Risk Factor For NAFLD Research Articles

Tcf7l2 in hepatocytes regulates de novo lipogenesis in diet-induced non-alcoholic fatty liver disease in mice

Aims/hypothesisNon-alcoholic fatty liver disease (NAFLD) associated with type 2 diabetes may more easily progress towards severe forms of non-alcoholic steatohepatitis (NASH) and cirrhosis. Although the Wnt effector transcription factor 7-like 2 (TCF7L2) is closely associated with type 2 diabetes risk, the role of TCF7L2 in NAFLD development remains unclear. Here, we investigated how changes in TCF7L2 expression in the liver affects hepatic lipid metabolism based on the major risk factors of NAFLD development.MethodsTcf7l2 was selectively ablated in the liver of C57BL/6N mice by inducing the albumin (Alb) promoter to recombine Tcf7l2 alleles floxed at exon 5 (liver-specific Tcf7l2-knockout [KO] mice: Alb-Cre;Tcf7l2f/f). Alb-Cre;Tcf7l2f/f and their wild-type (Tcf7l2f/f) littermates were fed a high-fat diet (HFD) or a high-carbohydrate diet (HCD) for 22 weeks to reproduce NAFLD/NASH. Mice were refed a standard chow diet or an HCD to stimulate de novo lipogenesis (DNL) or fed an HFD to provide exogenous fatty acids. We analysed glucose and insulin sensitivity, metabolic respiration, mRNA expression profiles, hepatic triglyceride (TG), hepatic DNL, selected hepatic metabolites, selected plasma metabolites and liver histology.ResultsAlb-Cre;Tcf7l2f/f essentially exhibited increased lipogenic genes, but there were no changes in hepatic lipid content in mice fed a normal chow diet. However, following 22 weeks of diet-induced NAFLD/NASH conditions, liver steatosis was exacerbated owing to preferential metabolism of carbohydrate over fat. Indeed, hepatic Tcf7l2 deficiency enhanced liver lipid content in a manner that was dependent on the duration and amount of exposure to carbohydrates, owing to cell-autonomous increases in hepatic DNL. Mechanistically, TCF7L2 regulated the transcriptional activity of Mlxipl (also known as ChREBP) by modulating O-GlcNAcylation and protein content of carbohydrate response element binding protein (ChREBP), and targeted Srebf1 (also called SREBP1) via miRNA (miR)-33-5p in hepatocytes. Eventually, restoring TCF7L2 expression at the physiological level in the liver of Alb-Cre;Tcf7l2f/f mice alleviated liver steatosis without altering body composition under both acute and chronic HCD conditions.Conclusions/interpretationIn mice, loss of hepatic Tcf7l2 contributes to liver steatosis by inducing preferential metabolism of carbohydrates via DNL activation. Therefore, TCF7L2 could be a promising regulator of the NAFLD associated with high-carbohydrate diets and diabetes since TCF7L2 deficiency may lead to development of NAFLD by promoting utilisation of excess glucose pools through activating DNL.Data availabilityRNA-sequencing data have been deposited into the NCBI GEO under the accession number GSE162449 (www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE162449).Graphical abstract

Hepatic steatosis after liver transplantation: a systematic review and meta-analysis.

NAFLD can occur after liver transplantation (LT), as recurrence or de novo hepatic steatosis (HS). We aimed to evaluate the literature on prevalence, risk factors, and prognosis of post-LT HS. Systematic review with meta-analysis through a search on: PUBMED, Scopus, and Web-of-Science, from inception until the September 30, 2021. Forty studies were included, representing 6979 patients. The post-LT HS prevalence was 39.76% (95% CI, 34.06-45.46), with a rising kinetics (11.06% increase per decade, p =0.04), and a geographical distribution (15.10% more prevalent in American continent compared with Europe and Asia). Recurrent HS was up to 5-fold more likely than de novo HS [OR: 5.38 (2.69-10.76)]. Metabolic disturbances were stronger risk factors in the post-LT recipient [obesity: OR: 4.62 (3.07-6.96); metabolic syndrome: OR: 3.26 (2.03-5.25)] as compared with pre-LT recipients, with the exception of diabetes mellitus, which doubled the risk at any set [pre-LT diabetes mellitus: OR: 2.06 (1.58-2.68); post-LT diabetes mellitus: OR: 2.12 (1.73-2.59)]. Donor factors were not the relevant risk factors for post-LT HS and the only immunosuppressive drug associated with increased risk was sirolimus [OR: 1.68 (1.07-2.64)]. The prevalence of post-LT steatohepatitis was 28.82% (19.62-38.03) and the strongest risk factor was pre-LT NAFLD. Limited outcomes data suggest that post-LT HS did not increase the risk for liver cirrhosis or mortality in these studies. Two out of 5 patients submitted to LT will develop post-LT HS, being recurrent HS more common than de novo HS. Diabetes mellitus and post-LT metabolic syndrome are the strongest risk factors for HS and baseline NAFLD for steatohepatitis. All transplanted patients should be enrolled in lifestyle interventions to prevent post-LT metabolic syndrome, and sirolimus should be avoided in high-risk patients.

LncRNA ZFAS1 ameliorates injury led by non-alcoholic fatty liver disease via suppressing lipid peroxidation and inflammation

BackgroundNonalcoholic fatty liver disease (NAFLD) is known to aggravate metabolic disturbance and increase the risk of complications. The purpose of the present study was to explore the mechanism underlying the clinical effects of ZFAS1 on NAFLD. MethodsExpression of the ZFAS1 RNA was quantified in patients with NAFLD through reverse transcription-quantitative polymerase chain reaction. The correlations were assessed using Pearson's correlation coefficient test. The receiver operating characteristic curve was used to evaluate the identification of ZFAS1. Commercial kits were purchased to detect the pertinent parameters to establish mice models. Luciferase report assay was used to identify and confirm the presence of ZFAS1 ceRNA. ResultsThe increase of ZFAS1 expression in patients with NAFLD was noted and the high expression level may be considered a risk factor for NAFLD. In mouse models fed with high-fat diet (HFD), the expression levels of ZFAS1 were increased; furthermore, sh-ZFAS1 reversed ZFAS1 overexpression. HFD administration resulted in liver injury, which was indicated by increased lipid deposition, aggressive oxidative stress, and imbalanced inflammatory reaction. However, sh-ZFAS1 attenuated the abovementioned adverse effects of HFD. MiR-144-5p was a ceRNA of ZFAS1; in addition, the expression of miR-144-5p was reduced in HFD-managed models and patients with NAFLD. ZFAS1 could successfully regulate the expression levels of miR-144-5p. In the present study, the negative relationship between ZFAS1 and miR-144-5p was documented. ConclusionExcessive expression of ZFAS1 and its diagnostic potential was noted in patients with NAFLD. It was evident that ZFAS1 may be responsible for exacerbating the worsening of liver function.

Global burden of non-alcoholic fatty liver disease in 204 countries and territories from 1990 to 2019

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a growing epidemic linked to metabolic disease and is the most prevalent cause of chronic liver disease. We, therefore, designed the study to analyze the global and regional burden of NAFLD from 1990 to 2019. MethodsWe collected data on NAFLD from the Global Burden of Disease study 2019, aiming to conduct a systematic assessment of the changes and trends in NAFLD in 204 countries. Secondary analysis of NAFLD was conducted using age-standardized rates (ASRs) and estimated annual percentage changes (EAPCs) to show the changing trends and development characteristics. Data statistics and visualization were executed with the R program. ResultsGlobally, incidence, deaths and disability-adjusted life years (DALYs) of NAFLD all showed an upward trend. Between 1990 and 2019, the incidence of NAFLD increased by 95.4%, from 88,177 to 172,330 cases. Meanwhile, the ASIR of the middle SDI region had the highest increase, followed by the low-middle SDI region. Of all countries, the most incident cases were in China, which accounted for approximately 23.6% of NAFLD. China was also the country with the largest cases of deaths and DALYs. And behavioral risk, metabolic factors, smoking and high fasting plasma glucose were the critical risk factors associated with the mortality and DALYs of NAFLD. ConclusionNAFLD has become a considerable health burden in many countries. Therefore, we should control the risk factors of NAFLD and take corresponding measures to achieve its early prevention and treatment.

OR10-5 Fructose Consumption and NAFLD in US Adult Population of NHANES 17-18

Abstract Non-alcoholic fatty liver disease (NAFLD) is a serious condition whose prevalence differs by race/ethnicity. Studies have suggested that consumption of high-fructose corn syrup is likely a risk factor for NAFLD. We investigated the associations between fructose consumption and NAFLD, and its distribution by race/ethnicity in the adult US population using NHANES 2017-2018 data (n=3292). NAFLD was diagnosed by FibroScan® using controlled attenuation parameter (CAP) values of =>260 and no exclusion criteria. Fructose consumption was calculated from 24-hour dietary recall data in combination with USDA food nutritional content data files. Fructose consumption was categorized into tertiles (low= <=0.95 g, middle= >0.95-<=2.1 g, and high= >2.1 g). We analyzed data in SAS 9.4 using Chi squared tests and multinomial logistic regression, adjusting for demographics, behavioral, and laboratory data, and including sample weights and design. Of the 3292 participants, 31.3% were in the middle tertile of the fructose consumption and 35.5% were in the high tertile. There was no significant difference in the prevalence of NAFLD by fructose consumption group [low=44%; middle=48%, and high=51%] (p=0.094). The highest percentage of participants in the high tertile of fructose consumption were in Mexican Americans (48%) and non-Hispanic Blacks (44%), with a much lower percentage of non-Hispanic Whites (33%) (p<0.0001). The highest prevalence of NAFLD was in Mexican Americans in the high tertile of fructose consumption (70%), which was significantly different than the prevalence in Mexican Americans in the low tertile (52%) (p=0.031). In the adjusted models, those in the high tertile of fructose consumption had higher odds of NAFLD relative to those in the low tertile (AOR = 1.6, 95%CI = 1.1 - 2.3, p=0.0224). Fructose consumption in the high tertile was associated with increased odds of NAFLD in non-Hispanic Whites (AOR = 2.0, 95%CI = 1.0 - 3.7, p=0.0387) and Mexican Americans (AOR = 1.8, 95%CI = 1.2 - 2.8, p=0.0050). We conclude that there is an association between fructose consumption and the odds of NAFLD. This association does not explain the racial/ethnic disparity in NAFLD. Interventions should aim to decrease consumption of fructose overall. Presentation: Sunday, June 12, 2022 12:00 p.m. - 12:15 p.m.

Obesity, but not glycemic control, predicts liver steatosis in children with type 1 diabetes

ObjectiveNonalcoholic fatty liver disease (NAFLD), the most common liver disease in children, is strongly associated with obesity and insulin resistance. Although type 1 diabetes (T1D) is characterized by insulin deficiency, increasing obesity rates among children with T1D is a major risk factor for NAFLD in this patient population. Predisposing factors for NAFLD in children with T1D are not known. Study designThis is a cross-sectional study comparing children with T1D across the range of body mass index (BMI) to the BMI-matched obese group without T1D. Hepatic steatosis was semi-quantitatively measured via the vibration-controlled transient elastogram (VCTE) method. Linear regression analysis was performed to assess the relationship between controlled-attenuated parameter (CAP) scores and clinical parameters. Receiver-operator curve (ROC) analysis was used to evaluate the diagnostic performance of several clinical parameters against NAFLD status determined via CAP. ResultsTwo-thirds of subjects with obesity had CAP scores suggestive of NAFLD, while 16 % (n = 6) of T1D patients without obesity had elevated CAP. Obese subjects were different from non-obese subjects in many laboratory and clinical characteristics, regardless of T1D status. CAP score was significantly associated with BMI, HDL-Cholesterol (HDL-c), and HbA1c in all subjects as well as the T1D-only subgroup. Among subjects with obesity only, age, HDL-cand ALT were the most significant predictors. Diagnostic performance of BMI, HDL-c, and BMI/HDL ratio were in the good to the excellent range for predicting NAFLD among all subjects, while performance varied for T1D-only or obesity-only groups. ConclusionThe clinical and imaging findings of children with T1D and obesity are comparable to non-diabetic children with a similar degree of obesity. Obesity is the major risk factor for NAFLD in pediatric T1D. BMI, HDL-c, and BMI/HDL ratio may be helpful markers to determine further workup for NAFLD in children with T1D, particularly those with obesity.

Cross-sectional study to estimate the prevalence and risk factors of nonalcoholic fatty liver disease in children and adolescents with psoriasis.

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent comorbidity in adult patients with psoriasis, but there is a paucity of data on NAFLD in paediatric patients with psoriasis. To estimate the prevalence of NAFLD in children and adolescents with psoriasis compared with age- and sex-matched healthy controls (HCs) and to evaluate risk factors for NAFLD in paediatric psoriasis. This was a cross-sectional study performed from July 2019 to December 2020 in a single tertiary care centre, which enrolled 52 children/adolescents aged 2-18 years diagnosed with psoriasis at least 6 months previously, and 52 HCs matched for age and sex. Anthropometric, metabolic and radiological assessment was performed for all participants. NAFLD prevalence was determined by liver enzyme (serum glutamic pyruvic transferase) levels, ultrasonography, shear wave elastography and aspartate aminotransferase/platelet index. Multivariate analysis was performed to determine the independent risk factors for NAFLD. The frequency of NAFLD was found to be 28·8% in patients with paediatric psoriasis compared with 3·8% in HCs. Logistic regression showed that greater disease severity (Psoriasis Area and Severity Index ≥ 10), obesity and decreased high-density lipoprotein cholesterol (HDL-C) level were independently associated with NAFLD, and thus can be considered risk factors for NAFLD. Patients with paediatric psoriasis have a higher prevalence of NAFLD compared with HCs. Children who are obese or have moderate to severe psoriasis or decreased HDL-C levels are at a higher risk of developing NAFLD.

A diet-induced murine model for non-alcoholic fatty liver disease with obesity and insulin resistance that rapidly develops steatohepatitis and fibrosis

AbstractNon-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide. Patients with NAFLD often suffer steatohepatitis, which can progress to cirrhosis and hepatocellular carcinoma. The presence of visceral obesity or type 2 diabetes mellitus (T2DM) is a major risk factor and potential therapeutic target for NAFLD. The establishment of animal models with these metabolic comorbidities and with the rapid progression of the disease is needed for developing treatments for NAFLD but remains to be archived. In the present study, KK-Ay mice, widely used as T2DM models, or C57BL6 mice were fed a high-fat, high-fructose, and high-cholesterol diet supplemented with cholic acid (NAFLD diet). The KK-Ay mice fed a NAFLD diet exhibited remarkable obesity and insulin resistance. A prominent accumulation of triglycerides and cholesterol in the liver was observed at 4 weeks. These mice developed steatohepatitis at 4 weeks and fibrosis at 12 weeks. In contrast, C57BL6 mice fed a NAFLD diet remained lean, although they still developed steatohepatitis and fibrosis. In summary, we established a diet-induced murine NAFLD model with the rapid development of steatohepatitis and fibrosis, bearing obesity and insulin resistance. This model could be useful as preclinical models for drug development of NAFLD.

Association between Mediterranean Diet and Fatty Liver in Women with Overweight and Obesity.

Obesity is a risk factor for NAFLD. However, not all people with obesity have an excessive intrahepatic fat content. Adherence to a high-quality dietary pattern may also promote liver health in obesity. A cross-sectional study of 2967 women with overweight and obesity was carried out to assess the association between a Mediterranean diet and fatty liver. All women underwent clinical examination, anthropometric measurements, blood sampling, ultrasound measurements of abdominal visceral and subcutaneous fat, and assessment of adherence to the Mediterranean diet using the 14-item MEDAS questionnaire. Fatty liver index (FLI), NAFLD fatty liver steatosis (NAFLD-FLS) and hepatic steatosis index (HSI) were calculated. In women with obesity, the MEDAS score was inversely associated with FLI (β = −0.60, 95% CI: −1.04, −0.16, p = 0.008), NAFLD-FLS (β = −0.092, 95% CI: −0.134, −0.049, p < 0.001) and HSI (β = −0.17, 95% CI: −0.30, −0.04, p = 0.011). Stronger associations were observed in premenopausal women with obesity. Mediterranean diet was inversely associated with NAFLD-FLS in women with overweight, independently of menopausal status. In conclusion, Mediterranean diet is associated with a better liver status in women with overweight and obesity. This may have a public health impact and be useful in drafting nutritional guidelines for NAFLD.

Association between the atherogenic index of plasma and new-onset non-alcoholic fatty liver disease in non-obese participants.

IntroductionNon-alcoholic fatty liver disease (NAFLD) in the non-obese population accounts for a large proportion of NAFLD. Atherogenic index of plasma (AIP, defined as the logarithm of the triglyceride/high-density lipoprotein cholesterol ratio.) can provide a stronger reflection of dyslipidemia and studies on the longitudinal association between AIP and NAFLD were limited in non-obese participants, especially in different BMI groups.MethodsWe performed a post-hoc analysis of data obtained from the Dryad data repository (Dryad is a nonprofit open database of medicine.) and explored the predictive value of AIP on the risk of NAFLD among non-obese participants.ResultsThis study included 16173 participants with AIP, of which 2322(14.4%) non-obese participants developed into individuals with NAFLD with the 5-year follow-up examination. The difference between AIP quartiles in the cumulative estimation of new-onset NAFLD was significant, and with increased AIP, the cumulative new-onset NAFLD gradually increased. Participants in higher AIP quartiles had a significantly increased risk of NAFLD. In the fully adjusted model 3, hazard ratios of the new-onset NAFLD for subjects in Q2, Q3, and Q4 of AIP were 2.00 (1.59, 2.53), 2.61 (2.09, 3.72), and 4.49 (3.62, 5.57) respectively. Meanwhile, the trend test for the association between AIP quartiles and the new-onset NAFLD presented that AIP quartile was positively and strongly associated with the new-onset NAFLD (adjusted hazard ratio (95%CI) in Model 3: 1.59 (1.51, 1.67), P<0.001). We found that AIP was also positively and strongly associated with new-onset NAFLD in different sex groups and different age groups in female patients. Moreover, the predictive ability of AIP was no significant difference in different sex groups and different age groups in female patients. In the subgroup analysis, we found that in the low BMI population, the predictive effect of AIP for new-onset NAFLD was expanded by 2-3 times for each quality increase of AIP.ConclusionThis study found that AIP was a strong independent risk factor for new-onset NAFLD among non-obese individuals especially in the low BMI participants, and screening for AIP in this population can be used to prevent future NAFLD.

NAFLD, pancreatic steatosis and atherosclerotic process

Background and Aims : The atherosclerotic process is closely related to steatosis of the liver and pancreas. The aim of the study was to establish the features of lipid metabolism and carbohydrate metabolism in patients with NAFLD and pancreatic steatosis (PS).Methods: We examined 172 patients with NAFLD with PS. All patients underwent ultrasound examination and fibroscan, determined markers of cytolysis and cholestasis, lipid metabolism, HOMA index. Correlation analysis was used to identify correlations between different indicators, calculating the correlation coefficient (d) and assessing its reliability (Pearson's test and Spearman's test).Results: There was a frequent combination of pancreatic steatosis with hepatic steatosis, gallbladder cholesterol, gastroesophageal reflux disease and coronary heart disease. Most patients have a decrease in HDL cholesterol and an increase in LDL cholesterol. Hypertriglyceridemia was in more than 76% patients. Coefficient of atherogenicity was 3.5 units. A direct significant correlation was found between insulinemia and body mass index (r = 0.48; P <0.05), waist circumference (r = 0.43; P <0.05), HOMA index (r = 0, 95; P <0,05) and serum concentration of C-peptide (r = 0,80; P <0,05). Serum of TG concentration was directly correlated with body mass index (r = 0.41; P <0.05), waist circumference (r = 0.38; P <0.05), mean blood pressure (r = 0, 40; P <0.05).Conclusions: The most prognostic risk factors of NAFLD with pancreatic steatosis were the degree of obesity, the presence of coronary heart disease, the value of the HOMA index, total cholesterol, and triglyceride levels. Background and Aims : The atherosclerotic process is closely related to steatosis of the liver and pancreas. The aim of the study was to establish the features of lipid metabolism and carbohydrate metabolism in patients with NAFLD and pancreatic steatosis (PS). Methods: We examined 172 patients with NAFLD with PS. All patients underwent ultrasound examination and fibroscan, determined markers of cytolysis and cholestasis, lipid metabolism, HOMA index. Correlation analysis was used to identify correlations between different indicators, calculating the correlation coefficient (d) and assessing its reliability (Pearson's test and Spearman's test). Results: There was a frequent combination of pancreatic steatosis with hepatic steatosis, gallbladder cholesterol, gastroesophageal reflux disease and coronary heart disease. Most patients have a decrease in HDL cholesterol and an increase in LDL cholesterol. Hypertriglyceridemia was in more than 76% patients. Coefficient of atherogenicity was 3.5 units. A direct significant correlation was found between insulinemia and body mass index (r = 0.48; P <0.05), waist circumference (r = 0.43; P <0.05), HOMA index (r = 0, 95; P <0,05) and serum concentration of C-peptide (r = 0,80; P <0,05). Serum of TG concentration was directly correlated with body mass index (r = 0.41; P <0.05), waist circumference (r = 0.38; P <0.05), mean blood pressure (r = 0, 40; P <0.05). Conclusions: The most prognostic risk factors of NAFLD with pancreatic steatosis were the degree of obesity, the presence of coronary heart disease, the value of the HOMA index, total cholesterol, and triglyceride levels.

Letter to the editor: Risk factors of NAFLD in preterm and low birthweight. More questions than answers!

Letter to the editor: Risk factors of NAFLD in preterm and low birthweight. More questions than answers!

Lifestyle Interventions for Non-Obese Patients Both with, and at Risk, of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease occurring in non-obese subjects (the so-called non-obese NAFLD) is a highly prevalent but neglected liver condition, which is closely associated with metabolic disorders and suboptimal lifestyles. Landmark studies have shown that lifestyle interventions are potentially beneficial in decreasing the risk of developing non-obese NAFLD and in ameliorating NAFLD in non-obese individuals with pre-existing NAFLD. Lifestyle interventions usually refer to changes in eating habits and physical activity, both of which have a powerful effect on non-obese NAFLD and on risk factors for non-obese NAFLD. However, to date, patients and health-care professionals have a poor awareness and understanding of non-obese NAFLD and the beneficial effects of lifestyle interventions in this patient population. The aim of this narrative review is to briefly discuss the evidence for the effects of lifestyle changes and what changes are needed amongst medical personnel and other stakeholders in order to raise awareness of non-obese NAFLD.

Sociodemographic and genetic determinants of nonalcoholic fatty liver disease in type 2 diabetes mellitus patients

BackgroundNonalcoholic fatty liver disease (NAFLD) showed significant association with PNPLA3 rs738409 polymorphism in unrelated individuals. However, it is still unknown whether the relationship of NAFLD with PNPLA3 variant exists or not among subjects with type 2 diabetes mellitus (T2DM). Therefore, the study aimed to evaluate sociodemographic and genetic determinants of NAFLD in type 2 diabetics. MethodsThe cross-sectional analytical study was conducted at the Department of Molecular Biology, Virtual University of Pakistan, Lahore, Pakistan, during 2019–2020. A total of 153 known cases of T2DM were enrolled using convenience sampling. After excluding patients (n = 24) with HCV, alcoholism, or missing information, data from 129 eligible diabetics with and without NAFLD were analyzed using SPSS. Odds ratios using crosstabs and adjusted odds ratios using binary and multinomial logistic regression were calculated to measure the risk of NAFLD. ResultsAdults 18–35 years were 7.0%, 36–55 years were 64.3%, ≥ 56 years were 28.7%, and females were 66.7%. A total of 41.1% of patients had obesity, 52.7% had NAFLD, and 29.05% carried mutant G allele of rs738409 polymorphism. Among overall diabetics, NAFLD showed association with female (OR = 2.998, p = 0.007), illiterate (OR = 3.067, p = 0.005), and obese (OR = 2.211, p = 0.046) but not with PNPLA3 genotype under any model (all p = > 0.05). Among obese diabetics, NAFLD showed association with female (AOR = 4.010, p = 0.029), illiterate (AOR = 3.506, p = 0.037), GG + CG/CC (AOR = 3.303, p = 0.033), and GG/CG + CC (AOR = 4.547, p = 0.034) using binary regression and with female (AOR = 3.411, p = 0.051), illiterate (AOR = 3.323, p = 0.048), GG + CG/CC (AOR = 3.270, p = 0.029), and GG/CG + CC (AOR = 4.534, p = 0.024) using multinomial regression. ConclusionsNAFLD and obesity were the most common comorbid diseases of T2DM. Gender female, being illiterate, and PNPLA3 rs738409 polymorphism were significant risk factors of NAFLD among obese diabetic patients.

BURDEN OF NON-ALCOHOLIC FATTY LIVER DISEASE AMONG PATIENTS WITH CROHN’S DISEASE: ANALYSIS OF THE NATIONWIDE READMISSION DATABASE

Abstract INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is a spectrum that ranges from hepatic steatosis to Non-alcoholic steatohepatitis (NASH). NASH can lead to liver fibrosis, cirrhosis, and hepatocellular carcinoma. (Chao CY et al. World J Gastroenterol). Both NAFLD and Crohn’s disease are associated with increased gut permeability. (Miele L et al Hepatology, Pearson AD et al. Br Med J). Current evidence has shown fatty liver disease to be the most common explanation for abnormal liver tests in patients with IBD. (Gisbert JP et al. Inflamm Bowel Dis). A practical approach may be pursued in identifying patients with IBD at risk for having NAFLD and subsequently identifying patients at an increased risk of morbidity and mortality. METHODS We collected data from the publicly available Healthcare Cost and Utilization Project (HCUP) Nationwide Readmission Databases (NRD) 2016, 2017, and 2018. We identified and analyzed the burden of NAFLD amongst individuals discharged with a diagnosis of CD or one of its complications (Figure 1). We studied the characteristics, co-morbidities, and hospitalization outcomes of CD patients with NAFLD. A subgroup analysis was performed for those with NASH. Patients who died in index hospitalization or were discharged in Dec. were excluded from the 30-day readmission analysis. Median and IQR were used to describe Continuous variables, and proportions were used with categorical variables. Comparison between groups was performed by Mann Whitney test for continuous variables and Chi-Square test for Categorical variables. We performed a binary logistic regression analysis for predictors of NAFLD among patients with CD. Statistical analyses were performed using SPSS Version 25 (IBM Corporation, Armonk, NY, USA). RESULTS We analyzed 215,049 index hospital discharges with Crohn’s disease or one of its complications. 2.4% had NAFLD. Hypertension, diabetes, Dyslipidemia, Obesity, and metabolic syndrome are the five most recognized risk factors for NAFLD in the general population. 35.9% of CD patients with NAFLD had none of those risk factors (Table 1). 0.42 % of CD patients had a diagnosis of NASH. Subgroup analysis for CD patients with NASH showed increased mortality, increased length of stay, and a higher rate of 30-day readmission among CD patients with NASH (Table 2). Predictors of NAFLD in patients with CD are illustrated in Table 3. The chi-square test results indicate that our regression model is a significant improvement in fit relative to an intercept-only model (χ2 = 1593.171, p&amp;lt;.001). CONCLUSION The presence of NAFLD in patients with CD is associated with metabolic syndrome components and CD-specific risk factors. The development of NASH is associated with increased morbidity and mortality in patients with CD. Further studies are needed to investigate the pathogenesis of NAFLD in CD patients.

Potential relation between non-alcoholic fatty liver disease and glycemic and metabolic parameters in subjects without diabetes

BackgroundNonalcoholic fatty liver disease (NAFLD) is proved to be related to insulin resistance and type 2 diabetes, and it is also not rare in individuals without diabetes. The present study attempts to identify the metabolic risk factors of NAFLD among those individuals.ResultsALT and HbA1c levels were independently associated with NAFLD development in individuals without diabetes. Receiver operating characteristic (ROC) analysis identified the optimal cutoff point of ALT (> 19 IU/ml) with AUC = 0.731, 95% CI 0.653–0.809. On the other hand, the optimal cutoff point of HbA1c was identified to be > 5.1% with AUC = 0.665, 95% CI 0.581–0.750.ConclusionsEarly identification of NAFLD among subjects without diabetes is crucial. In this study, ALT and HbA1c cutoff values had been identified, so we suggest that inclusion of both HbA1c and ALT levels may have significant implications for prediction of NAFLD among individuals without diabetes.

Inflammatory Bowel Disease-associated Fatty Liver Disease: the Potential Effect of Biologic Agents.

Inflammatory bowel diseases [IBD] exhibit intestinal and systemic manifestations. Nonalcoholic fatty liver disease [NAFLD] is a common co-existing condition, possibly contributing to the cardio-metabolic burden and overall morbidity. Εmerging therapeutic choices of biologic agents have modified the clinical course of IBD; however, their impact on IBD-associated NAFLD has not been extensively evaluated. The prevalence of NAFLD varies among IBD patients, but it appears higher than in the general population in the majority of quality studies. In terms of pathogenetic and risk factors of NAFLD, they may vary with IBD activity. Dysbiosis, mucosal damage, and cytokine release have been implicated in the pathogenesis during the relapses, whereas metabolic risk factors seem to play a dominant role during the remissions of IBD. Considering biologics, although quality data are scarce, agents suppressing tumour necrosis factor may offer potential benefits in IBD-associated NAFLD, whereas anti-integrins do not appear to confer any therapeutic advantage. In conclusion, IBD-associated NAFLD possibly follows two different patterns, one manifested during the relapses and one during the remissions of IBD. Some, but not all, biologics may benefit NAFLD in patients with IBD. Further mechanistic and prospective cohort studies are warranted to illuminate the effects of various biologics on NAFLD.

Study on the relationship between non-alcoholic fatty liver disease and sarcopenia in type 2 diabetes mellitus

Objective: To explore the relationship between non-alcoholic fatty liver disease and sarcopenia in patients with type 2 diabetes mellitus. Methods: 792 cases with type 2 diabetes mellitus who were hospitalized in the Endocrinology Department of the First Affiliated Hospital of Chongqing Medical University from June 2013 to December 2015 were enrolled in this cross-sectional study. Liver ultrasound examination and dual-energy X-ray absorptiometry (DXA) were used to examine the body composition. Patients were grouped according to gender and whether or not they had combined NAFLD, and indicators such as age, duration of diabetes, body mass index (BMI), waist circumference, biochemical indicators, skeletal muscle mass index (SMI), prevalence of sarcopenia, and medication status were collected. An independent-sample t-test, two-sample Kolmogorov-Smirnov test or χ (2) test were performed on the data. Logistic regression model was used to analyze the correlation between NAFLD, sarcopenia and SMI in diabetic patients of different genders. Results: The average age of 792 cases were (64.54 ± 9.61) years, and there were 301 (38%) patients with NAFLD. The prevalence of sarcopenia in male and female NAFLD patients was significantly higher than non-NAFLD patients (male 20.2% and 9.9%, χ(2) = 9.67, P = 0.002; female 12.2% and 5.1%, χ(2) = 5.64, P = 0.018). Male SMI (30.92 ± 2.31 and 31.81 ± 2.17, P < 0.001) and female SMI (25.48 ± 2.14 and 26.34 ± 2.28, P < 0.001) in NAFLD patients were significantly lower than non-NAFLD patients. Multivariate logistic regression analysis showed that sarcopenia was an independent risk factor for NAFLD in male patients with type 2 diabetes mellitus (OR = 2.006, 95% CI: 1.012 ~ 3.976, P = 0.046). There was no correlation between sarcopenia and NAFLD in female patients after adjusting for clinical risk factors. Conclusion: There is an independent correlation between sarcopenia and NAFLD in male patients with type 2 diabetes, and sarcopenia may be an independent risk factor for male patients with NAFLD.

Long working hours are associated with a higher risk of non-alcoholic fatty liver disease: A large population-based Korean cohort study.

Non-alcoholic fatty liver disease (NAFLD), a common chronic liver disease, may progress to fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure. But only a few cross-sectional studies have reported an association of NAFLD with working hours. This cohort study further examined the association between working hours and the development of NAFLD. We included 79,048 Korean adults without NAFLD at baseline who underwent a comprehensive health examination and categorized weekly working hours into 35-40, 41-52, 53-60, and >60 hours. NAFLD was defined as the presence of fatty liver, in the absence of excessive alcohol use, as observed by ultrasound. During a median follow-up of 6.6 years, 15,095 participants developed new-onset NAFLD (incidence rate, 5.55 per 100 person-years). After adjustment for confounders, the hazard ratios (95% confidence interval) for the development of NAFLD in 41-52, 53-60, and >60 working hours compared with that in 35-40 working hours were 1.07 (1.02-1.13), 1.06 (1.00-1.13), and 1.13 (1.05-1.23), respectively. Furthermore, the association remained significant after confounders were treated as time-varying covariates. In this large-scale cohort, long working hours, especially >60 working hours a week, were independently associated with incident NAFLD. Our findings indicate that long working hours are a risk factor for NAFLD.

Estimation of the Prevalence of Nonalcoholic Fatty Liver Disease in an Adult Population in Northern China Using the Data Mining Approach.

BackgroundNonalcoholic fatty liver disease (NAFLD) is the commonest form of chronic liver disease worldwide and its prevalence is rapidly increasing. Screening and early diagnosis of high-risk groups are important for the prevention and treatment of NAFLD; however, traditional imaging examinations are expensive and difficult to perform on a large scale. This study aimed to develop a simple and reliable predictive model based on the risk factors for NAFLD using a decision tree algorithm for the diagnosis of NAFLD and reduction of healthcare costs.MethodsThis retrospective cross-sectional study included 22,819 participants who underwent annual health examinations between January 2019 and December 2019 at Physical Examination Center in Shengjing Hospital of China Medical University. After rigorous data screening, data of 9190 participants were retained in the final dataset for use in the J48 decision tree algorithm for the construction of predictive models. Approximately 66% of these patients (n=6065) were randomly assigned to the training dataset for the construction of the decision tree, while 34% of the patients (n=3125) were assigned to the test dataset to evaluate the performance of the decision tree.ResultsThe results showed that the J48 decision tree classifier exhibited good performance (accuracy=0.830, precision=0.837, recall=0.830, F-measure=0.830, and area under the curve=0.905). The decision tree structure revealed waist circumference as the most significant attribute, followed by triglyceride levels, systolic blood pressure, sex, age, and total cholesterol level.ConclusionOur study suggests that a decision tree analysis can be used to screen high-risk individuals for NAFLD. The key attributes in the tree structure can further contribute to the prevention of NAFLD by suggesting implementable targeted community interventions, which can help improve the outcome of NAFLD and reduce the burden on the healthcare system.