The associations between modifiable risk factors and nonalcoholic fatty liver disease: A comprehensive Mendelian randomization study.

BACKGROUND AND AIMS: Early identification of modifiable risk factors is essential for the prevention of nonalcoholic fatty liver disease (NAFLD). We aimed to systematically explore the relationships between genetically predicted modifiable risk factors and NAFLD. APPROACH AND RESULTS: We applied univariable and multivariable Mendelian randomization analyses to explore the relationships between 35 modifiable risk factors and NAFLD. We also evaluated the combined results in three independent large genome-wide association studies. Genetically predicted alcohol frequency, elevated serum levels of liver enzymes, triglycerides, C-reactive protein, and obesity traits, including body mass index, waist circumference, and body fat mass, were associated with increased risks of NAFLD (all with p < 0.05). Poor physical condition had a suggestive increased risk for NAFLD (odds ratio [OR] = 2.63, p  = 0.042). Genetically instrumented type 2 diabetes (T2DM), hypothyroidism, and hypertension all increased the risk for NAFLD, and the ORs (95% confidence interval) were 1.508 (1.20-1.90), 13.08 (1.53-111.65), and 3.11 (1.33-7.31) for a 1-U increase in log-transformed odds, respectively. The positive associations of T2DM and hypertension with NAFLD remained significant in multivariable analyses. The combined results from the discovery and two replication datasets further confirmed that alcohol frequency, elevated serum liver enzymes, poor physical condition, obesity traits, T2DM, and hypertension significantly increase the risk of NAFLD, whereas higher education and high-density lipoprotein cholesterol (HDL-cholesterol) could lower NAFLD risk. CONCLUSIONS: Genetically predicted alcohol frequency, elevated serum liver enzymes, poor physical condition, obesity traits, T2DM, and hypertension were associated with an increased risk of NAFLD, whereas higher education and HDL-cholesterol were associated with a decreased risk of NAFLD.

Long-term Use of Proton Pump Inhibitors is Associated With An Increased Risk of Nonalcoholic Fatty Liver Disease.

BACKGROUNDS: The adverse effects of long-term use of proton pump inhibitors (PPIs) have led to growing concern. The association between PPIs use and the risks of nonalcoholic fatty liver disease (NAFLD) remains controversial. GOAL: The aim of this study was to investigate the association between PPIs use and the risks of NAFLD among the general adult population in the United States. STUDY: We performed a cross-sectional study by extracting data from the National Health and Nutrition Examination Survey of 2017 to 2018. The association between PPIs use and NAFLD risks was analyzed by weighted multivariate logistic regression. RESULTS: Among the 4238 participants included in this study, 2167 were diagnosed with NAFLD. In the multivariate logistic regression model, PPIs use was associated with increased risks of NAFLD [odds ratio (OR): 1.318, 95% CI: 1.044-1.663; P=0.020]. This association was nonsignificant in participants taking PPIs for ˂5 years (OR: 0.846, 95% CI: 0.579-1.238; P=0.390), whereas it remained significant in participants taking PPIs for more than 5 years (OR: 2.016, 95% CI: 1.366-2.975; P=0.031). Further analysis showed that the use of PPIs was positively associated with risks of severe hepatic steatosis (OR: 1.451, 95% CI: 1.034-2.036; P=0.031) but not with mild-to-moderate steatosis (OR: 1.242, 95% CI: 0.886-1.741; P=0.208). CONCLUSIONS: This study indicated that taking PPIs was associated with increased risks of NAFLD, especially severe hepatic steatosis. Awareness should be raised regarding the potential risks of NAFLD when prescribing PPIs.

Associations of serum uric acid levels with liver disease-related morbidity and mortality: A prospective cohort study of the UK Biobank.

BACKGROUND AND AIMS: The association of serum uric acid (SUA) levels with liver-related morbidity and mortality remains undetermined. Therefore, we aimed to explore the association of SUA levels with liver-related morbidity and mortality. METHODS: The present cohort study included 459 619 adults from the UK Biobank. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of SUA levels with morbidity and mortality of overall liver disease. Mendelian randomization (MR) analyses were conducted to explore the underlying causality. A polygenic risk score was generated to assess whether there was a gene-exposure interaction. RESULTS: During a median follow-up of 12.6 years, 14 302 nonfatal and 609 fatal cases of overall liver disease were identified. Compared to individuals in the lowest quartile, the HRs (95% CI) of incident overall liver disease were 1.08 (1.02-1.14), 1.13 (1.07-1.20) and 1.44 (1.36-1.53) for individuals with SUA levels in quartiles 2, 3 and 4 respectively. Similarly, the HRs (95% CI) of liver disease-associated mortality were 1.09 (0.78-1.52), 1.55 (1.14-2.13) and 1.96 (1.42-2.69) for individuals with SUA levels in quartiles 2, 3 and 4 respectively. The MR results did not support the causal association of SUA levels with liver disease. In addition, there was a significant modification effect of the polygenic risk score on the association of SUA levels with incident overall liver disease (pinteraction  = .003). CONCLUSIONS: Higher SUA levels were significantly associated with an increased risk of overall liver disease morbidity and mortality.

Association between ultra-processed foods consumption and risk of non-alcoholic fatty liver disease: a population-based analysis of NHANES 2011-2018.

An increasing number of studies have evaluated the association between ultra-processed foods (UPF) consumption and metabolic disorders. However, the association between UPF intake and non-alcoholic fatty liver disease (NAFLD) remains unclear. In this study, we analysed data from 6545 participants who were recruited in National Health and Nutrition Examination Surveys 2011-2018. UPF were defined in light of the NOVA food classification system and divided into quartiles based on its proportion of total weight intake. Complex logistic regression models were used to assess the association between UPF and NAFLD. Mediation analyses were conducted to reveal underlying mediators. We found that NAFLD patients consumed more UPF than controls (925·92 ± 18·08 v. 812·70 ± 14·32 g/d, P < 0·001). Dietary intake of UPF (% weight) was negatively related to the Healthy Eating Index-2015 score (Spearman r = -0·32, P < 0·001). In the multivariable model, the highest quartile compared with the lowest, the OR (95 % CI) were 1·83 (1·33, 2·53) for NAFLD (OR per 10 % increment: 1·15; 95 % CI: 1·09, 1·22; P for trend < 0·001) and 1·52 (1·12, 2·07) for insulin resistance (OR per 10 % increment: 1·11; 95 % CI: 1·05, 1·18; P for trend = 0·002). Mediation analyses revealed that poor diet quality, high saturated fat and refined grain intake partly mediated the association between UPF and NAFLD. In conclusion, high UPF intake was associated with an increased risk of NAFLD in US adults. Further prospective studies are needed to verify these findings.

Positive Association Between the Chinese Visceral Adiposity Index and Nonalcoholic Fatty Liver Disease in Lean Adults.

BACKGROUND: Chinese visceral adiposity index (CVAI) is a novel indicator that precisely evaluates visceral obesity and has been shown to be significantly associated with nonalcoholic fatty liver disease (NAFLD) in the general population. However, the relationship between CVAI and NAFLD in lean adults remains unclear. AIMS: This study aimed to explore the association of CVAI with NAFLD in a lean population and evaluate the diagnostic capability of CVAI for lean NAFLD. METHODS: A cross-sectional study was conducted among 9,607 lean adults (body mass index < 24 kg/m2), who underwent their annual health examinations at the First Affiliated Hospital, Zhejiang University School of Medicine in 2021. NAFLD was determined by ultrasonography to the exclusion of other known etiologies. RESULTS: The prevalence of NAFLD was 16.4% in this lean population. CVAI values were significantly higher in participants with NAFLD than those without NAFLD and the CVAI quartile was positively associated with the prevalence of NAFLD, which was 0.4%, 6.0%, 19.4%, and 39.8% among the participants with CVAI in quartile 1 to 4, respectively (P for trend < 0.001). Logistic regression analysis found that CVAI was positively associated with the risk of NAFLD (adjusted odds ratio: 1.025, 95% confidence interval: 1.021-1.028; P < 0.001). Furthermore, CVAI had a significantly higher area under curve value for detecting NAFLD than other visceral obesity indices. CONCLUSION: Our study showed that CVAI was positively associated with the prevalence and risk of NAFLD in lean adults, and CVAI showed the highest diagnostic ability for lean NAFLD.

Different dietary carbohydrate component intakes and long-term outcomes in patients with NAFLD: results of longitudinal analysis from the UK Biobank.

BACKGROUND: This study aimed to investigate the association between the intake of different dietary carbohydrate components and the long-term outcomes of non-alcoholic fatty liver disease (NAFLD). METHODS: We used prospective data from 26,729 NAFLD participants from the UK Biobank cohort study. Dietary information was recorded by online 24-hour questionnaires (Oxford WebQ). Consumption of different carbohydrate components was calculated by the UK Nutrient Databank Food Composition Table. Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). A substitution model was used to estimate the associations of hypothetical substitution for free sugars. RESULTS: During a median of 10.5 (IQR: 10.2-11.2) years and a total of 280,135 person-years of follow-up, 310 incident end-stage liver disease (ESLD) and 1750 deaths were recorded. Compared with the lowest quartile, the multi-adjusted HRs (95% CI) of incident ESLD in the highest quartile were 1.65 (1.14-2.39) for free sugars, 0.51 (0.35-0.74) for non-free sugars, and 0.55 (0.36-0.83) for fiber. For overall mortality, the multi-adjusted HRs (95% CI) in the highest quartile were 1.21 (1.04-1.39) for free sugars, 0.79 (0.68-0.92) for non-free sugars, and 0.79 (0.67-0.94) for fiber. Substituting free sugars with equal amounts of non-free sugars, starch or fiber was associated with a lower risk of incident ESLD and overall mortality. CONCLUSIONS: A lower intake of free sugars and a higher intake of fiber are associated with a lower incidence of ESLD and overall mortality in NAFLD patients. These findings support the important role of the quality of dietary carbohydrates in preventing ESLD and overall mortality in NAFLD patients.

Association between night shift work and NAFLD: a prospective analysis of 281,280 UK Biobank participants.

CONTEXT: This study aimed to investigate the association between night shift work and the risk of nonalcoholic fatty liver disease (NAFLD). METHODS: We conducted a prospective analysis of 281,280 UK Biobank participants. Cox proportional hazards models were used to estimate the association of night shift work with incident NAFLD. Polygenic risk score analyses were performed to assess whether a genetic predisposition to NAFLD modified the association. RESULTS: During a median follow-up of 12.1 years (3,373,964 person-years), 2,555 incident NAFLD cases were identified. Compared with workers who never/rarely worked night shifts, those who worked some night shifts or usual/permanent night shifts were 1.12 (95% CI: 0.96-1.31) and 1.27 (95% CI: 1.08-1.48) times more likely to develop NAFLD, respectively. Among the 75,059 participants who had reports on lifetime experience of night shift work, those with a longer duration, a higher frequency, more consecutive night shifts and a longer length per shift all showed higher risks of incident NAFLD. Further analyses showed that the association between night shift work and incident NAFLD was not modified by a genetic predisposition to NAFLD. CONCLUSIONS: Night shift work was associated with increased risks of incident NAFLD.

The efficacy of vitamin D supplementation for irritable bowel syndrome: a systematic review with meta-analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder involving gut-brain interactions with limited effective treatment options. Vitamin D deficiency is commonly observed in patients with IBS, but whether vitamin D supplementation ameliorates IBS is controversial in randomized controlled trials. The present systematic review and meta-analysis explored the efficacy of vitamin D supplementation in patients with IBS. METHODS: We performed a systematic search of potentially relevant publications from PubMed, EMBASE, the Cochrane Central Register of Controlled Studies and the Web of Science up until January 2022. We assessed the weighted mean difference (WMD) and 95% confidence interval (95% CI) of the IBS severity scoring system (IBS-SSS), IBS quality of life (IBS-QoL) and IBS total score (IBS-TS) before and after vitamin D supplementation intervention. RESULTS: We included four randomized, placebo-controlled trials involving 335 participants. The differences in IBS-SSS score between participants in the intervention group and the placebo group increased after intervention (WMD: -55.55, 95% CI: -70.22 to -40.87, I2 = 53.7%, after intervention; WMD: -3.17, 95% CI: -18.15 to 11.81, I2 = 0.0%, before intervention). Participants receiving vitamin D supplementation showed greater improvement in IBS-SSS after intervention than participants receiving placebo treatment (WMD: -84.21, 95% CI: -111.38 to -57.05, I2 = 73.2%; WMD: -28.29, 95% CI: -49.95 to -6.62, I2 = 46.6%, respectively). Vitamin D supplementation was also superior to placebo in IBS-QoL improvement (WMD: 14.98, 95% CI: 12.06 to 17.90, I2 = 0.0%; WMD: 6.55, 95% CI: -2.23 to 15.33, I2 = 82.7%, respectively). Sensitivity analyses revealed an unstable pooled effect on IBS-TS in participants receiving vitamin D supplementation. Therefore, we did not evaluate the efficacy of vitamin D intervention in IBS-TS. CONCLUSIONS: This systematic review and meta-analysis suggested that vitamin D supplementation was superior to placebo for IBS treatment.

Association between Monocyte to High-Density Lipoprotein Cholesterol Ratio and Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study.

BACKGROUND: The aim of the present study was to investigate the association between monocyte to high-density lipoprotein cholesterol ratio (MHR) and nonalcoholic fatty liver disease (NAFLD) in Chinese population. METHODS: We enrolled 14189 individuals who attended their annual health examinations in the study. We performed the anthropometric and laboratory measurements and diagnosed NAFLD by hepatic ultrasonography without evidence of other etiologies of chronic liver disease. Student's t-test, Mann-Whitney U test, and chi-squared (χ 2) test was used to compare the differences of clinical characteristics between participants with or without NAFLD. Pearson's and Spearman's analyses were performed to assess the correlation of MHR and NAFLD risk factors. Univariate and multivariate logistic regression analyses were conducted to explore whether MHR associated with NAFLD. RESULTS: Thirty-five percent of the participants enrolled were diagnosed with NAFLD. Compared with healthy controls, NAFLD patients were male predominant, older, and had higher body mass index, waist circumference, and systolic and diastolic blood pressure, as well as higher levels of alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, triglyceride, total cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, glycated hemoglobin A1c, and serum uric acid, but lower levels of serum high-density lipoprotein cholesterol. Besides, MHR was significantly higher in NAFLD patients than healthy controls [5.35 (4.18-6.84) versus 4.53 (3.48-5.93), P < 0.001]. MHR quartiles were positively related to the prevalence of NAFLD (P < 0.001 for trend). In multivariate logistic regression analysis, MHR was positively associated with the risk of NAFLD after adjusting age, gender, body mass index, waist circumference, diastolic blood pressure, alanine aminotransferase, triglyceride, total cholesterol, fasting plasma glucose, and serum uric acid (OR: 1.026, 95% CI: 1.002-1.052; P = 0.037). CONCLUSIONS: MHR is significantly and positively associated with the risk of NAFLD.

ZJU Index as a Predictive Tool for Diabetes Incidence: Insights from a Population-Based Cohort Study.

Background: In previous studies, the ZJU index was reported to be a superior predictor of nonalcoholic fatty liver disease in the Chinese population compared to the Fatty Liver Index. However, whether the ZJU Index is significantly associated with diabetes among Asian populations has not been determined. Methods: The NAGALA study was carried out at Murakami Memorial Hospital (Gifu, Japan) beginning in 1994. This study included the data of the subjects who underwent health check-ups from 2004 to 2015. The ZJU Index comprises body mass index (BMI), fasting plasma glucose, triglyceride, and alanine aminotransferase-to-aspartate aminotransferase (ALT) levels and an adjustment point for females. We conducted Cox proportional hazard regression to evaluate the association between quartiles of the ZJU Index and the risk of incident diabetes. Participants: A total of 15,464 individuals who underwent health check-ups were included in this study. Results: A total of 373 cases of incident diabetes were documented during 93,350 person-years of follow-up. As the ZJU index increased, the incidence of diabetes gradually increased (P <0.001). According to the multivariable model adjusted for metabolic covariates, the fourth quartile of the ZJU Index was positively associated with the risk of diabetes compared to the first quartile (HR=2.519, 95% CI=1.297-4.891). Subgroup analysis revealed that the association between the ZJU index and diabetes risk was significant in subjects aged younger than 40 years (HR=3.327, 95% CI=1.544-7.171), in females (HR=4.480, 95% CI=1.302-15.419), in individuals with a BMI<25 kg/m2 (HR=3.812, 95% CI=1.992-7.293) and in individuals with a nonregular exercise (HR=2.479, 95% CI=1.193-5.152). Conclusion: We observed a positive association between the ZJU Index and incident diabetes in the general population.

Modifiable lifestyle factors, genetic and acquired risk, and the risk of severe liver disease in the UK Biobank cohort: (Lifestyle factors and SLD).

BACKGROUND: Lifestyle intervention is important for the treatment of liver diseases. AIMS: To clarify the association of healthy lifestyle with severe liver disease (SLD) and assessed whether genetic susceptibility and acquired fibrosis risk can modify the association. METHODS: We included 417,986 UK Biobank participants who were free of SLD at baseline. Information on seven modifiable lifestyle factors was collected through a baseline questionnaire. SLD was defined as a medical diagnosis of cirrhosis, hepatocellular carcinoma or liver failure. Cox proportional hazards models were used to evaluate the association between healthy lifestyle factors and risk of incident SLD. The polygenic risk score (PRS) and fibrosis-4 index (FIB-4) were calculated and set as an interaction term. RESULTS: During a median follow-up of 12.6 years, 4542 fatal and non-fatal SLD incidents were identified. A higher overall lifestyle score was associated with a significantly lower SLD risk (Ptrend <0.001). An increment of 1-point lifestyle score combined with a 1-SD increment in FIB-4 or PRS was associated with an additional reduction of 3% or 2% in SLD risk. CONCLUSIONS: In European individuals, a healthy lifestyle is associated with a lower risk of incident SLD, which is more pronounced among individuals with a higher genetic and fibrosis risk.

The sulfur microbial diet and risk of nonalcoholic fatty liver disease: a prospective gene-diet study from the UK Biobank.

BACKGROUND: The gut microbiota is closely related to liver diseases. The dietary pattern associated with sulfur-metabolizing bacteria in stool has been found to influence intestinal health. OBJECTIVE: We aimed to investigate whether consuming the sulfur microbial diet is associated with nonalcoholic fatty liver disease (NAFLD). METHODS: We included 143,918 participants of European descent from the UK Biobank. Information on serving sizes used per diet component was recorded by an online 24-h dietary assessment tool (Oxford WebQ). The total sulfur microbial diet score was constructed by summing the product of ß-coefficients and corresponding serving sizes. NAFLD was ascertained using hospital inpatient and death records. Cox proportional hazard models were used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). Mediation analyses were used to investigate underlying mediators including body mass index, waist circumference, glucose, triglyceride, urate, and C-reactive protein. A polygenic risk score for NAFLD was constructed and stratified to assess whether the association is modified by genetic predisposition. RESULTS: After a median follow-up of 11.7 y (interquartile range: 11.3-12.5 y), we documented 1540 incident cases of NAFLD. After adjustment for covariates, we observed an overall J-shaped relationship between the sulfur microbial diet and risk of NAFLD. Those in the highest quartile of sulfur microbial diet score had a 46% increased risk of NAFLD [HRQ4vsQ1 (95% CI): 1.46 (1.26, 1.69)]. We also found that this association is partly mediated by metabolic disorders and systemic inflammation. In addition, the positive association was stronger among individuals at higher genetic risk for NAFLD (Pinteraction = 0.044). CONCLUSIONS: The sulfur microbial diet had adverse associations with incident NAFLD, particularly in those at a higher genetic risk. Our study may provide evidence on the role of sulfur-metabolizing bacteria in the diet-NAFLD association.

Circulating fatty acids and risk of hepatocellular carcinoma and chronic liver disease mortality in the UK Biobank.

Nuclear magnetic resonance (NMR)-based plasma fatty acids are objective biomarkers of many diseases. Herein, we aim to explore the associations of NMR-based plasma fatty acids with the risk of hepatocellular carcinoma (HCC) and chronic liver disease (CLD) mortality in 252,398 UK Biobank participants. Here we show plasma levels of n-3 poly-unsaturated fatty acids (PUFA) and n-6 PUFA are negatively associated with the risk of incident HCC [HRQ4vsQ1: 0.48 (95% CI: 0.33-0.69) and 0.48 (95% CI: 0.28-0.81), respectively] and CLD mortality [HRQ4vsQ1: 0.21 (95% CI: 0.13-0.33) and 0.15 (95% CI: 0.08-0.30), respectively], whereas plasma levels of saturated fatty acids are positively associated with these outcomes [HRQ4vsQ1: 3.55 (95% CI: 2.25-5.61) for HCC and 6.34 (95% CI: 3.68-10.92) for CLD mortality]. Furthermore, fibrosis stage significantly modifies the associations between PUFA and CLD mortality. This study contributes to the limited prospective evidence on the associations between plasma-specific fatty acids and end-stage liver outcomes.

Estimated small dense low-density lipoprotein cholesterol and nonalcoholic fatty liver disease in nonobese populations.

AIMS/INTRODUCTION: To explore the association between estimated small dense low-density lipoprotein cholesterol (sdLDL-C) and the risk of incident nonalcoholic fatty liver disease (NAFLD) in nonobese populations. MATERIALS AND METHODS: This study included participants who underwent health checkups in 2014 and were followed up until 2019. We carried out Cox proportional hazards regression analyses to evaluate the association of estimated sdLDL-C with NAFLD. Discordance analyses were carried out to estimate the relative NAFLD risk in estimated sdLDL-C versus low-density lipoprotein cholesterol (LDL-C) discordant/concordant groups. Estimated sdLDL-C was calculated by equations based on LDL-C and triglycerides. The diagnosis of NAFLD was based on the presence of abdominal ultrasonography after excluding other causes of chronic liver disease. RESULTS: Over a mean follow-up period of 26,694 person-years, 844 incident NAFLD cases were recorded. Compared with the first quartile of estimated sdLDL-C, the fourth quartile was associated with a 2.933-fold increased risk of NAFLD (95% confidence interval 2.095-4.107). With the increase in estimated sdLDL-C, the risk of NAFLD gradually increased both in participants within the normal range of LDL-C (hazard ratio 2.854, 95% confidence interval 1.650-5.617) and beyond the normal range of LDL-C (hazard ratio 2.636, 95% confidence interval 1.263-5.502). In addition, the inconsistent high estimated sdLDL-C/low LDL-C group was associated with an increased risk of NAFLD, but not the low estimated sdLDL-C/high LDL-C group. CONCLUSIONS: Estimated sdLDL-C was positively associated with the risk of incident NAFLD in a nonobese population, independent of LDL-C.

Dietary Patterns and Long-Term Outcomes in Patients with NAFLD: A Prospective Analysis of 128,695 UK Biobank Participants.

Large longitudinal studies exploring the role of dietary patterns in the assessment of long-term outcomes of NAFLD are still lacking. We conducted a prospective analysis of 128,695 UK Biobank participants. Cox proportional hazards models were used to estimate the risk associated with two dietary patterns for long-term outcomes of NAFLD. During a median follow-up of 12.5 years, 1925 cases of end-stage liver disease (ESLD) and 12,466 deaths occurred in patients with NAFLD. Compared with patients in the lowest quintile, those in the highest quintile of the diet quality score was negatively associated with the risks of ESLD and all-cause mortality (HRQ5vsQ1: 0.76, 95% CI: 0.66−0.87, p < 0.001; HRQ5vsQ1: 0.84, 95% CI: 0.79−0.88, p < 0.001, respectively). NAFLD patients with high-quality carbohydrate patterns carried a 0.74-fold risk of ESLD and a 0.86-fold risk of all-cause mortality (HRQ5vsQ1: 0.74, 95% CI: 0.65−0.86, p < 0.001; HRQ5vsQ1: 0.86, 95% CI: 0.82−0.91, p < 0.001, respectively). For prudent dietary patterns rich in vegetables, fruits and fish, the adjusted HR Q5vsQ1 (95% CI) was 0.87 (0.76−0.99) and 0.94 (0.89−0.99) for ESLD and all-cause mortality of NAFLD patients. There was a U-shaped association between the meat-rich dietary pattern and all-cause mortality in patients with NAFLD. These findings suggest that a diet characterized by a high-quality, high intake of vegetables, fruits, fish and whole grains as well as an appropriate intake of meat, was associated with a lower risk of adverse outcomes of NAFLD.

NAFLD does not increase the risk of incident dementia: A prospective study and meta-analysis.

The association between nonalcoholic fatty liver disease (NAFLD) and incident dementia remains unclear. This study aimed to explore whether NAFLD was associated with the risk of incident dementia. We conducted a prospective analysis of 179,222 UK Biobank participants. NAFLD was diagnosed based on the fatty liver index. Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI) of NAFLD for incident dementia. The results from this and six previous prospective studies were combined in meta-analyses. During a median follow-up of 12.4 years (2,149,839 person-years), 4950 incident dementia cases, including 2318 Alzheimer's disease (AD) cases and 1135 vascular dementia (VD) cases, were identified. There was no significant association between NAFLD and the risks of all-cause dementia (HR: 0.97, 95% CI: 0.90-1.06; P = 0.528). NAFLD was also not significantly associated with AD or VD (HR: 0.95, 95% CI: 0.84-1.07, P = 0.401; HR: 1.03, 95% CI: 0.88-1.22, P = 0.689, respectively). Our meta-analyses of prospective studies included 879,749 subjects. The pooled HR of NAFLD for all-cause dementia was 1.01 (95% CI: 0.94-1.08), and that for VD was 0.99 (95% CI: 0.86-1.13). All included cohort studies were of high quality as assessed by the Newcastle‒Ottawa scale. We found no evidence of an association between NAFLD and incident dementia.

Association between serum uric acid levels and long-term mortality of metabolic dysfunction-associated fatty liver disease: a nationwide cohort study.

BACKGROUND: The association between hyperuricemia and metabolic dysfunction-associated fatty liver disease (MAFLD) remains undetermined. This study aimed to examine the association of serum uric acid (SUA) levels with prevalence and long-term mortality of MAFLD in a nationally representative sample of US adults. METHODS: This analysis included 11,177 participants from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) with matched mortality data until 2019. We used logistic regression models to estimate the adjusted odd ratios (ORs) for factors associated with risk of MAFLD, and applied restricted cubic spline (RCS) regression to assess the non-linear associations of SUA levels with all-cause and cause-specific mortality of MAFLD. We also used Cox proportional hazards regression analysis to estimate hazard ratios (HRs) for the mortality. RESULTS: A higher SUA level contributed to a significant increased risk of MAFLD. every 1 mg/dL increment of SUA level was related to 17% (95% CI 9-24%) increased risk of MAFLD. Furthermore, a U-shaped association for males and a J-shaped association for females was discovered between SUA levels and all-cause mortality in participants with MAFLD. Specifically, among males, when SUA > 6.7 mg/dL, the higher SUA showed increased risk of cardio-cerebrovascular disease (CVD) mortality [HR (95% CI): 1.29 (1.05-1.58)]. As for females, only when SUA > 5.5 mg/dL, it showed a significantly positive association with risk of CVD and cancer mortality [HR (95% CI) 1.62 (1.24-2.13) and 1.95 (1.41-2.68)]. CONCLUSIONS: Elevated SUA level is significantly associated with an increased risk of MAFLD. Besides, SUA level is also a predictor of long-term mortality of MAFLD.

Association of the android to gynoid fat ratio with nonalcoholic fatty liver disease: a cross-sectional study.

Background: Nonalcoholic fatty liver disease (NAFLD) is becoming a severe global public health problem, and can developed into fibrotic nonalcoholic steatohepatitis (NASH), but its risk factors have not been fully identified. The objective of this study was to investigate the association between the android-to-gynoid fat ratio (A/G ratio) and the prevalence of NAFLD. Methods: This cross-sectional study is based on the 2003-2006 and 2011-2018 cycles of the National Health and Nutrition Examination Survey and included 10,989 participants. Participants aged 20 and older without viral hepatitis or significant alcohol consumption were included. Dual-energy X-ray absorptiometry was used to assess body composition. NAFLD was diagnosed using the United States fatty liver index (US FLI). Multivariable logistic regression models were used to evaluate the association between the A/G ratio and NAFLD. Results: The prevalence of NAFLD was 32.15% among the study population. Android percent fat and the A/G ratio were significantly higher in patients with NAFLD than in those without NAFLD [41.68% (0.25) vs. 32.80% (0.27), p < 0.001; 1.14 ± 0.01 vs. 0.94 ± 0.00, p < 0.001, respectively]. Logistic regression analysis showed that android percent fat was positively correlated to NAFLD (OR: 1.15, 95% CI: 1.11-1.18), while gynoid percent fat was negatively correlated to NAFLD (OR: 0.92, 95% CI: 0.90-0.94), and the A/G ratio was significantly associated with the prevalence of NAFLD (OR: 1.59, 95% CI: 1.38-1.82) and fibrotic NASH (OR: 2.01, 95% CI: 1.71-2.38). We also found that females had a notably diminished A/G ratio compared with males (0.91 vs. 1.12, p < 0.001). In addition, the female population proportion was negatively correlated with the A/G ratio, which may partly explain the lower prevalence of NAFLD in females. What is more, the OR value of the A/G ratio in the female subgroup was much higher than that in the male subgroup in all adjusted models. Conclusion: A/G ratio is significantly associated with NAFLD and fibrotic NASH. Women have a lower A/G ratio than men, which may explain the sex difference in NAFLD prevalence. Furthermore, with a higher A/G ratio, the association between females and NAFLD are greatly elevated.

Remnant cholesterol and severity of nonalcoholic fatty liver disease.

BACKGROUND: Serum remnant cholesterol levels are being increasingly acknowledged as a causal risk factor for atherosclerotic disease, regardless of conventional lipid parameters. The positive association between remnant cholesterol and nonalcoholic fatty liver disease (NAFLD) has been revealed in previous studies. However, whether remnant cholesterol is associated with the severity of NAFLD remains unknown. This study aimed to explore the association between serum remnant cholesterol and the risk of NAFLD severity. METHODS: This cross-sectional study included a total of 6,053 participants who attended health checkups. The severity of hepatic steatosis was evaluated by liver ultrasound transient elastography. Univariable and multivariable logistic regression analyses were performed to calculate the odds ratio (OR) and 95% confidence interval (95% CI) for the association between remnant cholesterol and the severity of hepatic steatosis. To explore whether the association between remnant cholesterol and NAFLD severity was independent of conventional lipid parameters, we further investigated this association in individuals with normal values of low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides. RESULTS: In total, 36.9% of individuals had mild steatosis, and 5.9% had moderate-to-severe steatosis. The serum level of remnant cholesterol in nonsteatosis, mild steatosis and moderate-to-severe steatosis gradually increased (0.71 ± 0.33, 0.97 ± 0.52 and 1.07 ± 0.63 mmol/L, respectively). In the multivariable mode, remnant cholesterol was positively associated with mild hepatic steatosis (OR: 1.730, 95% CI: 1.541 - 1.941, P < 0.001) and moderate-to-severe steatosis (OR: 2.342, 95% CI: 1.765 - 3.109, P < 0.001). These associations were not significantly altered in individuals with normal triglycerides, HDL-C and LDL-C (OR: 1.664, 95% CI: 1.448 - 1.911, P < 0.001; OR: 2.269, 95% CI: 1.619 - 3.180, P < 0.001, respectively). CONCLUSIONS: Higher levels of serum remnant cholesterol were associated with more severe hepatic steatosis, regardless of conventional lipid parameters. Individuals with higher remnant cholesterol may need more attention in regular surveillance of NAFLD.