Nonalcoholic Fatty Liver Disease Index Research Articles

MAFLD and Cardiovascular Disease Risk Assessment in the Primary Care Setting

Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of disorders, characterized by multisystemic manifestations and heterogenous etiology associated with varying cardiovascular disease (CVD) risk. The high risk-associated frequent NAFLD-phenotype, considered a consequence of the metabolic syndrome (MS), was recently renamed metabolic dysfunction-associated fatty liver disease (MAFLD). The complex bidirectional interplay between visceral obesity-type 2 diabetes (T2D)-NAFLD-CVD is incompletely clarified, and the role of fatty liver disease suspected as an independent CVD risk factor is less addressed in the medical practice.Simple identification of MAFLD and risk stratification of MS patients at increased CVD risk in the primary care could contribute to the reduction of morbidity and mortality associated with the growing NAFLD epidemic.In 221 central Romanian IDF-criteria-diagnosed MS patients, MAFLD diagnosis and NAFLD-developed indices (FLI/Fatty-Liver-Index, HSI/Hepatic-Steatosis-Index, ZJU/Zhejiang-University-Index) were investigated, related to HOMA/QUICKI-assessed insulin resistance and diagnosed CVD.In the 59.34+/-9.54 year-old MS patients, FLI, HSI, ZJU showed moderate correlation with obesity (BMI/waist circumference: r=0.5/0.7-0.8/0.48-0.64/0.5,p<0.001), insulin resistance (HOMA-IR/IRI: r=0.33-0.37-0.45,p=0.001), fasting glucose (r=0.28-0.33-0.34,p<0.01) and other NAFLD- indices (r=0.38-0.59,p<0.001). Increased CVD risk associated with elevated HSI (>36: OR=2,p=0.03) and FLI (>60: OR=7,p=0.006), without reaching statistical significance in case of ZJU, to our best knowledge uninvestigated in European populations (>38: OR=2.75,p>0.05), and MAFLD in the diagnosis (OR=1.7,p>0.05).In conclusion, in MS patients with visceral obesity, NAFLD indices available in the primary care setting, based on obesity measurements, T2D presence and liver enzymes, correlate with insulin resistance and associate with an increased CVD risk, and may assist identification of MAFLD cases needing imperious management.

Nonalcoholic fatty liver disease test: an external validation cohort

PurposeNon-invasive diagnosis of nonalcoholic fatty liver disease (NAFLD) and its advanced phenotypes (e.g., nonalcoholic steatohepatitis; NASH) is a hot research topic. The aim of this report was the validation of a novel non-invasive index of NAFLD, the “NAFLD test,” recently introduced for the diagnosis of NAFLD (vs. non-NAFLD controls).MethodsThis was a post-hoc analysis of a previous study. The NAFLD test was calculated in NAFLD patients and non-NAFLD controls; the performance of the test was compared with that of other non-invasive indices of NAFLD (fatty liver index [FLI] and hepatic steatosis index [HSI]), and other indices of NASH (index of NASH [ION] and cytokeratin-18/homeostasis model assessment-insulin resistance/aspartate transaminase index [CHAI]).ResultsThe NAFLD test was higher in NAFLD patients than in controls (1.89 ± 0.14 vs. 1.30 ± 0.06, respectively; p < 0.001). In NAFLD patients, the NAFLD test was higher in NASH patients than in those with simple nonalcoholic fatty liver (NAFL) (2.21 ± 0.24 vs. 1.57 ± 0.08, respectively; p = 0.007). The area under the receiver operating characteristic curve (AUC) of the NAFLD test was 0.84 (95% CI: 0.74–0.94; p < 0.001) for differentiation between NAFLD and non-NAFLD controls and its performance was similar to that for FLI and HSI. For differentiation between NASH and NAFL patients, the AUC of the NAFLD test was 0.88 (95% CI: 0.62–0.96; p = 0.007) and its performance was superior to that for ION and CHAI.ConclusionsThe NAFLD test was validated in this external cohort for the non-invasive diagnosis of NAFLD patients vs. non-NAFLD individuals. It was also shown to differentiate between NASH and NAFL patients with acceptable accuracy.

Early diagnosis of non-alcoholic fatty liver disease: the role of biomarkers and complex indices of non-alcoholic fatty liver steatosis

Metabolic syndrome is a series of pathologies united by a similar pathogenesis, the end of which, most often, is cardiovascular accidents, which are leaders among the causes of death in the population around the world. Non-alcoholic fatty liver disease (NAFLD) is the hepatic equivalent of the metabolic syndrome, registered earlier than all other equivalents, on the rights of the liver as a first-line energy depot. At the same time, according to multicenter studies, 95% of people with NAFLD (any stage) are not diagnosed with the disease. Clarification of additional risk factors for NAFLD and the presence of a specific biomarker of non-alcoholic liver steatosis would make it possible to stop the vicious cascade of metabolic processes, which in the future can lead to a significant increase in the life expectancy of the population. The potentially high role of Secreted Frizzled Related Protein-4 (SFRP4) adipokine in the early diagnosis of NAFLD is known. The aim of the study was to optimize the early diagnosis of non-alcoholic fatty liver disease using modern indices and biomarkers. Materials and methods. The work was carried out at the Department of Faculty and Hospital Therapy of the Chuvash State University named after I. N. Ulyanov” in the period from 2016 to 2020. This study included several stages: first of all, a retrospective analysis of 1150 outpatient records of patients from several medical organizations of the Chuvash Republic for the period 2016-2018 was carried out. to form two study groups: experimental and control. At the second stage, as a result of applying the exclusion criteria, 162 people remained in the experiment: 110 from the experimental group, 52 from the control group. The subjects of both groups were compared by gender and age, the age range of the subjects varied from 18 to 80 years old with an average value of 48.3 years. Further, the patients undergo a detailed examination, according to the presented plan: Collection of complaints, medical history, objective examination. Laboratory studies (general and biochemical blood tests, lipidogram, assessment of the level of serum adipokine SFRP4). Instrumental studies (ultrasound of the OBP, TE (SAR), ESP with elastometry). Evaluation of the most informative complex indices for the early diagnosis of NAFLD: MI, IVO indices, HSI, FLD-I. Further, all the necessary statistical processing and analysis of the obtained data were performed (Microsoft Office Excel 2016, StatTech v. 2.8.8 (developer - Stattech LLC, Russia)). Results. Accessible (not requiring the use of additional time and material costs) NAFLD indices with the highest sensitivity rates (99.1% and 98.2%, respectively) were MI and IVO. A noticeable direct correlation was traced between MI (p=0.640), moderate - between the IVO (p=0.398) and the elastographically determined index of non-alcoholic liver steatosis. High sensitivity and specificity of skin manifestations (xanthoma, xanthelasma - 69.6% and 89.7% and seborrheic dermatitis - 82.0% and 71.4%) were found in relation to early manifestations of NAFLD. From anthropometric indicators: the CW/CF index has a pronounced (ρ=0.643), CW - moderate (ρ=0.238), and BMI - a weak direct (ρ=0.223) correlation with the elastographically determined index of non-alcoholic liver steatosis. Adipokine SFRP4 correlates (ρ=0.841) with early manifestations of hepatic steatosis in patients, as determined by TE in CAP mode.

Non-alcoholic fatty liver disease is associated with hyperandrogenism in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a highly complex reproductive metabolic disorder and women with PCOS have high prevalence of non-alcoholic fatty liver disease (NAFLD). Despite both hyperandrogenism and insulin resistance are common pathophysiologies in NAFLD and PCOS, this association is still controversial. Therefore, the aim of this study is to evaluate the relationship between hyperandrogenism and NAFLD in females diagnosed with PCOS. We recruited 667 women diagnosed with PCOS and 289 women with regular menstrual cycles as control. The PCOS diagnosis was made using National Institute of Child Health and Human Disease criteria. Total and free testosterone levels (TT and TF, respectively), and free androgen index (FAI) were used as measures of hyperandrogenism. Fatty liver index and liver fat score (FLI and LFS, respectively), and hepatic steatosis index (HSI) were used to assess NAFLD. The prevalence of NAFLD in PCOS women evaluated by LFS, FLI, and HIS were 19.9, 10.3, and 32.2%, respectively. In the control group, the incidence was 2.1, 0.7, and 4.2%, respectively. Both FT and FAI levels showed significant association with increased NAFLD-related indices, after adjusting for insulin resistance and other factors (LFS (OR 3.18 (95% CI 1.53–6.63) in FT; 1.12 (1.04–1.22) in FAI), FLI (OR 2.68 (95% CI 1.43–5.03) in FT; 1.13 (1.06–1.20) in FAI), and HSI (OR 3.29 (95% CI 2.08–5.21) in FT; 1.5 (1.09–1.21) in FAI). TT did not exhibit association with any NAFLD index. In women with PCOS, significantly higher rate of NAFLD was observed compared to the control women. The FT and FAI were independently associated with NAFLD in women with PCOS. The findings suggest the possibility of hyperandrogenism contributing to the progression and/or development of NAFLD in PCOS.

Association of volatile methylsiloxanes exposure with non-alcoholic fatty liver disease among Chinese adults

Owing to the wide use of volatile methylsiloxanes (VMSs) in various industries and consumer products, both cyclic VMSs (cVMS) and linear VMSs (lVMS) have been detected in human plasma. Experimental studies suggest that exposure to cVMSs may induce liver disease. Whereas, there is no human evidence of the potential health effects of VMSs yet.In this cross-sectional study, we evaluated the association of plasma VMSs concentrations with liver enzymes and Nonalcoholic fatty liver disease (NAFLD) among adults located in southwestern China. We used the fibrosis 4 calculator (FIB-4) as the NAFLD index and defined FIB-4≥1.45 as the NAFLD case.Among 372 participants, 45 (12.1%) of them were classified as NAFLD. Positive associations of plasma cVMSs concentrations with liver enzymes and NAFLD were observed among all participants. With per doubling increase in the total cVMSs, we observed a 1.40 (95%CI: 0.31, 2.48) increase in Alanine aminotransferase (ALT), a 1.56 (95%CI: 0.52, 2.61) increase in aspartate aminotransferase (AST) and a 0.04 (0.00, 0.09) increase in NAFLD index. A 19% increased risk of NAFLD was also found to be associated with per doubling increase in total cVMSs. In addition, positive associations of total lVMSs with ALT, AST and NAFLD were also detected when restricting our analyses to 230 participants living in industrial areas. Our study first provides epidemiological evidence on the association between VMSs and liver health, indicating more careful usage of VMSs may potentially reduce the burden of NAFLD, though more well-designed cohort studies are needed to confirm these findings.

Analysis of risk factors related to nonalcoholic fatty liver disease: a retrospective study based on 31,718 adult Chinese individuals.

Nonalcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide. This study guides the prevention and diagnosis of NAFLD by analyzing its risk factors and the diagnostic value of each index for NAFLD. We collected the clinical information of adults individuals who underwent physical examination in the Physical Examination Center of Qingpu Branch of Zhongshan Hospital, Fudan University, from January 2016 to January 2020, including gender, age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). We performed logistic regression analysis and ROC diagnostic analysis. The results showed that age, BMI, SBP, ALT, AST, FBG, TBIL, TG, and LDL were risk factors for NAFLD in adults, and HDL was a protective factor (all p-values were less than 0.05). Among them, age, BMI, ALT, TG, and HDL had a predictive value for the occurrence of NAFLD in the adults (AUC = 0.708, 0.836, 0.767, 0.780, and 0.732, respectively). The combination of age, BMI, ALT, TG, and HDL had a diagnostic value for the occurrence of NAFLD (AUC = 0.881). Healthy people should pay attention to their BMI levels, manage blood pressure, blood glucose, and lipid levels, and pay attention to changes in ALT and AST index levels to prevent NAFLD. Age, BMI, ALT, TG, and HDL indexes are helpful factors in the diagnosis of NAFLD.

Development and validation of nonalcoholic fatty liver disease test: a simple sensitive and specific marker for early diagnosis of nonalcoholic fatty liver disease.

This study aimed to develop a noninvasive test for identifying patients with nonalcoholic fatty liver disease (NAFLD) based on clinical and routine laboratory data. The developed model 'NAFLD test' was compared to the most commonly used NAFLD scores and then validated in three groups of NAFLD patients from five centers in Egypt, China, and Chile. Patients were divided into the discovery cohort (n = 212) and the validation study (n = 859). The ROC curve and stepwise multivariate discriminant analysis were used to develop and validate the NAFLD test and evaluate its diagnostic performance, which was then compared to other NAFLD scores. Elevated C-reactive protein (CRP), cholesterol, BMI, and alanine aminotransferase (ALT) levels were significantly associated with NAFLD (P < 0.0001). NAFLD test is depicted as (-0.695 + 0.031 × BMI + 0.003 × cholesterol + 0.014 × ALT + 0.025 × CRP) to discriminate patients with NAFLD from healthy individuals. The area under the ROC curve (AUC) of the NAFLD test was 0.92 [95% confidence interval (CI): 0.88-0.96]. The NAFLD test was the most accurate diagnostic indicator of NAFLD when compared to widely used NAFLD indices. Upon validating the NAFLD test, its AUC (95% CI) for distinguishing patients with NAFLD from healthy individuals was 0.95 (0.94-0.97), 0.90 (0.87-0.93), and 0.94 (0.91-0.97) in Egyptian, Chinese, and Chilean patients with NAFLD respectively. The NAFLD test is a new validated diagnostic biomarker that can be utilized for the early diagnosis of NAFLD with high diagnostic performance.

The nonalcoholic fatty liver risk in prediction of unfavorable outcome after stroke: A nationwide registry analysis

Few researches have looked at the relationship between nonalcoholic fatty liver disease (NAFLD) at the time of admission and the long-term outcomes of patients suffering from acute ischemic stroke (AIS). We aimed to probe the relationship between NAFLD risk evaluated by NAFLD indices and long-term endpoints, along with the prognostic value of merging NAFLD indices with established risk markers for the prognosis of AIS patients. The fatty liver index (FLI) and the Hepatic steatosis index (HSI) were used to evaluate NAFLD risk in the Third China National Stroke Registry (CNSR-III), a large, prospective, national, multicenter cohort registry study. NAFLD was defined as FLI ≥35 for males and FLI ≥ 20 for females, as well as HSI>36. Death or major disability (modified Rankin Scale score ≥3) were the primary outcomes following the beginning of a stroke. On patient outcomes, the prognostic performance of two objective NAFLD parameters was evaluated. NAFLD was detected in 32.10-51.90% of AIS patients. After 1-year, 14.5% of the participants had died or suffered a severe outcome. After controlling for known risk factors, NAFLD was associated with a modest probability of adverse outcome (odds ratio,0.72[95% CI, 0.61-0.86] for FLI; odds ratio,0.68[95% CI, 0.55-0.85] for HSI). The inclusion of the two NAFLD indicators in the conventional prediction model was justified by the integrated discrimination index, continuing to increase the model's overall predictive value for long-term adverse outcomes. NAFLD risk was linked to a lower risk of long-term death or major disability in people with AIS. The predictive value of objective NAFLD after AIS was demonstrated in our study.

Association between the dual use of electronic and conventional cigarettes and NAFLD status in Korean men.

This study investigated the association between smoking types, including dual use (usage of both combustible cigarettes and e-cigarettes), and non-alcoholic fatty liver disease (NAFLD) status in Korean men. Data from the 7th and 8th Korea National Health and Nutrition Examination Survey (KNHANES) 2016-2020 were used. The presence of NAFLD was defined by the respective cut-off values for the Hepatic Steatosis Index (HSI), NAFLD Ridge Score (NRS), and Korea National Health and Nutrition Examination Survey NAFLD score (KNS). Multivariate logistic regression analyses were used to determine the associations between smoking types and NAFLD as determined by HSI, NRS, and KNS. After adjustment for confounders, an independent association was observed between dual use and NAFLD (HSI: AOR=1.47; 95% CI: 1.08-1.99, p=0.014; NRS: AOR=2.21; 95% CI: 1.70-2.86, p=0.000; KNS: AOR=1.35; 95% CI: 1.01-1.81, p=0.045). Cigarette only smokers also had significantly higher odds of NAFLD compared to never smokers for all of the NAFLD indices (HSI: AOR=1.22; 95% CI: 1.05-1.42, p=0.008; NRS: AOR=2.13; 95% CI: 1.87-2.42, p=0.000; KNS: AOR=1.33; 95% CI: 1.14-1.55, p=0.000). In subgroup analyses, no significant interaction effects were found for age, BMI, alcohol consumption, income, physical activity, and the diagnosis of T2DM. Moreover, cigarette only smokers and dual users differed significantly in terms of log-transformed urine cotinine and pack-years. The relationship between smoking type and pack-years was attenuated after stratification by age. This study shows that the dual use of e-cigarettes and combustible cigarettes is associated with NAFLD. Age differences may explain why dual users, with a greater proportion of young people, appear to have fewer pack-years than cigarette only smokers. Further research should be conducted to investigate the adverse effects of dual use on hepatic steatosis.

Cadmium, lead, and mercury mixtures interact with non-alcoholic fatty liver diseases

There is a scarcity of studies on the interactions between heavy metals and non-alcoholic fatty liver disease (NAFLD). Using a variety of statistical approaches, we investigated the impact of three common heavy metals on liver enzymes and NAFLD markers in a Korean adult population. We observed that cadmium, mercury, and lead all demonstrated positive correlations with liver enzymes and NAFLD indices. Our findings were mostly robust in secondary analysis, which included three novel mixture modeling approaches (WQS, qgcomp, and BKMR) as well as in silico investigation of molecular mechanisms (genes, miRNAs, biological processes, pathways, and illnesses). The 16 genes interacted with a mixture of heavy metals, which was linked to the development of NAFLD. Co-expression was discovered in nearly half of the interactions between the 18 NAFLD-linked genes. Key molecular pathways implicated in the pathogenesis of NAFLD generated by the heavy metal combination include activated oxidative stress, altered lipid metabolism, and increased cytokines and inflammatory response. Heavy metal exposure levels were related to liver enzymes and NAFLD indices, and cutoff criteria were revealed. More studies are needed to validate our findings and gain knowledge about the effects of chronic combined heavy metal exposure on adult and child liver function and the likelihood of developing NAFLD. To reduce the occurrence of NAFLD, early preventative and regulatory actions (half-yearly screening of workers at high-risk facilities; water filtration; avoiding excessive amounts of seafood, etc.) should be taken.

Effects of chemical mixtures on liver function biomarkers in the Korean adult population: thresholds and molecular mechanisms for non-alcoholic fatty liver disease involved.

There is a scarcity of research on the effects of a mixture of chemicals on liver function biomarkers and non-alcoholic fatty liver disease (NAFLD) indices, including FSI, HIS, and FBI-4. Thus, we aimed to explore whether there is an association between chemical mixtures, including 26 chemicals found in blood and urine, liver function biomarkers, and non-alcoholic fatty liver disease (NAFLD) indices in Korean adults. The effects of exposure to chemical mixtures on liver function biomarkers and NAFLD indices were investigated using linear regression models, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) among 3669 adults. In silico toxicogenomic data-mining, we evaluated molecular mechanisms associated with NAFLD, including pathways, diseases, genes, miRNAs, and biological processes. The linear regression models showed blood or urine Hg levels were the most important factors associated with AST, ALT, GGT, FSI, and HSI levels, and significant trends were observed for these chemical quartiles (p < 0.01). The WQS index was significantly associated with ALT, GGT, FSI, and HSI. The qgcomp index also found an association between chemicals and AST, ALT, GGT, and FSI. In the BKMR model, the overall effect of the mixture was significantly related to ALT, GGT, FSI, and HSI. In silico analysis, we found mixed chemicals interacted with the CYP1A2 gene and were associated with NAFLD. Seventy-eight percent of interactions were identified as physical interactions in the CYP1A2 gene related to NAFLD. Transcription factor regulation in adipogenesis and lipid metabolic processes are fundamental molecular mechanisms that could be influenced by NAFLD-related mixed chemicals. Cutoff thresholds for chemical exposure levels associated with liver function indicators and NAFLD indices were also reported. The strongest interactions and expression of miRNAs involved in NAFLD development were also identified.

Exposure to polycyclic aromatic hydrocarbons and volatile organic compounds is associated with a risk of obesity and diabetes mellitus among Korean adults: Korean National Environmental Health Survey (KoNEHS) 2015-2017.

Environmental pollutants have been known to increase the risks of not only respiratory and cardiovascular disease but also metabolic diseases such as obesity and diabetes mellitus (DM). Polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) such as benzene and toluene are major constituents of environmental pollution. In the present study, we employed the population of the Korean National Environmental Health Survey (KoNEHS) Cycle 3 conducted between 2015 and 2017, and assessed the associations of urinary biomarkers for PAHs and VOCs exposure with obesity and DM. A total of 3787 adult participants were included and the urinary concentrations of four PAH metabolites and two VOC metabolites were measured. For correcting urine dilution, a covariate-adjusted standardization method was used. The highest quartiles of urinary 2-hydroxynaphthalene (2-NAP) [OR (95% confidence interval (CI))=1.46 (1.13, 1.87)] and sum of PAH metabolites [OR (95% CI)=1.45 (1.13, 1.87)] concentrations were associated with a higher risk of obesity [body mass index (BMI)≥25kg/m2]. BMI was positively associated with urinary 2-NAP [β (95% CI)=0.25 (0.09, 0.41), p=0.003] and sum of PAH metabolites [β (95% CI)=0.29 (0.08, 0.49), p=0.006] concentrations. The risk of DM was increased with increasing quartile of 2-hydroxyfluorene (2-OHFlu) and trans, trans-muconic acid (t,t-MA) (p for trend<0.05 and<0.001, respectively). The highest quartile of t,t-MA showed a significantly higher risk of DM [OR (95% CI)=2.77 (1.74, 4.42)] and obesity [OR (95% CI)=1.42 (1.06, 1.90)]. Urinary t,t,-MA level was positively associated with BMI [(β (95% CI)=0.51 (0.31, 0.71), p<0.001] and non-alcoholic fatty liver disease index [(β (95% CI)=0.09 (0.06, 0.12), p<0.001]. In conclusion, the benzene metabolites t,t-MA and PAH metabolite 2-OHFlu were associated with an increased risk of DM. Urinary biomarkers for PAHs and VOCs were positively associated with BMI in the Korean adult population. Further studies to validate these observations in other populations are warranted.

NFI, a clinical scoring tool for predicting non-alcoholic fatty liver in the Chinese population

ObjectivesAccurate assessment of early non-alcoholic fatty liver disease (NAFLD) is important to reduce the possible complications. The purpose of the present study was to develop a simple algorithm for the screening of NAFLD in the Chinese population based on routine anthropometric data and laboratory tests. Study designThis is a cross-sectional design. MethodsThe subjects (1145) underwent routine physical examinations. The variables in the NAFLD index (NFI) were obtained by a stepwise multiple logistic regression analysis on 1000 bootstrap samples. The area under the receiver-operating characteristic (AUROC) was used to evaluate the accuracy of the NFI. ResultsMultivariate analysis showed that body mass index, fasting blood glucose, ratio of alanine aminotransferase to aspartate aminotransferase, and triglyceride were included in the final equation. The AUROC of the NFI was 0.919 (95% confidence interval = 0.901–0.937). An NFI of <31.0 excluded the possibility of NAFLD with a sensitivity of 96.9%, and at a value of >36.0, the NFI could detect NAFLD with a specificity of 98.9%. ConclusionsNFI was a cost-effective NAFLD-screening model, which had a high accuracy for predicting NAFLD at early stages in the Chinese population.

Machine learning models for predicting non-alcoholic fatty liver disease in the general United States population: NHANES database.

BACKGROUNDNon-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, affecting over 30% of the United States population. Early patient identification using a simple method is highly desirable.AIMTo create machine learning models for predicting NAFLD in the general United States population.METHODSUsing the NHANES 1988-1994. Thirty NAFLD-related factors were included. The dataset was divided into the training (70%) and testing (30%) datasets. Twenty-four machine learning algorithms were applied to the training dataset. The best-performing models and another interpretable model (i.e., coarse trees) were tested using the testing dataset.RESULTSThere were 3235 participants (n = 3235) that met the inclusion criteria. In the training phase, the ensemble of random undersampling (RUS) boosted trees had the highest F1 (0.53). In the testing phase, we compared selective machine learning models and NAFLD indices. Based on F1, the ensemble of RUS boosted trees remained the top performer (accuracy 71.1% and F1 0.56) followed by the fatty liver index (accuracy 68.8% and F1 0.52). A simple model (coarse trees) had an accuracy of 74.9% and an F1 of 0.33.CONCLUSIONNot every machine learning model is complex. Using a simpler model such as coarse trees, we can create an interpretable model for predicting NAFLD with only two predictors: fasting C-peptide and waist circumference. Although the simpler model does not have the best performance, its simplicity is useful in clinical practice.

The presence of NAFLD influences the transition of metabolically healthy to metabolically unhealthy obesity and the ten-year cardiovascular disease risk: A population-based cohort study

Background/objectivesWe evaluated the role of the presence of non-alcoholic fatty liver disease (NAFLD) at baseline in the transition from metabolically healthy to metabolically unhealthy obesity (MHO to MUO) ten years later. MethodsA prospective cohort study (ATTICA study, Greece) was performed between 2002 and 2012 studying a sample from the greater metropolitan Athens area. In total, 1514 (49·8%) men and 1528 (50.2%) women (aged >18 years old) free-of-CVD were included. Healthy metabolic status was defined as absence of all NCEP ATP III (2005) metabolic syndrome components. NAFLD was defined according to validated liver steatosis indices. Follow-up CVD assessment (2011–2012) was achieved in n = 2020 participants (n = 317 cases). ResultsNAFLD prevalence among MHO participants ranged from 29% to 39% according to the specific NAFLD score used. MHO participants who developed metabolically unhealthy status had about two times higher odds to have NAFLD at baseline compared with their metabolically healthy normal weight counterparts whereas stable MHO was not associated significantly with NAFLD. Moreover, MHO status accompanied by NAFLD was associated with increased CVD risk (Hazard Ratio = 2.90 95% Confidence Interval (1.35, 5.40)) in comparison to their non-NAFLD MHO counterparts. Further analysis revealed that in the obese, NAFLD indices and not simply visceral adiposity increased significantly the ability of metabolic status (using standard definition) to predict long-term CVD incidence. ConclusionsConsidering NAFLD, even when assessed using validated indices only, in the clinical assessment of apparently healthy obese individuals predicts who is to develop MUO and contributes independently and more accurately to defining future cardiometabolic risk.

Lead, mercury, and cadmium exposures are associated with obesity but not with diabetes mellitus: Korean National Environmental Health Survey (KoNEHS) 2015–2017

Associations of heavy metal exposures with obesity and obesity-related traits have been suggested, while those with nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM) are often inconsistent. This study included 3787 adults aged ≥19 years who participated in the Korean National Environmental Health Survey 2015-2017, and investigated the association of toxic heavy metals with metabolic diseases. Lead (Pb), mercury (Hg), and cadmium (Cd) were measured either in urine (uHg, uCd) or total blood (bPb, bHg). Body mass index (BMI) was calculated, and DM cases were identified through a self-answered medication history. Hepatic Steatosis Index (HSI) as a surrogating index of NAFLD, was calculated using hepatic enzyme measurements, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Adults in the highest quartile of bPb, bHg, and uHg showed significantly elevated odds of obesity (BMI ≥25kg/m2), compared to the lowest quartile (OR 1.58 for bPb, 1.92 for bHg, and 1.81 for uHg). HSI was positively correlated with bHg, uHg, and uCd concentrations. The odds of NAFLD (HSI ≥36) were also increased with increasing quartile of bHg, uHg, and uCd concentrations. For DM, bPb showed a significant negative association, while bHg and uCd exhibited non-monotonic and inconclusive associations. Among the general adult population of Korea, both Pb and Hg exposures were associated with an increased risk of obesity. In addition, both Hg and Cd exposures were associated with increased odds of NAFLD. These metals, however, were not associated with an increased risk of DM.

Non-alcoholic fatty liver disease, Mediterranean diet and 10-year cardiovascular disease incidence: the mediating role of adiponectin. Highlights from the ATTICA prospective (2002–2012) study

Abstract Background/Introduction The most updated set of guidelines (EASL-EASD-EASO 2016) suggests Mediterranean diet as a promising dietary pattern for non-alcoholic fatty liver disease (NAFLD) management. Purpose The association between NAFLD and adherence to Mediterranean diet as well as their interaction on 10-year fatal/non fatal cardiovascular disease incidence were evaluated. Methods Study population included 1,514 men and 1,528 women (&amp;gt;18 years old) in our city in Greece, free of CVD recruited during the 2001–2002 period. Liver steatosis and fibrosis assessment indices were calculated at baseline and specific cut-offs were used to capture NAFLD. Level of adherence to Mediterranean diet was assessed through MedDietScore. National and international food databases were used to estimate total daily carbohydrate intake. The cut-off point of 35% of total daily energy intake was set to define low vs. high carbohydrate intake. Circulating adiponectin level was measured at baseline (4.0 (2.0) μg/mL). Results MedDietScore was inversely associated with NAFLD indices of both steatosis and fibrosis yet only in Triglycerides-Glucose index [Odds Ratio (OR)3rd vs. 1st MedDietScore tertile = 0.53, 95% Confidence Interval (95% CI) (0.29, 0.95)] persisted in multi-adjusted models including adjustments for metabolic syndrome components, energy intake and overall and central obesity. This was more evident in men (p for sex interaction = 0.03). The protective role of Mediterranean diet was retained irrespective to the total carbohydrate content; however, sex-based stratified analysis revealed that in woman subsample only Mediterranean diet with low carbohydrate content (i.e. &amp;lt;35%) had an independent protective role against NAFLD presence [OR3rd vs. 1st MedDietScore tertile = 0.79, 95% CI (0.40, 0.96)]. NAFLD predicted CVD [Hazard Ratio (HR) = 3.01, 95% CI (2.28, 3.95)] in crude model as well as in multi-adjusted model [HR=1.37, 95% CI (1.10, 2.10)]. NAFLD effect on CVD remained significant only in MedDietScore below median [HR=1.38, 95% CI (1.00, 1.93)] whereas it was essentially null [HR=1.00, 95% CI (0.38, 2.63)] among subjects with lower score. Mediation analysis revealed that adiponectin was the strongest mediator of the examined associations. In particular, per 1 mg/dL serum adiponectin about 21% lower likelihood to have NAFLD was observed. Stratified analysis using the median value of adiponectin level (4.1 mg/dL) revealed that the inverse association between Mediterranean diet and NAFLD reached the level of significance only in case of adiponectin levels over the median values (OR (3rd vs. 1st MedDietScore tertile) = 0.69 95% CI (0.35, 0.98)). Conclusion Beyond the inverse association between Mediterranean diet and NAFLD several novelties were revealed; low-carbohydrate Mediterranean diet was more protective against NAFLD in women while an adiponectin-related mechanism was revealed. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This work was supported by a research grant from Hellenic Atherosclerosis Society. The ATTICA study is supported by research grants from the Hellenic Cardiology Society [HCS2002] and the Hellenic Atherosclerosis Society [HAS2003]

Analysis of the dietary factors associated with suspected pediatric nonalcoholic fatty liver disease and potential liver fibrosis: Korean National Health and Nutrition Examination Survey 2014-2017

BackgroundThe prevalence of nonalcoholic fatty liver disease (NAFLD) has increased as the obese pediatric population has increased. NAFLD causes progressive liver injury and the only effective treatment is lifestyle modifications. However, few studies have examined the dietary risk factors for pediatric NAFLD or liver fibrosis. Here, we evaluated the dietary factors associated with suspected NAFLD and potential liver fibrosis in Korean children.MethodsData collected from 1674 children and adolescents aged 10–18 years during the 2014–2017 Korean National Health and Nutrition Examination Surveys analyzed. The 24-h recall method measured the food consumed 1 day before the survey. The “suspected NAFLD” group included excessive body mass index (BMI) subjects ≥ 85th percentile) with alanine aminotransferase (ALT) levels exceeding the upper normal limit (24.1 U/L for boys and 17.7 U/L for girls); the “healthy control” group included subjects with a BMI and ALT level below these thresholds. Sodium intake was assessed by the urinary sodium-to-urinary specific gravity unit ratio (U-Na-to-SGU ratio). A pediatric NAFLD index (PNFI) higher than 3 indicated potential liver fibrosis.ResultsThe overall prevalence of suspected NAFLD and potential liver fibrosis was 8.2 and 4.5%, respectively. The suspected NAFLD group had a larger proportion of males and subject with a greater height, BMI standard deviation score (BMI-SDS), systolic and diastolic blood pressure SDS, waist circumference, hemoglobin A1c, and levels of total cholesterol, triglycerides, aspartate aminotransferase (AST) and ALT than the control group. The suspected NAFLD group presented significantly higher U-Na-to-SGU ratios and cholesterol intake. The PNFI > 3 subgroup included a significantly larger proportion of males and subjects with higher BMI-SDS, AST and ALT values, and intake of water, carbohydrate, protein, calcium, phosphorus, iron and vitamin B2. After adjusting for confounders, male, BMI-SDS, AST, and protein and carbohydrate intake were independent risk factors for potential liver fibrosis. Niacin intake was an independent protective factor for potential liver fibrosis.ConclusionsChildren with suspected NAFLD had higher urinary sodium level and cholesterol intake than healthy controls. Protein and carbohydrate intake were independent risk factors for potential liver fibrosis; niacin was an independent protective factor.

VISCERAL ADIPOSITY INDEX, NON-ALCOHOLIC FATTY LIVER DISEASE AND 10-YEAR CARDIOVASCULAR DISEASE INCIDENCE: A GENDER-BASED ANALYSIS FROM THE ATTICA PROSPECTIVE (2002–2012) STUDY

Visceral adiposity index (VAI), initially developed to predict cardiovascular disease (CVD) onset, is currently discussed on its association with non-alcoholic fatty liver disease (NAFLD). The association between VAI and NAFLD indices as well as the subsequent 10-year first fatal/non fatal CVD risk

Correlation analysis of gut microbiota and biochemical indexes in patients with non-alcoholic fatty liver disease

Objective: To investigate the relationship between gut microbiota structure and biochemical changes in patients with different types of nonalcoholic fatty liver disease (NAFLD), in order to provide evidence for clinical diagnosis and prevention of NAFLD. Methods: Forty-eight NAFLD cases (NAFLD group), 40 NAFLD cases with type 2 diabetes mellitus (NAFLD combined with type 2 diabetes mellitus group) and 30 healthy cases (healthy group) were randomly enrolled, and their body mass index, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein and uric acid were measured. Serum levels of TNF-alpha and fasting insulin were measured using ELISA, and then insulin resistance index was calculated. The gut microbiota of three groups of subjects was detected using 16S rDNA-based high-throughput sequencing. Lastly, the correlations between the various factors were analyzed. The comparison among groups was conducted by 2 test, and one-way ANOVA was used for comparison among groups with normal distribution and homogeneity of variance. Furthermore, the LSD method was used to compare the two groups. K-W rank sum test was used for comparison among groups without normal distribution or homogeneity of variance. Results: Body mass index, aspartate aminotransferase, triglyceride, total cholesterol, low density lipoprotein, uric acid, tumor necrosis factor-alpha, fasting insulin and insulin resistance index of NAFLD group were higher than healthy group, while the high-density lipoprotein was lower in the healthy group, and the difference was statistically significant (P< 0.05). Compared with NAFLD group, the life expectancy, fasting blood glucose and insulin resistance index of NAFLD combined with type 2 diabetes mellitus group were higher, while the body mass index, aspartic acid aminotransferase, total cholesterol and HDL levels were decreased, and the difference was statistically significant (P< 0.05). NAFLD group (P= 0.016) had decreased abundance of firmicutes than healthy group, and the abundancy of the firmicutes in the NAFLD combined with type 2 diabetes group was significantly lower (P< 0.001). The abundance of bacteroidetes in NAFLD combined with type 2 diabetes group was higher than healthy group, and the difference was statistically significant (P= 0.006). At the "genus level," the abundance of Roseburia and Subdoligranulum in the NAFLD group was decreased, while the Roseburia in the NAFLD group with type 2 diabetes group was significantly lower (P< 0.05). In addition, the abundance of Faecalibacterium, Blautia, Anaerostipes and Fusicatenibacter in NAFLD combined with type 2 diabetes group was lower than healthy group, and the difference was statistically significant (P< 0.001). Fusicatenibacter, Blautia, Anaerostipes, Faecalibacterium, and Roseburia were negatively correlated with fasting blood glucose and insulin resistance index levels (r< 0,P< 0.05), and positively correlated with high-density lipoprotein levels (r> 0,P< 0.05). Fusicatenibacter was negatively correlated with tumor necrosis factor-alpha (r= -0.211,P= 0.044), and Lachnoclostridium was positively correlated with body mass index, alanine aminotransferase, aspartate aminotransferase levels (r> 0,P< 0.05). Fusobacterium was positively correlated with aspartate aminotransferase level (r= 0.245,P= 0.019). Escherichia-shigella was positively correlated with fasting blood glucose, low-density lipoprotein, alanine aminotransferase, aspartate aminotransferase levels (r > 0,P< 0.05). Megamonas was negatively correlated with high-density lipoprotein levels (r= -0.231,P= 0.027). Conclusion: A structural change of gut microbiota had occurred in patients with NAFLD, suggesting changes in some of these bacterial genuses had relation to insulin resistance and inflammatory response, which may become a new target for the treatment of NAFLD.