Predictors of Liver Fat and Stiffness in Non-Alcoholic Fatty Liver Disease (NAFLD) - an 11-Year Prospective Study.
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ABSTRACT:
SUBMITTER: Lallukka S
PROVIDER: S-EPMC5674024 | biostudies-literature | 2017 Nov
REPOSITORIES: biostudies-literature
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Predictors of Liver Fat and Stiffness in Non-Alcoholic Fatty Liver Disease (NAFLD) - an 11-Year Prospective Study.
Lallukka Susanna S Sädevirta Sanja S Kallio Markus T MT Luukkonen Panu K PK Zhou You Y Hakkarainen Antti A Lundbom Nina N Orho-Melander Marju M Yki-Järvinen Hannele H
Scientific reports 20171106 1
Liver fat can be non-invasively measured by proton magnetic resonance spectroscopy (<sup>1</sup>H-MRS) and fibrosis estimated as stiffness using transient elastography (FibroScan). There are no longitudinal data on changes in liver fat in Europids or on predictors of liver stiffness using these methods. We determined liver fat (<sup>1</sup>H-MRS) and clinical characteristics including features of insulin resistance at baseline and after a median follow-up period of 11.3 (range 7.3-13.4) years in ...[more]
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Project description:ObjectivesTo clarify non-alcoholic fatty liver disease (NAFLD) prevalence, risk factors and clinical outcome in an exemplary Chinese population, a cohort of company employees was followed up for 11 years.DesignRetrospective cohort study.SettingBetween 2006 and 2016 in Ning bo, China.Participants13 032 company employees.ResultsOver 11 years, the prevalence of NAFLD increased from 17.2% to 32.4% (men 20.5%-37% vs women 9.8%-22.2%). Male peak prevalence was between 40 and 60 years of age, whereas highest prevalence in women was at an age of 60 years and older. Logistic and Cox regression revealed 16 risk factors, including body mass index (BMI), albumin, white blood cell, triglycerides (TG), high-density lipoprotein, glutamyl transpeptidase, alanine transaminase, creatinine, urea acid, glucose, systolic blood pressure, diastolic blood pressure, blood sedimentation, haemoglobin, platelet and apolipoprotein B2 (p<0.05 for all factors). The area under the curve of these variables for NAFLD is 0.88. However, cause-effect analyses showed that only BMI, gender and TG directly contributed to NAFLD development. Over an 11-year follow-up period, 12.6%, 37.7% and 14.2% of male patients with NAFLD and 11.6%, 44.7% and 22.6% of female patients with NAFLD developed diabetes, hypertension and hyperuricaemia, respectively. Except one male patient who developed cirrhosis, no patients with NAFLD progressed into severe liver disease.ConclusionDiabetes, hypertension and hyperuricaemia are the main clinical outcomes of NAFLD. Eleven years of NAFLD are not sufficient to cause severe liver disease. Age and obesity are direct risk factors for NAFLD. BMI, gender and TG are three parameters directly reflecting the occurrence of NAFLD.
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Project description:Irisin is a cytokine involved in many metabolic pathways occurring, among others, in muscles, adipose tissue and liver. Thus, fluctuations in irisin levels are suggested to be related to metabolic diseases. Therefore, the purpose of our study was to evaluate whether irisin may be associated with non-alcoholic fatty liver disease (NAFLD). A total of 138 patients (70/68 male/female, mean age 65.61 ± 10.44 years) were enrolled in the study. The patients were assigned to the NAFLD group (n = 72, including 46 patients with type 2 diabetes (T2DM]) and the group without NAFLD (n = 66, 31 patients with T2DM). NAFLD was diagnosed based on ultrasound examination, Hepatic Steatosis Index (HSI) and Fatty Liver Index. Baseline anthropometric, blood pressure and biochemical parameters were collected. The serum irisin level was determined using an ELISA test. We observed that NAFLD was associated with an increased concentration of irisin. Moreover, Spearman correlations and linear regression analysis revealed that irisin level correlates with some anthropometric and biochemical parameters such as body mass index, glycated hemoglobin, aspartic aminotransferase, creatinine and urea. Logistic regression analysis depicted that odds for NAFLD increase 1.17 times for each 1 μg/mL rise of irisin concentration. Finally, ROC analysis showed that the concentration of irisin possesses a discriminate capacity for NAFLD and optimal cut points concentration could be designed. The risk of NAFLD in the subgroup with irisin concentration above 3.235 μg/mL was 4.57 times higher than in patients with the lower concentration of irisin. To conclude, the obtained results suggest that irisin concentration is associated with some anthropometric and biochemical parameters and should be further investigated toward its usage as a diagnostic biomarker of NAFLD.
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Project description:Vitamin A is required for important physiological processes, including embryogenesis, vision, cell proliferation and differentiation, immune regulation, and glucose and lipid metabolism. Many of vitamin A's functions are executed through retinoic acids that activate transcriptional networks controlled by retinoic acid receptors (RARs) and retinoid X receptors (RXRs).The liver plays a central role in vitamin A metabolism: (1) it produces bile supporting efficient intestinal absorption of fat-soluble nutrients like vitamin A; (2) it produces retinol binding protein 4 (RBP4) that distributes vitamin A, as retinol, to peripheral tissues; and (3) it harbors the largest body supply of vitamin A, mostly as retinyl esters, in hepatic stellate cells (HSCs). In times of inadequate dietary intake, the liver maintains stable circulating retinol levels of approximately 2 ?mol/L, sufficient to provide the body with this vitamin for months. Liver diseases, in particular those leading to fibrosis and cirrhosis, are associated with impaired vitamin A homeostasis and may lead to vitamin A deficiency. Liver injury triggers HSCs to transdifferentiate to myofibroblasts that produce excessive amounts of extracellular matrix, leading to fibrosis. HSCs lose the retinyl ester stores in this process, ultimately leading to vitamin A deficiency. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is a spectrum of conditions ranging from benign hepatic steatosis to non-alcoholic steatohepatitis (NASH); it may progress to cirrhosis and liver cancer. NASH is projected to be the main cause of liver failure in the near future. Retinoic acids are key regulators of glucose and lipid metabolism in the liver and adipose tissue, but it is unknown whether impaired vitamin A homeostasis contributes to or suppresses the development of NAFLD. A genetic variant of patatin-like phospholipase domain-containing 3 (PNPLA3-I148M) is the most prominent heritable factor associated with NAFLD. Interestingly, PNPLA3 harbors retinyl ester hydrolase activity and PNPLA3-I148M is associated with low serum retinol level, but enhanced retinyl esters in the liver of NAFLD patients. Low circulating retinol in NAFLD may therefore not reflect true "vitamin A deficiency", but rather disturbed vitamin A metabolism. Here, we summarize current knowledge about vitamin A metabolism in NAFLD and its putative role in the progression of liver disease, as well as the therapeutic potential of vitamin A metabolites.
| S-EPMC5793257 | biostudies-other
Project description: Not available
| S-EPMC1954961 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) is a series of diseases, involving excessive lipid deposition in the liver and is often accompanied by obesity, diabetes, dyslipidemia, abnormal blood pressure, and other metabolic disorders. In order to more accurately reflect its pathogenesis, an international consensus renamed NAFLD in 2020 as metabolic (dysfunction) associated with fatty liver disease (MAFLD). The changes in diet and lifestyle are recognized the non-drug treatment strategies; however, due to the complex pathogenesis of NAFLD, the current drug therapies are mainly focused on its pathogenic factors, key links of pathogenesis, and related metabolic disorders as targets. There is still a lack of specific drugs. In clinical studies, the common NAFLD treatments include the regulation of glucose and lipid metabolism to protect the liver and anti-inflammation. The NAFLD treatments based on the enterohepatic axis, targeting gut microbiota, are gradually emerging, and various new metabolism-regulating drugs are also under clinical development. Therefore, this review article has comprehensively discussed the research advancements in NAFLD treatment in recent years.
| S-EPMC9884828 | biostudies-literature
Project description:PurposeThe Trivandrum non-alcoholic fatty liver disease (NAFLD) cohort is a population-based study designed to examine the interaction between genetic and lifestyle factors and their association with increased risk of NAFLD within the Indian population.ParticipantsBetween 2013 and 2016, a total of 2222 participants were recruited to this cohort through multistage cluster sampling across the whole population of Trivandrum-a district within the state of Kerala, South India. Data were collected from all inhabitants of randomly selected households over the age of 25.Findings to dateFull baseline clinical and pathological data were collected from 2158 participants. This included detailed demographic profiles, anthropometric measures and lifestyle data (food frequency, physical activity and anxiety and depression questionnaires). Biochemical profile and ultrasound assessment of the liver were performed and whole blood aliquots were collected for DNA analysis.The NAFLD prevalence within this population was 49.8% which is significantly higher than the global pooled prevalence of 25%. This highlights the importance of robust, prospective studies like this to enable collection of longitudinal data on risk factors, disease progression and to facilitate future interventional studies.Future plansThe complete analysis of data collected from this cohort will give valuable insights into the interaction of the phenotypic and genotypic profiles that result in such a dramatic increased risk of NAFLD within the Indian population. The cohort will also form the basis of future lifestyle interventional studies, aimed at improving liver and metabolic health.
| S-EPMC6502065 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) refers to a spectrum of diseases involving the deposition of fat in the hepatocytes of people with little to no alcohol consumption. NAFLD is associated with hypertension, diabetes, obesity, etc. As their prevalence increases, the propensity and severity of NAFLD might increase. As per the recently developed multi-hit hypothesis, factors like oxidative stress, genetic predisposition, lipotoxicity, and insulin resistance have been found to play a key role in the development of NAFLD and its associated complications. This article focuses on NAFLD, its pathophysiology, risk factors, and the various genetic and epigenetic factors involved in its development along with possible treatment modalities. We conducted an all-language literature search on Medline, Cochrane, Embase, and Google Scholar until October 2021. The following search strings and Medical Subject Heading (MeSH) terms were used: "NAFLD," "NASH," "Fibrosis," and "Insulin Resistance." We explored the literature on NAFLD for its epidemiology, pathophysiology, the role of various genes, and how they influence the disease and associated complications about the disease and its hepatic and extrahepatic complications. With its rapidly increasing prevalence rates across the world and serious complications like NASH and hepatocellular carcinoma, NAFLD is becoming a major public health issue and more research is needed to formulate better screening tools and treatment protocols.
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Project description:Non-alcoholic fatty liver disease (NAFLD) is a serious health problem due to its high incidence and consequences. In view of the existing controversies, new therapeutic options for NAFLD are still being sought. Therefore, the aim of our review was to evaluate the recently published studies on the treatment of NAFLD patients. We searched for articles in the PubMed database using appropriate terms, including "non-alcoholic fatty liver disease", "nonalcoholic fatty liver disease", "NAFLD", "diet", "treatment", "physical activity", "supplementation", "surgery", "overture" and "guidelines". One hundred forty-eight randomized clinical trials published from January 2020 to November 2022 were used for the final analysis. The results show significant benefits of NAFLD therapy associated with the use of not only the Mediterranean but also other types of diet (including low-calorie ketogenic, high-protein, anti-inflammatory and whole-grain diets), as well as enrichment with selected food products or supplements. Significant benefits in this group of patients are also associated with moderate aerobic physical training. The available therapeutic options indicate, above all, the usefulness of drugs related to weight reduction, as well as the reduction in insulin resistance or lipids level and drugs with anti-inflammatory or antioxidant properties. The usefulness of therapy with dulaglutide and the combination of tofogliflozin with pioglitazone should be emphasized. Based on the results of the latest research, the authors of this article suggest a revision of the therapeutic recommendations for NAFLD patients.
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Project description:AimsTo investigate the association between overweight/obesity and fatty liver index (FLI) on the odds of incident prediabetes/type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) in 2020 participants after 10 years follow up.MethodsAt baseline (in 2001) 2020 participants, males and females, aged 24-39 years, were stratified according to body mass index (BMI), normal weight (<25 kg/m2), overweight (≥25-<30 kg/m2), or obese (≥30 kg/m2) and FLI (as high FLI ≥60 or low FLI <60). We examined the incidence of prediabetes/type 2 diabetes and NAFLD (ultrasound assessed) over 10 years to 2011 to determine the relative impact of FLI and BMI.Results514 and 52 individuals developed prediabetes and type 2 diabetes during follow-up. Such individuals were older, with higher BMI, serum glucose, insulin, alanine aminotransferase (ALT) and triglyceride (TG) concentrations than those who did not develop prediabetes or type 2 diabetes (n = 1454). The additional presence of high FLI significantly increased the risk of developing prediabetes and type 2 diabetes above the risk of being overweight/obese. Compared with normal weight, low FLI participants, the odds of prediabetes were ∼2-fold higher and the odds of type 2 diabetes were 9-10-fold higher respectively in the overweight/obese, high FLI group. No difference was observed between normal weight, low FLI and overweight/obese and low FLI groups.ConclusionsAn increased FLI significantly increases the odds of incident prediabetes, type 2 diabetes and NAFLD in individuals with overweight/obese highlighting the contributory role of liver fat accumulation in the pathophysiology of prediabetes/type 2 diabetes.Key messagesObesity is a risk factor for non-alcoholic fatty liver disease (NAFLD), prediabetes and type 2 diabetes.Additionally, NAFLD is more prevalent in people with prediabetes and type 2 diabetes when compared to age- and BMI-matched individuals.The presence of a raised fatty liver index (FLI) confers a significantly increased risk of developing prediabetes, type 2 diabetes and NAFLD above that conferred by being overweight/obese.The degree of elevation of FLI can risk stratify for incident prediabetes and type 2 diabetes in people with obesity.
| S-EPMC8317942 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD), which affects both adults and children, is the most common liver disorder worldwide. NAFLD is characterized by excess fat accumulation in the liver in the absence of significant alcohol use. NAFLD is strongly associated with obesity, insulin resistance, metabolic syndrome, as well as specific genetic polymorphisms. Severe NAFLD cases can further progress to cirrhosis, hepatocellular carcinoma (HCC), or cardiovascular complications. Here, we describe the pathophysiological features and critical genetic variants associated with NAFLD. Recent advances in genome-engineering technology have provided a new opportunity to generate in vitro and in vivo models that reflect the genetic abnormalities of NAFLD. We review the currently developed NAFLD models generated using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) genome editing. We further discuss unique features of CRISPR/Cas9 and Cas9 variants, including base editors and prime editor, that are useful for replicating genetic features specific to NAFLD. We also compare advantages and limitations of currently available methods for delivering genome-editing tools necessary for optimal genome editing. This review should provide helpful guidance for selecting "good fit" genome-editing tools and appropriate gene-delivery methods for the successful development of NAFLD models and clinical therapeutics.
| S-EPMC7760008 | biostudies-literature