• Cross-sectional
• NAFLD
• NHANES
• United States
• Urinary incontinence

• Humans
• Female
• United States/epidemiology
• Non-alcoholic Fatty Liver Disease/epidemiology
• Middle Aged
• Nutrition Surveys
• Urinary Incontinence/epidemiology
• Adult
• Risk Factors
• Prevalence
• Cross-Sectional Studies

• 2019YFA0802301 National Key Research and Development Program of China
• 2019YFA0802301 National Key Research and Development Program of China
• 2019YFA0802301 National Key Research and Development Program of China

• Curcumin
• Nano-micelle
• Non-alcoholic fatty liver disease
• hepatic enzymes

• Cross-sectional studies
• Environmental poisons
• Glyphosate
• Hepatorenal function
• National Health and Nutrition Examination Survey

• Burden of illness
• NAFLD
• Nonalcoholic fatty liver disease
• Type 2 diabetes
• US

The pandemics of coronavirus disease 2019 (COVID-19) and non-alcoholic fatty liver disease (NAFLD) coexist. Elevated liver function tests are frequent in COVID-19 and may influence liver damage in NAFLD, while preexisting liver damage from NAFLD may influence the course of COVID-19. However, the prognostic relevance of this interaction, though, is unclear. Obesity is a risk factor for the presence of NAFLD as well as a severe course of COVID-19. Cohort studies reveal conflicting results regarding the influence of NAFLD presence on COVID-19 illness severity. Striking molecular similarities of cytokine pathways in both diseases, including postacute sequelae of COVID-19, suggest common pathways for chronic low-activity inflammation. This review will summarize existing data regarding the interaction of both diseases and discuss possible mechanisms of the influence of one disease on the other.

• COVID-19
• Postacute sequelae of COVID-19
• Non-alcoholic fatty liver disease
• Non-alcoholic steatohepatitis
• Inflammation
• Fatty liver

• Humans
• Non-alcoholic Fatty Liver Disease/complications
• Non-alcoholic Fatty Liver Disease/diagnosis
• Non-alcoholic Fatty Liver Disease/epidemiology
• COVID-19/complications
• COVID-19/metabolism
• Risk Factors
• Inflammation/metabolism
• Obesity/complications
• Obesity/epidemiology
• Obesity/metabolism
• Liver/metabolism

Electroacupuncture, which is the most widely used alternative medicine treatment, has been gradually recognized for its effectiveness; however, its mechanism of action is not fully understood. The NLR family pyrin domain containing 3 (NLRP3) inflammasome is a thoroughly studied inflammasome that is closely associated with Alzheimer’s disease, spinal cord injury, and other diseases and plays an important role in the diagnosis and treatment of human immune system diseases. In recent years, some scholars have found that the NLRP3 inflammasome is a part of the mechanism of action of electroacupuncture, which has attracted further attention. In the current review, using “electroacupuncture” and “NLRP3 inflammasome” as keywords and based on the existing randomized controlled trials or clinical trials, we summarize the mechanisms of electroacupuncture targeting NLRP3 inflammasome in the treatment of different diseases and discuss how to optimize the electroacupuncture protocol to obtain thorough mechanisms of NLRP3 inflammasome in electroacupuncture and improve the level of evidence.

• bioencapsulation
• furin cleavage site
• liver-targeting PLUS peptide
• transferrin-mediated oral delivery
• transient and stable transformation

• Deutsche Forschungsgemeinschaft

• Metabolic dysfunction-associated fatty liver disease
• National Health and Nutrition Examination Survey
• Osteoporosis
• bone mineral density
• cross-sectional study

• Adult
• Aged
• Bone Density
• Cross-Sectional Studies
• Female
• Humans
• Liver Cirrhosis
• Male
• Middle Aged
• Nutrition Surveys
• Osteoporosis/epidemiology
• Osteoporosis/etiology
• United States/epidemiology

Nonalcoholic fatty liver disease (NAFLD) is characterized by lipotoxicity and ectopic lipid deposition within hepatocytes. Sulforaphane (SFA), an active compound used for inhibiting tumors, was found to have the potency to improve lipid metabolism. However, its molecular mechanisms on ameliorating NAFLD are still incompletely understood. This research evaluated if SFA could inhibit hepatic steatosis and apoptosis. The effects of SFA on cell viability, lipid accumulation, triglyceride (TG) contents, apoptosis, ceramide contents, and reactive oxygen species (ROS) levels were analyzed in palmitic acid (PA)-treated HepG2 cells and high-fat diet (HFD)-fed mice. The related molecular mechanisms were further explored in hepatocytes. The results showed SFA alleviated lipid accumulation and regulated AMPK/SREBP1c/FAS signaling pathway in PA-stressed HepG2 cells. In addition, SFA alleviated PA-mediated apoptosis, downregulated the expressions of cleaved caspase 3, as well as reduced ceramide contents and ROS levels. Moreover, SFA treatment reduced HFD-induced body weight gain, alleviated insulin resistance, decreased serum TG, total cholesterol (TC), and alanine aminotransferase (ALT) levels, and prevented lipid deposition and apoptosis in the liver. This study showed SFA suppressed lipid deposition and apoptosis both in vitro and in vivo, indicating that SFA may be a potential candidate for preventing and treating NAFLD.

• apoptosis
• hepatic steatosis
• lipid
• nonalcoholic fatty liver disease
• sulforaphane

• general endocrinology
• hepatobiliary disease
• hepatology

• Adult
• Aged
• China/epidemiology
• Cross-Sectional Studies
• Female
• Government Employees
• Humans
• Male
• Middle Aged
• Non-alcoholic Fatty Liver Disease/diagnosis
• Prevalence

• the Natural Science Foundation of Tianjin

Patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are associated with progression to advanced liver diseases that include compensated cirrhosis, decompensated cirrhosis, liver transplantation, and hepatocellular carcinoma (HCC). This study characterized comorbidities, healthcare resource utilization (HRU), and associated costs among NAFLD patients in Germany.

German healthcare claims data between 2011 and 2016 were analyzed retrospectively. Adult patients diagnosed with NAFLD and/or NASH were categorized as NAFLD, NAFLD non-progressors, compensated cirrhosis, decompensated cirrhosis, liver transplant, or HCC. Within each stage, annual all-cause HRU and costs were measured during the pre- and post-index periods.

Among 4,580,434 patients in the database, proportion of NAFLD was 4.7% (n=215,655). Of them, 36.8% were non-progressors, 0.2% compensated cirrhosis, 9.6% decompensated cirrhosis, 0.0005% liver transplant, and 0.2% HCC. Comorbidity rates were significantly higher in compensated cirrhosis, decompensated cirrhosis, and HCC compared with non-progressors (52.07%, 56.46%, 57.58% vs. 27.49% for cardiovascular disease; 77.13%, 76.61%, 83.47% vs. 54.89% for hypertension; 47.20%, 53.81%, 52.89% vs. 35.21% for hyperlipidemia; 49.88%, 36.67%, 48.21% vs. 20.38% for type 2 diabetes mellitus). The mean annual numbers of post-index outpatient visits and inpatient hospitalizations were significantly higher in patients with advanced liver diseases versus non-progressors. Mean annual costs were significantly higher among patients with advanced liver diseases (compensated cirrhosis, €10,291; decompensated cirrhosis, €22,561; liver transplant, €34,089; HCC, €35,910) than non-progressors (€3,818, P<0.001, except liver transplant cohort). This trend remained consistent after adjusting for baseline demographics and comorbidities.

NAFLD patients in Germany are grossly underdiagnosed and exert substantial healthcare resource use and economic burden, particularly those with advanced liver diseases. Optimal strategies for early identification and management are needed to prevent disease progression and limit the rising costs.

• Disease burden
• Germany
• advanced liver diseases
• nonalcoholic fatty liver disease (NAFLD)
• nonalcoholic steatohepatitis (NASH)

• children
• controlled attenuation parameter
• diagnosis
• magnetic resonance imaging
• meta-analysis
• non-alcoholic fatty liver disease

MicroRNAs (miRNAs) are short, non-coding RNA species that are important post-transcriptional regulators of gene expression and play an important role in the pathogenesis of non-alcoholic fatty liver disease. Here, we investigated the phosphodiesterase 5 (PDE5) inhibitor induced effects on hepatic and plasma exosomal miRNA expression in CCl₄-treated rats. In the present study, hepatic miRNA profiling was conducted using the Nanostring nCounter technology and mRNA profiling using RNA sequencing from PDE5 treated rats in the model of CCl₄-induced liver fibrosis. To evaluate if the PDE5 inhibitor affected differentially expressed miRNAs in the liver can be detected in plasma exosomes, qRT-PCR specific assays were used. In livers from CCl₄-treated rats, the expression of 22 miRNAs was significantly increased (>1.5-fold, adj. p < 0.05), whereas the expression of 16 miRNAs was significantly decreased (>1.5-fold, adj. p < 0.05). The majority of the deregulated miRNA species are implicated in fibrotic and inflammatory processes. The PDE5 inhibitor suppressed the induction of pro-fibrotic miRNAs, such as miR-99b miR-100 and miR-199a-5p, and restored levels of anti-fibrotic miR-122 and miR-192 in the liver. In plasma exosomes, we observed elevated levels of miR-99b, miR-100 and miR-142-3p after treatment with the PDE5-inhibitor compared to CCl₄/Vehicle-treated. Our study demonstrated for the first time that during the development of hepatic fibrosis in the preclinical model of CCl₄-induced liver fibrosis, defined aspects of miRNA regulated liver pathogenesis are influenced by PDE5 treatment. In conclusion, miRNA profiling of plasma exosomes might be used as a biomarker for NASH progression and monitoring of treatment effects.

• CCl4
• PDE 5 inhibitor
• exosomes
• gene expression
• liver fibrosis
• microRNAs

• Animals
• Biomarkers/analysis
• Carbon Tetrachloride/toxicity
• Exosomes/genetics
• Gene Expression Regulation/drug effects
• Liver Cirrhosis/chemically induced
• Liver Cirrhosis/drug therapy
• Liver Cirrhosis/genetics
• Liver Cirrhosis/pathology
• Male
• MicroRNAs/genetics
• Phosphodiesterase 5 Inhibitors/pharmacology
• Rats
• Rats, Sprague-Dawley
• Sequence Analysis, RNA

To determine how soy protein isolate (SPI) ameliorated liver steatosis in male obese Zucker rats, we conducted global transcriptomic expression (RNAseq) analysis on liver samples of male rats fed either the SPI or a control casein (CAS)-based diet (n = 8 per group) for 16 weeks. Liver transcriptomics were analyzed using an Ilumina HiSeq system with 2 × 100 base pair paired-end reads method. Bioinformatics was conducted using Ingenuity Pathway Analysis (IPA) software (Qiagen, CA) with P < 0.05 and 1.3-fold differential expression cutoff values. Regression analysis between RNAseq data and targeted mRNA expression analysis of 12 top differentially expressed genes (from the IPA program) using quantitative PCR (qPCR) revealed a significant regression analysis (r² = 0.69, P = 0.0008). In addition, all qPCR values had qualitatively similar direction of up- or down-regulation compared to the RNAseq transcriptomic data. Diseases and function analyses that were based on differentially expressed target molecules in the dataset predicted that lipid metabolism would be enhanced whereas inflammation was predicted to be inhibited in SPI-fed compared to CAS-fed rats at 16 weeks. Combining upstream regulator and regulator effects functions in IPA facilitates the prediction of upstream regulators (e.g., transcription regulators) that could play important roles in attenuating or promoting liver steatosis due to SPI or CAS diets. Upstream regulators that were predicted to be activated (from expression of down-stream targets) linked to increased conversion of lipid and transport of lipid in SPI-fed rats included hepatocyte nuclear factor 4 alpha (HNF4A) and aryl hydrocarbon receptor (AHR). Upstream regulators that were predicted to be activated in CAS-fed rats linked to activation of phagocytosis and neutrophil chemotaxis included colony stimulating factor 2 and tumor necrosis factor. The results provide clear indication that long-term SPI-fed rats exhibited diminished inflammatory response and increased lipid transport in liver compared to CAS-fed rats that likely would contribute to reduced liver steatosis in this obese Zucker rat model.

• RNAseq
• liver steatosis
• liver transcriptomics
• obesity
• soy protein isolate
• zucker rat

The present study aimed to evaluate the effects of folic acid supplementation in high-fructose-induced hepatic steatosis and clarify the underlying mechanism of folic acid supplementation.

Male SD rats were fed control, 64% high-fructose diet, or 64% high-fructose diet with folic acid for eight weeks. Plasma glutamate-pyruvate transaminase, glutamate-oxaloacetate transaminase, lipid profiles, hepatic lipid content, S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) were measured.

The HF diet significantly increased hepatic total lipid and triglyceride (TG) and decreased hepatic SAM, SAH, and SAM:SAH ratio. In rats fed a high fructose diet, folic acid supplementation significantly reduced hepatic TG, increased hepatic SAM, and alleviated hepatic steatosis. Moreover, folic acid supplementation in rats fed high fructose enhanced the levels of phosphorylated AMP-activated protein kinase (AMPK) and liver kinase B (LKB1) and inhibited phosphorylation of acetyl coenzyme A carboxylase (ACC) in the liver.

These results suggest that the protective effect of folic acid supplementation in rats fed high fructose may include the activation of LKB1/AMPK/ACC and increased SAM in the liver, which inhibit hepatic lipogenesis, thus ameliorating hepatic steatosis. The present study may provide evidence for the beneficial effects of folic acid supplementation in the treatment of non-alcoholic fatty liver disease.

• AMP-activated protein kinase
• Folic acid
• S-adenosylmethionine
• fatty liver
• fructose

Non-alcoholic steatohepatitis (NASH) leads to cirrhosis and is associated with a substantial socioeconomic burden, which, coupled with rising prevalence, is a growing public health challenge. However, there are few real-world data available describing the impact of NASH.

The Global Assessment of the Impact of NASH (GAIN) study is a prevalence-based burden of illness study across Europe (France, Germany, Italy, Spain, and the UK) and the USA. Physicians provided demographic, clinical, and economic patient information via an online survey. In total, 3,754 patients found to have NASH on liver biopsy were stratified by fibrosis score and by biomarkers as either early or advanced fibrosis. Per-patient costs were estimated using national unit price data and extrapolated to the population level to calculate the economic burden. Of the patients, 767 (20%) provided information on indirect costs and health-related quality of life using the EuroQOL 5-D (EQ-5D; n = 749) and Chronic Liver Disease Questionnaire – Non-Alcoholic Fatty Liver Disease (CLDQ-NAFLD) (n = 723).

Mean EQ-5D and CLDQ-NAFLD index scores were 0.75 and 4.9, respectively. For 2018, the mean total annual per patient cost of NASH was €2,763, €4,917, and €5,509 for direct medical, direct non-medical, and indirect costs, respectively. National per-patient cost was highest in the USA and lowest in France. Costs increased with fibrosis and decompensation, driven by hospitalisation and comorbidities. Indirect costs were driven by work loss.

The GAIN study provides real-world data on the direct medical, direct non-medical, and indirect costs associated with NASH, including patient-reported outcomes in Europe and the USA, showing a substantial burden on health services and individuals.

There has been little research into the socioeconomic burden associated with non-alcoholic steatohepatitis (NASH). The GAIN study provides real-world data on the direct medical, direct non-medical, and indirect costs associated with NASH, including patient-reported outcomes in five European countries (UK, France, Germany, Spain, and Italy) and the USA. Mean total annual per patient cost of NASH was estimated at €2,763, €4,917, and €5,509 for the direct medical, direct non-medical, and indirect cost categories, respectively.

•

There has been little research into the socioeconomic burden associated with non-alcoholic steatohepatitis (NASH).

• CLDQ, Chronic Liver Disease Questionnaire
• CLDQ-NAFLD, Chronic Liver Disease Questionnaire – Non-Alcoholic Fatty Liver Disease
• CRF, case record form
• Cost of illness
• Cross-sectional studies
• EU5, five European
• Europe
• FIB-4, Fibrosis-4
• GAIN, Global Assessment of the Impact of NASH
• HRQoL, health-related quality of life
• NAFL non-alcoholic fatty liver NAFLD, non-alcoholic fatty liver disease
• NASH, non-alcoholic steatohepatitis
• Non-alcoholic steatohepatitis
• OTC, over-the-counter
• PPIE, Patient Public Involvement Engagement
• T2DM, type 2 diabetes mellitus

• Atherosclerosis
• Lard
• Non-alcoholic fatty liver disease
• Obesity
• Soybean oil
• Sunflower oil

• Animals
• Atherosclerosis/metabolism
• Blotting, Western
• Body Weight/drug effects
• Diet, High-Fat/adverse effects
• Dietary Fats/pharmacology
• Dietary Fats, Unsaturated/pharmacology
• Lipid Metabolism/drug effects
• Male
• Mice
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease/metabolism
• Obesity/metabolism
• Soybean Oil/pharmacology
• Sunflower Oil/pharmacology

• 2016YDF0501200 National Key R&D Program of China
• National Key R&D Program of China

• NAFLD
• NASH
• beneficial effects
• stress
• sympathetic activation

• Adipose Tissue/metabolism
• Animals
• Cholesterol/metabolism
• Diet, High-Fat/adverse effects
• Inflammation/metabolism
• Lipogenesis/physiology
• Liver/metabolism
• Mice
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease/metabolism
• Receptors, Adrenergic, beta-2/analysis
• Stress, Physiological/physiology
• Sympathetic Nervous System/physiology
• Triglycerides/metabolism

• Insulin resistance
• Magnetic resonance spectroscopy
• Saturated fats

• Adult
• Aged
• Biomarkers/metabolism
• Case-Control Studies
• Cross-Sectional Studies
• Dyslipidemias/diagnosis
• Dyslipidemias/metabolism
• Dyslipidemias/physiopathology
• Exercise Tolerance
• Female
• Humans
• Insulin Resistance
• Lipid Metabolism
• Lipidomics/methods
• Liver/metabolism
• Liver/physiopathology
• Male
• Middle Aged
• Non-alcoholic Fatty Liver Disease/diagnosis
• Non-alcoholic Fatty Liver Disease/metabolism
• Non-alcoholic Fatty Liver Disease/physiopathology
• Obesity, Abdominal
• Phenotype
• Predictive Value of Tests
• Proton Magnetic Resonance Spectroscopy

• T32 HL007887 NHLBI NIH HHS
• UL1 RR024989 NCRR NIH HHS
• UL1 TR002548 NCATS NIH HHS

• fatty liver
• gestational diabetes
• hyperglycemia
• liver fat scoring indices
• pregnancy
• 妊娠
• 妊娠糖尿病
• 肝脏脂肪评分指标
• 脂肪肝
• 高血糖

• Adult
• Alanine Transaminase/metabolism
• Aspartate Aminotransferases/metabolism
• Biomarkers/metabolism
• Body Mass Index
• Denmark/epidemiology
• Diabetes, Gestational/physiopathology
• Fatty Liver/diagnosis
• Fatty Liver/epidemiology
• Fatty Liver/metabolism
• Female
• Follow-Up Studies
• Humans
• Longitudinal Studies
• Pregnancy
• Prognosis
• Prospective Studies
• Risk Factors

• 6-FY97-0521 March of Dimes Birth Defects Foundation
• FP7-289346 European Union
• 11/263-96 'Centre for Fetal Programming', The Health Foundation
• ZIA HD008916-07 Intramural NIH HHS
• ZIA HD008916-08 Intramural NIH HHS
• 6-FY00-407 March of Dimes Birth Defects Foundation
• 11-115923 Innovation Fund Denmark
• Danish Diabetes Academy
• HSN275201100002I Eunice Kennedy Shriver National Institute of Child Health and Human Development
• ZIA HD008916-05 Intramural NIH HHS
• ZIA HD008916-06 Intramural NIH HHS
• ZIA HD008916-02 Intramural NIH HHS
• 6-FY-96-0240 March of Dimes Birth Defects Foundation
• 96-2-4-83-22450 Heart Foundation
• Novo Nordisk Foundation
• 09-67124 Innovation Fund Denmark
• ZIA HD008916-03 Intramural NIH HHS
• ZIA HD008916-04 Intramural NIH HHS
• P20 GM109036 NIGMS NIH HHS
• 6-FY97-0553 March of Dimes Birth Defects Foundation

• diabetes mellitus
• economic evaluation
• fatty liver
• non-alcoholic steatohepatitis

• Burden of disease
• Epidemiology
• NASH
• Non-alcoholic steatohepatitis

Data on the economic and humanistic burden of non-alcoholic steatohepatitis (NASH) are scarce. This study assessed the comparative burden of NASH, relative to a representative sample from the general population and a type 2 diabetes mellitus (T2DM) cohort, in terms of health-related quality of life, work productivity and activity impairment (WPAI), and healthcare resource use.

Data across 5 European countries came from the 2016 National Health and Wellness Survey, a nationally representative patient-reported outcomes survey. Outcomes included mental (MCS) and physical (PCS) component scores from the Short-Form (SF)-36v2, WPAI scores, self-reported physician diagnosis of sleep difficulties, anxiety, and depression, and healthcare resource use: healthcare professional visits, hospital visits, and emergency room visits in the previous 6 months. Bivariate and multivariable analyses were conducted for each outcome and comparative group.

After adjusting for matching criteria and covariates, patients with NASH (n = 184) reported significantly worse health-related quality of life, worse WPAI scores, and more healthcare resource use than the general population (n = 736) (MCS 39.22 vs. 45.16, PCS 42.84 vs. 47.76; overall work impairment 49.15% vs. 30.77%, healthcare professional visits 10.73 vs. 6.01, emergency room visits 0.57 vs. 0.22, hospitalizations 0.47 vs. 0.17, p ≪0.05 for all). Patients with NASH did not differ from patients with T2DM (n = 368) on PCS and WPAI scores, suggesting a similar impairment on work and daily activities, but did report significantly worse mental status (MCS 39.64 vs. 43.64, p ≪0.05) and more healthcare resource use than those with T2DM (healthcare professional visits 10.85 vs. 7.86, emergency room visits 0.65 vs. 0.23, hospitalizations 0.39 vs. 0.19, p ≪0.05 for all).

These findings suggest that the burden of NASH may be underestimated, highlighting the unmet needs of patients with NASH.

These findings show that patients with non-alcoholic steatohepatitis (NASH) experience a significant burden of illness, in terms of health-related quality of life, work productivity and activity impairment, and healthcare resource use. As there is currently no approved treatment for NASH, these findings highlight the unmet medical need of patients with NASH.

•

Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease.

• burden of illness
• non-alcoholic fatty liver disease
• non-alcoholic steatohepatitis
• type 2 diabetes

Metabolic related nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases around the world. A single nucleotide polymorphism (SNP) rs1501299 (+276G>T) in the adiponectin gene has been recently revealed to be responsible for susceptibility to NAFLD. This meta-analysis intended to assess the association risk of NAFLD and rs1501299 polymorphism.

We conducted a literature search on PubMed, Embase, and Cochrane Library databases. All involved studies were selected based on our search criteria. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to quantify the strength of the association. Subgroup analysis considered the effects of ethnicity, subject scope, and source of control. Publication bias was assessed by Begg’s tests.

Eight qualified case-control studies with 1639 patients and 1426 controls demonstrated a significant correlation between rs1501299 polymorphism in adiponectin and NAFLD under the dominant model (OR=1.18, 95% CI=1.02–1.36), allelic contrast (OR=1.21, 95% CI=1.09–1.36), homozygote comparison (OR=1.63, 95% CI=1.26–2.01) and the recessive allele model (OR=1.58, 95% CI=1.23–2.02) with evident heterogeneity. No association was observed between the risk of NAFLD and the genotypic variants in heterozygote comparison (OR=1.11, 95% CI=0.95–1.29) without heterogeneity. Subgroup analysis suggested that the sample size could be the potential source of heterogeneity. Source of control was not the reason for between-study heterogeneity and further sensitivity analysis and publication bias revealed good consistency and symmetry in the pooling studies.

Results from our current meta-analysis gave insight into the correlation between rs1501299 polymorphism and the risk of NAFLD, indicating the variant of rs1501299 might be related to increased NAFLD susceptibility.

Genetic factors affect the risk of non-alcoholic fatty liver disease (NAFLD) and colorectal adenoma (CRA) importantly. Transmembrane protein 6 superfamily member 2 (TM6SF2) rs58542926 is a significant genetic susceptibility site for NAFLD. The relationships of TM6SF2 rs58542926 with the risk of NAFLD and CRA in Chinese Han population were unclear. The aim of this study was to investigate the association of TM6SF2 rs58542926 with the risk of NAFLD and CRA, and the effect of CRA on TM6SF2 rs58542926 carried NAFLD patients.

A total of 839 Chinese Han population were included in this retrospective study. TM6SF2 rs58542926 polymorphism was genotyped in B-type ultrasonography proven NAFLD patients with or without CRA, CRA patients and healthy controls, using polymerase chain reaction. Serum lipid profiles were determined using biochemical methods. Statistical analyses were performed using SPSS statistical software, version 16.0 for mac. There was a significant difference in the distribution of genotype and allele of TM6SF2 rs58542926 in NAFLD and NAFLD&CRA patients compared to controls. The CT + TT genotypes were tightly associated with the risk of NAFLD and NAFLD&CRA. TM6SF2 rs58542926 T allele promotes the abnormal regulation of lipids metabolism and liver injury in NAFLD patients and NAFLD&CRA patients. CRA aggravates the clinical performance of NAFLD in T allele carriers.

We demonstrated the significant association between TM6SF2 rs58542926 polymorphism and the risk of NAFLD and NAFLD&CRA in a Chinese Han population. The TM6SF2 rs58542926 T allele promotes the abnormal regulation of lipid profiles and liver injury in NAFLD patients, NAFLD&CRA patients, and overall subjects.

• Colorectal adenomas
• NAFLD
• TM6SF2
• rs58542926

The liver is well known as the center of glucose and lipid metabolism in the human body. It also functions as an immune organ. Previous studies have suggested that liver nonparenchymal cells are crucial in the progression of NAFLD. In recent years, NAFLD's threat to human health has been becoming a global issue. And by far, there is no effective treatment for NAFLD. Liver nonparenchymal cells are stimulated by lipid antigens, adipokines, or other factors, and secreted immune factors can alter the expression of key proteins such as SREBP-1c, ChREBP, and PPARγ to regulate lipid metabolism, thus affecting the pathological process of NAFLD. Interestingly, some ncRNAs (including miRNAs and lncRNAs) participate in the pathological process of NAFLD by changing body fat homeostasis. And even some ncRNAs could regulate the activity of HSCs, thereby affecting the progression of inflammation and fibrosis in the course of NAFLD. In conclusion, immunotherapy could be an effective way to treat NAFLD.

• NAFLD
• NASH
• gut–liver axis
• inflammation
• intestine
• obesity
• vitamin D

• Animals
• Blood Glucose/drug effects
• Body Composition
• Body Weight/drug effects
• Cholesterol 7-alpha-Hydroxylase/genetics
• Cholesterol 7-alpha-Hydroxylase/metabolism
• Diet, High-Fat/adverse effects
• Dietary Carbohydrates/administration & dosage
• Fibroblast Growth Factors/genetics
• Fibroblast Growth Factors/metabolism
• Gene Expression Regulation/drug effects
• Glucose Intolerance/drug therapy
• Intestines/drug effects
• Intestines/physiology
• Liver/anatomy & histology
• Liver/drug effects
• Mice
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease/metabolism
• Obesity/chemically induced
• Steroid 12-alpha-Hydroxylase/genetics
• Steroid 12-alpha-Hydroxylase/metabolism
• Up-Regulation/drug effects
• Vitamin D/therapeutic use

To investigate [¹¹C]acetate PET-surrogate parameter of fatty acid synthase activity—as suitable tool for diagnosis and monitoring of liver steatosis.

In this retrospective study, data were obtained from 83 prostatic carcinoma patients from 1/2008 to 1/2014. Mean HU was calculated from unenhanced CT of all patients from liver with liver HU less than 40 as threshold for liver steatosis. SUV_max of the liver and of the blood pool in thoracic aorta (as background for calculation of a liver/background ratio [SUV_l/b]) was measured. t test was used with a P < 0.05 considered as statistically significant difference and ROC analysis was used for calculating specificity and sensitivity.

19/83 patients (20%) had diagnosis of hepatic steatosis according to CT. Uptake of [¹¹C]acetate was significantly higher in patients with hepatic steatosis as compared to control group (SUV_max 7.96 ± 2.0 vs. 5.48 ± 2.3 [P < 0.001]). There was also a significant correlation between both SUV_max (r = − 0.52, P < 0.001) and SUV_l/b (r = − 0.59, P < 0.001) with the density (HU) of the liver. In ROC analysis for detection of liver steatosis SUV_max (threshold: 5.86) had a sensitivity of 94% and specificity of 69% with an AUC of 0.81. Increasing body mass index is correlated with the severity of steatosis.

We showed for the first time that hepatic steatosis associates with increased [¹¹C]acetate uptake. Also, severity of steatosis correlates with [¹¹C]acetate uptake. [¹¹C]acetate uptake PET seems promising for the assessment of liver steatosis.

The online version of this article (10.1007/s00261-018-1558-4) contains supplementary material, which is available to authorized users.

• Liver
• Liver steatosis
• NAFLD
• PET
• [11C]acetate

• Epidemiology
• Fatty liver index
• Hypertension
• Nonalcoholic fatty liver

• Adult
• Area Under Curve
• Body Mass Index
• China/epidemiology
• Fatty Liver/complications
• Fatty Liver/epidemiology
• Fatty Liver/physiopathology
• Female
• Humans
• Hypertension/complications
• Hypertension/epidemiology
• Hypertension/physiopathology
• Longitudinal Studies
• Male
• Middle Aged
• Risk Factors
• Severity of Illness Index
• Triglycerides/blood
• Waist Circumference

• Inflammation
• NAFLD
• PPARs

• Animals
• Gene Expression Regulation
• Humans
• Inflammation/genetics
• Inflammation/metabolism
• Lipid Metabolism/genetics
• Liver/metabolism
• Liver/pathology
• Non-alcoholic Fatty Liver Disease/genetics
• Non-alcoholic Fatty Liver Disease/metabolism
• Peroxisome Proliferator-Activated Receptors/classification
• Peroxisome Proliferator-Activated Receptors/metabolism
• Protein Isoforms/metabolism

Nonalcoholic fatty liver disease (NAFLD) has been reported to have a negative effect on bone mineral density (BMD) in Asian populations. Whether such an association exists in Western populations is less clear.

This cross-sectional analysis of data from NHANES III, a United States national health survey conducted from 1988 to 1994, included 6089 participants aged 40–75 years, selected after excluding people with hepatitis virus serology, elevated alcohol consumption, decreased renal function, or steroid use, and pregnant females. The main outcome, BMD at the femoral neck, was measured using dual-energy X-ray absorptiometry. The primary exposure, NAFLD, was defined as moderate or severe hepatic steatosis diagnosed using abdominal ultrasonography.

After controlling for gender and menopausal status, race/ethnicity, age and body mass index, NAFLD was not significantly associated with BMD (beta coefficient: −0.006, 95%CI: −0.016, 0.003). A secondary analysis categorized participants with NAFLD according to their serum alanine aminotransferase (ALT) levels into high and normal ALT NAFLD groups, and compared these with the non-NAFLD group. NAFLD with higher levels of ALT was associated with lower levels of BMD (beta coefficient: −0.023, 95% CI: −0.044, −0.002).

This study showed a relationship between NAFLD with high ALT and lower BMD in the general U.S. population.

To assess the renal function in patients with nonalcoholic fatty liver disease (NAFLD) and to identify the risk factors for renal dysfunction.

A total of 856 volunteers who underwent health examination were initially enrolled in this study to identify those with NAFLD. The biochemical indexes of patients with NAFLD and healthy volunteers were statistically analyzed, and the renal function with estimated glomerular filtration rate was calculated. In addition, the risk factors for renal damage were identified.

A total of 253 patients with NAFLD were identified, and the remaining 603 cases were used as a control group. There was no significant difference in serum BUN between the two groups (t = 1.678, P = 0.062), while other biochemical indexes differed significantly (P < 0.05). The prevalence of renal function impairment was higher in individuals with NAFLD compared to those without (28.8% vs 17.5%, P < 0.0001). Logistic regression analysis showed that NAFLD was associated with renal function impairment, even after adjustment for demographics and components of metabolic syndrome (OR = 2.85, 95%CI: 1.93-4.21, P = 0.000).

The biochemical indexes of NAFLD patients are significantly abnormal, and renal function impairment is associated with NAFLD. Patients with NAFLD should be regularly assessed for renal function to avoid progressing into chronic kidney disease and increasing the medical burden.

• Nonalcoholic fatty liver disease
• Chronic kidney disease
• Glomerular filtration rate
• Renal function impairment

• Non-alcoholic fatty liver disease
• cirrhosis
• liver transplantation
• non-alcoholic steatohepatitis

• Metabolically Healthy Obesity
• adolescents
• antioxidants
• obesity

• Adolescent
• Adolescent Nutritional Physiological Phenomena
• Body Mass Index
• Brazil/epidemiology
• Cardiovascular Diseases/epidemiology
• Cardiovascular Diseases/etiology
• Female
• Humans
• Male
• Metabolic Syndrome/epidemiology
• Metabolic Syndrome/etiology
• Non-alcoholic Fatty Liver Disease/epidemiology
• Non-alcoholic Fatty Liver Disease/etiology
• Nutritional Status
• Obesity, Metabolically Benign/blood
• Obesity, Metabolically Benign/metabolism
• Obesity, Metabolically Benign/physiopathology
• Obesity, Morbid/blood
• Obesity, Morbid/metabolism
• Obesity, Morbid/physiopathology
• Oxidative Stress
• Pediatric Obesity/blood
• Pediatric Obesity/metabolism
• Pediatric Obesity/physiopathology
• Prevalence
• Risk Factors
• Selenium/blood
• Severity of Illness Index
• Vitamins/blood
• Waist Circumference
• Zinc/blood

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and correlated with obesity. To evaluate the role of body mass index (BMI) and gender difference in NAFLD, 8817 general adult subjects underwent physical examinations and were divided into four groups: underweight, normal, overweight and obese. The risk factor compositions for NAFLD were evaluated in each group by gender. The percentage of subjects with NAFLD increased sharply from 0.4% in the underweight group up to 81.9 % in the obese group. BMI stratification showed distinct risk factor compositions associated with NAFLD in males and females according to BMI and improved the performance of NAFLD prediction models in each group. Triglycerides (TG), alanine transaminase (ALT), aspartate transaminase (AST), and uric acid were steady risk factors for NAFLD in males. Total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), ALT, and uric acid were steady risk factors for NAFLD in females. TG, ALT and uric acid were common risk factors in both genders with high performance for NAFLD discrimination. Our data provide gender- and BMI-specific risk factor compositions that will facilitate individualised treatment and benefit NAFLD control and prevention.

• Pathology Section
• body mass index
• gender difference
• nonalcoholic fatty liver disease
• nonalcoholic steato-hepatitis
• risk factor compositions