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.

Metabolic-associated fatty liver disease and sarcopenia:A double whammy

The prevalence of metabolic-associated fatty liver disease(MAFLD)has increased substantially in recent years because of the global obesity pandemic.MAFLD,now recognized as the number one cause of chronic liver disease in the world,not only increases liver-related morbidity and mortality among sufferers but also worsens the complications associated with other comorbid conditions such as cardiovascular disease,type 2 diabetes mellitus,obstructive sleep apnoea,lipid disorders and sarcopenia.Understanding the interplay between MAFLD and these comorbidities is important to design optimal therapeutic strategies.Sarcopenia can be either part of the disease process that results in MAFLD(e.g.,obesity or adiposity)or a consequence of MAFLD,especially in the advanced stages such as fibrosis and cirrhosis.Sarcopenia can also worsen MAFLD by reducing exercise capacity and by the production of various muscle-related chemical factors.Therefore,it is crucial to thoroughly understand how we deal with these diseases,especially when they coexist.We explore the pathobiological interlinks between MAFLD and sarcopenia in this comprehensive clinical update review article and propose evidence-based therapeutic strategies to enhance patient care.

Prevalence,clinical characteristics,risk factors,and indicators for lean Chinese adults with nonalcoholic fatty liver disease

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic diseases in the world.Nowadays,the percentage of non-obese or lean patients with NAFLD is increasing.NAFLD in non-obese populations,especially the lean subgroup with a normal waist circumference(WC),might lead to more problems than obese individuals,as these individuals may not visit clinics for NAFLD diagnosis or ignore the diagnosis of NAFLD.If the precise characteristics of these populations,especially the lean subgroup,are identified,the clinicians would be able to provide more appropriate advice and treatment to these populations.AIM To investigate the prevalence,clinical characteristics,risk factors,and possible indicators for NAFLD in lean Chinese adults with a normal WC.METHODS People without diabetes mellitus or significant alcohol consumption who underwent routine health examinations were included.Their fatty liver index(FLI),abdominal ultrasonography results,and controlled attenuation parameter were all assessed.Genotyping for single-nucleotide polymorphisms associated with NAFLD was performed in another small group consisting of biopsy-proven NAFLD subjects and healthy controls.RESULTS A total of 2715 subjects who underwent routine health examinations were included in the study.Among 810 lean participants with a normal WC,142(17.5%)fulfilled the diagnostic criteria for NAFLD.Waist-height ratio,hemoglobin,platelets,and triglycerides were significant factors associated with the presence of NAFLD in these participants.The appropriate cut-off value of the FLI score in screening for NAFLD in the lean subjects with a normal WC was 25.15,which had a 77.8%sensitivity and 75.9%specificity.There was no significant difference in the single-nucleotide polymorphisms in the SIRT1,APOC3,PNPLA3,AGTR1,and PPARGC1A genes between lean subjects with and without NAFLD(P<0.05).CONCLUSION NAFLD is not uncommon in lean Chinese adults even with a normal WC.Metabolic factors,rather than genetic factors,may play important roles in the development of NAFLD in this population.A lower cut-off value of the FLI score in screening for NAFLD should be used for lean Chinese adults with a normal WC.

Update in lean metabolic dysfunction-associated steatotic liver disease

BACKGROUND A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease(MAFLD).They are now defined as metabolic dysfunction-associated steatotic liver disease(MASLD),which includes cardiometabolic criteria in adults.This condition,extensively studied in obese or overweight patients,constitutes around 30%of the population,with a steady increase worldwide.Lean patients account for approximately 10%-15%of the MASLD population.However,the pathogenesis is complex and is not well understood.AIM To systematically review the literature on the diagnosis,pathogenesis,characteristics,and prognosis in lean MASLD patients and provide an interpretation of these new criteria.METHODS We conducted a comprehensive database search on PubMed and Google Scholar between January 2012 and September 2023,specifically focusing on lean NAFLD,MAFLD,or MASLD patients.We include original articles with patients aged 18 years or older,with a lean body mass index categorized according to the World Health Organization criteria,using a cutoff of 25 kg/m2 for the general population and 23 kg/m2 for the Asian population.RESULTS We include 85 studies in our analysis.Our findings revealed that,for lean NAFLD patients,the prevalence rate varied widely,ranging from 3.8%to 34.1%.The precise pathogenesis mechanism remained elusive,with associations found in genetic variants,epigenetic modifications,and adaptative metabolic response.Common risk factors included metabolic syndrome,hypertension,and type 2 diabetes mellitus,but their prevalence varied based on the comparison group involving lean patients.Regarding non-invasive tools,Fibrosis-4 index outperformed the NAFLD fibrosis score in lean patients.Lifestyle modifications aided in reducing hepatic steatosis and improving cardiometabolic profiles,with some medications showing efficacy to a lesser extent.However,lean NAFLD patients exhibited a worse prognosis compared to the obese or overweight counterpart.CONCLUSION MASLD is a complex disease comprising epigenetic,genetic,and metabolic factors in its pathogenesis.Results vary across populations,gender,and age.Limited data exists on clinical practice guidelines for lean patients.Future studies employing this new nomenclature can contribute to standardizing and generalizing results among lean patients with steatotic liver disease.

Lean-non-alcoholic fatty liver disease increases risk for metabolic disorders in a normal weight Chinese population

AIM:To study the prevalence and clinical biochemical,blood cell and metabolic features of lean-non-alcoholic fatty liver disease(lean-NAFLD)and its association with other diseases.METHODS:Demographic,biochemical and blood examinations were conducted in all the subjects in this study.We classified the subjects into four groups according to their weight and NAFLD status:lean-control,lean-NAFLD[body mass index(BMI)<24 kg/m2],overweight-obese control and overweight-obese NAFLD.One-way analysis of variance(ANOVA)was used to compare the means of continuous variables(age,BMI,blood pressure,glucose,lipid,insulin,liver enzymes and blood cell counts)and theχ2 test was used to compare the differences in frequency of categorical variables(sex,education,physical activity,smoking,alcohol consumption and prevalence of hypertension,hyperlipidemia,diabetes,metabolic syndrome central obesity and obesity).Both univariate and multivariate logistic regression models were adopted to calculate odds ratios(ORs)and predict hyperlipidemia,hypertension,diabetes and metabolic syndrome when we respectively set all controls,lean-control and overweightobese-control as references.In multivariate logistic regression models,we adjusted potential confounding factors,including age,sex,smoking,alcohol consumption and physical activity.RESULTS:The prevalence of NAFLD was very high in China.NAFLD patients were older,had a higher BMI,waist circumference,blood pressure,fasting blood glucose,insulin,blood lipid,liver enzymes and uric acid than the controls.Although lean-NAFLD patients had lower BMI and waist circumstance,they had significantly higher visceral adiposity index than overweightobese controls.Lean-NAFLD patients had comparable triglyceride,cholesterin and low-density lipoprotein cholesterin to overweight-obese NAFLD patients.In blood cell examination,both lean and overweightobese NAFLD was companied by higher white blood cell count,red blood cell count,hemoglobin and hematocrit value.All NAFLD patients were at risk of hyperlipidemia,hypertension,diabetes and metabolic syndrome(Met S).Lean-NAFLD was more strongly associated with diabetes(OR=2.47,95%CI:1.14-5.35),hypertension(OR=1.72,95%CI:1.00-2.96)and Met S(OR=3.19,95%CI:1.17-4.05)than overweight-obese-NAFLD(only OR for Met S was meaningful:OR=1.89,95%CI:1.29-2.77).NAFLD patients were more likely to have central obesity(OR=1.97,95%CI:1.38-2.80),especially in lean groups(OR=2.17,95%CI:1.17-4.05).CONCLUSION:Lean-NAFLD has unique results in demographic,biochemical and blood examinations,and adds significant risk for diabetes,hypertension and Met S in lean individuals.

Nonalcoholic fatty liver disease in lean subjects:Prognosis,outcomes and management

Nonalcoholic fatty liver disease(NAFLD)accounts for most cases of chronic liver disease worldwide,with an estimated global prevalence of approximately 25%and ranges from simple steatosis to nonalcoholic steatohepatitis and cirrhosis.NAFLD is strongly connected to metabolic syndrome,and for many years,fatty liver was considered to be an exclusive feature of obese patients.However,recent studies have highlighted the presence of NAFLD in non-obese subjects,with or without increased visceral fat or even in lean subjects without increased waist circumference.“Lean NAFLD”is a relatively new concept and there is significant scientific interest in understanding the differences in pathophysiology,prognosis and management compared with NAFLD in overweight/obese patients.In the present editorial,we discuss the clinical and metabolic profiles and outcomes of lean NAFLD compared with both obese NAFLD and lean healthy individuals from Asian and Western countries.Moreover,we shed light to the challenging topic of management of NAFLD in lean subjects since there are no specific guidelines for this population.Finally,we discuss open questions and issues to be addressed in the future in order to categorize NAFLD patients into lean and nonlean cohorts.

Shifting perspectives-interplay between non-alcoholic fatty liver disease and insulin resistance in lean individuals

Non-alcoholic fatty liver disease(NAFLD)has become a significant public health burden affecting not only obese individuals but also people with normal weight.As opposed to previous beliefs,this particular subset of patients has an increased risk of all-cause mortality and worse outcomes than their obese counterparts.The development of NAFLD in lean subjects seems to be interconnected with metabolic phenotype,precisely visceral fat tissue,sarcopenia,and insulin resistance.Here,we summarize available data focusing on the co-dependent relationship between metabolic phenotype,insulin resistance,and development of NAFLD in lean individuals,suggesting more appropriate tools for measuring body fat distribution for the screening of patients at risk.

Determination of “indeterminate score” measurements in lean nonalcoholic fatty liver disease patients from western Saudi Arabia

BACKGROUND Noninvasive measures to estimate liver fibrosis in lieu of biopsy in nonalcoholic liver disease(NAFLD)can broadly differentiate high vs low degrees of condition extent.However,an“indeterminate score”necessitates further clinical investigation and biopsy becomes essential,highlighting the need for identification of other noninvasive factors with accuracy for this midlevel extent and its prognosis.Lean NAFLD cases are of particular interest regarding this issue,as they present as otherwise healthy,and will benefit greatly from the less invasive assessment.AIM To estimate the agreement of two noninvasive assessment tools in lean NAFLD patients,and assess factors related to indeterminate scores.METHODS Ultrasound-diagnosed NAFLD patients,without sign of other chronic liver disease(n=1262),were enrolled from a tertiary private medical centre between 2016-2019.After grouping by body mass index(obese,overweight,and lean),each participant underwent FibroScan.NAFLD fibrosis score(NFS)was used for subclassification(lower,higher,and indeterminate).No patient underwent liver biopsy.The kappa statistic was used to assess inter-rater agreement between the three groups on liver fibrosis degree assessed via FibroScan and NFS.Indeterminate score among the three groups was assessed to identify factors that predict its determination.RESULTS The NAFLD study cohort was composed of lean(159/1262,12.6%),overweight(365/1262,29%)and obese(737/1262,58.4%)individuals.The lean patients were significantly younger(49.95±15.3 years,P<0.05),with higher serum high density lipoprotein(52.56±16.27 mg/dL,P<0.001)and lower prevalences of type 2 diabetes mellitus,hypertension and hyperlipidaemia.All groups showed a predominance of lower fibrosis degree.The lean NAFLD patients showed a significantly lower NFS(P<0.001).Degree of agreement between FibroScan and NFS was fair between the lean and obese NAFLD categories,and moderate in the overweight category.NFS was predictive of indeterminate score.Age was a factor among all the body mass index(BMI)categories;other associated factors,but with less strength,were serum alanine aminotransferase in the overweight category and BMI in the obese category.CONCLUSION Lean NAFLD patients showed lower degree and prevalence of liver fibrosis by NFS;however,follow-up biopsy is still needed.

A Cross Sectional Study on the Correlation between Waist Circumference and Fatty Liver on Ultrasonography among Non-Alcoholic Filipino Adults

Objectives: This study aimed to determine the correlation between waist circumference and fatty liver on ultrasonography among non-alcoholic Filipino adults. This will aid in detecting non-alcoholic fatty liver disease in its early course, hence improving our current therapeutic recommendations in preventing and managing the adverse health outcomes of NAFLD. Methods and Materials: A cross-sectional study with a total of 65 recruited participants. The data collected were age, sex, waist-circumference, co-morbidities with maintenance medications, history of alcohol intake with emphasis on the quantity and duration, and history of drug intake. Waist circumference was measured and recorded. The presence of NAFLD was determined through a review of the ultrasonography results of all subjects. The demographic profile and waist circumference of all subjects were described using descriptive statistics. The chi-square test was utilized to test the independence of the NAFLD and WC in the quartile. Pearson correlation was used to determine the linear relationship between the variables. Pearson correlation coefficient was statistically significant at p 0.05. Results: Among the subjects, 26 (42%) presented with fatty liver based on ultrasonography, 15 (58%) and 11 (42%), males and females, respectively. The mean waist circumference of 97.5 ± 12.43 was significantly related to the fatty liver with a p-value of 0.0001. Waist circumference showed a positive correlation with the frequency of fatty liver on ultrasonography with p-values of 0.000755 (r = 0.590083) and 3.04366E—05 (r = 0.659143523), in males and females, correspondingly. The overall correlation between waist circumference and fatty liver on ultrasonography is statistically significant with a p-value of 4.10503E—08 (r = 0.634737127). Conclusion: One measure used to assess central obesity is waist circumference. In addition, it can also be utilized to assess risk for NAFLD since they are strongly correlated as reported in this study. Waist circumference cut-off values for the Filipinos proposed in this study are the following: >88 cm and >95 cm, in males and females, respectively.

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.

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.

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.

Silymarin in non alcoholic fatty liver disease

AIM: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD). METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory parameters were assayed after 3 mo of a restricted diet and before silymarin treatment (twice a day orally). The brightness of liver echography texture (hepatorenal ratio brightness) was also defined at same time. These evaluations were repeated after 6 mo of treatment. RESULTS: Serum levels of some metabolic and anti-inflammatory data nonsignificantly lowered after 6 mo of silymarin. On the contrary, Steato test, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase were significantly (P < 0.001) reduced. Instead, the AST/ALT ratio unchanged. Finally, the hepatorenal brightness ratio, as an index of hepatic steatosis, significantly (P < 0.05) dropped. CONCLUSION: The obtained results indicate that silymarin appears to be effective to reduce the biochemical, inflammatory and ultrasonic indices of hepatic steatosis. Some parameters indicative of early stage of atherosclerosis were also lowered.

Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions

Non-alcoholic fatty liver disease(NAFLD) in children is becoming a major health concern. A "multiple-hit" pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance(IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis(NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data(BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR(acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy(the "imperfect" gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention.Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended lifestyle changes. When morbid obesity prevails, bariatric surgery should be considered.

Pathogenesis and management issues for non-alcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) has, although it is a very common disorder, only relatively recently gained broader interest among physicians and scientists. Fatty liver has been documented in up to 10 to 15 percent of normal individuals and 70 to 80 percent of obese individuals. Although the pathophysiology of NAFLD is still subject to intensive research, several players and mechanisms have been suggested based on the substantial evidence. Excessive hepatocyte triglyceride accumulation resulting from insulin resistance is the first step in the proposed 'two hit' model of the pathogenesis of NAFLD. Oxidative stress resulting from mitochondrial fatty acids oxidation, NF-κB-dependent inflammatory cytokine expression and adipocytokines are all considered to be the potential factors causing second hits which lead to hepatocyte injury, inflammation and fibrosis. Although it was initially believed that NAFLD is a completely benign disorder, histologic follow-up studies have showed that fibrosis progression occurs in about a third of patients. A small number of patients with NAFLD eventually ends up with end-stage liver disease and even hepatocellular carcinoma. Although liver biopsy is currently the only way to confirm the NAFLD diagnosis and distinguish between fatty liver alone and NASH, no guidelines or firm recommendations can still be made as for when and in whom it is necessary. Increased physical activity, gradual weight reduction and in selected cases bariatric surgery remain the mainstay of NAFLD therapy. Studies with pharmacologic agents are showing promising results, but available data are still insufficient to make specific recommendations; their use therefore remains highly individual.

Role of cytokines and chemokines in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological conditions (ranging from liver steatosis and steatohepatitis, to fibrosis and hepatocarcinoma) that are characterized by an increased fat content within the liver. The accumulation/deposition of fat within the liver is essential for diagnosis of NAFLD and might be associated with alterations in the hepatic and systemic inflammatory state. Although it is still unclear if each histological entity represents a different disease or rather steps of the same disease, inflammatory processes in NAFLD might influence its pathophysiology and prognosis. In particular, non-alcoholic steatohepatitis (the most inflamed condition in NAFLDs, which more frequently evolves towards chronic and serious liver diseases) is characterized by a marked activation of inflammatory cells and the upregulation of several soluble inflammatory mediators. Among several mediators, cytokines and chemokines might play a pivotal active role in NAFLD and are considered as potential therapeutic targets. In this review, we will update evidence from both basic research and clinical studies on the potential role of cytokines and chemokines in the pathophysiology of NAFLD.

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.

Non-alcoholic fatty liver disease in 2015

There is worldwide epidemic of non-alcoholic fatty liver disease(NAFLD). NAFLD is a clinical entity related to metabolic syndrome. Majority of the patients are obese but the disease can affect non-obese individuals as well. Metabolic factors and genetics play important roles in the pathogenesis of this disorder. The spectrum of disorders included in NAFLD are benign macrovesicular hepatic steatosis, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhosis of liver and hepatocellular carcinoma. Although the disease remains asymptomatic most of the time, it can slowly progress to end stage liver disease. It will be the most common indication of liver transplantation in the future. It is diagnosed by abnormal liver chemistry, imaging studies and liver biopsy. As there are risks of potential complications during liver biopsy, many patients do not opt for liver biopsy. There are some noninvasive scoring systems to find out whether patients have advanced hepatic fibrosis. At the present time, there are limited treatment options which include lifestyle modification to loose weight, vitamin E and thioglitazones. Different therapeutic agents are being investigated for optimal management of this entity. There are some studies done on incretin based therapies in patients with NAFLD. Other potential agents will be silent information regulator protein Sirtuin and antifibrotic monoclonal antibody Simtuzumab against lysyl oxidase like molecule 2. But they are still in the investigational phase.

Pathogenesis of non-alcoholic fatty liver disease in children and adolescence: From “two hit theory” to “multiple hit model”

Nonalcoholic fatty liver disease(NAFLD) has become the dominant form of chronic liver disease in children and adolescents with the increasing prevalence of obesity worldwide. NAFLD represents a wide spectrum of conditions, ranging from fatty liver-which generally follows a benign, non-progressive clinical course-to non-alcoholic steatohepatitis, a subset of NAFLD that may progress to cirrhosis and end-stage liver disease or liver carcinoma. The underlying pathophysiological mechanism of "pediatric" NAFLD remains unclear, although it is strongly associated with obesity and insulin resistance. In this review we provide a general overview on the current understanding of NAFLD in children and adolescents, which underpins practice, enabling early diagnosis and appropriate therapeutic intervention for this life-threatening liver disease.