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...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.展开更多
Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that have insulin resistance in common and are associated with metabolic conditions such as obesity, type 2 diabetes mellitus, and dyslipidemia...Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that have insulin resistance in common and are associated with metabolic conditions such as obesity, type 2 diabetes mellitus, and dyslipidemia. NAFLD ranges from simple liver steatosis, which follows a benign course, to nonalcoholic steatohepatitis (NASH), a more severe entity, with necroinflmmation and f ibrosis, which can progress to cryptogenic cirrhosis and end-stage liver disease. Liver biopsy remains the gold standard for evaluating the degree of hepatic necroinflammation and f ibrosis; however, several noninvasive investigations, such as serum biomarkers, have been developed to establish the diagnosis and also to evaluate treatment response. These markers are currently neither available in all centers nor validated in extensive studies. Examples include high-sensitivity C reactive protein and plasma pentraxin 3, which are associated with extensive liver f ibrosis in NASH. Interleukin-6 correlates with inflammation, and cytokeratin-18 represents a marker of hepatocyte apoptosis (prominent in NASH and absent in simple steatosis). Tissue polypep-tide specif ic antigen seems to have a clinical utility in the follow-up of obese patients with NASH.展开更多
The occurrence of Metabolic Syndrome (MS) represents an independent risk factor for developing cardiovascular disease states in patients suffering from type 2 diabetes mellitus. Moreover, both the size of LDL particle...The occurrence of Metabolic Syndrome (MS) represents an independent risk factor for developing cardiovascular disease states in patients suffering from type 2 diabetes mellitus. Moreover, both the size of LDL particles and liver dysfunction identified as non alcoholic fatty liver disease (NAFLD) represent important biomarkers for the development of cardiometabolic risk in patients with MS. Here we studied the effect of bergamot polyphenolic fraction (BPF) in patients with MS and NAFLD. 107 patients were enrolled at the San Raffaele IRCCS (Rome). All of them showed ultrasonografic evidences of NAFLD and at least three out of five previous identified criteria for the diagnosis of MS. Patients were divided into two groups: one receiving placebo and the second receiving BPF 650 mg twice a day for 120 consecutive days. In the group receiving BPF 650 mg twice a day, a significant reduction of fasting plasma glucose, serum LDL cholesterol and triglycerides alongside with an increase of HDL cholesterol was found. This effect was accompanied by significant reduction of both ultrasonographic and metabolic biomarkers of NAFLD. Moreover, a significant reduction of small dense LDL particles, as detected via proton NMR Spectroscopy, was found after BPF treatment. In conclusion, our data confirm the beneficial effect of bergamot-extract in patients with MS an effect highlighted by significant reduction of small dense LDL particles and by improvement of NAFLD biomarkers. This suggests a potential preventive role of bergamot derivatives in reducing cardiometabolic risk.展开更多
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 inclus...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.展开更多
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 diseas...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.展开更多
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 cirrhosi...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.展开更多
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 establ...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.展开更多
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 ...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.展开更多
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 steatohepatiti...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.展开更多
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 child...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.展开更多
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 ...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.展开更多
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 retrieve...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.展开更多
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 co...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.展开更多
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...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.展开更多
BACKGROUND:Gut microbiota plays a significant role in the pathogenesis of non-alcoholic fatty liver disease(NAFLD)This study aimed to assess the contribution of gut microbiota dysbiosis to the pathogenesis of NAFLD.ME...BACKGROUND:Gut microbiota plays a significant role in the pathogenesis of non-alcoholic fatty liver disease(NAFLD)This study aimed to assess the contribution of gut microbiota dysbiosis to the pathogenesis of NAFLD.METHODS:Forty-seven human feces samples(25 NAFLD patients and 22 healthy subjects) were collected and 16 S r DNA amplicon sequencing was conducted on Hiseq 2000 platform Discrepancy of species composition between controls and NAFLD group was defined by Metastats analysis under P value<0.01.RESULTS:NAFLD patients harbored lower gut microbiota diversity than healthy subjects did.In comparison to the control group,the Proteobacteria(13.50%) and Fusobacteria(2.76%) phyla were more abundant in NAFLD patients.Additionally,the Lachnospiraceae(21.90%),Enterobacteriaceae(12.02%),Erysipelotrichaceae(3.83%),and Streptococcaceae(1.39%) families,as well as the Escherichia_Shigella(10.84%)Lachnospiraceae_Incertae_Sedis(7.79%),and Blautia(4.95%)genera were enriched in the NAFLD group.However,there was a lower abundance of Prevotella in the NAFLD group than that in the control group(5.83% vs 27.56%,P<0.01)The phylum Bacteroidetes(44.63%) also tended to be more abundant in healthy subjects,and the families Prevotellaceae(28.66%) and Ruminococcaceae(26.44%) followed the same trend.Compared to those without non-alcoholic steatohepatitis(NASH),patients with NASH had higher abundance of genus Blautia(5.82% vs 2.25%;P=0.01) and the corresponding Lachnospiraceae family(24.33% vs 14.21%;P<0.01).Patients with significant fibrosis had a higher abundance of genus Escherichia_Shigella(12.53% vs 1.97%;P<0.01) and the corresponding Enterobacteriaceae family(13.92% vs 2.07%;P<0.01) compared to those with F0/F1 fibrosis.CONCLUSIONS:NAFLD patients and healthy subjects harbor varying gut microbiota.In contrast to the results of previous research on children,decreased levels of Prevotella might be detrimental for adults with NAFLD.The increased level of the genus Blautia,the family Lachnospiraceae,the genus Escherichia_Shigella,and the family Enterobacteriaceae may be a primary contributor to NAFLD progression.展开更多
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 condit...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.展开更多
AIM: To investigate the prevalence of and risk factors for non-alcoholic fatty liver disease(NAFLD) in a Chinese population.METHODS: A total of 1948 adults from China was followed for 8 years. A cross-sectional study ...AIM: To investigate the prevalence of and risk factors for non-alcoholic fatty liver disease(NAFLD) in a Chinese population.METHODS: A total of 1948 adults from China was followed for 8 years. A cross-sectional study was performed to investigate the prevalence of NAFLD at baseline, and then the participants were followed for 8 years to investigate risk factors for the development of NAFLD.RESULTS: A total of 1948 participants were enrolled at baseline, of whom 691 were diagnosed with NAFLD. During the 8-year follow-up, 337 baseline NAFLD-free participants developed NAFLD. They had a greaterincrease in body mass index(BMI), serum uric acid, fasting plasma glucose, very low-density lipoprotein cholesterol and a considerable decrease in high-density lipoprotein cholesterol. 123 participants who had NAFLD at baseline lost NAFLD during the 8-year follow-up period. They had a greater decrease in BMI, fasting plasma glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase.CONCLUSION: NAFLD is prevalent in Chinese population with a rapidly increasing tendency. It can be reversed when patients lose their weight, control their hyperlipidemia and hyperglycemia, and reduce the liver enzyme levels.展开更多
Non-alcoholic fatty liver disease(NAFLD)is the most common liver disease in the world.Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis(NASH).NAFLD is a hepatic manifestation of...Non-alcoholic fatty liver disease(NAFLD)is the most common liver disease in the world.Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis(NASH).NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components.Up to80%of patients with NAFLD are obese,defined as a body mass index(BMI)>30 kg/m2.However,the distribution of fat tissue plays a greater role in insulin resistance than the BMI.The large amount of visceral adipose tissue(VAT)in morbidly obese(BMI>40 kg/m2)individuals contributes to a high prevalence of NAFLD.Free fatty acids derived from VAT tissue,as well as from dietary sources and de novo lipogenesis,are released to the portal venous system.Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD.In addition,secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways,which are also activated by free fatty acids,and contribute to insulin resistance.Most NAFLD patients are asymptomatic on clinical presentation,even though some may present with fatigue,dyspepsia,dull pain in the liver and hepatosplenomegaly.Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications,anti-obesity medication and bariatric surgery.This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease.The relative contribution of visceral and liver fat to insulin resistance is discussed,and recommendations for clinical evaluation of affected individuals is provided.展开更多
The current epidemic of non-alcoholic fatty liver disease(NAFLD) is reshaping the field of hepatology all around the world.The widespread diffusion of metabolic risk factors such as obesity,type2-diabetes mellitus,and...The current epidemic of non-alcoholic fatty liver disease(NAFLD) is reshaping the field of hepatology all around the world.The widespread diffusion of metabolic risk factors such as obesity,type2-diabetes mellitus,and dyslipidemia has led to a worldwide diffusion of NAFLD.In parallel to the increased availability of effective anti-viral agents,NAFLD is rapidly becoming the most common cause of chronic liver disease in Western Countries,and a similar trend is expected in Eastern Countries in the next years.This epidemic and its consequences have prompted experts from all over the word in identifying effective strategies for the diagnosis,management,and treatment of NAFLD.Different scientific societies from Europe,America,and Asia-Pacific regions have proposed guidelines based on the most recent evidence about NAFLD.These guidelines are consistent with the key elements in the management of NAFLD,but still,show significant difference about some critical points.We reviewed the current literature in English language to identify the most recent scientific guidelines about NAFLD with the aim to find and critically analyse the main differences.We distinguished guidelines from 5 different scientific societies whose reputation is worldwide recognised and who are representative of the clinical practice in different geographical regions.Differences were noted in: the definition of NAFLD,the opportunity of NAFLD screening in high-risk patients,the noninvasive test proposed for the diagnosis of NAFLD and the identification of NAFLD patients with advanced fibrosis,in the follow-up protocols and,finally,in the treatment strategy(especially in the proposed pharmacological management).These difference have been discussed in the light of the possible evolution of the scenario ofNAFLD in the next years.展开更多
The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistan...The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride(TG)accumulation.An olive oil-rich diet decreases accumulation of TGs in the liver,improves postprandial TGs,glucose and glucagonlike peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver.The principal mechanisms include:decreased nuclear factor-kappaB activation,decreased lowdensity lipoprotein oxidation,and improved insulin resistance by reduced production of inflammatory cytokines(tumor necrosis factor,interleukin-6)and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1.The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids,mainly from olive oil.In this review,we describe the dietary sources of the monounsaturated fatty acids,the composition of olive oil,dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis,clinical and experimental studies that assess the relationship between olive oil and NAFLD,and the mechanism by which olive oil ameliorates fatty liver,and we discuss future perspectives.展开更多
文摘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.
文摘Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that have insulin resistance in common and are associated with metabolic conditions such as obesity, type 2 diabetes mellitus, and dyslipidemia. NAFLD ranges from simple liver steatosis, which follows a benign course, to nonalcoholic steatohepatitis (NASH), a more severe entity, with necroinflmmation and f ibrosis, which can progress to cryptogenic cirrhosis and end-stage liver disease. Liver biopsy remains the gold standard for evaluating the degree of hepatic necroinflammation and f ibrosis; however, several noninvasive investigations, such as serum biomarkers, have been developed to establish the diagnosis and also to evaluate treatment response. These markers are currently neither available in all centers nor validated in extensive studies. Examples include high-sensitivity C reactive protein and plasma pentraxin 3, which are associated with extensive liver f ibrosis in NASH. Interleukin-6 correlates with inflammation, and cytokeratin-18 represents a marker of hepatocyte apoptosis (prominent in NASH and absent in simple steatosis). Tissue polypep-tide specif ic antigen seems to have a clinical utility in the follow-up of obese patients with NASH.
文摘The occurrence of Metabolic Syndrome (MS) represents an independent risk factor for developing cardiovascular disease states in patients suffering from type 2 diabetes mellitus. Moreover, both the size of LDL particles and liver dysfunction identified as non alcoholic fatty liver disease (NAFLD) represent important biomarkers for the development of cardiometabolic risk in patients with MS. Here we studied the effect of bergamot polyphenolic fraction (BPF) in patients with MS and NAFLD. 107 patients were enrolled at the San Raffaele IRCCS (Rome). All of them showed ultrasonografic evidences of NAFLD and at least three out of five previous identified criteria for the diagnosis of MS. Patients were divided into two groups: one receiving placebo and the second receiving BPF 650 mg twice a day for 120 consecutive days. In the group receiving BPF 650 mg twice a day, a significant reduction of fasting plasma glucose, serum LDL cholesterol and triglycerides alongside with an increase of HDL cholesterol was found. This effect was accompanied by significant reduction of both ultrasonographic and metabolic biomarkers of NAFLD. Moreover, a significant reduction of small dense LDL particles, as detected via proton NMR Spectroscopy, was found after BPF treatment. In conclusion, our data confirm the beneficial effect of bergamot-extract in patients with MS an effect highlighted by significant reduction of small dense LDL particles and by improvement of NAFLD biomarkers. This suggests a potential preventive role of bergamot derivatives in reducing cardiometabolic risk.
文摘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.
文摘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.
基金Supported by Merit Review grants BX001155 from the Department of Veterans Affairs,Office of Research and Development(Biomedical Laboratory Research and Development)to Kharbanda KK
文摘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.
基金Supported by the Spanish Ministry of Science and Innovation,Instituto de Salud Carlos Ⅲ and the European Union FEDER funds,Una manera de hacer Europa,(No.PI16/01548 to Miguel Marcos and No.RD16/0017/0023 to Francisco-Javier Laso)Junta de Castilla y León GRS 1362/A/16 and INT/M/17/17 to Miguel Marcos and GRS 1587/A/17 to Jorge-Luis Torres
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
基金Supported by The Medical Faculty of the Heinrich Heine University Düsseldorf
文摘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.
基金Supported by The Swiss National Science Foundation, No. 32003B-134963/1"Sir Jules Thorn Trust Reg" Foundation+4 种基金Gustave and Simone Prévot Foundation to Montecucco FEU FP7 AtheroRemo, No. 201668Swiss National Science Foundation, No. 310030B-133127Novartis FoundationSwiss Heart Foundation to Mach F
文摘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.
文摘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.
基金supported by grants from the National Key Basic Research Project(2012CB517501)the Chinese Foundation for Hepatitis Prevention and Control--“Wang Bao-En” Liver Fibrosis Research Foundation(XJS20120501)the National Natural Science Foundation of China(81400610)
文摘BACKGROUND:Gut microbiota plays a significant role in the pathogenesis of non-alcoholic fatty liver disease(NAFLD)This study aimed to assess the contribution of gut microbiota dysbiosis to the pathogenesis of NAFLD.METHODS:Forty-seven human feces samples(25 NAFLD patients and 22 healthy subjects) were collected and 16 S r DNA amplicon sequencing was conducted on Hiseq 2000 platform Discrepancy of species composition between controls and NAFLD group was defined by Metastats analysis under P value<0.01.RESULTS:NAFLD patients harbored lower gut microbiota diversity than healthy subjects did.In comparison to the control group,the Proteobacteria(13.50%) and Fusobacteria(2.76%) phyla were more abundant in NAFLD patients.Additionally,the Lachnospiraceae(21.90%),Enterobacteriaceae(12.02%),Erysipelotrichaceae(3.83%),and Streptococcaceae(1.39%) families,as well as the Escherichia_Shigella(10.84%)Lachnospiraceae_Incertae_Sedis(7.79%),and Blautia(4.95%)genera were enriched in the NAFLD group.However,there was a lower abundance of Prevotella in the NAFLD group than that in the control group(5.83% vs 27.56%,P<0.01)The phylum Bacteroidetes(44.63%) also tended to be more abundant in healthy subjects,and the families Prevotellaceae(28.66%) and Ruminococcaceae(26.44%) followed the same trend.Compared to those without non-alcoholic steatohepatitis(NASH),patients with NASH had higher abundance of genus Blautia(5.82% vs 2.25%;P=0.01) and the corresponding Lachnospiraceae family(24.33% vs 14.21%;P<0.01).Patients with significant fibrosis had a higher abundance of genus Escherichia_Shigella(12.53% vs 1.97%;P<0.01) and the corresponding Enterobacteriaceae family(13.92% vs 2.07%;P<0.01) compared to those with F0/F1 fibrosis.CONCLUSIONS:NAFLD patients and healthy subjects harbor varying gut microbiota.In contrast to the results of previous research on children,decreased levels of Prevotella might be detrimental for adults with NAFLD.The increased level of the genus Blautia,the family Lachnospiraceae,the genus Escherichia_Shigella,and the family Enterobacteriaceae may be a primary contributor to NAFLD progression.
基金Supported by The National Key Research and Development Program of China,No.2016YFC1305301
文摘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.
基金Supported by the National Natural Science Foundation of China,No.81372425 and No.81460634the Key Lab Project of the Xinjiang Science and Technology Bureau,No.2014KL002
文摘AIM: To investigate the prevalence of and risk factors for non-alcoholic fatty liver disease(NAFLD) in a Chinese population.METHODS: A total of 1948 adults from China was followed for 8 years. A cross-sectional study was performed to investigate the prevalence of NAFLD at baseline, and then the participants were followed for 8 years to investigate risk factors for the development of NAFLD.RESULTS: A total of 1948 participants were enrolled at baseline, of whom 691 were diagnosed with NAFLD. During the 8-year follow-up, 337 baseline NAFLD-free participants developed NAFLD. They had a greaterincrease in body mass index(BMI), serum uric acid, fasting plasma glucose, very low-density lipoprotein cholesterol and a considerable decrease in high-density lipoprotein cholesterol. 123 participants who had NAFLD at baseline lost NAFLD during the 8-year follow-up period. They had a greater decrease in BMI, fasting plasma glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase.CONCLUSION: NAFLD is prevalent in Chinese population with a rapidly increasing tendency. It can be reversed when patients lose their weight, control their hyperlipidemia and hyperglycemia, and reduce the liver enzyme levels.
文摘Non-alcoholic fatty liver disease(NAFLD)is the most common liver disease in the world.Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis(NASH).NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components.Up to80%of patients with NAFLD are obese,defined as a body mass index(BMI)>30 kg/m2.However,the distribution of fat tissue plays a greater role in insulin resistance than the BMI.The large amount of visceral adipose tissue(VAT)in morbidly obese(BMI>40 kg/m2)individuals contributes to a high prevalence of NAFLD.Free fatty acids derived from VAT tissue,as well as from dietary sources and de novo lipogenesis,are released to the portal venous system.Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD.In addition,secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways,which are also activated by free fatty acids,and contribute to insulin resistance.Most NAFLD patients are asymptomatic on clinical presentation,even though some may present with fatigue,dyspepsia,dull pain in the liver and hepatosplenomegaly.Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications,anti-obesity medication and bariatric surgery.This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease.The relative contribution of visceral and liver fat to insulin resistance is discussed,and recommendations for clinical evaluation of affected individuals is provided.
文摘The current epidemic of non-alcoholic fatty liver disease(NAFLD) is reshaping the field of hepatology all around the world.The widespread diffusion of metabolic risk factors such as obesity,type2-diabetes mellitus,and dyslipidemia has led to a worldwide diffusion of NAFLD.In parallel to the increased availability of effective anti-viral agents,NAFLD is rapidly becoming the most common cause of chronic liver disease in Western Countries,and a similar trend is expected in Eastern Countries in the next years.This epidemic and its consequences have prompted experts from all over the word in identifying effective strategies for the diagnosis,management,and treatment of NAFLD.Different scientific societies from Europe,America,and Asia-Pacific regions have proposed guidelines based on the most recent evidence about NAFLD.These guidelines are consistent with the key elements in the management of NAFLD,but still,show significant difference about some critical points.We reviewed the current literature in English language to identify the most recent scientific guidelines about NAFLD with the aim to find and critically analyse the main differences.We distinguished guidelines from 5 different scientific societies whose reputation is worldwide recognised and who are representative of the clinical practice in different geographical regions.Differences were noted in: the definition of NAFLD,the opportunity of NAFLD screening in high-risk patients,the noninvasive test proposed for the diagnosis of NAFLD and the identification of NAFLD patients with advanced fibrosis,in the follow-up protocols and,finally,in the treatment strategy(especially in the proposed pharmacological management).These difference have been discussed in the light of the possible evolution of the scenario ofNAFLD in the next years.
文摘The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride(TG)accumulation.An olive oil-rich diet decreases accumulation of TGs in the liver,improves postprandial TGs,glucose and glucagonlike peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver.The principal mechanisms include:decreased nuclear factor-kappaB activation,decreased lowdensity lipoprotein oxidation,and improved insulin resistance by reduced production of inflammatory cytokines(tumor necrosis factor,interleukin-6)and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1.The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids,mainly from olive oil.In this review,we describe the dietary sources of the monounsaturated fatty acids,the composition of olive oil,dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis,clinical and experimental studies that assess the relationship between olive oil and NAFLD,and the mechanism by which olive oil ameliorates fatty liver,and we discuss future perspectives.
