Odds Of Non-alcoholic Fatty Liver Disease Research Articles

Food Insecurity and Lipid Profile Abnormalities Are Associated with an Increased Risk of Nonalcoholic Fatty Liver Disease (NAFLD): A Case–Control Study

ABSTRACT This case–control study aimed to assess the relationship between food insecurity, its related risk factors and NAFLD among 210 subjects. The demographic and socioeconomic characteristics, anthropometric indices, and food insecurity and depression status were assessed. The prevalence of food insecurity was 56.8% and 26.1% in cases and controls (p < .001), respectively. The chance of NAFLD in the food insecure, depressed, overweight, and obese subjects was 2.2 (95%CI: 1.12–3.43), 1.9 (95%CI: 1.02–3.62), 2.6 (95%CI: 1.81–3.92), and 2.9 (95%CI: 2.02–5.34) times higher than food secured, normal, and normal weight subjects, respectively. A higher waist circumference (men, OR = 2.9, p < .001; women, OR = 2.6, p < .001), a high waist-to-hip ratio (men, OR = 2.3, p < .001; women, OR = 2.7, p < .001), an increased waist-to-height ratio (OR = 2.9, p < .001), and a higher body fat percentage (men, OR = 3.0, p < .001; women, OR = 3.3, p < .001) were associated with an increased risk of NAFLD. The odds of NAFLD increased by increment in serum triglyceride (TG) levels (OR = 2.6, p < .001) and decreased by increase in serum high-density lipoprotein cholesterol (HDL-C) (OR = 0.34, p < .001). Compared to controls, patients with NAFLD were more likely to have higher TG/HDL-C ratio (OR = 3.3, p < .001). It seems food insecurity was an important risk factor for NAFLD. Additionally, some indicators of dyslipidemia significantly increased the risk of NAFLD.

Metabolic and Hepatic Effects of Energy-Reduced Anti-Inflammatory Diet in Younger Adults with Obesity.

Background Associated with epidemics of obesity, nonalcoholic fatty liver disease (NAFLD) is becoming the most prevalent liver disease worldwide. The cornerstone of therapy for NAFLD is lifestyle intervention, mainly focused on weight loss. Significant weight loss results from energy-restricted diets, regardless of macronutrient distribution. An anti-inflammatory diet was related to lower odds of NAFLD among daily alcohol drinkers and individuals with metabolic syndrome. This study aims to evaluate the effect of an energy-reduced anti-inflammatory diet on liver status in younger adults with obesity after a 6-month follow-up. Methods A two-arm randomized controlled trial surveyed 81 participants' (mean age, 43 years) anthropometric and body composition changes. Metabolic status was determined with glycaemic and lipid status, inflammatory status with hs-CRP, IL-6, and TNF-α, and liver status with liver enzymes, NAFLD-FLS, FLI, and FIB-4 indices. The inflammatory potential of the diet was assessed by the Dietary Inflammatory Index, DII®. Results Energy-restricted anti-inflammatory diet resulted in significant weight loss (−7.1%, p < 0.001), in reducing the visceral adiposity (−22.3%, p < 0.001), metabolic (HOMA-IR, −15.5%; total cholesterol, −5.3%; LDL-C, −4.6%; triglycerides, −12.2%), and inflammatory biomarkers (hs-CRP, −29.5%; IL-6, −18.2%; TNF-α, −34.2%), with significant improvement of liver parameters (NAFLD-FLS, −143.4%; FLI, −14.3%; FIB-4, −2.5%). Conclusion The study showed the effectiveness of the anti-inflammatory diet with significant improvement of liver parameters in younger adults with obesity, which may reinforce the effectiveness of nutrition-based lifestyle programs, with an anti-inflammatory dietary approach for the treatment and resolution of NAFLD.

The association of sex steroid hormone concentrations with non-alcoholic fatty liver disease and liver enzymes in US men.

This study aimed to analyse the association of sex hormone levels with liver enzyme levels and non-alcoholic fatty liver disease (NAFLD) in a nationally representative sample of men. A total of 919 men from the US National Health and Nutrition Examination Study (NHANES) III were included in this cross-sectional analysis of data from 1988 to 1991. We used existing data on serum total and free testosterone, total and free estradiol, androstanediol glucuronide (AAG) and sex steroid-binding globulin (SHBG), and estimated their associations with aspartate aminotransferase (AST), and alanine aminotransferase (ALT) and NAFLD, as determined using ultrasound, after adjusting for possible confounders including age, race, smoking, alcohol, physical activity, waist circumference and steroid hormones. Lower total testosterone (TT) and higher free estradiol were associated with higher odds of NAFLD after adjusting for confounders including the other sex hormones. Lower TT was associated with higher odds of elevated AST, but not ALT. Free testosterone, total estradiol, SHBG and AAG were not associated with NAFLD or liver enzymes. This study supports an inverse association between TT concentration and NAFLD in men independent of other sex hormones (SHBG, AAG and estradiol) and known risk factors, such as obesity, age and lifestyle. Exploration of whether TT might be a non-invasive marker for NAFLD diagnosis is warranted.

The Association Between Dietary Intake of Sodium, Potassium, and Na:K Ratio with the Risk of NAFLD: A Case-Control Study Among Iranian Adults.

Dietary sodium (Na) and potassium (K) relationship with chronic disease has drawn more attention recently. Epidemiological studies reported controversial findings about high salt and Na diets with the risk of nonalcoholic fatty liver disease (NAFLD) and studies about the association between K and NAFLD are scare. Present study aimed to examine the associations between dietary intake of Na, K, and Na:K ratio with the risk of NAFLD. We analyzed data from a case-control study of 225 patients with NAFLD cases and 450 controls. Dietary intake of Na and K measured using a validated 168 item food frequency questionnaire. Adjusted logistic regression models were used to report odds ratio (OR) 95% confidence interval (CI) of NAFLD across tertiles of Na, K, and Na:K ratio. The mean ± standard deviation of age and body mass index of participants (47% female) were 38.1 ± 8.8 years and 26.8 ± 4.3 Kg/m2. In the age- and sex-adjusted model, there was any significant association between Na, K, and Na: K ratio with the risk of NAFLD. In the final adjusted model, the OR (95%CI) of the highest vs the lowest tertiles of K, Na, and Na:K was 0.39 (0.19-0.80), 0.71 (0.40-1.25), and 1.10 (0.61-1.97), respectively. The present study indicates that higher dietary K was related to lower odds of NAFLD; however, there was no association between dietary Na and Na: K ratio with odds of NAFLD.

Association between Dietary Patterns and Non-alcoholic Fatty Liver Disease: Results from a Case-Control Study.

This study aimed to investigate the association between dietary patterns and non-alcoholic fatty liver disease (NAFLD) among Iranian adults. This case-control study was conducted on 210 subjects. NAFLD diagnosis was made by ultrasound examination. Anthropometric measures, physical activity, fasting serum levels of glucose, alanine aminotransferase (ALT), aspartate aminotransferase, and lipid profile were assessed. A three-day food diary was used to assess dietary intakes of the subjects. Dietary patterns were determined using factor analysis. To determine the relationship between dietary patterns and NAFLD, multivariable-adjusted odds ratio (OR) obtained from the logistic regression analysis was used. Two dietary patterns were extracted as follows: vegetables, legumes, fruits, and low-fat dairy products (VLFD) ; and sweet, hydrogenated fat, red and processed meat, and soft drink (SHMS) dietary patterns. By taking all possible confounders into account, the VLFD dietary pattern was found to be significantly related to lower odds of NAFLD, while the SHMS dietary pattern was independently related to higher odds of NAFLD (P < 0.05). Among major food groups, high consumption of processed meat, hydrogenated fats, sweets and desserts, and soft drinks was positively related to NAFLD (P < 0.05), whereas vegetable consumption exhibited a protective role against NAFLD (P = 0.01). The VLFD dietary pattern was associated with reduced likelihood of having NAFLD, while the SHMS dietary pattern was associated with higher likelihood. Therefore, the VLFD dietary pattern might be useful in the nutritional strategies for NAFLD patients. Further studies with larger sample sizes and prospective design are warranted.

Mediterranean dietary pattern and non-alcoholic fatty liver diseases: a case-control study.

The Mediterranean (MED) diet was associated with a reduced risk of chronic disease, but the epidemiological studies reported inconsistent findings related to the MED diet and non-alcoholic fatty liver disease (NAFLD) risk. This age and the gender-matched case-control study were conducted among 247 adult patients. The MED diet score was obtained based on the Trichopoulou model. Multivariate logistic regression was used to examine the association between the MED diet and NAFLD risk. NAFLD prevalence in people with low, moderate and high adherence to the MED diet was 33, 13⋅1 and 4⋅6%, respectively. The increasing intake of the MED diet was significantly related to the increment intake of nuts and fruits, vegetables, monounsaturated fatty acid/polyunsaturated fatty acid ratio, legumes, cereals and fish. However, total energy consumption, low-fat dairy and meats intake were reduced (P for all < 0⋅05). Following control for age, the person in the highest of the MED diet tertile compared with the lowest, the odds of NAFLD decreased (OR: 0⋅40, 95% CI: 0⋅17-0⋅95). This relation became a little stronger after further adjusting for sex, diabetes, physical activity and supplement intake (OR: 0⋅36, 95% CI: 0⋅15-0⋅89). However, this association disappeared after adjusting for body mass index, waist and hip circumference (OR: 0⋅70, 95% CI: 0⋅25-1⋅97). High adherence to the MED diet was associated with a 64% reduction in NAFLD odds before some anthropometric variable adjustments. However, further prospective studies are required, particularly in BMI-stratified models.

Life's Simple 7 and Nonalcoholic Fatty Liver Disease: The Multiethnic Study of Atherosclerosis

BackgroundThe American Heart Association (AHA) has defined Life's Simple 7 (LS7) as a measure of overall cardiovascular health . Nonalcoholic fatty liver disease (NAFLD) has been involved as a risk factor for cardiovascular disease. We evaluated the association between LS7 and NAFLD. MethodsWe evaluated participants form the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Cardiovascular health score was calculated from the Life's Simple 7 metrics. A score of 0-8 was considered inadequate, 9-10 average, and 11-14 optimal. NAFLD was defined using noncontrast cardiac computed tomography (CT) and a liver/spleen attenuation ratio (L/S) < 1. Multivariable regression were performed to evaluate the association. ResultsOur cross-sectional analysis of 3901 participants showed 19% (n = 747) had optimal cardiovascular health, 33% (n = 1270) had average, and 48% (n = 1884) had inadequate. White participants were most likely to have an optimal score (51%, n = 378), whereas African American participants had the lowest proportion with optimal scores (16%, n = 120; P < 0.001). The overall prevalence of NAFLD was 18% with a distribution of 7%, 14%, and 25% in the optimal, average, and inadequate score categories, respectively (P < 0.001). Adjusted for risk factors, average and optimal health categories had lower odds of NAFLD compared to those with inadequate scores: odds ratio for average, 0.44 (95% confidence interval 0.36-0.54); optimal, odds ratio 0.19 (95% confidence interval 0.14-0.26). This association was similar across gender, race and age groups. ConclusionA more favorable cardiovascular health score was associated with a lower prevalence of NAFLD. This study may suggest a potential of Life's Simple 7 in the prevention of liver disease.

The association between dietary antioxidant index (DAI) and nonalcoholic fatty liver disease (NAFLD) onset; new findings from an incident case-control study.

Evidence suggests an increasing global trend in non-alcoholic fatty liver disease (NAFLD) prevalence. Researchers have noted the importance of the role of dietary antioxidants in reducing the incidence of NAFLD. The dietary antioxidant index (DAI) is a valid indicator that considers the -diet's total antioxidant properties. The present study was designed and conducted to investigate the relationship between DAI and NAFLD. We hypothesized that there is a link between the DAI and the NAFLD. This case-control study included 295 patients with NAFLD and 704 controls. The patients' dietary intake was assessed through a valid and reliable semi-quantitative food frequency questionnaire. We standardized each of vitamin A, C, E, and selenium, manganese, and zinc by subtracting the global mean and dividing by the global SD to calculate the DAI. Subjects with DAI score-0.46<were at higher odds of having NAFLD compared to subjects with DAI -0.46≥(ORDAI<-0.46/≥-0.46=0.55; 95% CI=0.41-0.73). After adjustment for age, gender, and total energy intake (model B) a reverse and significant association was seen (ORDAI<-0.46/≥-0.46=0.57; 95% CI=0.39-0.82). The role of antioxidants in reducing the odds of NAFLD is fundamental. Taking antioxidants such as vitamins A, E, C, zinc, selenium, and manganese through food can effectively reduce NAFLD odds. On the other hand, studies should examine DAI's sensitivity and specificity in various settings and outcomes to use it in clinical work.

Dietary polyphenols and the odds of non-alcoholic fatty liver disease: A case-control study.

Few epidemiological data are available regarding the associations of dietary intakes of polyphenols with non-alcoholic fatty liver disease (NAFLD). We sought to examine the associations of dietary intake of polyphenols with the prevalence of NAFLD. We analyzed data from a case-control study of 225 patients with NAFLD cases and 450 controls. All participants completed a validated 168-item food frequency questionnaire, the results of which were subsequently used to calculate dietary polyphenol. Based on multivariate logistic regression analysis, after adjustment for age and sex, it was shown that participants who were in the highest tertile of total flavonoids (OR=0.65, 95% CI=0.44-0.98) and total phenolic acids (OR=0.63, 95% CI=0.42-0.94) were associated with a lower odds of NAFLD compared with the lowest tertile. Although the association of total flavonoids and the odds of NAFLD disappeared after additional adjustment for BMI, physical activity, smoking, SES, dietary fat, and energy intake (OR=0.67, 95% CI=0.38-1.19). The odds of NAFLD was 66% lower (OR=0.44, CI=0.24-0.78, p for trend=0.006) among participants who were in the highest tertile of lignans intake compared with the lowest tertile. Our study showed that a high intake of lignans lowers the odds of NAFLD. We strongly recommend that the concepts proposed in this study must be tested in future longitudinal researches, to determine the association of total and subgroup of polyphenol intake with different stages of fatty liver diseases.

Prevalence of non-alcoholic fatty liver disease and factors associated with it in Indian women with a history of gestational diabetes mellitus.

Aims/IntroductionThis study aims to evaluate the prevalence of and factors associated with non‐alcoholic fatty liver disease (NAFLD) in Indian women with prior gestational diabetes mellitus (GDM) diagnosed using International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria.Materials and MethodsThis cross‐sectional study (2018–2019) enrolled women with and without prior GDM. Study participants underwent detailed assessments, including relevant medical, obstetric and demographic details; 75‐g oral glucose tolerance test with glucose and insulin estimation at 0, 30 and 120 min; and other relevant biochemical and anthropometric measurements. NAFLD status was defined by ultrasonography.ResultsWe evaluated a total of 309 women (201 and 108 with and without prior GDM, respectively) at a mean age of 31.9 ± 5.0 years and median of 16 months (interquartile range 9–38 months) following the index delivery. The prevalence of NAFLD was significantly higher in women with prior GDM (62.7% vs 50.0%, P = 0.038; grade 2 and 3 disease, 13.9% vs 6.5%). On logistic regression analysis (fully adjusted model), the odds of NAFLD were 2.11‐fold higher in women with prior GDM (95% confidence interval 1.16–3.85, P = 0.014). Overweight/obesity, metabolic syndrome, prediabetes and homeostasis model of assessment of insulin resistance (a measure of insulin resistance) were positively associated with NAFLD, whereas the Matsuda index (a measure of insulin sensitivity) showed a negative association with NAFLD.ConclusionsThe prevalence of NAFLD is high in women with prior GDM. Such women also have a high burden of cardiometabolic risk factors. Future studies should evaluate the intermediate and long‐term hepatic and cardiovascular risk, and the impact of lifestyle interventions in reducing morbidity in such women.

Inadequate Physical Activity and Sedentary Behavior Are Independent Predictors of Nonalcoholic Fatty Liver Disease.

In general, physical activity (PA) and nonalcoholic fatty liver disease (NAFLD) have an inverse association. However, studies assessing the impact of the widely accepted Physical Activity Guidelines for Americans (PA Guidelines) on NAFLD are lacking. We performed a serial, cross-sectional analysis among adults by using the 2007-2016 US National Health and Nutrition Examination Survey. NAFLD and advanced fibrosis were defined by using various noninvasive panels. A PA questionnaire assessed the leisure-time PA, occupation-related PA, transportation-related PA, and total sitting time as sedentary behavior. PA was categorized according to the PA Guidelines. Of the 24,588 individuals (mean age, 47.4years; 47.9% males), leisure-time PA (≥150minutes per week) demonstrated 40% lower odds of NAFLD, whereas transportation-related PA was associated with a 33% risk reduction in NAFLD. Analysis of total PA and sitting times simultaneously showed a dose-response association between sitting time and NAFLD (P for trend<0.001). Compliance with the PA Guidelines was lower in individuals with NAFLD versus those without NAFLD. The trends in compliance with the PA Guidelines for any type of PA remained stable in individuals with NAFLD except for a downtrend in transportation-related PA. In contrast, an improvement in compliance with the PA Guidelines for leisure time was noted in the cohort without NAFLD. Although PA demonstrated a 10% stronger association with risk reduction of NAFLD in women, women showed a lower tendency of meeting the PA Guidelines. Trends in total sitting time increased significantly regardless of NAFLD status. Sedentary behavior emerged as an independent predictor of NAFLD. Overall compliance with the PA Guidelines was lower in the cohort with NAFLD, with sex- and ethnicity-based differences. Implementation of these observations in clinical practice may improve our understanding as well as clinical outcomes.

Association between Thyroid Function and Nonalcoholic Fatty Liver Disease in Euthyroid Type 2 Diabetes Patients.

Thyroid function and type 2 diabetes mellitus (T2DM) are both associated with increased risks of adverse clinical outcomes in nonalcoholic fatty liver disease (NAFLD). Our study is aimed at evaluating the association between thyroid function and NAFLD in T2DM patients with normal thyroid function (euthyroid) and analyzing the potential effects of metformin on the pathological process. Overall, 369 T2DM patients were enrolled between July 2017 and September 2018 and stratified into NAFLD and non-NAFLD groups. Data on age, gender, body mass index (BMI, kg/m2), metformin use, and basal metabolic rate (BMR) were obtained from participants' records. All patients were tested for biochemical markers, indexes of glucose metabolism, lipid metabolism, bone metabolism, and thyroid function at baseline. Multivariate analyses detected increased odds of NAFLD among individuals with T2DM per unit increase in their BMI and free triiodothyronine (FT3) and thyroid stimulating hormone (TSH); the odds ratios (OR) were 1.25, 3.02, and 1.58, respectively (all p < 0.05). Positive correlations were detected between alanine aminotransferase (ALT) and FT3 (r = 0.221, p = 0.010), and negative correlations were noted between TSH and BMR (r = −0.618, p < 0.001) and between BMR and FT3 (r = −0.452, p < 0.001) in T2DM subjects with NAFLD. A significant difference in serum FT3 (t = 2.468, p = 0.0167) and TSH (t = 2.658, p = 0.010) levels was found between obese individuals with NAFLD who used and did not use metformin. The pathological mechanism of T2DM complicated by NAFLD in euthyroid patients may be associated with insulin resistance and a thyroid hormone resistance-like manifestation, i.e., relevant hypothyroidism. Metformin can potentially decrease the double-resistance situation, especially in obese individuals.

Association between remnant lipoprotein cholesterol levels and non-alcoholic fatty liver disease in adolescents

Background & AimsRemnant lipoprotein cholesterol (RLP-C) is an atherogenic lipid profile associated with non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). With increased rates of CVD seen in adults with NAFLD, RLP-C has the potential to identify individuals with NAFLD who are at increased risk of CVD. This study examined in adolescents sex-different associations among RLP-C, NAFLD, and cardiometabolic risk factors, and whether RLP-C is associated with NAFLD beyond traditional cardiometabolic risk factors.MethodsAdolescents in the Raine Study had anthropometry, clinical, biochemistry and arterial stiffness measurements recorded at 17 years of age. Fatty liver, subcutaneous and visceral adipose thickness were assessed using abdominal ultrasound. Relationships among RLP-C, NAFLD, liver biochemistry, insulin resistance, adipokines, adiposity and arterial stiffness were assessed.ResultsNAFLD was diagnosed in 15.1% (19.6% females and 10.7% males) of adolescents. Increasing RLP-C levels were associated with increasing severity of hepatic steatosis and metabolic syndrome. Adolescents with NAFLD and serum RLP-C levels in the highest quartile compared with the lowest quartile, had higher serum leptin, homeostatic model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein, low-density-lipoprotein cholesterol, triglycerides, BMI, subcutaneous and visceral adipose thickness, systolic blood pressure and arterial stiffness, but lower adiponectin and high-density-lipoprotein cholesterol. Using multivariable logistic regression, RLP-C in the lowest quartile compared with the highest quartile was associated with 85% lower odds of NAFLD in males and 55% in females, after adjusting for waist circumference, leptin, ALT, adiponectin and HOMA-IR.ConclusionsThere is an association between RLP-C and NAFLD beyond traditional risk factors of adiposity and insulin resistance in adolescents. Although raised serum RLP-C levels were associated with the severity of hepatic steatosis and markers of cardiometabolic risk, lower serum RLP-C might reflect reduced cardiovascular risk.Lay summaryRemnant lipoprotein cholesterol (RLP-C) is a part of the blood cholesterol that is linked with heart disease and non-alcoholic fatty liver disease (NAFLD) in adults. In the Raine Study, teenagers with high RLP-C levels had more severe fat accumulation in their liver. Thus, RLP-C might be the hidden link between NAFLD and future risk of heart disease.

Association of the dietary patterns with the risk of non-alcoholic fatty liver disease among Iranian population: a case-control study

BackgroundDiet-based recommendations can be developed for preventing and treating non-alcoholic fatty liver disease (NAFLD) after investigating the effects of whole diets on NAFLD. The aim of this study was to identify major dietary patterns and their association with the risk of NAFLD.MethodsA total of 244 individuals (122 NAFLD patients and 122 controls) participated in this case-control study. The patients with NAFLD were diagnosed by a gastroenterologist. The participants’ dietary intake data were collected using a 147-item semi-quantitive food frequency questionnaire and major dietary patterns were identified by principal component analysis. Adherence to dietary patterns was divided into tertiles and its association with odds of NAFLD was investigated by multivariate logistic regression.ResultsThe results showed four major dietary patterns, among which adherence to the “ordinary pattern” was positively associated with NAFLD risk. After adjusting for all confounding factors, individuals in the highest tertile of “ordinary pattern” exhibited a significantly elevated risk of NAFLD compared to the lowest tertile (OR = 3.74, 95%CI = 1.23–11.42, P trend< 0.001). As well as, Individuals in the second and third tertiles of the “traditional pattern” were associated with the risk of NAFLD compared to the lowest tertile (medium vs. lowest tertile OR = 2.37, 95%CI = 1.02–5.53; highest vs. lowest tertile OR = 3.58, 95% CI = 1.48–8.68, P trend< 0.001). The highest tertile of “vegetable and dairy pattern” compared to the lowest tertile was inversely associated with NAFLD risk (OR = 0.23, 95%CI = 0.09–0.58, P trend = 0.02). No significant association was found between “fast food type pattern” and the risk of NAFLD.ConclusionA significant association was observed between different dietary patterns and the risk of NAFLD. These results can potentially serve as a dietary strategy for preventing NAFLD in individuals who are at a high risk for progression of NAFLD.

Review article: the emerging role of genetics in precision medicine for patients with non-alcoholic steatohepatitis.

SummaryBackgroundNon‐alcoholic steatohepatitis (NASH) is a severe form of non‐alcoholic fatty liver disease (NAFLD) characterised by liver fat accumulation, inflammation and progressive fibrosis. Emerging data indicate that genetic susceptibility increases risks of NAFLD, NASH and NASH‐related cirrhosis.AimsTo review NASH genetics and discuss the potential for precision medicine approaches to treatment.MethodPubMed search and inclusion of relevant literature.ResultsSingle‐nucleotide polymorphisms in PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13 are clearly associated with NASH development or progression. These genetic variants are common and have moderate‐to‐large effect sizes for development of NAFLD, NASH and hepatocellular carcinoma (HCC). The genes play roles in lipid remodelling in lipid droplets, hepatic very low‐density lipoprotein (VLDL) secretion and de novo lipogenesis. The PNPLA3 I148M variant (rs738409) has large effects, with approximately twofold increased odds of NAFLD and threefold increased odds of NASH and HCC per allele. Obesity interacts with PNPLA3 I148M to elevate liver fat content and increase rates of NASH. Although the isoleucine‐to‐methionine substitution at amino acid position 148 of the PNPLA3 enzyme inactivates its lipid remodelling activity, the effect of PNPLA3 I148M results from trans‐repression of another lipase (ATGL/PNPLA2) by sequestration of a shared cofactor (CGI‐58/ABHD5), leading to decreased hepatic lipolysis and VLDL secretion. In homozygous Pnpla3 I148M knock‐in rodent models of NAFLD, targeted PNPLA3 mRNA knockdown reduces hepatic steatosis, inflammation and fibrosis.ConclusionThe emerging genetic and molecular understanding of NASH paves the way for novel interventions, including precision medicines that can modulate the activity of specific genes associated with NASH.

Abstract P277: Lower Gut Microbial Diversity in Non-alcoholic Fatty Liver Disease: Results From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Introduction: Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and a leading cause of chronic liver disease in the United States (US). Prevalence of both conditions is higher in US Hispanics/Latinos compared to non-Hispanic whites. Composition of the gut microbiome, comprising the microorganisms in the gastrointestinal tract, has been associated with both NAFLD and obesity in animal and human studies, but there is currently no consensus on which microbial changes are associated with these two conditions. Data on the relation of the gut microbiome with NAFLD in Hispanic/Latino populations are limited. Hypothesis: We hypothesized that gut bacterial diversity is associated with NAFLD in Hispanic/Latino adults. Methods: This analysis included 2587 Hispanic/Latino adults in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) with fecal samples. The gut microbiome was characterized using shotgun metagenomic sequencing and taxonomic classification by the SHOGUN pipeline with the RefSeq 82 prokaryotic genome database. NAFLD was defined based on gender-specific liver function test thresholds developed in the National Health and Nutrition Examination Survey (NHANES) after excluding participants with other known causes of liver dysfunction. Alpha and beta diversity were compared between groups defined by NAFLD and obesity using multinomial logistic regression and PERMANOVA, respectively. The difference in relative abundance for the 15 most abundant species were compared using the Wilcoxon rank sum test. Results: There were 395 (15%) NAFLD cases among 2587 participants, and 1718 (66%) were women. Prevalence of obesity (BMI ≥ 30) was 58% and 42% among those with and without NAFLD, respectively. Higher bacterial alpha diversity (Shannon index) was associated with lower odds of NAFLD with (OR = 0.58, p = 0.0005) or without obesity (OR = 0.70, p = 0.04) compared to participants with neither condition after adjusting for age, gender, Hispanic background, diabetes, dyslipidemia and hypertension. In the same model, higher Shannon index was also associated with lower odds of obesity in the absence of NALFD (OR = 0.78, p = 0.01). Beta diversity (Bray-Curtis) did not differ significantly by NAFLD/obesity groups (p = 0.78) or by NAFLD alone (p = 0.30). Among the 15 most abundant species across samples, 4 ( Bacteroides uniformis , Odoribacter splanchnicus , Oscillibacter sp. ER4, and Alistipes shahii ) had significantly lower abundance in those with NAFLD compared to those without NAFLD irrespective of obesity. Conclusion: This study reveals that bacterial alpha diversity but not beta diversity is independently associated with the related conditions, NAFLD and obesity, in US Hispanic/Latino adults. Future work will explore associations between NAFLD and functional capacity of gut microbial components as well as considering relevant host genetic variants in this population.

Rotating night shift work and non-alcoholic fatty liver disease among steelworkers in China: a cross-sectional survey

ObjectivesIn a 24/7 society, the negative metabolic effects of rotating night shift work have been increasingly explored. This study aimed to examine the association between rotating night shift work and...

Higher phenolic acid intake independently associates with lower prevalence of insulin resistance and non-alcoholic fatty liver disease.

Background & AimsThe inverse association between non-alcoholic fatty liver disease (NAFLD) and diets rich in fruit and vegetables has been demonstrated, but the specific compounds that may be responsible for this association need to be elucidated. The aim of this study was to test the association between phenolic acid consumption, NAFLD, and insulin resistance (IR).MethodsA cross-sectional cohort of individuals included in a metabolic screening program was studied. Liver steatosis was evaluated by ultrasonography and quantified by the hepatorenal index (HRI); fibrosis was assessed by FibroTest; IR by the sample upper quartile of the homeostatic model assessment score. Dietary intake was measured by a food frequency questionnaire. The phenolic acid content of food was calculated according to Phenol-Explorer.ResultsA total of 789 individuals were included (52.6% men, age 58.83 ± 6.58 years). Higher (above the upper median) phenolic acid intake was inversely associated with the presence of NAFLD (odds ratio [OR] 0.69; 95% CI 0.49–0.98; p = 0.036), higher HRI (OR 0.64; 95% CI 0.45–0.91; p = 0.013) and higher IR (OR 0.61; 95% CI 0.42–0.87; p = 0.007), when adjusted for age, gender, body mass index, and lifestyle factors. Considering specific classes of phenolic acids, higher hydroxybenzoic acid intake was independently associated with lower odds of NAFLD, higher HRI and fibrosis. Higher hydroxycinnamic acid intake was independently associated with lower odds of IR.ConclusionA higher intake of phenolic acids is associated with a lower prevalence of liver steatosis and IR in a cross-sectional study, suggesting a possible protective effect that requires confirmation in prospective studies.Lay summaryHigh dietary intake of total phenolic acids is associated with a lower prevalence of non-alcoholic fatty liver disease and insulin resistance. A high intake of hydroxybenzoic acids, a class of phenolic acids, is associated with a lower prevalence of steatosis and clinically significant fibrosis, while a high intake of hydroxycinnamic acids, another class of phenolic acids, is associated with a lower prevalence of insulin resistance.

Associations between dietary total antioxidant capacity and odds of non-alcoholic fatty liver disease (NAFLD) in adults: a case-control study.

The relationships between the total antioxidant capacity (TAC) of the diet and the risk of non-alcoholic fatty liver disease (NAFLD) have not previously been assessed. The aim of this study was to assess relationships between DTAC and odds of NAFLD in a case-control study. This case-control study was carried out in 158 patients with NAFLD and 357 healthy individuals aged 18-55 years. Dietary data were collected using validated 168-item quantitative food frequency questionnaires. Triacylglycerols (TAGs), total cholesterol (TC), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) and fasting blood glucose (FBS) concentrations were assessed using enzymatic methods and commercial kits. The DTAC was calculated based on the oxygen radical absorbance capacity of each food reported by the U.S. Department of Agriculture. The mean ± sd (standard deviation) for age and body mass index (BMI) of the study participants were 43⋅9 years ±5⋅9 and had 30⋅5 kg/m2 ±2⋅6. The NAFLD patients included higher BMI and female proportion, compared with the control group. The NAFLD patients included higher smoking rates, biochemical parameters (TG, TC, LDL-C and FBS) and DTAC scores, compared with control groups (P-value < 0⋅05). However, patients with NAFLD had lower HDL levels and physical activities, compared with the control group. The highest tertile of DTAC showed lower odds of NAFLD, compared with the lowest tertile. This association was significant after adjustment for potential confounders (OR, 0⋅19; 95 % CI, 0⋅9-0⋅34; P for trend 0⋅001). Findings suggest that the promotion of naturally increased antioxidant capacities may help prevent odds of NAFLD.

Circulating ectodysplasin A is a potential biomarker for nonalcoholic fatty liver disease

BackgroundEctodysplasin A (EDA), a new hepatokine, may be involved in energy metabolism. This study aims to 1) investigate the role of EDA in hepatic steatosis in C57BL/6 mice and HepG2 cells; 2) evaluate serum EDA in nonalcoholic fatty liver disease (NAFLD) in human. MethodsThis study comprises an experimental study in vitro and in vivo and a hospital based case-control study. Western blotting, qPCR and ELISA were used to measure EDA levels. siRNA and shRNA were performed to knockdown EDA. An Adipokine Magnetic Bead Panel was performed to measure serum adipokines. ResultsIncreased levels of hepatic and secreted EDA were detected in steatosis, in vivo and in vitro. Steatosis was ameliorated by EDA knockdown in vitro, while intrahepatic triglycerides content and liver enzymes were improved in vivo. Furthermore, knockdown of EDA upregulated lipolytic genes and suppressed lipogenic genes. Serum EDA in subjects with NAFLD was higher. Moreover, it reveals associations between circulating EDA and higher odds of NAFLD, while circulating EDA presented a practicable performance to identify NAFLD. Lastly, serum EDA level was dependent on BMI, TNF-α, T2DM and obesity. ConclusionsEDA aggravates steatosis by striking balance between lipid deposition and elimination. It was a potential biomarker of NAFLD.