Risk Of Nonalcoholic Fatty Liver Disease Research Articles

Effect of brominated flame retardants exposure on liver function and the risk of non-alcoholic fatty liver disease in the US population

BackgroundThe relationship between brominated flame retardants (BFRs) exposure and the human liver was still not well understood. MethodsA total of 3108 participants (age > 12) from the National Health and Nutrition Examination Survey (NHANES) database spanning from 2005 to 2016 were included as the study population, with nine BFRs exhibiting a detection rate of over 70% serving as the exposure factor. The singular effects and combined effects of BFRs exposure on liver injury, non-alcoholic fatty liver disease (NAFLD), and advanced hepatic fibrosis (AHF) were evaluated separately. Finally, COX regression was employed to explore the hazard ratios associated with individual BFRs. ResultsIn our analysis of individual exposures, we found significant positive association of PBB153 with alanine aminotransferase (ALT), PBB153 with aspartate aminotransferase (AST), PBDE47, PBDE85, PBDE99, PBDE100, and PBDE154 with alkaline phosphatase (ALP), PBDE28 and PBB153 with gamma-glutamyl transaminase (GGT), PBB153 with the risk of NAFLD and AHF; and significant negative association of PBB153 with ALP, PBDE28, PBDE47, PBDE99, PBDE100, PBDE85, PBDE209, and PBDE154 with albumin (ALB), PBB153 with AST/ALT. The nonlinear analysis results from Restricted Cubic Spline (RCS) further validated these associations (all P<0.05). In the mixed analysis combining Weighted Quantile Sum (WQS) regression and Quantile G-computation (QGC) analysis, BFRs were positively associated with ALT (β>0, P<0.001), GGT (β>0, P<0.001), and the risk of NAFLD (OR>1, P=0.007). Conversely, BFRs exhibited significant negative correlations with ALP (β<0, P<0.001), ALB (β<0, P<0.001), and AST/ALT (β<0, P<0.001). Furthermore, the COX regression analysis revealed that PBB153 had the highest hazard ratio among the BFRs. ConclusionsBFR exposure may increase the risk of liver injury and NAFLD, with no significant association with AHF risk. The impact of BFR exposure on liver health should not be overlooked, especially in individuals residing in impoverished areas.

Hub Genes Involved in the Progression of Nonalcoholic Fatty Liver Disease to Hepatocellular Carcinoma.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. With an increasing number of patients, NAFLD has been identified as a risk factor for Hepatocellular Carcinoma (HCC). The precise pathophysiology of NAFLD-related HCC has not been completely understood recently. We analyzed the hub genes related to NAFLD and HCC to predict the risk of NAFLD progressing to HCC. Two datasets of NAFLD were used to identify differentially expressed genes. Lasso-Cox regression analysis was performed to determine a gene model to predict the risk of the progression from NAFLD to HCC. Three validation datasets were analyzed to evaluate the performance of the gene model, including normal and NAFLD with fibrosis, NAFLD with fibrosis and NAFLD-related HCC, and normal and NASH-related HCC. Seven genes, including COL1A1, TIPM1, VCAN, FOS, CD79A, CXCL9, and VWF, were identified as the hub genes, and then a gene model was constructed. By calculating, the area under the receiver operating characteristic curves (AUCs) for risk prediction were 0.97, 0.886, and 0.751 in the three validation datasets, respectively. Gene set enrichment analysis indicated that the MAPK, TGFβ, p53, PPAR, insulin signaling pathways, and fatty acid metabolism were significantly upregulated in the high-risk group. GTPase activity and intrinsic apoptotic signaling pathway had significant upregulation in the low-risk group. The seven hub genes may predict the risk of NAFLD developing into HCC by mediating the potential molecular mechanism, which could be used as biomarkers for predicting the progression, diagnosis, and treatment of NAFLD.

Depression and NAFLD risk: A meta-analysis and Mendelian randomization study

BackgroundBoth depression and nonalcoholic fatty liver disease (NAFLD) have a high global prevalence. Growing evidence suggests an association between depression and NAFLD, while the association remains unclear. Thus, in this study, we aimed to explore the effect of depression on the risk of developing NAFLD. MethodsThe meta-analysis examined the association between depression and the risk of NAFLD by including observational studies. Relevant studies were searched in PubMed, Embase, the Cochrane Library, and Web of Science. Then a two-sample Mendelian randomization (MR) analysis was performed to explore causal association using genetic instruments identified from a genome-wide association study. ResultsSix eligible studies were included in the meta-analysis, involving 289,22 depression cases among 167,554 participants. Meta-analysis showed a significant association between depression and a higher risk of developing NAFLD (OR = 1.14, 95 % CI: [1.05, 1.24], P = 0.002). However, we found no convincing evidence supporting a causal role of genetically predicted depression with NAFLD risk (OR = 0.861, 95 % CI: [0.598, 1.238], P = 0.420). LimitationsThe insufficient number of included studies, the use of summary-level data, and restrictions on population sources are the major limiting factors. ConclusionsMeta-analysis and MR analysis demonstrated inconsistent results on the relationship between depression and a high risk of developing NAFLD. Specifically, meta-analysis confirmed that depression increases the risk of developing NAFLD, while MR analysis did not support a causal association between genetically determined depression and the risk of NAFLD.

17-Beta-Hydroxysteroid Dehydrogenase 13 Loss of Function Does Not Confer Protection to Nonalcoholic Fatty Liver Disease in Indian Population

A splice variant in HSD17B13 gene is demonstrated to protect against nonalcoholic fatty liver disease (NAFLD), and mitigate the effect of Patatin-like phospholipase domain-containing 3 (PNPLA3-I148M). It is being explored as a putative drug target and in polygenic risk scores. Based on whole exome sequencing (WES) in our cohort of biopsy proven NAFLD and limited data on the variant in our ethnicity, we sought to explore its role. This is a cross-sectional study that recruited 1,020 individuals with ultrasound/biopsy-confirmed NAFLD and matched controls. Liver enzymes and lipid profiles were estimated (Beckman coulter LX750/DXH800); WES was performed in NAFLD patients and controls (Illumina; HiSeqX); HSD17B13-A-INS/I148M-PNPLA3 variants were genotyped (sequencing/qR T-PCR); HSD17B13 protein expression was estimated (immunohistochemistry); the Student's t-test/Mann-Whitney U/Chi-square test and odds ratio (95% confidence interval) were used. There was no significant difference (Odds ratio=0.76; 95% CI -0.57 to 1.03; P=0.76) in the frequency of the rs72613567-A-INS between controls and patients (17.8% vs. 14.4%). No difference in the ALT (Alanine transaminase; 72.24±65.13 vs. 73.70±60.06; P=0.51) and AST levels (Aspartate aminotransferase; 60.72±55.59 vs. 61.63±60.33; P=0.91) between HSD17B13-wild and variant carriers were noted. Significantly elevated liver enzymes were seen in PNPLA3-148-variant/HSD17B13-wild compared with PNPLA3-148-variant/HSD17B13-variant (90.44±59.0 vs. 112.32±61.78; P=0.02). No difference in steatosis (P=0.51) between HSD17B13-wild and variant carriers was noted. No other variants in the intron-exon boundaries were identified. Although, protein expression differences were noted between wild and variant carriers, no difference in the extent of steatosis was seen. Our study reports lack of association of the splice variant with reduced risk of NAFLD, and mitigating the effect of PNPLA3 variant. Ethnicity-based validation must be carried out before including it in assessing protection against NAFLD.

Association between weight-adjusted waist index and non-alcoholic fatty liver disease: a population-based study

BackgroundObesity is the most important driver of non-alcoholic fatty liver disease (NAFLD); nevertheless, the relationship of weight-adjusted waist index (WWI), a new obesity index, with NAFLD is unclear.MethodsThis retrospective study used data from the NAGALA project from 1994 to 2016. WWI values were calculated using waist circumference (WC) and weight measurements of the participants. Three stepwise adjusted logistic regression models were developed to assess the relationship of WWI with NAFLD in the whole population and in both sexes. Additionally, we also conducted a series of exploratory analysis to test the potential impact of body mass index (BMI), age, smoking status and exercise habits on the association of WWI with NAFLD. Receiver operating characteristic (ROC) curves were used to estimate cut-off points for identifying NAFLD in the entire population and in both sexes.ResultsThe current study included a population of 11,805 individuals who participated in health screenings, including 6,451 men and 5,354 women. After adjusting for all non-collinear variables in the multivariable logistic regression model, we found a significant positive correlation of WWI with NAFLD. For each unit increase in WWI, the risk of NAFLD increased by 72% in the entire population, by 84% in men, and by 63% in women. Furthermore, subgroup analyses revealed no significant discrepancies in the correlation of WWI with NAFLD across individuals with varying ages, exercise habits, and smoking status (all P-interaction > 0.05), except for different BMI groups (P-interaction < 0.05). Specifically, compared to the overweight/obese group, the relationship of WWI with NAFLD was significantly stronger in the non-obese group, especially in non-obese men. Finally, based on the results of ROC analysis, we determined that the WWI cut-off point used to identify NAFLD was 9.7675 in men and 9.9987 in women.ConclusionsThis study is the first to establish a positive correlation between WWI and NAFLD. Moreover, assessing the influence of WWI on NAFLD in individuals without obesity may yield more valuable insights compared to those who are overweight or obese.

Sex-Specific Association between Sodium Intake Estimated by 24-Hour Urinary Sodium Excretion and Nonalcoholic Fatty Liver Disease: The Community-Based Prospective Cohort Study.

Evidence for the association between high sodium intake and the onset of nonalcoholic fatty liver disease (NAFLD) is insufficient. This study examined the sex-specific association between sodium intake and the risk of NAFLD. This study included 2582 adults (aged 40-69 years; 1011 males and 1571 females). The total sodium excreted over 24 h was estimated from spot urine specimens using Tanaka's equation. Based on these estimates, participants were categorized into three groups according to their 24-h urinary sodium excretion levels: lowest (T1), middle (T2), and highest (T3). In addition, the participants were divided into non-NAFLD (≤36) and NAFLD (>36) groups based on the hepatic steatosis index. During the follow-up period (14 years), NAFLD was observed in 551 participants. The estimated 24-h urinary sodium excretion levels were positively associated with the incidence of NAFLD in all subjects. Upon sex stratification, females in the T2 and T3 groups exhibited adjusted hazard ratios of 1.35 and 1.51, respectively, compared with the T1 group. However, a significant relationship was not observed in males. High intake of sodium, especially among females, may be an important factor contributing to the development of NAFLD. Individuals with high sodium intake should be appropriately counselled and monitored for the risk of NAFLD.

Dietary pattern associated with non-alcoholic fatty liver disease (NAFLD) in non-diabetic adult patients: A case control study

BackgroundDietary intake is an important factor in the development and management of non-alcoholic fatty liver disease (NAFLD) however, optimal food group composition remains unclear. Data on detailed food group intake of NAFLD patients from India is scarce. Methods& Materials: In this study with 320 participants (160 NAFLD cases and 160 controls), dietary habits were assessed using a 24-hour dietary recall for two days and a validated 142-item food frequency questionnaire over the past year. Principal component analysis identified dietary patterns associated with NAFLD among the participants. ResultsCases were having a significantly higher intake of edible oils and fats along with nuts and oilseeds as compared to controls (p<0.05). There was a positive and significant association with edible oils and fats with NAFLD [OR (95 % CI):1.7(1.11-2.49) p=0.013). In dietary pattern analysis western dietary pattern was found to be a risk for NAFLD whereas protective dietary pattern was associated with the decreased risk of NAFLD. ConclusionThe overall food groups intake in NAFLD cases and controls was low suggesting lower diet quality. Protective dietary pattern found to be beneficial for NAFLD. High intake of sugars and edible oils associated with western dietary pattern increases the risk of NAFLD.

Vegetarian diets and risk of nonalcoholic fatty liver disease: An observational study of National Health and Nutrition Examination Survey2005-2018 using propensity score methods.

Studies on the association between vegetarian diets and nonalcoholic fatty liver disease (NAFLD) are limited and have inconsistent results. This study aims to explore the association between vegetarian diets and NAFLD and compare the stage of fibrosis between vegetarians and nonvegetarians in a US representative sample. Cross-sectional data from 23,130 participants aged ≥20 years were obtained from the National Health and Nutrition Examination Survey, 2005-2018. Vegetarian status was classified based on two 24-h dietary recalls. We examined the association between vegetarian diets and the risk of NAFLD using the propensity score weighting method. Vegetarian diets were significantly associated with decreases in hepatic steatosis index (HSI), US fatty liver index and nonalcoholic fatty liver disease fibrosis score with mean differences of -2.70 (95% confidence interval [CI]: -3.69, -1.70), -3.03 (95% CI: -7.15, -0.91) and -0.12 (95% CI: -0.26, -0.01), respectively. While modelling the risk of NAFLD, we estimated that vegetarians were 53% less likely to have NAFLD assessed by HSI (odds ratios [OR]: 0.47; 95% CI: 0.34, 0.65). The effect of vegetarian diets was higher among individuals with lower waist circumferences (OR: 0.20) than among those with higher waist circumferences (OR: 0.53, = 0.004). However, the association was largely attenuated after adjusting for body mass index and diabetes status. No significant association was identified between vegetarian diets and advanced fibrosis. Vegetarian diets were associated with a lower prevalence of NAFLD among US adults, and the association appeared to be stronger in people with lower waist circumferences. Further studies are warranted to replicate our findings.

Association between the ZJU index and risk of new-onset non-alcoholic fatty liver disease in non-obese participants: a Chinese longitudinal prospective cohort study.

Non-alcoholic fatty liver disease (NAFLD) is increasingly observed in non-obese individuals. The ZJU (Zhejiang University) index has been established as a new and efficient tool for detecting NAFLD, but the relationship between the ZJU index and NAFLD within non-obese individuals still remains unclear. A post-hoc evaluation was undertaken using data from a health assessment database by the Wenzhou Medical Center. The participants were divided into four groups based on the quartile of the ZJU Index. Cox proportional hazards regression, Kaplan-Meier analysis and tests for linear trends were used to evaluate the relationship between the ZJU index and NAFLD incidence. Subgroup analysis was conducted to test the consistency of the correlation between ZJU and NAFLD in subsgroups. Receiver operative characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the ZJU index, compared with the Atherogenic index of plasma (AIP) and Remnant lipoprotein cholesterol (RLP-C) index. A total of 12,127 were included in this study, and 2,147 participants (17.7%) developed NAFLD in 5 years follow-up. Participants in higher ZJU quartiles tended to be female and have higher liver enzymes (including ALP, GGT, ALT, AST), GLU, TC, TG, LDL and higher NAFLD risk. Hazard Ratios (HR) and 95% confidence intervals (CI) for new-onset NAFLD in Q2, Q3, and Q4 were 3.67(2.43 to 5.55), 9.82(6.67 to 14.45), and 21.67(14.82 to 31.69) respectively in the fully adjusted model 3. With increased ZJU index, the cumulative new-onset NAFLD gradually increased. Significant linear associations were observed between the ZJU index and new-onset NAFLD (p for trend all<0.001). In the subgroup analysis, we noted a significant interaction in sex, with HRs of 3.27 (2.81, 3.80) in female and 2.41 (2.21, 2.63) in male (P for interaction<0.01). The ZJU index outperformed other indices with an area under the curve (AUC) of 0.823, followed by AIP (AUC=0.747) and RLP-C (AUC=0.668). The ZJU index emerges as a promising tool for predicting NAFLD risk in non-obese individuals, outperforming other existing parameters including AIP and RLP-C. This could potentially aid in early detection and intervention in this specific demographic.

Proanthocyanidins-Based Synbiotics as a Novel Strategy for Nonalcoholic Fatty Liver Disease (NAFLD) Risk Reduction.

Nonalcoholic fatty liver disease (NAFLD), the most common liver disease worldwide, is a spectrum of liver abnormalities ranging from steatosis to nonalcoholic steatohepatitis (NASH) characterized by excessive lipid accumulation. The prevalence of NAFLD is predicted to increase rapidly, demanding novel approaches to reduce the global NAFLD burden. Flavonoids, the most abundant dietary polyphenols, can reduce the risk of NAFLD. The majority of dietary flavonoids are proanthocyanidins (PACs), which are oligomers and polymers of the flavonoid sub-group flavan-3-ols. The efficacy of PAC in reducing the NAFLD risk can be significantly hindered by low bioavailability. The development of synbiotics by combining PAC with probiotics may increase effectiveness against NAFLD by biotransforming PAC into bioavailable metabolites. PAC and probiotic bacteria are capable of mitigating steatosis primarily through suppressing de novo lipogenesis and promoting fatty acid β-oxidation. PAC and probiotic bacteria can reduce the progression of steatosis to NASH mainly through ameliorating hepatic damage and inflammation induced by hepatic oxidative stress, endoplasmic reticulum stress, and gut microbiota dysbiosis. Synbiotics of PAC are superior in reducing the risk of NAFLD compared to independent administration of PAC and probiotics. The development of PAC-based synbiotics can be a novel strategy to mitigate the increasing incidence of NAFLD.

U-Shaped relationship of insulin-like growth factor I and incidence of nonalcoholic fatty liver in patients with pituitary neuroendocrine tumors: a cohort study.

Although the role of insulin-like growth factor I (IGF-1) in nonalcoholic fatty liver disease (NAFLD) has garnered attention in recent years, few studies have examined both reduced and elevated levels of IGF-1. The aim of this study was to examine the potential relationship between IGF-1 levels and the risk of new-onset NAFLD in patients with pituitary neuroendocrine tumors (PitNET). We employed multivariable Cox regression models and two-piecewise regression models to assess the association between IGF-1 and new-onset NAFLD. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated to quantify this association. Furthermore, a dose-response correlation between lgIGF-1 and the development of NAFLD was plotted. Additionally, we also performed subgroup analysis and a series sensitivity analysis. A total of 3,291 PitNET patients were enrolled in the present study, and the median duration of follow-up was 65 months. Patients with either reduced or elevated levels of IGF-1 at baseline were found to be at a higher risk of NAFLD compared to PitNET patients with normal IGF-1(log-rank test, P < 0.001). In the adjusted Cox regression analysis model (model IV), compared with participants with normal IGF-1, the HRs of those with elevated and reduced IGF-1 were 2.33 (95% CI 1.75, 3.11) and 2.2 (95% CI 1.78, 2.7). Furthermore, in non-adjusted or adjusted models, our study revealed a U-shaped relationship between lgIGF-1 and the risk of NAFLD. Moreover, the results from subgroup and sensitivity analyses were consistent with the main results. There was a U-shaped trend between IGF-1 and new-onset NAFLD in patients with PitNET. Further evaluation of our discoveries is warranted.

Lipid accumulation product is a valid predictor of hepatic steatosis and nonalcoholic fatty liver disease.

Aims: To evaluate and compare lipid accumulation product (LAP) with alanine aminotransferase (ALT), aspartate aminotransferase (AST), visceral adiposity index (VAI) and triglyceride-glucose index (TyG) as biomarkers for hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). Methods: LAP, ALT, AST, VAI and TyG were measured in 52 biopsy-proven NAFLD patients and 21 control subjects. Additionally, LAP was also measured in 448 ultrasound-proven NAFLD patients and 1009 control subjects. Results: LAP was positively associated with hepatic steatosis and inflammation in biopsy-proven NAFLD. The risk of NAFLD was positively related to LAP and TyG, but LAP showed a better area under the receiver operating characteristic curve for hepatic steatosis and NAFLD. LAP also performed well in recognizingultrasound-proven NAFLD. Conclusion: LAP is an ideal biomarker of hepatic steatosis and NAFLD.

Tea and coffee consumption impact on the non-alcoholic fatty liver disease: a systematic review and meta-analysis

Introduction: Non-alcoholic fatty liver disease (NAFLD) is diagnosed when≥5–10% of hepatocytes display macroscopic steatosis in the absence of other etiologies of liver disease. Consumption of coffee or tea or both may decrease the risk of NAFLD, as recommended by studies of liver enzymes. Methods: The required data was collected from different databases such as EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Web of Science as well as the database inception to July 2021. In addition, pooled mean difference and 95% confidence intervals (CIs) were considered in the random effects model. Results: Of the total collected 218 articles, 8 met our inclusion criteria to be involved in the meta-analysis. Four studies assessed green tea and one study assessed sour tea consumption in NAFLD patients. Three studies assessed coffee use. All studies have shown an inverse correlation of coffee intake with elevated serum enzyme levels. Based on the meta-analysis outcome, the mean alanine aminotransferase (ALT) in the intervention group was measured as 12.50 points less than that of the control group. The mean aspartate aminotransferase (AST) of the intervention group was 9.23 points lower than that of the control group (P value&lt;0.001). Conclusion: There is increasing evidence that steadily revealed an opposite relationship between the consumption amount of green tea and coffee and the risk of liver diseases. This meta-analysis supports the protective role of the mentioned beverages in patients suffering from NAFLD.

An Artificial Neural Network Model Combined with Dietary Retinol Intake from Different Sources to Predict the Risk of Nonalcoholic Fatty Liver Disease

ObjectiveThis study aimed to develop an artificial neural network (ANN) model combined with dietary retinol intake from different sources to predict the risk of non-alcoholic fatty liver disease (NAFLD) in American adults. MethodsData from the 2007 to 2014 National Health and Nutrition Examination Survey (NHANES) 2007–2014 were analyzed. Eligible subjects (n = 6,613) were randomly divided into a training set (n1 = 4,609) and a validation set (n2 = 2,004) at a ratio of 7:3. The training set was used to identify predictors of NAFLD risk using logistic regression analysis. An ANN was established to predict the NAFLD risk using a training set. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the accuracy of the model using the training and validation sets. ResultsOur study found that the odds ratios (ORs) and 95% confidence intervals (CIs) of NAFLD for the highest quartile of plant-derived dietary retinol intake (i.e., provitamin A carotenoids, such as β-carotene) (OR = 0.75, 95% CI: 0.57 to 0.99) were inversely associated with NAFLD risk, compared to the lowest quartile of intake, after adjusting for potential confounders. The areas under the ROC curves were 0.874 and 0.883 for the training and validation sets, respectively. NAFLD occurs when its incidence probability is greater than 0.388. ConclusionThe ANN model combined with plant-derived dietary retinol intake showed a significant effect on NAFLD. This could be applied to predict NAFLD risk in the American adult population when government departments formulate future health plans.

Association between dietary vitamin A intake from different sources and non-alcoholic fatty liver disease among adults

Non-alcoholic fatty liver disease (NAFLD) has become an urgent public health issue with high global prevalence, but data on NAFLD are inconsistent. The association of total dietary vitamin A intake with the NAFLD risk was not well documented in previous studies. To explore the relationship between dietary vitamin A intake from different sources and NAFLD risk among American adults. Data were collected from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2014. Logistic regression and restricted cubic spline models were used to estimate the relationship between total dietary vitamin A intake and NAFLD risk. 6,613 adult participants were included. After adjusting potential confounders, the odds ratios (ORs) with 95% confidence intervals (CIs) of NAFLD for the highest quartile intake of total vitamin A, preformed vitamin A, provitamin A carotenoids were respectively 0.86 (0.69–1.06), 0.97 (0.74–1.28), and 0.78 (0.61–0.99), compared to the lowest quartile. Stratifying gender and age, provitamin A carotenoids intake was inversely associated with NAFLD risk in females and participants aged < 45 years. Dose–response analysis indicated a linear negative relationship between provitamin A carotenoids intake and NAFLD risk. Provitamin A carotenoids intake was inversely associated with NAFLD, especially in women and those aged < 45 years among adult American.

Trend of Non-Alcoholic Fatty Liver Disease in Type II Diabetes Mellitus

Background: Non-alcoholic fatty liver disease (NAFLD) is becoming quite common in Type II Diabetes Mellitus (TIIDM) as obesity and insulin resistance are common within TIIDM and it is becoming a widespread liver condition globally. This study evaluated the prevalence of NAFLD patients who also had type II diabetes. Methods: The demographic data (name, age, body mass index (BMI), gender, occupation, duration of TIIDM, and treatment taking for TIIDM), as well as the results of the tests for these enzymes, were also recorded. Alanine transaminase (ALT) and Aspartate transaminase (AST) levels, as well as abdominal ultrasound findings of the liver, were recorded in a proforma after informed consent for a total of 200 Type II diabetic patients. Using SPSS, the data were analyzed, and stratified groups were subjected to the Chi-square tests. Results: There was a significant difference (p&lt;0.05) observed in NAFLD patients of TIIDM concerning age, gender, BMI, treatment, occupation, and duration of diabetes. The sample size consisted of 200 patients of which 111 (55.5%) were men and 89 (44.5%) were women. Patients ranged in the age range of 40-70 years old, with a mean age of 55.08 ± 8.98 years and a mean BMI of 29.69±4.04, respectively. It was concluded that 64% of cases with diabetes mellitus had NAFLD. Conclusion: TIIDM is an independent risk factor for NAFLD so early screening, diagnosis, and appropriate treatment are mandatory to reduce the risk of NAFLD and its related complications.

The association between dietary inflammatory index (DII) scores and c-reactive protein (CRP) and nonalcoholic fatty liver disease (NAFLD) in a general population cohort

Although there is extensive literature showing the ability of the dietary inflammation index (DII®) to predict concentrations of plasma inflammatory markers, few studies are testing the association between DII scores and nonalcoholic fatty liver disease (NAFLD). Considering the high prevalence of NAFLD and its complications, we conducted a validation study of DII scores and examined its association with NAFLD in the general adult population of Iran. This cross-sectional study was conducted on 3110 adult participants in the Amol Cohort Study (AmolCS) who underwent abdominal ultrasonography to diagnose NAFLD. DII and energy-adjusted DII (E-DII™) scores were computed using data from a valid semi-quantitative 168-item food frequency questionnaire (FFQ). Multivariable logistic regression adjusting for socio-demographic, lifestyle, and health-related factors was used to assess association. The EDII was associated with CRP inflammatory biomarker. Participants in the highest, i.e., most pro-inflammatory tertile had the highest odds of NAFLD by ultrasound in all models [fully adjusted model: OR (95% CI) tertile3vs.1:1.54 (1.05-2.05); Ptrend=0.04, and 1.63 (1.19-2.21); Ptrend=0.03 in women and men, respectively]. The highest tertile had the highest OR for NAFLD by fatty liver index (FLI) only in men [fully adjusted model OR (95% CI) tertile3vs.1: 1.77 (1.15-2.71); Ptrend=0.01]. Similar results were also obtained for NAFLD by hepatic steatosis index (HSI) in women [fully adjusted model: OR (95% CI) tertile3vs.1: 1.70 (1.12-2.58); Ptrend=0.03]. The results of the fully adjusted multivariable model of liver markers and NAFLD status, stratified by gender and abdominal obesity, revealed that the highest tertiles had the highest OR for NAFLD by ultrasound and NAFLD by FLI only in men without abdominal obesity [fully adjusted model: OR (95% CI) tertile3vs.1: 1.83 (1.17-2.84); Ptrend=0.03, and, respectively]. NAFLD by FLI tended to increase strongly with tertile E-DII scores in men without abdominal obesity in crude and three adjusted models [full-adjusted model: OR (95% CI) tertile3vs.1: 3.64 (1.56-8.46); Ptrend=0.005]. By contrast, women with abdominal obesity in the highest tertile had the highest OR for NAFLD by ultrasound in all models [full-adjusted model: OR (95% CI) tertile3vs.1: 1.67 (1.07-2.62); Ptrend=0.02]. Our results suggest that diet plays a role in regulating inflammation. Additionally, we observed an inflammatory diet predicts the risk of NAFLD in Iranian adults. However, longitudinal studies are required in order to further substantiate the utility of the DII in the development of more effective dietary interventions among populations at risk of chronic disease.

Causal effects from inflammatory bowel disease on liver function and disease: a two-sample Mendelian randomization study.

Accumulating evidence has shown that patients with inflammatory bowel disease (IBD) have liver function abnormalities and are susceptible to liver diseases. However, the existence of a causal relationship between IBD and liver function or disease remains unclear. A two-sample Mendelian randomization (MR) analysis was performed using genetic associations from publicly available genome-wide association studies (GWAS). These associations encompass ulcerative colitis (UC), Crohn's disease (CD), liver function traits, and liver disease phenotypes. The liver function traits comprised hepatic biochemistries, percent liver fat, and liver iron content from the UK Biobank. Furthermore, the liver disease phenotypes included cholelithiasis, non-alcoholic fatty liver disease (NAFLD), primary sclerosing cholangitis (PSC), and primary biliary cholangitis (PBC) in cohorts of European ancestry. The primary estimation used the inverse-variance weighted method, with GWAS of C-reactive protein (CRP) in the UK Biobank serving as a positive control outcome. Genetically predicted UC is causally associated with decreased levels of albumin (ALB) and liver iron content, while genetically predicted CD is causally associated with increased levels of alkaline phosphatase (ALP). Moreover, genetically predicted UC or CD increases the risk of PSC, and CD increases the risk of PBC. Neither UC nor CD causally increases the risk of cholelithiasis and NAFLD. UC affects the levels of ALB and liver iron content, while CD affects the levels of ALP. Both UC and CD increase the risk of PSC, and CD increases the risk of PBC.

Genetically determined circulating micronutrients and the risk of nonalcoholic fatty liver disease

Evidence from epidemiological literature on the association of circulating micronutrients with risk of nonalcoholic fatty liver disease (NAFLD) is inconsistent. We aimed to elucidate the causal relationships using Mendelian randomization (MR). Single-nucleotide polymorphisms associated with 14 circulating micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B6, B12, C, D, K1 and zinc) were employed as instrumental variables. Summary level data for NAFLD were obtained from a genome-wide association study (GWAS) meta-analysis of 8434 cases and 770,180 controls (discovery stage) and another two datasets including 1483 NAFLD cases and 17,781 controls (replication stage 1) and 2134 NAFLD cases and 33,433 controls (replication stage 2). Inverse variance-weighted method (IVW) was used as primary analysis, supplemented with a series of sensitivity analysis. Genetically predicted higher β‑carotene levels were suggestively associated with reduced NAFLD risk [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.66–0.99; P = 0.047], whereas the association did not survive the false discovery rates (FDR) correction (PFDR = 0.164). Genetically predicted circulating iron (OR 1.16, 95% CI 1.05–1.29; P = 0.006, PFDR = 0.028), selenium (OR 1.11, 95% CI 1.03–1.20; P = 0.005, PFDR = 0.028) and vitamin B12 (OR 1.08, 95% CI 1.03–1.13; P = 0.002, PFDR = 0.028) were significantly associated with increased risk of NAFLD. Moreover, the findings were consistent in individual datasets (Pheterogeneity > 0.05) and confirmed in sensitivity analysis. Our study provided evidence that circulating iron, selenium and vitamin B12 might be causally linked to the risk of NAFLD, which deserves further exploration of the potential biological mechanism.

Association between nonalcoholic fatty liver disease and increased glucose-to-albumin ratio in adults without diabetes.

Nonalcoholic fatty liver disease (NAFLD) affects approximately 30% of individuals globally. Both serum glucose and albumin were demonstrated to be potential markers for the development of NAFLD. We hypothesized that the risk of NAFLD may be proportional to the glucose-to-albumin ratio (GAR). Based on information from the National Health and Nutrition Examination Survey (NHANES) 1999-2018, it was determined that GAR was associated with an increased risk of NAFLD and liver fibrosis utilizing weighted multivariable logistic regression. Participants with a fatty liver index (FLI) over 60 were identified with NAFLD, and those with an NAFLD fibrosis score (NFS) >0.676 with evidence of NAFLD were labeled with advanced hepatic fibrosis (AHF). The liver biopsy was utilized to verify the relationship between GAR and FLD in our center cohort. Mendelian randomization analysis investigated the genetic relationship between GAR and NAFLD. Of 15,534 eligible participants, 36.4% of participants were identified as NAFLD without AHF. GAR was positively correlated with the probability of NAFLD following full adjustment for possible variables (OR = 1.53, 95% CI: 1.39-1.67). It was confirmed that patients with NAFLD and AHF had an inferior prognosis. The relationship between GAR and NFS was favorable (R = 0.46, P< 0.0001), and NAFLD patients with a higher GAR tended to develop poor survival. In our center cohort, the association between GAR and NAFLD was verified. Among participants without diabetes, greater GAR was linked to higher risks of NAFLD. In addition, NAFLD patients with higher GAR tended to develop liver fibrosis and adverse outcomes.