Comparison between metabolic-associated fatty liver disease and nonalcoholic fatty liver disease:From nomenclature to clinical outcomes

As a result of the obesity epidemic,Nonalcoholic fatty liver disease(NAFLD)and its complications have increased among millions of people.Consequently,a group of experts recommended changing the term NAFLD to an inclusive terminology more reflective of the underlying pathogenesis;metabolic-associated fatty liver disease(MAFLD).This new term of MAFLD has its own disease epidemiology and clinical outcomes prompting efforts in studying its differences from NAFLD.This article discusses the rationale behind the nomenclature change,the main differences,and its clinical implications.

Hospitalizations for alcoholic liver disease during the COVID-19 pandemic increased more for women,especially young women,compared to men

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.

Ginsenoside Rk2, a dehydroprotopanaxadiol saponin, alleviates alcoholic liver disease via regulating NLRP3 and NLRP6 inflammasome signaling pathways in mice

Heavy alcohol consumption results in alcoholic liver disease(ALD)with inadequate therapeutic options.Here,we first report the potential beneficial effects of ginsenoside Rk2(Rk2),a rare dehydroprotopanaxadiol saponin isolated from streamed ginseng,against alcoholic liver injury in mice.Chronic-plus-single-binge ethanol feeding caused severe liver injury,as manifested by significantly elevated serum aminotransferase levels,hepatic histological changes,increased lipid accumulation,oxidative stress,and inflammation in the liver.These deleterious effects were alleviated by the treatment with Rk2(5 and 30 mg/kg).Acting as an nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)inhibitor,Rk2 ameliorates alcohol-induced liver inflammation by inhibiting NLRP3 inflammasome signaling in the liver.Meanwhile,the treatment with Rk2 alleviated the alcohol-induced intestinal barrier dysfunction via enhancing NLRP6 inflammasome in the intestine.Our findings indicate that Rk2 is a promising agent for the prevention and treatment of ALD and other NLPR3-driven diseases.

Protective mechanism of Coprinus comatus polysaccharide on acute alcoholic liver injury in mice,the metabolomics and gut microbiota investigation

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.

Treatment options for alcoholic and non-alcoholic fatty liver disease: A review

Alcoholic liver disease(ALD)and non-alcoholic fatty liver disease(NAFLD)are serious health problems worldwide.These two diseases have similar pathological spectra,ranging from simple steatosis to hepatitis to cirrhosis and hepatocellular carcinoma.Although most people with excessive alcohol or calorie intake display abnormal fat accumulation in the liver(simple steatosis),a small percentage develops progressive liver disease.Despite extensive research on understanding the pathophysiology of both these diseases there are still no targeted therapies available.The treatment for ALD remains as it was 50 years ago:abstinence,nutritional support and corticosteroids(or pentoxifylline as an alternative if steroids are contraindicated).As for NAFLD,the treatment modality is mainly directed toward weight loss and co-morbidity management.Therefore,new pathophysiology directed therapies are urgently needed.However,the involvement of several inter-related pathways in the pathogenesis of these diseases suggests that a single therapeutic agent is unlikely to be an effective treatment strategy.Hence,a combination therapy towards multiple targets would eventually be required.In this review,we delineate the treatment options in ALD and NAFLD,including various new targeted therapies that are currently under investigation.We hope that soon we will be having an effective multi-therapeutic regimen for each disease.

Role of microRNAs in alcohol-induced liver disorders and non-alcoholic fatty liver disease

MicroRNAs(miRNAs) are small non-coding RNAs that regulate multiple physiological and pathological functions through the modulation of gene expression at the post-transcriptional level. Accumulating evidence has established a role for miRNAs in the development and pathogenesis of liver disease. Specifically, a large number of studies have assessed the role of miRNAsin alcoholic liver disease(ALD) and non-alcoholic fatty liver disease(NAFLD), two diseases that share common underlying mechanisms and pathological characteristics. The purpose of the current review is to summarize and update the body of literature investigating the role of miRNAs in liver disease. In addition, the potential use of miRNAs as biomarkers and/or therapeutic targets is discussed. Among all miRNAs analyzed, miR-34 a, miR-122 and miR-155 are most involved in the pathogenesis of NAFLD. Of note, these three miRNAs have also been implicated in ALD, reinforcing a common disease mechanism between these two entities and the pleiotropic effects of specific miRNAs. Currently, no single miRNA or panel of miRNAs has been identified for the detection of, or staging of ALD or NAFLD. While promising results have been shown in murine models, no therapeutic based-miRNA agents have been developed for use in humans with liver disease.

Growing burden of alcoholic liver disease in China: A review

Explosive economic growth and increasing social openness in China over the last30 years have significantly boosted alcohol consumption, and consequently, the incidence of alcoholic liver disease(ALD) in China has increased. Because the epidemiologic and clinical features of ALD in the Chinese population may differ from those of the Caucasian population, this review describes the epidemiology,pathogenesis, genetic polymorphisms, diagnosis, and treatment of ALD in the Chinese population. This updated knowledge of ALD in China provides information needed for a global understanding of ALD and may help in the development of useful strategies for reducing the global ALD burden.

Distinctive aspects of peptic ulcer disease,Dieulafoy'slesion,and Mallory-Weiss syndrome in patients withadvanced alcoholic liver disease or cirrhosis

AIM:To systematically review the data on distinctive aspects of peptic ulcer disease(PUD),Dieulafoy’s lesion(DL),and Mallory-Weiss syndrome(MWS)in patients with advanced alcoholic liver disease(a ALD),including alcoholic hepatitis or alcoholic cirrhosis.METHODS:Computerized literature search performed via Pub Med using the following medical subject heading terms and keywords:"alcoholic liver disease","alcoholic hepatitis","alcoholic cirrhosis","cirrhosis","liver disease","upper gastrointestinal bleeding","nonvariceal upper gastrointestinal bleeding","PUD",‘‘DL’’,‘‘Mallory-Weiss tear",and"MWS’’.RESULTS:While the majority of acute gastrointestinal(GI)bleeding with a ALD is related to portal hypertension,about 30%-40%of acute GI bleeding in patients with a ALD is unrelated to portal hypertension.Such bleeding constitutes an important complication of a ALD because of its frequency,severity,and associated mortality.Patients with cirrhosis have a markedly increased risk of PUD,which further increases with the progression of cirrhosis.Patients with cirrhosis or a ALD and peptic ulcer bleeding(PUB)have worse clinical outcomes than other patients with PUB,including uncontrolled bleeding,rebleeding,and mortality.Alcohol consumption,nonsteroidal anti-inflammatory drug use,and portal hypertension may have a pathogenic role in the development of PUD in patients with a ALD.Limited data suggest that Helicobacter pylori does not play a significant role in the pathogenesis of PUD in most cirrhotic patients.The frequency of bleeding from DL appears to be increased in patients with a ALD.DL may be associated with an especially high mortality in these patients.MWS is strongly associated with heavy alcohol consumption from binge drinking or chronic alcoholism,and is associated with a ALD.Patients with a ALD have more severe MWS bleeding and are more likely to rebleed when compared to non-cirrhotics.Preendoscopic management of acute GI bleeding in patients with a ALD unrelated to portal hypertension is similar to the management of a ALD patients with GI bleeding from portal hypertension,because clinical distinction before endoscopy is difficult.Most patients require intensive care unit admission and attention to avoid over-transfusion,to correct electrolyte abnormalities and coagulopathies,and to administer antibiotic prophylaxis.Alcoholics should receive thiamine and be closely monitored for symptoms of alcohol withdrawal.Prompt endoscopy,after initial resuscitation,is essential to diagnose and appropriately treat these patients.Generally,the same endoscopic hemostatic techniques are used in patients bleeding from PUD,DL,or MWS in patients with a ALD as in the general population.CONCLUSION:Nonvariceal upper GI bleeding in patients with a ALD has clinically important differences from that in the general population without a ALD,including:more frequent and more severe bleeding from PUD,DL,or MWS.

Alcoholic disease: Liver and beyond

The harmful use of alcohol is a worldwide problem.It has been estimated that alcohol abuse represents the world’s third largest risk factor for disease and disability;it is a causal factor of 60 types of diseases and injuries and a concurrent cause of at least 200 others.Liver is the main organ responsible for metabolizing ethanol,thus it has been considered for long time the major victim of the harmful use of alcohol.Ethanol and its bioactive products,acetaldehyde-acetate,fatty acid ethanol esters,ethanol-protein adducts,have been regarded as hepatotoxins that directly and indirectly exert their toxic effect on the liver.A similar mechanism has been postulated for the alcohol-related pancreatic damage.Alcohol and its metabolites directly injure acinar cells and elicit stellate cells to produce and deposit extracellular matrix thus triggering the"necrosis-fibrosis"sequence that finally leads to atrophy and fibrosis,morphological hallmarks of alcoholic chronic pancreatitis.Even if less attention has been paid to the upper and lower gastrointestinal tract,ethanol produces harmful effects by inducing:(1)direct damaging of the mucosa of the esophagus and stomach;(2)modification of thesphincterial pressure and impairment of motility;and(3)alteration of gastric acid output.In the intestine,ethanol can damage the intestinal mucosa directly or indirectly by altering the resident microflora and impairing the mucosal immune system.Notably,disruption of the intestinal mucosal barrier of the small and large intestine contribute to liver damage.This review summarizes the most clinically relevant alcohol-related diseases of the digestive tract focusing on the pathogenic mechanisms by which ethanol damages liver,pancreas and gastrointestinal tract.

Diagnosis of alcoholic liver disease

Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease(ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean cor-puscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential.

Alcoholic liver disease

Alcohol use disorders affect millions of individuals worldwide.Alcohol consumption is directly associated with liver disease mortality and accounts for elevated social and economic costs.Alcoholic liver disease(ALD) may take the form of acute involvement(alcoholic hepatitis)or chronic liver disease(steatosis,steatohepatitis,fibrosis and cirrhosis).The severity and prognosis of alcohol-induced liver disease depends on the amount,pattern and duration of alcohol consumption,as well as on the presence of liver inflammation,diet,nutritional status and genetic predisposition of an individual.While steatosis is an almost completely benign disease,liver cirrhosis is associated with marked morbidity,mortal-ity and life expectancy shortening.The median survival of patients with advanced cirrhosis is 1-2 years.Se-vere acute alcoholic hepatitis(AH)is associated with mortality as high as 50%.It has been managed with corticoids,pentoxifylline and enteral nutrition,although evidence based data are still conflicting.Some author suggest that pentoxifylline could be a better first-line treatment in patients with severe AH.Absolute abstinence is a basic condition for any treatment of acute or chronic ALD,the other therapeutical procedure being of a supportive nature and questionable significance.Acamprosate appears to be an effective treatment strategy for supporting continuous abstinence in alco-hol dependent patients.Patients with advanced liver cirrhosis who demonstrably abstain can be considered for liver transplantation,which leads to a markedly pro-longed life expectancy.The crucial step in ALD preven-tion is in the prevention of alcohol abuse,whereas the prevention of liver injury in active alcohol abusers is not clinically applicable.

Alcoholic liver disease:Utility of animal models

Alcoholic liver disease(ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options for ALD are very limited due to the lack of suitable in vivo models that recapitulate the full spectrum of ALD. Experimental animal models of ALD, particularly rodents, have been used extensively to mimic human ALD. An ideal animal model should recapitulate all aspects of the ALD process, including significant steatosis, hepatic neutrophil infiltration, and liver injury. A better strategy against ALD depends on clear diagnostic biomarkers, accurate predictor(s) of its progression and new therapeutic approaches to modulate stop or even reverse the disease. Numerous models employing rodent animals have been established in the last decades to investigate the effects of acute and chronic alcohol exposure on the initiation and progression of ALD. Although significant progress has been made in gaining better knowledge on the mechanisms and pathology of ALD, many features of ALD are unknown, and require further investigation, ideally with improved animal models that more effectively mimic human ALD. Although differences in the degree and stages of alcoholic liver injury inevitably exist between animal models and human ALD, the acquisition and translational relevance will be greatly enhanced with the development of new and improved animal models of ALD.

Role of mitochondria in alcoholic liver disease

Alcohol abuse is the leading cause of liver related morbidity and mortality.Chronic or binge alcohol drinking causes hepatic steatosis which can develop to steatohepatitis,cirrhosis and ultimately hepatocellular carcinoma.The pathogenesis of alcoholic liver disease(ALD)is poorly characterized,however several recent studies point to a major role of mitochondria in this process.Mitochondria play a crucial role in cellular energy metabolism and in reactive species formation.Alcohol treatment causes mitochondrial DNA damage,lipid accumulation and oxidative stress.Studies in both animal models and in humans showed that alcohol administration causes changes in the mitochondrial morphology and function suggesting a role of these changes in the pathogenesis of ALD.We review recent findings on mechanisms by which alcohol negatively impacts mitochondrial biogenesis and function and we will discuss the specific intracellular pathways affected by alcohol consumption.Interestingly,recent findings indicate that a large number of mitochondrial proteins are acetylated and that mitochondrial proteins acetylation and sirtuins are modulated by alcohol.Un-derstanding the mechanisms behind alcohol mediated impaired mitochondrial biogenesis and function may help identify potential therapeutic targets for treating ALD in humans.

Gut microbiota in alcoholic liver disease: Pathogenetic role and therapeutic perspectives

Alcoholic liver disease(ALD) is the commonest cause of cirrhosis in many Western countries and it has a high rate of morbidity and mortality. The pathogenesis is characterized by complex interactions between metabolic intermediates of alcohol. Bacterial intestinal flora is itself responsible for production of endogenous ethanol through the fermentation of carbohydrates. The intestinal metabolism of alcohol produces a high concentration of toxic acetaldehyde that modifies gut permeability and microbiota equilibrium. Furthermore it causes direct hepatocyte damage. In patients who consume alcohol over a long period, there is a modification of gut microbiota and, in particular, an increment of Gram negative bacteria. This causes endotoxemia and hyperactivation of the immune system. Endotoxin is a constituent of Gram negative bacteria cell walls. Two types of receptors, cluster of differentiation 14 and Toll-like receptors-4, present on Kupffer cells, recognize endotoxins. Several studies have demonstrated the importance of gut-liver axis and new treatments have been studied in recent years to reduce progression of ALD modifying gut microbiota. It has focused attention on antibiotics, prebiotics, probiotics and synbiotics.

Liver transplantation in alcoholic liver disease current status and controversies

Alcoholic cirrhosis remains the second most common indication for liver transplantation.A comprehensive medical and psychosocial evaluation is needed when making a decision to place such patients on the transplant list.Most transplant centers worldwide need a minimum of 6 mo of alcohol abstinence for listing these patients.Patients with alcohol dependence are at high risk for relapse to alcohol use after transplantation(recidivism).These patients need to be identified and require alcohol rehabilitation treatment before transplantation.Recidivism to the level of harmful drinking is reported in about 15%-20%cases.Although,recurrent cirrhosis and graft loss from recidivism is rare,occurring in less than 5%of all alcoholic cirrhosis-related transplants,harmful drinking in the post-transplant pe-riod does impact the long-term outcome.The development of metabolic syndrome with cardiovascular events and de novo malignancy are important contributors to non liver-related mortality amongst transplants for alcoholic liver disease.Surveillance protocols for earlier detection of de novo malignancy are needed to improve the long-term outcome.The need for a minimum of 6 mo of abstinence before listing makes transplant a nonviable option for patients with severe alcoholic hepatitis who do not respond to corticosteroids.Emerging data from retrospective and prospective studies has challenged the 6 mo rule,and beneficial effects of liver transplantation have been reported in select patients with a first episode of severe alcoholic hepatitis who are unresponsive to steroids.

Non-alcoholic fatty liver disease and thyroid dysfunction:A systematic review

Thyroid hormones are totally involved in the regulation of body weight, lipid metabolism, and insulin resistance. Therefore it is anticipated that thyroid hormones may have a role in the pathogenesis of non alcoholic fatty liver disease(NAFLD) and non alcoholic steatohepatitis(NASH). In this study, we reviewed the current literature on the association between thyroid dysfunction and NAFLD/NASH. A search for English language medical literature reporting an association between thyroid dysfunction and NAFLD/NASH in humans was conducted across PubMed, ISI Web of Science, and Scopus in August, 2013. Out of 140 studies initially identified through the search, 11 relevant articles were included in the final review. Thyroid dysfunctions in the form of overt or subclinical hypothyroidism are prevalent among patients with NAFLD/NASH. Hypothyroidism appears to be an independent risk factor for NAFLD/NASH in some studies; however, other newly published studies failed to find such anassociation. The results of the studies on the role of thyroid abnormalities in NAFLD/NASH are inconsistent, and further research is recommended to determine the relationship between hypothyroidism and NAFLD/NASH and the underlying mechanisms.

Alcoholic liver disease: Treatment

The excess consumption of alcohol is associated with alcoholic liver diseases(ALD). ALD is a major healthcare problem, personal and social burden, and significant reason for economic loss worldwide. The ALD spectrum includes alcoholic fatty liver, alcoholic hepatitis, cirrhosis, and the development of hepatocellular carcinoma. The diagnosis of ALD is based on a combination of clinical features, including a history of significant alcohol intake, evidence of liver disease, and laboratory findings. Abstinence is the most important treatment for ALD and the treatment plan varies according to the stage of the disease. Various treatments including abstinence, nutritional therapy, pharmacological therapy, psychotherapy, and surgery are currently available. For severe alcoholic hepatitis, corticosteroid or pentoxifylline are recommended based on the guidelines. In addition, new therapeutic targets are being under investigation.

Optimal management for alcoholic liver disease: Conventional medications, natural therapy or combination?

Alcohol consumption is the principal factor in thepathogenesis of chronic liver diseases.Alcoholic liver disease(ALD)is defined by histological lesions on the liver that can range from simple hepatic steatosis to more advanced stages such as alcoholic steatohepatitis,cirrhosis,hepatocellular carcinoma and liver failure.As one of the oldest forms of liver injury known to humans,ALD is still a leading cause of liver-related morbidity and mortality and the burden is exerting on medical systems with hospitalization and management costs rising constantly worldwide.Although the biological mechanisms,including increasing of acetaldehyde,oxidative stress with induction of cytochrome p4502E1,inflammatory cytokine release,abnormal lipid metabolism and induction of hepatocyte apoptosis,by which chronic alcohol consumption triggers serious complex progression of ALD is well established,there is no universally accepted therapy to prevent or reverse.In this article,we have briefly reviewed the pathogenesis of ALD and the molecular targets for development of novel therapies.This review is focused on current therapeutic strategies for ALD,including lifestyle modification with nutrition supplements,available pharmacological drugs and new agents that are under development,liver transplantation,application of complementary medicines,and their combination.The relevant molecular mechanisms of each conventional medication and natural agent have been reviewed according to current available knowledge in the literature.We also summarized efficacy vs safety on conventional and herbal medicines which are specifically used for the prevention and treatment of ALD.Through a system review,this article highlighted that the combination of pharmaceutical drugs with naturally occurring agents may offer an optimal management for ALD and its complications.It is worthwhile to conduct large-scale,multiple centre clinical trials to further prove the safety and benefits for the integrative therapy on ALD.

Clinical differences between alcoholic liver disease and nonalcoholic fatty liver disease

Alcoholic liver disease(ALD)and nonalcoholic fatty liver disease(NAFLD)are serious health problems worldwide.These two diseases have similar pathological spectra,ranging from simple hepatic steatosis to steatohepatitis,liver cirrhosis,and hepatocellular carcinoma.Although most subjects with excessive alcohol or food intake experience simple hepatic steatosis,a small percentage of individuals will develop progressive liver disease.Notably,both ALD and NAFLD are frequently accompanied by extrahepatic complications,including cardiovascular disease and malignancy.The survival of patients with ALD and NAFLD depends on various disease-associated conditions.This review delineates the clinical characteristics and outcomes of patients with ALD and NAFLD by comparing their epidemiology,the factors associated with disease susceptibility and progression,and the predictors and characteristics of outcomes.A comprehensive understanding of the characteristics and outcomes of ALD and NAFLD is imperative in the management of these chronic liver diseases.

Therapy for alcoholic liver disease

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 containing1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting.Corticosteroids are firstline 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 6mo of proven abstinence for eligibility.Alcoholic cirrhotics who maintain abstinence generally have a relatively favorable prognosis after liver transplantation.