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.

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.

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.

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.

Increased liver stiffness in alcoholic liver disease:Differentiating fibrosis from steatohepatitis

AIM:To test if inflammation also interferes with liver stiffness (LS) assessment in alcoholic liver disease (ALD) and to provide a clinical algorithm for reliable fibrosis assessment in ALD by FibroScan (FS).METHODS:We first performed sequential LS analysis before and after normalization of serum transaminases in a learning cohort of 50 patients with ALD admitted for alcohol detoxification. LS decreased in almost all patients within a mean observation interval of 5.3 d. Six patients (12%) would have been misdiagnosed with F3and F4 fibrosis but LS decreased below critical cut-off values of 8 and 12.5 kPa after normalization of trans-aminases. RESULTS:Of the serum transaminases,the decrease in LS correlated best with the decrease in glutamic oxaloacetic transaminase (GOT). No significant chang-es in LS were observed below GOT levels of 100 U/L. After establishing the association between LS and GOT levels,we applied the rule of GOT < 100 U/L for reliable LS assessment in a second validation cohort of 101 patients with histologically confi rmed ALD. By ex-cluding those patients with GOT > 100 U/L at the time of LS assessment from this cohort,the area under the receiver operating characteristic (AUROC) for cirrhosis detection by FS improved from 0.921 to 0.945 while specificity increased from 80% to 90% at a sensitivity of 96%. A similar AUROC could be obtained for lower F3 fibrosis stage if LS measurements were restricted to patients with GOT < 50 U/L. Histological grading of inflammation did not further improve the diagnostic accuracy of LS.CONCLUSION:Coexisting steatohepatitis markedly increases LS in patients with ALD independent of fibrosis stage. Postponing cirrhosis assessment by FS during alcohol withdrawal until GOT decreases to < 100 U/mL signif icantly improves the diagnostic accuracy.

Current understanding of the metabolism of micronutrients in chronic alcoholic liver disease

Alcoholic liver disease(ALD)remains an important health problem worldwide.Perturbation of micronutrients has been broadly reported to be a common characteristic in patients with ALD,given the fact that micronutrients often act as composition or coenzymes of many biochemical enzymes responsible for the inflammatory response,oxidative stress,and cell proliferation.Mapping the metabolic pattern and the function of these micronutrients is a prerequisite before targeted intervention can be delivered in clinical practice.Recent years have registered a significant improvement in our understanding of the role of micronutrients on the pathogenesis and progression of ALD.However,how and to what extent these micronutrients are involved in the pathophysiology of ALD remains largely unknown.In the current study,we provide a review of recent studies that investigated the imbalance of micronutrients in patients with ALD with a focus on zinc,iron,copper,magnesium,selenium,vitamin D and vitamin E,and determine how disturbances in micronutrients relates to the pathophysiology of ALD.Overall,zinc,selenium,vitamin D,and vitamin E uniformly exhibited a deficiency,and iron demonstrated an elevated trend.While for copper,both an elevation and deficiency were observed from existing literature.More importantly,we also highlight several challenges in terms of low sample size,study design discrepancies,sample heterogeneity across studies,and the use of machine learning approaches.

Traditional Chinese medicine Kang Xian Fu Fang Ⅰ is effective for prophylaxis and treatment of alcoholic liver disease in rats

BACKGROUND: Reversal of liver fibrosis is one of the key steps in the prevention and treatment of alcoholic liver disease (ALD), but the mechanism is unknown. This study was to investigate the effects of the Chinese medicine Kang Xian Fu Fang Ⅰ (KXⅠ) on prophylaxis and treatment of ALD in rats and its possible mechanism of action. METHODS: Eighty male Wistar rats were randomly divided into four groups: normal control; ALD model; treatment of ALD with KXⅠ; and prophylaxis of ALD by KXⅠ. At the end of 4, 8, 12 and 16 weeks, five rats from each group were anesthetized and their livers were removed for pathological studies using hematoxylin-eosin and Masson stain, immunohistochemical studies, and flow cytometry for matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Blood samples were taken for hyaluronic acid (HA) assay. RESULTS: Serum HA level and liver collagen content were lower in the groups given KXⅠ for prophylaxis and treatment than in ALD model group (P<0.05). The levels of MMP-2 and MMP-9 were also decreased in the prophylaxis and treatment groups (P<0.05). Immunohistochemistry showed immunoreactive MMP-2 in endothelial cells of the hepatic artery and portal vein, sinusoidal endothelial cells, and sinusoidal cells. Immunoreactive MMP-9 occurred in the hepatic cells around the veins and sinusoidal cells. CONCLUSIONS: KXⅠ can effectively inhibit or reverse the course of ALD. This may be attributable to its capacity to inhibit the expression of MMP-2 and MMP-9.

Liver transplantation for alcoholic liver disease

Alcoholic liver disease(ALD) is the second commonest indication for liver transplantation after viral hepatitis in the United States and Europe.Controversies surround the indications and allocation of scarce and expensive resource for this so called self inflicted disease.Controversies stem from the apprehension that alcoholic recipients are likely to relapse and cause damage to the graft.There is a need to select those candidates with lower risk for relapse with the available predictive factors and scores.Substance abuse specialist and psychiatrists are mandatory in the pre-transplant evaluation and in the post-transplant follow-up.There is conflicting evidence to support a fixed period of pretransplant abstinence,although most units do follow this.Alcoholic hepatitis(AH) continues to be a contraindication for transplantation,however there is a need for further research in this f ield as a subset of patients with AH who do not respond to medical treatment,have high early mortality and could benefit from transplantation.One year,3-year,and 5-year survival post-transplant is similar for both ALD and non-ALD recipients.The incidence of post-transplant rejection and retransplantation is also similar to other recipients.ALD with viral hepatitis especially hepatitis C virus leads to a more aggressive liver disease with early presentation for transplantation.ALD patients are more prone to develop de-novo malignancy;this is attributed to the long term effect of alcohol,tobacco combined with immunosuppression.Post-transplant surveillance is important to detect early relapse to alcoholism,presence of de-novo malignancy and treat the same adequately.

Meta-analysis reveals up-regulation of cholesterol processes in non-alcoholic and down-regulation in alcoholic fatty liver disease

AIM To compare transcriptomes of non-alcoholic fatty liver disease(NAFLD) and alcoholic liver disease(ALD) in a meta-analysis of liver biopsies.METHODS Employing transcriptome data from patient liver biopsies retrieved from several public repositories we performed a meta-analysis comparing ALD and NAFLD.RESULTS We observed predominating commonalities at the transcriptome level between ALD and NAFLD,most prominently numerous down-regulated metabolic pathways and cytochrome-related pathways and a few up-regulated pathways which include ECM-receptor interaction,phagosome and lysosome.However some pathways were regulated in opposite directions in ALD and NAFLD,for example,glycolysis was down-regulated in ALD and up-regulated in NAFLD.Interestingly,we found rate-limiting genes such as HMGCR,SQLE and CYP7A1 which are associated with cholesterol processes adversely regulated between ALD(down-regulated) and NAFLD(up-regulated).We propose that similar phenotypes in both diseases may be due to a lower level of the enzyme CYP7A1 compared to the cholesterol synthesis enzymes HMGCR and SQLE.Additionally,we provide a compendium of comparative KEGG pathways regulation in ALD and NAFLD.CONCLUSION Our finding of adversely regulated cholesterol processes in ALD and NAFLD draws the focus to regulation of cholesterol secretion into bile.Thus,it will be interesting to further investigate CYP7A1-mediated cholesterol secretion into bile-also as possible drug targets.The list of potential novel biomarkers may assist differential diagnosis of ALD and NAFLD.

Is the hypoxia-inducible factor-1 alpha mRNA expression activated by ethanol-induced injury, the mechanism underlying alcoholic liver disease?

BACKGROUND: Excessive alcohol consumption can result in multiple organ injury, of which alcoholic liver disease (ALD) is the most common. With economic development and improvement of living standards, the incidence of diseases caused by alcohol abuse has been increasing in China, although its pathogenesis remains obscure. The aim of this study was to investigate the role of hypoxia in chronic ALD. METHODS: Twenty-eight male Sprague-Dawley rats were randomized into a control group (n=12) with a normal history and an experimental group (n=16) fed with 10 ml/ kg of 56% (vol/vol) ethanol once per day by gastric lavage for 24 weeks. At 24 weeks, blood samples were collected and then the rats were killed. Liver samples were frozen at -80 ℃ and used for RT-PCR; other liver samples were obtained for immunohistochemical staining. RESULTS: When the period of alcohol consumption increased, the positive rate of expression of hypoxia- inducible factor-1 alpha (HIF-1α) mRNA was more significantly elevated in the liver of the alcohol group than in the control group (P≤0.05). The HIF-1α protein located in the cytoplasm was seldom expressed in the control group, but significantly in the alcohol group (P≤0.01). CONCLUSION: HIF-1α mRNA expression was activated by ethanol-induced injury in this study, suggesting that hypoxia is involved in the underlying mechanism of ALD.

Recent trends in liver transplantation for alcoholic liver disease in the United States

AIM To examine temporal changes in the indications for liver transplantation(LT) and characteristics of patients transplanted for alcoholic liver disease(ALD).METHODS We performed a retrospective cohort analysis of trends in the indication for LT using the United Network for Organ Sharing(UNOS) database between 2002 and 2015. Patients were grouped by etiology of the liver disease and characteristics were compared using χ~2 and t-tests. Time series analysis was used identifying any year with a significant change in the number of transplants per year for ALD, and before and after eras were modeled using a general linear model. Subgroup analysis of recipients with ALD was performed by age group, gender, UNOS region and etiology(alcoholic cirrhosis, alcoholic hepatitis and hepatitis C-alcoholic cirrhosis dual listing).RESULTS Of 74216 liver transplant recipients, ALD(n = 9400, 12.7%) was the third leading indication for transplant after hepatitis C and hepatocellular carcinoma. Transplants for ALD, increased from 12.8%(553) in 2002 to 16.5%(1020) in 2015. Time series analysis indicated a significant increase in the number of transplants per year for ALD in 2013(P = 0.03). There were a stable number of transplants per year between 2002 and 2012(linear coefficient 3, 95%CI:-4.6, 11.2) an increase of 177 per year between 2013 and 2015(95%CI: 119, 234). This increase was significant for all age groups except those 71-83 years old, was observed for both genders, and was incompletely explained by a decrease in transplants for hepatitis C and ALD dual listing. All UNOS regions except region 9 saw an increase in the mean number of transplants per year when comparing eras, and this increase was significant in regions 2, 3, 4, 5, 6, 8, 10 and 11.CONCLUSION There has been a dramatic increase in the number of transplants for ALD starting in 2013.

Genetic polymorphism and mRNA levels of cytochrome P450ⅡE1 and glutathione S-transferase P1 in patients with alcoholic liver disease in different nationalities

BACKGROUND:Alcohol abuse and dependence are major factors in the pathogenesis of alcoholic liver disease(ALD).Alcohol abuse is becoming an increasingly severe problem among the Han,Mongol,and Korean nationalities in northeast China.This study aimed to investigate the relationship between ALD and the genetic polymorphism and expression levels of two enzymes,cytochrome P450ⅡE1(CYPⅡE1)and glutathione S-transferase P1(GSTP1)in patients of three nationalities.METHODS:Peripheral blood was collected from 353 Chinese patients with ALD,300 alcohol dependent patients without liver disease(alcoholic),and 360 healthy controls.Each group included patients from the Han,Mongol and Korean nationalities.Real-time polymerase chain reaction(PCR)and PCR-restriction fragment length polymorphism(PCR-RFLP)were used.RESULTS:Regardless of nationality,patients who carried the rare CYPⅡE1 C2 and GSTP1 Val alleles were at higher risk of ALD.The frequency of C2 and Val in patients with ALD was respectively 50.00%and 26.98%in the Han,31.36%and 22.87%in the Mongol,and 45.87%and 22.02% in the Korean nationality.No significant differences were seen in the frequency of either C2 or Val alleles in ALD patients among the three nationalities.In each nationality,the frequency of both C2 and Val alleles was significantly higher in ALD compared to alcoholic and healthy controls.Except for nationality,the average mRNA levels of CYPⅡ E1 in ALD patients and healthy controls were 10.05%and 2.21%,respectively.The average mRNA levels of GSTP1 in ALD patients and healthy controls were 0.53%and 2.12%,respectively.The mRNA level of CYPⅡE1 was higher,and that of GSTP1 was lower in patients with ALD compared to the controls.CONCLUSIONS:Except for nationality,patients with ALD in this series tended to have a higher mRNA expression of CYPⅡE1 and to carry the C2 allele,and tended to have a lower mRNA expression of GSTP1 and to carry the Val allele.There is a causal relationship between the polymorphic alleles,which leads to different mRNA levels and the development of ALD.

Experimental models of metabolic and alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is a multi-systemic disease that is considered the hepatic manifestation of metabolic syndrome(MetS).Because alcohol consumption in NAFLD patients is common,there is a significant overlap in the pathogenesis of NAFLD and alcoholic liver disease(ALD).Indeed,MetS also significantly contributes to liver injury in ALD patients.This“syndrome of metabolic and alcoholic steatohepatitis”(SMASH)is thus expected to be a more prevalent presentation in liver patients,as the obesity epidemic continues.Several pre-clinical experimental models that couple alcohol consumption with NAFLDinducing diet or genetic obesity have been developed to better understand the pathogenic mechanisms of SMASH.These models indicate that concomitant MetS and alcohol contribute to lipid dysregulation,oxidative stress,and the induction of innate immune response.There are significant limitations in the applicability of these models to human disease,such as the ability to induce advanced liver injury or replicate patterns in human food/alcohol consumption.Thus,there remains a need to develop models that accurately replicate patterns of obesogenic diet and alcohol consumption in SMASH patients.

Significance of gut microbiota in alcoholic and non-alcoholic fatty liver diseases

Liver-gut communication is vital in fatty liver diseases,and gut microbes are the key regulators in maintaining liver homeostasis.Chronic alcohol abuse and persistent overnutrition create dysbiosis in gut ecology,which can contribute to fatty liver disease.In this review,we discuss the gut microbial compositional changes that occur in alcoholic and nonalcoholic fatty liver diseases and how this gut microbial dysbiosis and its metabolic products are involved in fatty liver disease pathophysiology.We also summarize the new approaches related to gut microbes that might help in the diagnosis and treatment of fatty liver disease.

Characteristics of alcoholic liver disease and predictive factors for mortality of patients with alcoholic cirrhosis

BACKGROUND:Alcoholic liver disease is one of the major chronic liver diseases worldwide.The aim of the study was to describe the clinical characteristics of alcoholic liver disease and to compare the predictive values of biochemical parameters,complications,Child-Turcotte-Pugh score,model for end-stage liver disease(MELD)score and discriminant function score for the mortality of in-hospital or 3-month after discharge of patients with alcoholic cirrhosis(AC).METHODS:A retrospective record review and statistical analysis were performed on 205 consecutive patients with the discharge diagnosis of alcoholic liver disease.Three models were used to predict the mortality of patients with AC.The number of variceal hemorrhage,infection,hepatic encephalopathy and hepatocellular carcinoma was analyzed as"numbers of complications".Model 1 consisted of creatinine,white blood cell count,international normalized ratio and"numbers of complications".Model 2 consisted of MELD score.Model 3included"numbers of complications"and MELD score.RESULTS:The risk of developing AC was significant for patients with alcohol consumption of higher than 80 g/d(OR=2.807,P【0.050)and drinking duration of longer than 10 years(OR=3.429,P【0.028).The area under curve for predicting inhospital mortality of models 1,2 and 3 was 0.950,0.886 and 0.911(all P【0.001),respectively.The area under curve for predicting the 3-month mortality of models 1,2 and 3 was 0.867,0.878 and0.893(all P【0.001),respectively.CONCLUSIONS:There is a dose-dependent relationship between alcohol consumption and the risk of developing AC.MELD score has a better predictive value than Child-TurcottePugh or discriminant function score for patients with AC,and model 1 or 3 is better than model 2.

Dietary supplementation in patients with alcoholic liver disease: a review on current evidence

BACKGROUND：Alcoholic liver disease（ALD）is one of the main causes of liver disease worldwide.Although the pathogenesis of ALD has not yet been well elucidated,the oxidative metabolites of ethanol such as acetaldehyde and reactive oxygen species play a pivotal role in the clinical and pathological spectrum of the disease.This review summarizes the existing evidences on dietary supplements considered to have antioxidant,and/or anti-inflammatory properties,and their role in the management of ALD and the proposed mechanisms.DATA SOURCES：The present study reviewed all studies published in Pub Med,Science Direct and Scopus,from 1959 to2015,indicating the role of different dietary supplementation in attenuation of many pathophysiological processes involved in development and progression of ALD.Full-texts of citations were used except for those that were published in languages other than English.RESULTS：Significant progress has been made to understand the key events and molecular players for the onset and progression of ALD from both experimental and clinical studies;however,there is no successful treatment currently available.The present review discussed the role of a variety of dietary supplements（e.g.vitamin A,carotenoids,vitamins B3,C and E,in addition to antioxidants and anti-inflammatory agents）in treating ALD.It has been shown that supplementation with some carotenoids,vitamin B3,vitamin C,silymarin,curcumin,probiotics,zinc,S-adenosylmethionine and garlic may havepotential beneficial effects in animal models of ALD;however,the number of clinical studies is very limited.In addition,supplementation should be accompanied with alcohol cessation.CONCLUSIONS：Since oxidative stress and inflammation are involved in the pathogenesis of ALD,dietary supplements that can modulate these pathologies could be useful in the treatment of ALD.In addition to alcohol cessation,these supplements have shown beneficial effects on animal models of ALD.Clinical trials are needed to validate the beneficiary role of these supplements in patients with ALD.

Epidemiological profile of alcoholic liver disease hospital admissions in a Latin American country over a 10-year period

BACKGROUND Alcoholic liver disease(ALD)is a major cause of chronic liver disease worldwide.AIM To describe the epidemiological profile and mortality rates of patients with ALD admitted to public hospitals in different regions of Brazil from 2006 to 2015.METHODS This is a descriptive study that evaluated aggregate data from the five Brazilian geographic regions.RESULTS A total of 160093 public hospitalizations for ALD were registered.There was a 34.07%increase in the total number of admissions over 10 years,from 12879 in 2006 to 17267 in 2015.The region with the highest proportion(49.01%)of ALD hospitalizations was Southeast(n=78463).The North region had the lowest absolute number of patients throughout the study period,corresponding to 3.9%of the total(n=6242).There was a 24.72%increase in the total number of ALD deaths between 2006 and 2015.We found that the age group between 50 and 59 years had the highest proportion of both hospitalizations and deaths:28.94%(n=46329)of total hospital admissions and 29.43%(n=28864)of all deaths.Men were more frequently hospitalized than women and had the highest proportions of deaths in all regions.Mortality coefficient rates increased over the years,and simple linear regression analysis indicated a statistically significant upward trend in this mortality(R^2=0.744).CONCLUSION Our study provides a landscape of the epidemiological profile of public hospital admissions due to ALD in Brazil.We detected an increase in the total number of admissions and deaths due to ALD over 10 years.

Metabolic dysfunction associated fatty liver disease: The new nomenclature and its impact

BACKGROUND In 2020,an international expert panel proposed a new definition of fatty liver:Metabolic dysfunction-associated fatty liver disease(MAFLD).The MAFLD added the criteria for defining metabolic dysfunctions,which are high-risk factors for liver-related and cardiovascular events.Contrary to the non-alcoholic fatty liver disease(NAFLD)definition,it allows the coexistence of MAFLD and significant alcohol use in the same patient.AIM To review the existing data that evaluate the clinical profile and long-term outcome difference between the patients identified as MAFLD and NAFLD.METHODS Databases MEDLINE via PubMed and EMBASE were searched and relevant publications up to June 28,2022 were assessed.Studies were included if they involved human participants diagnosed with MAFLD.RESULTS A total of 2324 records were reviewed,of which 1575 duplicate citations were removed.Of the 2324 records screened,207 articles were excluded,and 542 articles were assessed for their eligibility,for which 511 were excluded.The remaining 31 articles were selected for review.MAFLD diagnostic criteria were able to identify more individuals with fatty liver.Studies have shown that patients included using the MAFLD criteria were associated with higher risks of hepatic fibrosis when compared to NAFLD.All-cause mortality,cardiovascular diseaserelated,and cancer-related mortality were shown to be higher in MAFLD patients.MAFLD patients also had higher baseline metabolic derangement,and risks of developing obesity,diabetes,and cardiovascular events.Of the 3 subtypes,diabetes mellitus has the strongest association with negative outcomes,followed by metabolic dysfunction and elevated body mass index.Within the subtypes of MAFLD,patients with more metabolic conditions at the time of diagnosis had worse hepatic and liver injury compared to those with a single metabolic condition.CONCLUSION MAFLD is a new definition of fatty liver disease that is gaining increasing acceptance.It is based on empirical clinical practice on positive inclusion of metabolic risk factors and recent evidence suggests that it helps to identify patients with higher risk for liver-related as well as cardiovascular events.

Madelung’s disease with alcoholic liver disease and acute kidney injury: A case report

BACKGROUND Madelung’s disease(MD)is a rare disorder of lipid metabolism,characterized by the growth of unencapsulated masses of adipose tissue symmetrically deposited around the neck,shoulders,or other sites around the body.Its pathological mechanism is not yet known.One of the most common comorbidities in MD patients is liver disease,especially chronic alcoholic liver disease(CALD);however,no reports exist of acute kidney injury(AKI)with MD.CASE SUMMARY We report a 60-year-old man who presented with complaint of edema in the lower limbs that had persisted for 3 d.Physical examination showed subcutaneous masses around the neck,and history-taking revealed the masses to have been present for 2 years and long-term heavy drinking.Considering the clinical symptoms,along with various laboratory test results and imaging characteristics,a diagnosis was made of MD with acute exacerbation of CALD and AKI.The patient was treated with liver function protection and traditional Chinese medicine,without surgical intervention.He was advised to quit drinking.After 10 d,the edema had subsided,renal function indicators returned to normal,liver function significantly improved,and size of subcutaneous masses remained stable.CONCLUSION In MD,concomitant liver or kidney complications are possible and monitoring of liver and kidney functions can be beneficial.