HCC)is the most common primary liver malignancy,with increasing incidence worldwide.Alcohol-related cirrhosis(AC)accounts for 30%of the global incidence of HCC and HCC-related deaths.With the decline of hepatitis C virus(HCV)and decreasing HCV-related HCC,AC will soon become the leading cause of HCC.Excess alcohol consumption(>80 g per day for>10 years)increases the risk of HCC by 5-fold.However,only up to 35%of excessive drinkers develop cirrhosis and its associated HCC risk.Individual variation in susceptibility to HCC is known,but there is limited information to predict who among the patients is at high risk of progressing to HCC.Clinical risk factors for HCC include male gender,older age,severity of cirrhosis,obesity and presence of type 2 diabetes.In addition to ethnic variability in HCC risk,genetic variants are known to alter the risk of alcohol-related HCC.For example,single nucleotide polymorphisms in PNPLA3(rs738409,C>G)and TM6SF2(rs58542926,C>T)increase the risk of AC-related HCC,whereas HSD17B13(T>A)reduces the risk for HCC.Studies have also confirmed PNPLA3 and TM6SF2 to be independent risk factors for AC-related(but not HCV-related)HCC.Combining genetic risk factors with phenotypic/clinical risk factors has been explored for stratification of patients for HCC development.Risk allele rs378409-G in PNPLA3 when combined with phenotypic/clinical risk factors(BMI,age,sex)has enabled HCC risk stratification of AC patients into low-,intermediate-and high-risk subgroups.Similarly,a combination of the two genetic variants PNPLA3-G and TM6SF2-T has been independently associated with risk of HCC onset.Using a polygenic risk score approach of incorporating several genetic variants,prognostic performance of polygenic risk score that included PNPLA3 rs378409 and TM6SF2 rs58542926 improved HCC prediction better than with either variant alone.Incorporating new variants and risk factors has the potential to build better algorithms/models to predict onset,early diagnosis and treatments for AC-related HCC.However,clinical usefulness of these approaches is yet to be determined.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyl...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyle habits.Earlier studies have do-cumented a correlation between the occurrence and development of prevalent mental disorders and fatty liver.AIM To investigate the correlation between fatty liver and mental disorders,thus ne-cessitating the implementation of a mendelian randomization(MR)study to elu-cidate this association.METHODS Data on NAFLD and ArLD were retrieved from the genome-wide association studies catalog,while information on mental disorders,including Alzheimer's disease,schizophrenia,anxiety disorder,attention deficit hyperactivity disorder(ADHD),bipolar disorder,major depressive disorder,multiple personality dis-order,obsessive-compulsive disorder(OCD),post-traumatic stress disorder(PTSD),and schizophrenia was acquired from the psychiatric genomics consor-tium.A two-sample MR method was applied to investigate mediators in signifi-cant associations.RESULTS After excluding weak instrumental variables,a causal relationship was identified between fatty liver disease and the occurrence and development of some psychia-tric disorders.Specifically,the findings indicated that ArLD was associated with a significantly elevated risk of developing ADHD(OR:5.81,95%CI:5.59-6.03,P<0.01),bipolar disorder(OR:5.73,95%CI:5.42-6.05,P=0.03),OCD(OR:6.42,95%CI:5.60-7.36,P<0.01),and PTSD(OR:5.66,95%CI:5.33-6.01,P<0.01).Meanwhile,NAFLD significantly increased the risk of developing bipolar disorder(OR:55.08,95%CI:3.59-845.51,P<0.01),OCD(OR:61.50,95%CI:6.69-565.45,P<0.01),and PTSD(OR:52.09,95%CI:4.24-639.32,P<0.01).CONCLUSION Associations were found between genetic predisposition to fatty liver disease and an increased risk of a broad range of psychiatric disorders,namely bipolar disorder,OCD,and PTSD,highlighting the significance of preven-tive measures against psychiatric disorders in patients with fatty liver disease.展开更多
Background:Alcohol-related liver disease(ALRD)has emerged as a significant global health concern,primarily attributed to the overconsumption of alcohol.While alcoholism has the potential to impact various organs,it is...Background:Alcohol-related liver disease(ALRD)has emerged as a significant global health concern,primarily attributed to the overconsumption of alcohol.While alcoholism has the potential to impact various organs,it is the liver that is especially vulnerable.Methods:This review comprehensively examines the challenges encountered during the pre-transplant,intra-transplant,and post-transplant phases,a significant number of which are attributable to alcohol misuse.Historically,liver transplant(LT)programmes have excluded patients with alcohol-related liver disease(ARLD)due to mandatory abstinence requirements and apprehensions regarding potential graft shortages for other hepatic diseases.This review counters these concerns by highlighting the minimal usage of grafts for early liver transplantation.It strongly advocates for the incorporation of severe alcoholic hepatitis into the model for end-stage liver disease allocation,devoid of any stigmatization.The selection of ARLD individuals for LT necessitates the critical involvement of a multidisciplinary team,inclusive of addiction specialists.Results:Despite the complexities associated with LT for patients with ARLD,this review underscores its therapeutic advantages,particularly for those anticipated to experience severe adverse effects.This review accentuates the necessity of ensuring equitable access to medical interventions for all patients,irrespective of their lifestyle choices.Conclusion:The examination of genetic and epigenetic variables that play a role in the onset and advancement of ALD.The identification of potential therapy strategies is also an important area of study.The formulation of intricate eligibility rules for LT in patients with a past of alcohol abuse needs essential interactions between medical practitioners and researchers.The use of new technologies such as genomics and epigenomics could boost the accuracy of ALD diagnostic and prognostic approaches.These targeted investigations could potentially lead to major improvements in the management and treatment results of ALD.展开更多
BACKGROUND Alcoholic liver disease(ALD)remains one of the major indications for liver transplantation in the United States and continues to place a burden on the national healthcare system.There is evidence of increas...BACKGROUND Alcoholic liver disease(ALD)remains one of the major indications for liver transplantation in the United States and continues to place a burden on the national healthcare system.There is evidence of increased alcohol consumption during the coronavirus disease 2019(COVID-19)pandemic,and the effect of this on the already burdened health systems remains unknown.AIM To assess the trends for ALD admissions during the COVID-19 pandemic,and compare it to a similar pre-pandemic period.METHODS This retrospective study analyzed all admissions at a tertiary health care system,which includes four regional hospitals.ALD admissions were identified by querying a multi-hospital health system’s electronic database using ICD-10 codes.ALD admissions were compared for two one-year periods;pre-COVID-19 from April 2019 to March 2020,and during-COVID-19 from April 2020 to March 2021.Data were analyzed using a Poisson regression model and admission rates were compared using the annual quarterly average for the two time periods,with stratification by age and gender.Percent increase or decrease in admissions from the Poisson regression model were reported as incident rate ratios.RESULTS One thousand three hundred and seventy-eight admissions for ALD were included.80.7%were Caucasian,and 34.3%were female.An increase in the number of admissions for ALD during the COVID-19 pandemic was detected.Among women,a sharp rise(33%)was noted in those below the age of 50 years,and an increase of 22%in those above 50 years.Among men,an increase of 24%was seen for those below 50 years,and a 24%decrease in those above 50 years.CONCLUSION The COVID-19 pandemic has had widespread implications,and an increase in ALD admissions is just one of them.However,given that women are often prone to rapid progression of ALD,this finding has important preventive health implications.展开更多
Alcohol-related cirrhosis is a consequence of heavy and prolonged drinking. Similarly to patients with cirrhosis of other etiologies, patients with alcoholic cirrhosis develop portal hypertension and the hepatic, spla...Alcohol-related cirrhosis is a consequence of heavy and prolonged drinking. Similarly to patients with cirrhosis of other etiologies, patients with alcoholic cirrhosis develop portal hypertension and the hepatic, splanchnic and systemic hemodynamic alterations that follow. However, in alcoholic cirrhosis, some specific features can be observed. Compared to viral cirrhosis, in alcohol-related cirrhosis sinusoidal pressure is generally higher, hepatic venous pressure gradient reflects portal pressure better, the portal flow perfusing the liver is reduced despite an increase in liver weight, the prevalence of reversal portal blood flow is higher, a patent paraumbilical vein is a more common finding and signs of hyperdynamic circulations, such as an increased cardiac output and decreased systemic vascular resistance, are more pronounced. Moreover, alcohol consumption can acutely increase portal pressure and portal-collateral blood flow. Alcoholic cardiomyopathy, another pathological consequence of prolonged alcohol misuse, may contribute to the hemodynamic changes occurring in alcohol-related cirrhosis. The aim of this review was to assess the portal-hepatic changes thatoccur in alcohol-related cirrhosis, focusing on the differences observed in comparison with patients with viral cirrhosis. The knowledge of the specific characteristics of this pathological condition can be helpful in the management of portal hypertension and its complications in patients with alcohol-related cirrhosis.展开更多
Alcohol is the most commonly used and abused drug in the world, and alcohol use disorders pose a tremendousburden to healthcare systems around the world. The lifetime prevalence of alcohol abuse in the United States i...Alcohol is the most commonly used and abused drug in the world, and alcohol use disorders pose a tremendousburden to healthcare systems around the world. The lifetime prevalence of alcohol abuse in the United States is estimated to be around 18%, and the economic consequences of these disorders are staggering. Studies on hospitalized patients demonstrate that about one in four patients admitted to critical care units will have alcohol-related issues, and unhealthy alcohol consumption is responsible for numerous clinical problems encountered in intensive care unit(ICU) settings. Patients with alcohol use disorders are not only predisposed to developing withdrawal syndromes and other conditions that often require intensive care, they also experience a considerably higher rate of complications, longer ICU and hospital length of stay, greater resource utilization, and significantly increased mortality compared to similar critically ill patients who do not abuse alcohol. Specific disorders seen in the critical care setting that are impacted by alcohol abuse include delirium, pneumonia, acute respiratory distress syndrome, sepsis, gastrointestinal hemorrhage, trauma, and burn injuries. Despite the substantial burden of alcoholinduced disease in these settings, critical care providers often fail to identify individuals with alcohol use disorders, which can have significant implications for this vulnerable population and delay important clinical interventions.展开更多
An increase in the average life expectancy,paralleled by a demographic shift in the population with end-stage liver disease lies behind the rising demand for liver transplantation(LT)among the elderly.Some of the most...An increase in the average life expectancy,paralleled by a demographic shift in the population with end-stage liver disease lies behind the rising demand for liver transplantation(LT)among the elderly.Some of the most common indications for LT including hepatocellular carcinoma,alcohol-related liver disease,chronic hepatitis C and non-alcoholic fatty liver disease tend to affect older patients.Transplant professionals are faced with an increasing demand for LT among elderly patients in an age of organ shortage and it is important that risk and benefits are carefully weighed in order to achieve the optimum use of precious liver grafts.展开更多
BACKGROUND A progressive reduction in the secretion of pancreatic enzymes in patients with chronic pancreatitis(CP)results in malabsorption and ultimate malnutrition.However,the pathogenesis of malnutrition is multifa...BACKGROUND A progressive reduction in the secretion of pancreatic enzymes in patients with chronic pancreatitis(CP)results in malabsorption and ultimate malnutrition.However,the pathogenesis of malnutrition is multifactorial and other factors such as chronic inflammation,alcohol excess and poor dietary intake all contribute.Patients may restrict their dietary intake due to poor appetite or to avoid gastrointestinal symptoms and abdominal pain.Whilst up to half of patients with chronic pancreatitis are reportedly malnourished,the dietary intake of patients with CP is relatively understudied and has not been systematically reviewed to date.AIM To perform a systematic review and meta-analysis of the dietary intakes of patients with CP compared to healthy controls,and to compare the dietary intake of patients with alcohol-related CP and non-alcohol-related CP.METHODS A systematic literature search was performed using EMBASE,MEDLINE,and Cochrane review on studies published between 1946 and August 30th,2019.Adult subjects with a diagnosis of CP who had undergone dietary assessment were included in the systematic review(qualitative analysis).Studies on patients with other pancreatic diseases or who had undergone pancreatic surgery were not included.Studies comparing the dietary intake of patients with CP to that of healthy controls were included in the meta-analysis(quantitative analysis).Metaanalysis was performed using Review Manager 5.3.Newcastle Ottawa Scale(NOS)was used to assess quality of studies.RESULTS Of 6715 studies retrieved in the search,23 were eligible for qualitative analysis while 12 were eligible for quantitative analysis.In the meta-analysis,the total energy(calorie)intake of patients with CP was similar to that of healthy controls[mean difference(MD):171.3;95%confidence interval(CI):-226.01,568.5;P=0.4],however patients with CP consumed significantly fewer non-alcohol calories than controls[MD:-694.1;95%CI:-1256.1,(-132.1);P=0.02].CP patients consumed more protein,but carbohydrate and fat intakes did not differ significantly.Those with alcohol-related CP consumed more mean(standard deviation)calories than CP patients with a non-alcohol aetiology[2642(1090)kcal and 1372(394)kcal,respectively,P=0.046],as well as more protein,fat,but not carbohydrate.CONCLUSION Although patients with CP had similar calorie intake to controls,studies that analysed the contribution of alcohol to energy intake showed that patients with CP consumed fewer non-alcohol calories than healthy controls.A high calorie intake,made up to a large degree by alcohol,may in part contribute to poor nutritional status in CP.展开更多
Severe alcoholic hepatitis(AH)is a distinct entity in the spectrum of alcoholrelated liver disease,with limited treatment options and high mortality.Supportive medical care with corticosteroids in selected patients is...Severe alcoholic hepatitis(AH)is a distinct entity in the spectrum of alcoholrelated liver disease,with limited treatment options and high mortality.Supportive medical care with corticosteroids in selected patients is the only currently available treatment option,often with poor outcomes.Based on the insights into the pathogenetic mechanisms of AH,which are mostly obtained from animal studies,several new treatment options are being explored.Studies have implicated impaired and deranged liver regeneration processes as one of the culprit mechanisms and a potential therapeutic target.Acknowledging evidence for the beneficial effects of granulocyte colony-stimulating factor(G-CSF)on liver regeneration and immunomodulation in animal models,several human studies investigated its role in the treatment of advanced alcohol-related liver disease and AH.Contrary to the previously published studies suggesting benefits of G-CSF in the outcomes of patients with severe AH,these effects were not confirmed by a recently published multicenter randomized trial,suggesting that other options should rather be pursued.Stem cell transplantation represents another option for improving liver regeneration,but evidence for its efficacy in patients with severe AH and advanced alcohol-related liver disease is still very scarce and unconvincing,with established lack of efficacy in patients with compensated cirrhosis.In this review,we summarize the current knowledge on the pathogenesis and experimental therapies targeting liver regeneration.The lack of high-quality studies and evidence is a major obstacle in further treatment development.New insights into the pathogenesis of not only liver injury,but also liver regeneration processes are mandatory for the development of new treatment options.A reliable experimental model of the pathogenesis of AH and processes involved in liver recovery is still missing,and data obtained from animal studies are essential for future research.展开更多
Autophagy is a highly conserved process in which cytosolic contents are degraded by the lysosome,which plays an important role in energy and nutrient balance,and protein or organelle quality control.The liver is the m...Autophagy is a highly conserved process in which cytosolic contents are degraded by the lysosome,which plays an important role in energy and nutrient balance,and protein or organelle quality control.The liver is the most important organ for metabolism.Studies to date have revealed a significant role of autophagy in the maintenance of liver homeostasis under basal and stressed conditions,and the impairment of autophagy has been closely linked to various liver diseases.Therefore,a comprehensive understanding of the roles of autophagy in liver diseases may help in the development of therapeutic strategies via targeting autophagy.In this review,we will summarize the latest understanding of the molecular mechanisms of autophagy and systematically discuss its implications in various liver diseases,including alcohol-related liver disease,non-alcoholic fatty liver disease,viral hepatitis,hepatocellular carcinoma,and acetaminophen-induced liver injury.展开更多
Alcohol-related liver disease(ALD)encompasses a spectrum of diseases caused by excessive alcohol consumption.ALD includes hepatic steatosis,steatohepatitis,variable degrees of fibrosis,cirrhosis,and alcohol-associated...Alcohol-related liver disease(ALD)encompasses a spectrum of diseases caused by excessive alcohol consumption.ALD includes hepatic steatosis,steatohepatitis,variable degrees of fibrosis,cirrhosis,and alcohol-associated hepatitis(AH),the latter being the most severe acute form of the disease.Severe AH is associated with high mortality(reaching up to 30%e50%)at 90 days.The cornerstone of ALD,and particularly AH,treatment continues to be abstinence,accompanied by support measures such as nutritional supplementation and management of alcohol withdrawal syndrome(AWS).In severe AH with model for end-stage liver disease(MELD)score21,corticosteroids can be used,especially MELD score between 25 and 39,where the highest benefit is achieved.Other key aspects of treatment include the early identification of infections and their associated management and the proper identification of potential candidates for liver transplantation.The development of new therapies based on the pathophysiology and mechanisms of liver injury are underway.This includes the modulation and management of the innate immune response,gut dysbiosis,bacterial translocation,and bacteria-derived products from the intestine.These hold promise for the future of AH treatment.展开更多
基金Supported by National Key R&D Program of China,No.21YFC2301801Capital's Funds for Health Improvement and Research of China,No.2020-1-2171.
文摘BACKGROUND Alterations in plasma and intestinal metabolites contribute to the pathogenesis and progression of alcohol-related liver cirrhosis(ALC).AIM To explore the common and different metabolites in the plasma and feces of patients with ALC and evaluate their clinical implications.METHODS According to the inclusion and exclusion criteria,27 patients with ALC and 24 healthy controls(HCs)were selected,and plasma and feces samples were collected.Liver function,blood routine,and other indicators were detected with automatic biochemical and blood routine analyzers.Liquid chromatography-mass spectrometry was used to detect the plasma and feces metabolites of the two groups and the metabolomics of plasma and feces.Also,the correlation between metabolites and clinical features was analyzed.RESULTS More than 300 common metabolites were identified in the plasma and feces of patients with ALC.Pathway analysis showed that these metabolites are enriched in bile acid and amino acid metabolic pathways.Compared to HCs,patients with ALC had a higher level of glycocholic acid(GCA)and taurocholic acid(TCA)in plasma and a lower level of deoxycholic acid(DCA)in the feces,while L-threonine,L-phenylalanine,and L-tyrosine increased simultaneously in plasma and feces.GCA,TCA,L-methionine,L-phenylalanine,and L-tyrosine in plasma were positively correlated with total bilirubin(TBil),prothrombin time(PT),and maddrey discriminant function score(MDF)and negatively correlated with cholinesterase(CHE)and albumin(ALB).The DCA in feces was negatively correlated with TBil,MDF,and PT and positively correlated with CHE and ALB.Moreover,we established a P/S BA ratio of plasma primary bile acid(GCA and TCA)to fecal secondary bile acid(DCA),which was relevant to TBil,PT,and MDF score.CONCLUSION The enrichment of GCA,TCA,L-phenylalanine,L-tyrosine,and L-methionine in the plasma of patients with ALC and the reduction of DCA in feces were related to the severity of ALC.These metabolites may be used as indicators to evaluate the progression of alcohol-related liver cirrhosis.
文摘Alcohol consumption is one of the leading causes of the global burden of disease and results in high healthcare and economic costs.Heavy alcohol misuse leads to alcohol-related liver disease,which is responsible for a significant proportion of alcohol-attributable deaths globally.Other than reducing alcohol consumption,there are currently no effective treatments for alcohol-related liver disease.Oxidative stress refers to an imbalance in the production and elimination of reactive oxygen species and antioxidants.It plays important roles in several aspects of alcohol-related liver disease pathogenesis.Here,we review how chronic alcohol use results in oxidative stress through increased metabolism via the cytochrome P4502E1 system producing reactive oxygen species,acetaldehyde and protein and DNA adducts.These trigger inflammatory signaling pathways within the liver leading to expression of pro-inflammatory mediators causing hepatocyte apoptosis and necrosis.Reactive oxygen species exposure also results in mitochondrial stress within hepatocytes causing structural and functional dysregulation of mitochondria and upregulating apoptotic signaling.There is also evidence that oxidative stress as well as the direct effect of alcohol influences epigenetic regulation.Increased global histone methylation and acetylation and specific histone acetylation inhibits antioxidant responses and promotes expression of key pro-inflammatory genes.This review highlights aspects of the role of oxidative stress in disease pathogenesis that warrant further study including mitochondrial stress and epigenetic regulation.Improved understanding of these processes may identify novel targets for therapy.
基金The survey was accepted by the local ethics committee of the Medical University of Lublin(No.KE-0254/86/2016).
文摘BACKGROUND Looking for undiscovered blood markers of liver fibrosis and steatosis still remains an issue worth exploring.There are still plenty of unresolved issues related to the actual role of hematological indices as potential markers of liver function.AIM To study red blood cell distribution width(RDW),RDW-to-platelet ratio(RPR)and RDW-to-lymphocyte ratio(RLR) in alcohol-related liver cirrhosis(ALC) and metabolic-associated fatty liver disease(MAFLD).METHODS The study group was composed of 302 people:142 patients with ALC and 92 with MAFLD;68 persons were included as controls.RDW,RPR and RLR were measured in each person.Indirect and direct parameters of liver fibrosis were also assessed [aspartate transaminase to alkaline transaminase ratio,aspartate transaminase to platelet ratio index(APRI),fibrosis-4(FIB-4),gamma-glutamyl transpeptidase to platelet ratio(GPR),procollagen I carboxyterminal propeptide,procollagen Ⅲ aminoterminal propeptide,transforming growth factor-α,plateletderived growth factor AB,laminin].MELD score in ALC patients and nonalcoholic fatty liver disease(NAFLD) fibrosis score together with BARD score were obtained in the MAFLD group.The achieved results were compared to controls.Then a correlation between assessed markers was done.Diagnostic value of each investigated parameter and its suggested cut-off in the research group RESULTS RDW,RPR and RLR values turned out to be significantly higher in ALC and MAFLD groups compared to controls(ALC:P<0.0001;NAFLD:P<0.05,P<0.0001 and P<0.0001,respectively).RPR correlated positively with MELD score(P<0.01) and indirect indices of liver fibrosis(FIB-4 and GPR;P<0.0001) in ALC patients;negative correlations were found between PDGF-AB and both:RDW and RPR(P<0.01 and P<0.0001,respectively).RPR correlated positively with NAFLD fibrosis score and APRI(P<0.0001) in the MAFLD group;a positive relationship was observed between RDW and FIB-4,too(P<0.05).AUC values and suggested cut-offs for RDW,RPR and RLR in ALC patients were:0.912(>14.2%),0.965(>0.075) and 0.914(>8.684),respectively.AUC values and suggested cut-offs for RDW,RPR and RLR in MAFLD patients were:0.606(>12.8%),0.724(>0.047) and 0.691(>6.25),respectively.CONCLUSION RDW with its derivatives appear to be valuable diagnostic markers in patients with ALC.They can also be associated with a deterioration of liver function in this group.
文摘Malnutrition encompassing both macro-and micro-nutrient deficiency,remains one of the most frequent complications of alcohol-related liver disease(ArLD).Protein-energy malnutrition can cause significant complications including sarcopenia,frailty and immunodepression in cirrhotic patients.Malnutrition reduces patient’s survival and negatively affects the quality of life of individuals with ArLD.Moreover,nutritional deficit increases the likelihood of hepatic decompensation in cirrhosis.Prompt recognition of at-risk individuals,early diagnosis and treatment of malnutrition remains a key component of ArLD management.In this review,we describe the pathophysiology of malnutrition in ArLD,review the screening tools available for nutritional assessment and discuss nutritional management strategies relevant to the different stages of ArLD,ranging from acute alcoholic hepatitis through to decompensated end stage liver disease.
基金Supported by the Agency for Healthcare Research and Quality,No.T32HS 000066-24 from
文摘BACKGROUND Alcohol-related liver disease(ALD) is a leading cause of liver failure and indication for liver transplantation that arises in the setting of alcohol use disorder(AUD). Previous reviews of transplantation for ALD are limited in scope of outcomes and type of ALD studied. A comprehensive systematic review could improve use of transplantation in ALD and improve future research. We hypothesize that while transplanting ALD may improve mortality and relapse,findings will be limited by pre-specified causes of heterogeneity-assessment and treatment of AUD, definition of ALD, spectrum of ALD studied, assessment and rates of relapse, and study quality and bias.AIM To optimize liver transplantation for ALD, understanding existing research to guide future research, we conducted a systematic review with meta-analysis.METHODS We conducted a systematic review, comparing liver transplant to no-transplant in patients with ALD, with a primary outcome of both short-and long-term mortality and relapse. We performed a comprehensive search of MEDLINE,EMBASE, Web of Science, and The Cochrane Library databases for peer-reviewed journal articles comparing use of liver transplant in ALD to no-transplant. Two reviewers independently conducted screening, full text review, and data extraction according to the PRISMA guidelines. We report the quality of the evidence according to the GRADE criteria.RESULTS We analyzed data from 10 studies. Of 1332 participants, 34.2%(456/1332) had undergone liver transplantation, while 65.8%(876/1332) had not. While random effects meta-analysis suggested transplant in comparison to no-transplant had an association of reduced mortality that did not reach statistical significance, relative risk(RR) = 0.51(0.25-1.05), but not relapse risk, RR = 0.52(0.18-1.53), significant heterogeneity limited these findings. When restricted to prospective data,transplant compared to no-transplant significantly reduced mortality, RR = 0.25(0.13-0.46, P < 0.01), and relapse, RR = 0.25(0.14-0.45, P < 0.01), with insignificant heterogeneity but persistent small-study effects. The overall quality of the evidence was Very Low. Heterogeneity analysis suggested that AUD assessment and treatment was often not reported while ALD, relapse assessment and rate,and data collection were institutionally rather than standardly defined.CONCLUSION Systematic review of liver transplantation for ALD suggests reduced mortality and relapse in heterogeneous, institution-specific populations with inherent bias.To understand efficacy of transplanting ALD, our research approach must change.
文摘BACKGROUND The United Kingdom government introduced lockdown restrictions for the first time on 23 March 2020 due to coronavirus disease 2019(COVID-19)pandemic.These were partially lifted on 15 June and further eased on 4 July.Changes in social behaviour,including increased alcohol consumption were described at the time.However,there were no data available to consider the impact of these changes on the number of alcohol-related disease admissions,specifically alcoholrelated acute pancreatitis(AP).This study evaluated the trend of alcohol-related AP admissions at a single centre during the initial COVID-19 lockdown.AIM To evaluate the trend in alcohol-related AP admissions at a single centre during the initial COVID-19 lockdown in the United Kingdom.METHODS All patients admitted with alcohol-related AP from March to September 2016 to 2020 were considered in this study.Patient demographics,their initial presentation with AP,any recurrent admissions,disease severity and length of stay,were evaluated using ANOVA andχ^(2)and Kruskal–Wallis tests.RESULTS One hundred and thirty-six patients were included in the study.The highest total number of AP admissions was seen in March–September 2019 and the highest single-month period was in March–May 2020.Admissions for first-time presentations of AP were highest in 2020 compared to other year groups and were significantly higher compared to previous years,for example,2016(P<0.05).Furthermore,the rate of admissions decreased by 38.89%between March–May 2020 and June–September 2020(P<0.05),coinciding with the easing of lockdown restrictions.This significant decrease was not observed in the previous year groups during those same time periods.Admissions for recurrent AP were highest in 2019.The median length of hospital stay did not differ between patients from each of the year groups.CONCLUSION An increased number of admissions for alcohol-related AP were observed during months when lockdown restrictions were enforced;a fall in figures was noted when restrictions were eased.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Ministry of Science and ICT,Korean goverment(2021R1A2C3004589,2014M3A9D5A01073556).
文摘Alcohol-related liver disease(ALD)became an important health issue worldwide.Following chronic alcohol consumption,the development of ALD might be caused by metabolic and immunologic factors,such as reactive oxygen species(ROS)and pro-inflammatory cytokines.For example,hepatic cytochrome P4502E1 enzyme increases ROS production and stimulates de novo lipogenesis after alcohol exposure.In addition,damage-and pathogen-associated molecular patterns stimulate their specific receptors in nonparenchymal cells,including Kupffer cells,hepatic stellate cells(HSCs),and lymphocytes,which result in hepatocyte death and infiltration of pro-inflammatory cells(e.g.,neutrophils and macrophages)in the liver.Moreover,our studies have suggested the novel involvement of neurologic signaling pathways(e.g.,endocannabinoid and glutamate)through the metabolic synapse between hepatocytes and HSCs in the development of alcohol-related hepatic steatosis.Additionally,agouti-related protein and beta2-adrenergic receptors aggravate hepatic steatosis.Furthermore,organ-crosstalk has emerged as a critical issue in ALD.Chronic alcohol consumption induces dysbiosis and barrier disruption in the gut,leading to endotoxin leakage into the portal circulation,or lipolysis-mediated transport of triglycerides from the adipose tissue to the liver.In summary,this review addresses multiple pathogeneses of ALD,provides novel neurologic signaling pathways,and emphasizes the importance of organ-crosstalk in the development of ALD.
基金This study was supported,in part,by grants from NIH(Nos.R01 AA021978 and P30 DK120531).
文摘Louvet et al.recently published the French Association for the Study of the Liver(AFEF)and the French Alcohol Society clinical guidelines(1).The AFEF guidelines are the first specific to the screening and care of alcohol-related liver disease(ALD)in France.We compared these to the guidelines of American Association for the Study of Liver Diseases[AASLD,2020;(2)]and European Association for the Study of Liver[EASL,2018(3)];some noticeable differences and similarities emerge(Table 1).
基金This work was supported by the National Natural Science Foundation of China(81900554)the Major Program for Sup-porting Outstanding Talents in Colleges of Ministry of Human Re-sources and Social Security of the People's Republic of Anhui(gxyqZD2020013).
文摘Alcohol-related liver disease(ALD),which is caused by excessive alcohol consumption,is one of the most common types of liver disease and a primary cause of hepatic injury,with a disease spectrum that in-cludes steatosis,steatohepatitis,fibrosis,cirrhosis,and hepatocellular carcinoma.Various lines of evi-dence have indicated that immune cells play a significant role in the inflammatory processes of ALD.On the one hand,the liver contains various resident immune cells that have been proven to perform different functions in ALD.For example,in the progression of the disease,Kupffer cells(KCs)are activated by lipopolysaccharide-Toll-like receptor 4 signaling and release various proinflammatory cytokines.Moreover,alcohol intake has been shown to depress the function of natural killer cells.Additionally,two types of unconventional T cells(natural killer T cells and mucosal-associated invariant T cells)are involved in the development of ALD.On the other hand,alcohol and many different cytokines stimulate the recruitment and infiltration of circulating immune cells(neutrophils,T cells,macrophages,and mast cells)into the liver.The neutrophils can produce proinflammatory mediators and cause the dysfunction of anti-infection processes.Additionally,alcohol intake can change the phenotype of T cells,resulting in their increased production of interleukin-17.Aside from KCs,infiltrating macrophages have also been observed in patients with ALD,but the roles of all of these cells in the progression of the disease have shown both similarities and differences.Additionally,the activated mast cells are also associated with the development of ALD.Herein,we review the diverse roles of the various immune cells in the progression of ALD.
文摘Hepatocellular carcinoma(HCC)is the most common primary liver malignancy,with increasing incidence worldwide.Alcohol-related cirrhosis(AC)accounts for 30%of the global incidence of HCC and HCC-related deaths.With the decline of hepatitis C virus(HCV)and decreasing HCV-related HCC,AC will soon become the leading cause of HCC.Excess alcohol consumption(>80 g per day for>10 years)increases the risk of HCC by 5-fold.However,only up to 35%of excessive drinkers develop cirrhosis and its associated HCC risk.Individual variation in susceptibility to HCC is known,but there is limited information to predict who among the patients is at high risk of progressing to HCC.Clinical risk factors for HCC include male gender,older age,severity of cirrhosis,obesity and presence of type 2 diabetes.In addition to ethnic variability in HCC risk,genetic variants are known to alter the risk of alcohol-related HCC.For example,single nucleotide polymorphisms in PNPLA3(rs738409,C>G)and TM6SF2(rs58542926,C>T)increase the risk of AC-related HCC,whereas HSD17B13(T>A)reduces the risk for HCC.Studies have also confirmed PNPLA3 and TM6SF2 to be independent risk factors for AC-related(but not HCV-related)HCC.Combining genetic risk factors with phenotypic/clinical risk factors has been explored for stratification of patients for HCC development.Risk allele rs378409-G in PNPLA3 when combined with phenotypic/clinical risk factors(BMI,age,sex)has enabled HCC risk stratification of AC patients into low-,intermediate-and high-risk subgroups.Similarly,a combination of the two genetic variants PNPLA3-G and TM6SF2-T has been independently associated with risk of HCC onset.Using a polygenic risk score approach of incorporating several genetic variants,prognostic performance of polygenic risk score that included PNPLA3 rs378409 and TM6SF2 rs58542926 improved HCC prediction better than with either variant alone.Incorporating new variants and risk factors has the potential to build better algorithms/models to predict onset,early diagnosis and treatments for AC-related HCC.However,clinical usefulness of these approaches is yet to be determined.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyle habits.Earlier studies have do-cumented a correlation between the occurrence and development of prevalent mental disorders and fatty liver.AIM To investigate the correlation between fatty liver and mental disorders,thus ne-cessitating the implementation of a mendelian randomization(MR)study to elu-cidate this association.METHODS Data on NAFLD and ArLD were retrieved from the genome-wide association studies catalog,while information on mental disorders,including Alzheimer's disease,schizophrenia,anxiety disorder,attention deficit hyperactivity disorder(ADHD),bipolar disorder,major depressive disorder,multiple personality dis-order,obsessive-compulsive disorder(OCD),post-traumatic stress disorder(PTSD),and schizophrenia was acquired from the psychiatric genomics consor-tium.A two-sample MR method was applied to investigate mediators in signifi-cant associations.RESULTS After excluding weak instrumental variables,a causal relationship was identified between fatty liver disease and the occurrence and development of some psychia-tric disorders.Specifically,the findings indicated that ArLD was associated with a significantly elevated risk of developing ADHD(OR:5.81,95%CI:5.59-6.03,P<0.01),bipolar disorder(OR:5.73,95%CI:5.42-6.05,P=0.03),OCD(OR:6.42,95%CI:5.60-7.36,P<0.01),and PTSD(OR:5.66,95%CI:5.33-6.01,P<0.01).Meanwhile,NAFLD significantly increased the risk of developing bipolar disorder(OR:55.08,95%CI:3.59-845.51,P<0.01),OCD(OR:61.50,95%CI:6.69-565.45,P<0.01),and PTSD(OR:52.09,95%CI:4.24-639.32,P<0.01).CONCLUSION Associations were found between genetic predisposition to fatty liver disease and an increased risk of a broad range of psychiatric disorders,namely bipolar disorder,OCD,and PTSD,highlighting the significance of preven-tive measures against psychiatric disorders in patients with fatty liver disease.
文摘Background:Alcohol-related liver disease(ALRD)has emerged as a significant global health concern,primarily attributed to the overconsumption of alcohol.While alcoholism has the potential to impact various organs,it is the liver that is especially vulnerable.Methods:This review comprehensively examines the challenges encountered during the pre-transplant,intra-transplant,and post-transplant phases,a significant number of which are attributable to alcohol misuse.Historically,liver transplant(LT)programmes have excluded patients with alcohol-related liver disease(ARLD)due to mandatory abstinence requirements and apprehensions regarding potential graft shortages for other hepatic diseases.This review counters these concerns by highlighting the minimal usage of grafts for early liver transplantation.It strongly advocates for the incorporation of severe alcoholic hepatitis into the model for end-stage liver disease allocation,devoid of any stigmatization.The selection of ARLD individuals for LT necessitates the critical involvement of a multidisciplinary team,inclusive of addiction specialists.Results:Despite the complexities associated with LT for patients with ARLD,this review underscores its therapeutic advantages,particularly for those anticipated to experience severe adverse effects.This review accentuates the necessity of ensuring equitable access to medical interventions for all patients,irrespective of their lifestyle choices.Conclusion:The examination of genetic and epigenetic variables that play a role in the onset and advancement of ALD.The identification of potential therapy strategies is also an important area of study.The formulation of intricate eligibility rules for LT in patients with a past of alcohol abuse needs essential interactions between medical practitioners and researchers.The use of new technologies such as genomics and epigenomics could boost the accuracy of ALD diagnostic and prognostic approaches.These targeted investigations could potentially lead to major improvements in the management and treatment results of ALD.
文摘BACKGROUND Alcoholic liver disease(ALD)remains one of the major indications for liver transplantation in the United States and continues to place a burden on the national healthcare system.There is evidence of increased alcohol consumption during the coronavirus disease 2019(COVID-19)pandemic,and the effect of this on the already burdened health systems remains unknown.AIM To assess the trends for ALD admissions during the COVID-19 pandemic,and compare it to a similar pre-pandemic period.METHODS This retrospective study analyzed all admissions at a tertiary health care system,which includes four regional hospitals.ALD admissions were identified by querying a multi-hospital health system’s electronic database using ICD-10 codes.ALD admissions were compared for two one-year periods;pre-COVID-19 from April 2019 to March 2020,and during-COVID-19 from April 2020 to March 2021.Data were analyzed using a Poisson regression model and admission rates were compared using the annual quarterly average for the two time periods,with stratification by age and gender.Percent increase or decrease in admissions from the Poisson regression model were reported as incident rate ratios.RESULTS One thousand three hundred and seventy-eight admissions for ALD were included.80.7%were Caucasian,and 34.3%were female.An increase in the number of admissions for ALD during the COVID-19 pandemic was detected.Among women,a sharp rise(33%)was noted in those below the age of 50 years,and an increase of 22%in those above 50 years.Among men,an increase of 24%was seen for those below 50 years,and a 24%decrease in those above 50 years.CONCLUSION The COVID-19 pandemic has had widespread implications,and an increase in ALD admissions is just one of them.However,given that women are often prone to rapid progression of ALD,this finding has important preventive health implications.
文摘Alcohol-related cirrhosis is a consequence of heavy and prolonged drinking. Similarly to patients with cirrhosis of other etiologies, patients with alcoholic cirrhosis develop portal hypertension and the hepatic, splanchnic and systemic hemodynamic alterations that follow. However, in alcoholic cirrhosis, some specific features can be observed. Compared to viral cirrhosis, in alcohol-related cirrhosis sinusoidal pressure is generally higher, hepatic venous pressure gradient reflects portal pressure better, the portal flow perfusing the liver is reduced despite an increase in liver weight, the prevalence of reversal portal blood flow is higher, a patent paraumbilical vein is a more common finding and signs of hyperdynamic circulations, such as an increased cardiac output and decreased systemic vascular resistance, are more pronounced. Moreover, alcohol consumption can acutely increase portal pressure and portal-collateral blood flow. Alcoholic cardiomyopathy, another pathological consequence of prolonged alcohol misuse, may contribute to the hemodynamic changes occurring in alcohol-related cirrhosis. The aim of this review was to assess the portal-hepatic changes thatoccur in alcohol-related cirrhosis, focusing on the differences observed in comparison with patients with viral cirrhosis. The knowledge of the specific characteristics of this pathological condition can be helpful in the management of portal hypertension and its complications in patients with alcohol-related cirrhosis.
基金Ashish J Mehta is supported by a Career Development Award(1IK2CX000643)from the Department of Veterans Affairs(Clinical Science Research and Development)
文摘Alcohol is the most commonly used and abused drug in the world, and alcohol use disorders pose a tremendousburden to healthcare systems around the world. The lifetime prevalence of alcohol abuse in the United States is estimated to be around 18%, and the economic consequences of these disorders are staggering. Studies on hospitalized patients demonstrate that about one in four patients admitted to critical care units will have alcohol-related issues, and unhealthy alcohol consumption is responsible for numerous clinical problems encountered in intensive care unit(ICU) settings. Patients with alcohol use disorders are not only predisposed to developing withdrawal syndromes and other conditions that often require intensive care, they also experience a considerably higher rate of complications, longer ICU and hospital length of stay, greater resource utilization, and significantly increased mortality compared to similar critically ill patients who do not abuse alcohol. Specific disorders seen in the critical care setting that are impacted by alcohol abuse include delirium, pneumonia, acute respiratory distress syndrome, sepsis, gastrointestinal hemorrhage, trauma, and burn injuries. Despite the substantial burden of alcoholinduced disease in these settings, critical care providers often fail to identify individuals with alcohol use disorders, which can have significant implications for this vulnerable population and delay important clinical interventions.
文摘An increase in the average life expectancy,paralleled by a demographic shift in the population with end-stage liver disease lies behind the rising demand for liver transplantation(LT)among the elderly.Some of the most common indications for LT including hepatocellular carcinoma,alcohol-related liver disease,chronic hepatitis C and non-alcoholic fatty liver disease tend to affect older patients.Transplant professionals are faced with an increasing demand for LT among elderly patients in an age of organ shortage and it is important that risk and benefits are carefully weighed in order to achieve the optimum use of precious liver grafts.
基金The Meath Foundation of Tallaght University Hospital,No.117/2020.
文摘BACKGROUND A progressive reduction in the secretion of pancreatic enzymes in patients with chronic pancreatitis(CP)results in malabsorption and ultimate malnutrition.However,the pathogenesis of malnutrition is multifactorial and other factors such as chronic inflammation,alcohol excess and poor dietary intake all contribute.Patients may restrict their dietary intake due to poor appetite or to avoid gastrointestinal symptoms and abdominal pain.Whilst up to half of patients with chronic pancreatitis are reportedly malnourished,the dietary intake of patients with CP is relatively understudied and has not been systematically reviewed to date.AIM To perform a systematic review and meta-analysis of the dietary intakes of patients with CP compared to healthy controls,and to compare the dietary intake of patients with alcohol-related CP and non-alcohol-related CP.METHODS A systematic literature search was performed using EMBASE,MEDLINE,and Cochrane review on studies published between 1946 and August 30th,2019.Adult subjects with a diagnosis of CP who had undergone dietary assessment were included in the systematic review(qualitative analysis).Studies on patients with other pancreatic diseases or who had undergone pancreatic surgery were not included.Studies comparing the dietary intake of patients with CP to that of healthy controls were included in the meta-analysis(quantitative analysis).Metaanalysis was performed using Review Manager 5.3.Newcastle Ottawa Scale(NOS)was used to assess quality of studies.RESULTS Of 6715 studies retrieved in the search,23 were eligible for qualitative analysis while 12 were eligible for quantitative analysis.In the meta-analysis,the total energy(calorie)intake of patients with CP was similar to that of healthy controls[mean difference(MD):171.3;95%confidence interval(CI):-226.01,568.5;P=0.4],however patients with CP consumed significantly fewer non-alcohol calories than controls[MD:-694.1;95%CI:-1256.1,(-132.1);P=0.02].CP patients consumed more protein,but carbohydrate and fat intakes did not differ significantly.Those with alcohol-related CP consumed more mean(standard deviation)calories than CP patients with a non-alcohol aetiology[2642(1090)kcal and 1372(394)kcal,respectively,P=0.046],as well as more protein,fat,but not carbohydrate.CONCLUSION Although patients with CP had similar calorie intake to controls,studies that analysed the contribution of alcohol to energy intake showed that patients with CP consumed fewer non-alcohol calories than healthy controls.A high calorie intake,made up to a large degree by alcohol,may in part contribute to poor nutritional status in CP.
文摘Severe alcoholic hepatitis(AH)is a distinct entity in the spectrum of alcoholrelated liver disease,with limited treatment options and high mortality.Supportive medical care with corticosteroids in selected patients is the only currently available treatment option,often with poor outcomes.Based on the insights into the pathogenetic mechanisms of AH,which are mostly obtained from animal studies,several new treatment options are being explored.Studies have implicated impaired and deranged liver regeneration processes as one of the culprit mechanisms and a potential therapeutic target.Acknowledging evidence for the beneficial effects of granulocyte colony-stimulating factor(G-CSF)on liver regeneration and immunomodulation in animal models,several human studies investigated its role in the treatment of advanced alcohol-related liver disease and AH.Contrary to the previously published studies suggesting benefits of G-CSF in the outcomes of patients with severe AH,these effects were not confirmed by a recently published multicenter randomized trial,suggesting that other options should rather be pursued.Stem cell transplantation represents another option for improving liver regeneration,but evidence for its efficacy in patients with severe AH and advanced alcohol-related liver disease is still very scarce and unconvincing,with established lack of efficacy in patients with compensated cirrhosis.In this review,we summarize the current knowledge on the pathogenesis and experimental therapies targeting liver regeneration.The lack of high-quality studies and evidence is a major obstacle in further treatment development.New insights into the pathogenesis of not only liver injury,but also liver regeneration processes are mandatory for the development of new treatment options.A reliable experimental model of the pathogenesis of AH and processes involved in liver recovery is still missing,and data obtained from animal studies are essential for future research.
基金supported by research grants from Guangzhou Basic and Applied Basic Research Foundation(Grant No.2023A04J1951)Guangdong Basic and Applied Basic Research Foundation(Grant No.2022A1515111047)funded by research grant from Guangdong Basic and Applied Basic Research Foundation(Grant No.2021A1515010999).
文摘Autophagy is a highly conserved process in which cytosolic contents are degraded by the lysosome,which plays an important role in energy and nutrient balance,and protein or organelle quality control.The liver is the most important organ for metabolism.Studies to date have revealed a significant role of autophagy in the maintenance of liver homeostasis under basal and stressed conditions,and the impairment of autophagy has been closely linked to various liver diseases.Therefore,a comprehensive understanding of the roles of autophagy in liver diseases may help in the development of therapeutic strategies via targeting autophagy.In this review,we will summarize the latest understanding of the molecular mechanisms of autophagy and systematically discuss its implications in various liver diseases,including alcohol-related liver disease,non-alcoholic fatty liver disease,viral hepatitis,hepatocellular carcinoma,and acetaminophen-induced liver injury.
文摘Alcohol-related liver disease(ALD)encompasses a spectrum of diseases caused by excessive alcohol consumption.ALD includes hepatic steatosis,steatohepatitis,variable degrees of fibrosis,cirrhosis,and alcohol-associated hepatitis(AH),the latter being the most severe acute form of the disease.Severe AH is associated with high mortality(reaching up to 30%e50%)at 90 days.The cornerstone of ALD,and particularly AH,treatment continues to be abstinence,accompanied by support measures such as nutritional supplementation and management of alcohol withdrawal syndrome(AWS).In severe AH with model for end-stage liver disease(MELD)score21,corticosteroids can be used,especially MELD score between 25 and 39,where the highest benefit is achieved.Other key aspects of treatment include the early identification of infections and their associated management and the proper identification of potential candidates for liver transplantation.The development of new therapies based on the pathophysiology and mechanisms of liver injury are underway.This includes the modulation and management of the innate immune response,gut dysbiosis,bacterial translocation,and bacteria-derived products from the intestine.These hold promise for the future of AH treatment.
