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.

Context Elevated serum remnant cholesterol independently predicts risks of cardiovascular diseases. However, the association between remnant cholesterol and metabolic dysfunction-associated fatty liver disease (MAFLD) remains unclear. Objectives This study aimed to explore the association of remnant cholesterol with MAFLD and its long-term mortality. Methods We extracted data from the NHANES Ⅲ, 1988−1994 and the linked mortality data till December 31, 2015. The association between remnant cholesterol and MAFLD was analyzed by multivariate logistic regression. Cox proportional hazards regression was performed to assess whether elevated remnant cholesterol increased all-cause and cause-specific mortalities in MAFLD patients. Results At baseline, 28.6% (1474/5156) of participants had MAFLD. In multivariate logistic regression, the fourth quartile of remnant cholesterol was associated with an increased risk of MAFLD compared with the first quartile (OR: 1.714, 95% CI: 1.586–1.971; P &lt;0.001). In participants with normal levels of triglyceride, LDL- and HDL-cholesterol, the relationship between remnant cholesterol and MAFLD risk remained significant (OR: 1.346, 95% CI: 1.248–1.761; P &lt;0.001). During a median follow-up of 307 months, MAFLD patients with serum remnant cholesterol in the fourth quartile were associated with a higher risk of all-cause mortality (HR: 2.183, 95% CI: 1.825–2.407; P &lt;0.001), as well as a higher risk of cardiovascular mortality (HR: 2.346, 95% CI: 2.046–2.885; P &lt;0.001) and cancer-related mortality (HR: 2.366, 95% CI: 1.864–2.932; P &lt;0.001) compared with MAFLD patients in the first quartile. Conclusions Remnant cholesterol was independently associated with the risk of MAFLD and predicted all-cause, cardiovascular, and cancer-related mortalities in MAFLD patients.

Background: Balancing calorie control to prevent cardiovascular diseases (CVDs) by skipping breakfast while guarding against its potential risks is a challenge. Aims:To explore the association between skipping breakfast and cardiovascular mortality in individuals with metabolic dysfunction-associated fatty liver disease (MAFLD).Methods: A total of 9926 individuals (including 3004 MAFLD participants) aged 20 years or older were enrolled in the Third National Health and Nutrition Examination Survey and followed for up to 27 years. All participants were classified according to the frequency of breakfast consumption (every day, some days, rarely and never).Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular mortality. Results:During the 212 239 person-years of follow-up, we documented a total of 2595 deaths including 603 deaths from CVDs. Of these, 1039 deaths including 253 deaths from CVDs were recorded in MAFLD individuals. MAFLD individuals showed higher cardiovascular mortality than MAFLD-free controls (P < 0.001). Furthermore, skipping breakfast was independently associated with high cardiovascular mortality risk (adjusted HR: 2.850, 95% CI: 1.490-5.452; P = 0.002), and a high cerebrovascular disease mortality risk (adjusted HR: 5.570, 95% CI: 1.814-17.099; P = 0.003) in participants with MAFLD. However, skipping breakfast was not associated with cardiovascular mortality in MAFLD-free individuals (adjusted HR: 1.526, 95% CI: 0.701-3.326; P = 0.280). Conclusions:In this US population-based study, skipping breakfast was associated with a high risk of cardiovascular mortality in MAFLD but not MAFLD-free individuals.| 213 XIE Et al. | INTRODUC TI ONCardiovascular diseases (CVDs), a leading cause of death that claimed 18.6 million lives globally in 2019, 1 pose growing health and economic burdens to all societies. Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly named non-alcoholic fatty liver disease (NAFLD), affects up to a third of the world's adult population and is an independent risk factor for the increased cardiovascular mortality. [2][3][4] Considering that CVDs are the most common cause of death in the MAFLD population, it is urgent to take strategies to reduce cardiovascular mortality in the MAFLD population. Given the absence of FDA-approved pharmacological therapies for MAFLD, dietary interventions remain the cornerstone. 5 Multiple diets, including Dietary Approaches to Stop Hypertension diets, low-carbohydrate diets, and Mediterranean diets, have been evaluated. However, dietary patterns remain largely unexplored. 6 Only caloric restriction was proved effective and consistently recommended in the current guidelines. 7 The American Association for the Study of Liver Diseases (AASLD), the European Association for the Study of the Liver/European Association for the Study of Diabetes/ European Association for the Study of Obesity (EASL-EASD-EASO), the National Institute for Health and Care Excellence (NICE...

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 (χ2) 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.

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.