Risk Of Nonalcoholic Fatty Liver Disease Research Articles

Exercise, weight maintenance, and nonalcoholic fatty liver disease risk: a Chinese cohort study.

Background: Exercise has been reported to be associated with a reduced risk of nonalcoholic fatty liver disease (NAFLD), but there is no consensus on the role of weight changes in this association. This study aims to investigate whether the impact of exercise on NAFLD is mainly dependent on weight changes or is inherent to exercise itself. Methods: The study recruited 1671 Chinese NAFLD-free adults in 2019, and collected their exercise habits as well as 3years of medical examination data including anthropometric measurements, blood biochemistry parameters, and liver ultrasound results. Univariate and multivariate logistic regression models were employed to examine the impact of exercise habits on NAFLD risk, with mediation analysis utilized to estimate the magnitude of the role of weight maintenance in the association between exercise and NAFLD. Results: After adjusting for confounders, moderate to high-intensity exercisers were 1.56 times (95% CIs = 1.09-2.22) more likely to successfully control their body weight, and therefore the weight-controlled group had a lower NAFLD risk of 34.9% (95% CIs = 21.8%-56.0%) compared to the weight-gain group. Mediation analysis reveals that exercise can significantly reduce the risk of NAFLD both through weight maintenance (37.1%) and independent of weight maintenance (62.9%). Conclusion: It might be more crucial to emphasize the adoption of regular moderate to high-intensity exercise for preventing NAFLD in the general population, rather than solely focusing on weight maintenance.

The Arg/Arg genotype of leptin receptor gene Gln223Arg polymorphism may be an independent risk factor for nonalcoholic fatty liver disease.

Given that obesity and insulin resistance play key roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the connection between leptin and these metabolic diseases, the association between NAFLD and a leptin receptor gene (LEPR) polymorphism was examined. In this genetic case-control association study, 144 biopsy-proven NAFLD patients and 144 controls were genotyped for the LEPR gene Gln223Arg (rs1137101) polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method. The distributions of genotypes and alleles of Gln223Arg variant were in accordance with the Hardy-Weinberg equilibrium in the study groups (P > .05). Multivariate logistic regression analysis showed that the LEPR Gln223Arg Arg/Arg genotype was an independent risk factor for NAFLD; the Arg/Arg genotype, compared with the Gln/Gln genotype, was associated with a 2.09-fold increased risk for NAFLD (P = .036, odds ratio = 2.09 [95% CI = 1.31-5.95]). We found that the LEPR Gln223Arg Arg/Arg genotype was independently associated with a more than 2-fold rise in biopsy-proven NAFLD risk. Our findings, however, need to be corroborated by further studies.

Associations of Urinary Nickel with NAFLD and Liver Fibrosis in the USA: A Nationwide Cross‑Sectional Study.

Despite the robust correlation between metabolic disorders and heavy metals, there has been limited research on the associations between nickel levels and non-alcoholic fatty liver disease (NAFLD) as well as liver fibrosis. This study aimed to examine the associations among urinary nickel, NAFLD, and liver fibrosis. The data utilized in this study were obtained from the National Health and Nutrition Examination Survey 2017-2020. A comprehensive screening process was conducted, resulting in the inclusion of a total of 3169 American adults in the analysis. The measurement of urinary nickel was conducted through inductively coupled-plasma mass spectrometry. Vibration-controlled transient elastography was employed to assess the controlled attenuation parameter and liver stiffness measurement as indicators for NAFLD and liver fibrosis, respectively. Multivariable logistic regression models were employed to evaluate the associations among urinary nickel, NAFLD, and liver fibrosis. Restricted cubic splines were employed to explored the nonlinear associations. After adjusting for all covariates, the correlation between the highest quartile of urinary nickel and NAFLD was found to be significant (OR = 1.65; 95% CI, 1.19-2.27). Subgroup analysis revealed that the correlation was significant only in men. A significant association occurred between the second quartile of urinary nickel and liver fibrosis (OR 1.88; 95% CI, 1.22-2.90). Restricted cubic spline showed that the relationship was linear between urinary nickel and NAFLD and non-monotonic, inverse U-shaped between urinary nickel and liver fibrosis. This cross-sectional study indicated that the risk of NAFLD is associated with urinary nickel, and this correlation was only present among males.

Mendelian randomization suggests a causal relationship between gut microbiota and nonalcoholic fatty liver disease in humans.

Targeting the gut microbiota is an emerging strategy to treat nonalcoholic fatty liver disease (NAFLD). Nonetheless, the causal relationship between specific gut microbiota and NAFLD remains unclear. We first obtained genome-wide association study statistics on gut microbiota and NAFLD from publicly available databases. We then performed the Mendelian randomization (MR) analysis to determine the potential causal relationship between the gut microbiota and NAFLD by 5 different methods, and conducted a series of sensitivity analyses to validate the robustness of the MR analysis results. Furthermore, we investigated the direction of causality by bidirectional MR analysis. For 211 gut microbiota, 2 MR methods confirmed that phylum Tenericutes, class Deltaproteobacteria and class Mollicutes were significantly associated with the risk of NAFLD. Heterogeneity (P > .05) and pleiotropy (P > .05) analyses validated the robustness of the MR results. There was no causal effect of NAFLD on these bacterial taxa in the reverse MR analysis. We identified specific gut microbiota with causal effects on NAFLD through gene prediction, which may provide useful guidance for targeting the gut microbiota to intervene and treat NAFLD.

Investigation of the Association between Air Pollution and Non-Alcoholic Fatty Liver Disease in the European Population: A Mendelian Randomization Study.

Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent chronic liver disease worldwide. At the same time, the relationship between air pollution and the likelihood of developing NAFLD has been a subject of debate due to conflicting findings in previous observational research. Our objective was to examine the potential correlation between air pollutant levels and the risk of NAFLD in the European population by employing a two-sample Mendelian randomization (MR) analysis. The UK Biobank Consortium provided the summary statistics for various air pollution indicators (PM2.5, PM2.5 absorbance, PM2.5-10, PM10, NO2, and NOx). Additionally, information on NAFLD was obtained from three studies, including one derivation set and two validation sets. Heterogeneity, pleiotropy, and sensitivity analyses were performed under different MR frameworks, and instrumental variables associated with confounders (such as education, smoking, alcohol, and BMI) were detected by tools. In the derivation set, causal relationships between PM2.5, NO2, and NAFLD were observed in univariable Mendelian randomization (UVMR) (Odds Ratio (OR) = 1.99, 95% confidence interval (95% CI) = [1.22-3.22], p = 0.005; OR = 2.08, 95% CI = [1.27-3.40], p = 0.004, respectively). After adjustment for air pollutants or alcohol intake frequency in multivariable Mendelian randomization (MVMR), the above genetic correlations disappeared. In validation sets, the null associations remained in UVMR. Our findings from MR analysis using genetic data did not provide evidence for a causal association between air pollution and NAFLD in the European population. The associations observed in epidemiological studies could be partly attributed to confounders.

Polyphenol consumption and Nonalcoholic fatty liver disease risk in adults

In this cross-sectional investigation, the primary objective was to explore the correlation between the consumption of polyphenols and the likelihood of non-alcoholic fatty liver disease (NAFLD) in the adult population participating in the Hoveyzeh cohort. Data from the Hoveyzeh cohort study, part of the Persian Cohort Study, involving 10,009 adults aged 35–70, were analyzed. Exclusions were made for missing data, extreme energy intake, and liver cancer patients. Dietary habits were assessed using a food frequency questionnaire, and polyphenol intake was calculated using the Phenol Explorer database. Logistic regression analyses, adjusted for confounders, were performed to assess the relationship between polyphenol subclasses (total polyphenols, total flavonoids, phenolic acid, and lignin) and NAFLD. Among 9894 participants, those in the highest quintile of total polyphenol (OR 0.65, CI 0.5–0.84; P = 0.007), phenolic acid (OR 0.67, CI 0.52–0.86; P < 0.001), and lignin intake (OR 0.69, CI 0.52–0.87; P = 0.001) demonstrated lower odds of NAFLD compared to the lowest quintile, even after adjusting for confounding factors. However, no significant association was found between total flavonoid intake and NAFLD (OR 1.26, CI 0.96–1.67; P = 0.47). Subgroup analysis indicated a significant inverse association between total polyphenols and NAFLD in women (OR 0.64, CI 0.42–0.93; P = 0.001). Higher intake of total polyphenols, phenolic acid, and lignin was associated with reduced odds of NAFLD among adults in the Hoveyzeh cohort. This suggests that dietary patterns rich in these polyphenols may play a role in mitigating the risk of NAFLD. Further interventional and longitudinal studies are needed to validate these findings and explore potential preventive strategies involving polyphenol-rich diets.

Abstract P181: Association Between Non-Alcoholic Fatty Liver Disease Risk SNP Variants and Lipid Metabolism

Introduction: The impact of non-alcoholic fatty liver disease (NAFLD) risk SNP variants on ipid metabolism in the general population has yet to be determined. We aimed to assess this association using a large prospective cohort study. Methods: A total of 1488 Japanese men and women (median age 62 years and median body mass index 24.7 kg/m2) free of cardiovascular disease were studied. Among NAFLD risk SNPs, variants of patatin-like phospholipase domain containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), glucokinase regulator (GCKR), and neurocan (NCAN) were assessed. Plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), LDL-triglycerides (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL3-C, triglycerides (TG), lipoprotein(a), and adiponectin were measured at both baseline and after a five-year follow-up. Univariate and multivariate analyses, Kruskal-Wallis, Wilcoxon’s rank sum, and paired t-tests were performed to examine the associations between NAFLD risk SNPs and lipoproteins. Results: All of the measured lipoproteins increased significantly over the 5 years. The TM6SF2 variant did not affect lipoproteins at baseline. However, after 5 years, the non-major allele group had significantly lower HDL-C and HDL3-C and significantly higher LDL-C, sdLDL-C, and LDL-TG than the major allele group. For the GCKR variant, TG, LDL-C, sdLDL-C, and LDL-TG were significantly higher in the non-major allele group at baseline; LDL-C, sdLDL-C, and LDL-TG were still significantly higher in the non-major allele group at 5 years than the CC group. The PNPLA3 and NCAN variants did not affect lipoproteins in this study. Conclusions: NAFLD risk SNP variants might influence atherogenic lipoprotein metabolism.

Association between alanine aminotransferase to high-density lipoprotein cholesterol ratio and nonalcoholic fatty liver disease: a retrospective cohort study in lean Chinese individuals

There is limited research on the association between the alanine aminotransferase to high-density lipoprotein cholesterol ratio (ALT/HDL-C) ratio and nonalcoholic fatty liver disease (NAFLD). The purpose of the current research was to look into the connection between the ALT/HDL-C ratio and the risk of NAFLD in lean Chinese individuals. Between January 2010 and December 2014, 11,975 non-obese people participated in this prospective cohort research. The relationship between the ALT/HDL-C ratio and the risk of developing NAFLD was assessed using the Cox proportional-hazards regression model, Cox proportional hazards regression with cubic spline functions and smooth curve fitting, sensitivity analysis, and subgroup analyses. The ALT/HDL-C ratio’s potential value as a NAFLD prognostic marker was to be evaluated using the receiver operating characteristic curve analysis. A total of 5419 (45.253%) women comprised the research's participant population, and the research participants’ average age was 43.278 ± 14.941 years. The ALT/HDL-C ratio was 11.607 (7.973–17.422) at the median (interquartile ranges). 2087 (17.428%) patients had NAFLD diagnoses throughout a median follow-up of 24.967 months. The study's findings demonstrated a positive connection between the ALT/AHDL-C ratio and the incident NAFLD (HR = 1.037, 95% CI: 1.031–1.042) when adjusting for relevant factors. The ALT/HDL-C ratio and NAFLD risk had a nonlinear connection, with 12.963 as the ratio's inflection point. Effect sizes (HR) were 1.023 (95% CI: 1.017–1.029) and 1.204 (95% CI: 1.171–1.237), respectively, on the right and left sides of the inflection point. The sensitivity analysis also showed how reliable our findings were. According to subgroup analysis, those with BMI < 24 kg/m2 and DBP < 90 mmHg had a stronger correlation between the ALT/HDL-C ratio and NAFLD risk. The current study shows a positive and non-linear connection between the ALT/HDL-C ratio and NAFLD risk in lean Chinese individuals. When the ALT/HDL-C ratio is less than 12.963, it is significantly linked to NAFLD. Therefore, from a therapy standpoint, it is advised to keep the ALT/HDL-C ratio less than the inflection point.

The association between platelet-related parameters and nonalcoholic fatty liver disease in a metabolically healthy nonobese population

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease characterized by subclinical inflammation and is related to obesity and metabolic syndrome (MS), but it is also frequently observed in nonobese populations. We aimed to evaluate the relationship between the white blood cell count-to-mean platelet volume ratio (WBC/MPV), platelet-to-lymphocyte count ratio (PLR) and lymphocyte-monocyte ratio (LMR) in association with NAFLD, considering the presence of obesity and MS. Additionally, we aimed to investigate whether these parameters exhibited similar correlations in metabolic dysfunction-associated steatotic liver disease (MASLD) as observed in NAFLD. This cross-sectional study included subjects who underwent a comprehensive health evaluation, including blood tests and abdominal ultrasonography. Subgroup analyses were conducted based on obesity and MS. Out of a total 5929 subjects (3271 males, mean age 49.7 ± 10.6 years), 2253 (38.0%) had NAFLD. WBC/MPV was significantly higher, and PLR was significantly lower in subjects with NAFLD. In the analysis restricted to the nonobese (BMI < 25 kg/m2) population without MS, both WBC/MPV and PLR were independently associated with NAFLD: WBC/MPV (adjusted OR 3.366; 95% CI 2.238–5.066) and PLR (adjusted OR 0.997; 95% CI 0.996–0.999). When assessing the risk of NAFLD based on the WBC/MPV and PLR quartiles, the adjusted OR and 95% CI for the lowest quartile compared to the highest were 2.055 (95% CI 1.626–2.602) for WBC/MPV and 0.660 (95% CI 0.523–0.832) for PLR in the nonobese, metabolically healthy group. The levels of WBC/MPV and PLR were independently associated with NAFLD. Furthermore, in MASLD, an association with WBC/MPV, PLR and LMR was identified, similar to the results observed in NAFLD, even after adjusting for confounding variables. In conclusion, the present study demonstrated a significant association between NAFLD and platelet-related parameters, especially in nonobese, metabolically healthy subjects.

Investigating the impact of elevated urinary trace elements on non-alcoholic fatty liver disease using vibration-controlled transient elastography.

Non-alcoholic fatty liver disease (NAFLD) is a global public health concern. However, limited data are available on urinary trace elements and NAFLD caused by various exposure factors. This study aimed to investigate the relationship between the presence of 16 trace elements in urine and NAFLD using data from the National Health and Nutrition Examination Survey (NHANES). By utilizing the NHANES data from 2017 to 2018, 1613 participants who fulfilled the research criteria were identified from the initial pool of 2979 participants with available urine trace element detection data. Among them, 706 individuals had been diagnosed with NAFLD based on a coefficient of attenuation parameter (CAP) value of at least 274 db/m, determined using vibration-controlled transient elastography (VCTE); whereas the remaining 907 participants were classified as non-NAFLD. The data obtained were used to construct univariate and multivariate logistic regression models and restricted cubic spline models (RCS) analyses. The presence of arsenic, iodine, barium, cesium, molybdenum, lead, tin, and tungsten in the urine of individuals with NAFLD showed a positive correlation with the likelihood of developing NAFLD. The risk of NAFLD had a non-linear dose-dependent relationship with urinary iodine, molybdenum, barium, and cesium. NAFLD was also associated with elevated levels of barium and cesium in urine, which were identified as significant risk factors. These findings suggest a positive association between exposure to trace elements in the urine and the risk of NAFLD. Specifically, urinary barium and cesium appeared to have the greatest impact on the risk of NAFLD. These results provide novel insights into the diagnosis and treatment of NAFLD.

Relation between Body Composition Trajectories from Childhood to Adolescence and Nonalcoholic Fatty Liver Disease Risk.

NAFLD has become the leading cause of chronic liver disease in children, as a direct consequence of the high prevalence of childhood obesity. This study aimed to characterize body composition trajectories from childhood to adolescence and their association with the risk of developing nonalcoholic fatty liver disease (NAFLD) during adolescence. The participants were part of the 'Chilean Growth and Obesity Cohort Study', comprising 784 children who were followed prospectively from age 3 years. Annual assessments of nutritional status and body composition were conducted, with ultrasound screening for NAFLD during adolescence revealing a 9.8% prevalence. Higher waist circumference measures were associated with NAFLD from age 3 years (p = 0.03), all skin folds from age 4 years (p < 0.01), and DXA body fat measurements from age 12 years (p = 0.01). The fat-free mass index was higher in females (p = 0.006) but not in males (p = 0.211). The second and third tertiles of the fat mass index (FMI) had odds ratios for NAFLD during adolescence of 2.19 (1.48-3.25, 95% CI) and 6.94 (4.79-10.04, 95% CI), respectively. Elevated waist circumference, skin folds, and total body fat were identified as risk factors for future NAFLD development. A higher FMI during childhood was associated with an increased risk of NAFLD during adolescence.

Gut microbiome features and metabolites in non-alcoholic fatty liver disease among community-dwelling middle-aged and older adults

BackgroundThe specific microbiota and associated metabolites linked to non-alcoholic fatty liver disease (NAFLD) are still controversial. Thus, we aimed to understand how the core gut microbiota and metabolites impact NAFLD.MethodsThe data for the discovery cohort were collected from the Guangzhou Nutrition and Health Study (GNHS) follow-up conducted between 2014 and 2018. We collected 272 metadata points from 1546 individuals. The metadata were input into four interpretable machine learning models to identify important gut microbiota associated with NAFLD. These models were subsequently applied to two validation cohorts [the internal validation cohort (n = 377), and the prospective validation cohort (n = 749)] to assess generalizability. We constructed an individual microbiome risk score (MRS) based on the identified gut microbiota and conducted animal faecal microbiome transplantation experiment using faecal samples from individuals with different levels of MRS to determine the relationship between MRS and NAFLD. Additionally, we conducted targeted metabolomic sequencing of faecal samples to analyse potential metabolites.ResultsAmong the four machine learning models used, the lightGBM algorithm achieved the best performance. A total of 12 taxa-related features of the microbiota were selected by the lightGBM algorithm and further used to calculate the MRS. Increased MRS was positively associated with the presence of NAFLD, with odds ratio (OR) of 1.86 (1.72, 2.02) per 1-unit increase in MRS. An elevated abundance of the faecal microbiota (f__veillonellaceae) was associated with increased NAFLD risk, whereas f__rikenellaceae, f__barnesiellaceae, and s__adolescentis were associated with a decreased presence of NAFLD. Higher levels of specific gut microbiota-derived metabolites of bile acids (taurocholic acid) might be positively associated with both a higher MRS and NAFLD risk. FMT in mice further confirmed a causal association between a higher MRS and the development of NAFLD.ConclusionsWe confirmed that an alteration in the composition of the core gut microbiota might be biologically relevant to NAFLD development. Our work demonstrated the role of the microbiota in the development of NAFLD.

Investigating the causal associations between five anthropometric indicators and nonalcoholic fatty liver disease: Mendelian randomization study

BACKGROUND Although the etiology of nonalcoholic fatty liver disease (NAFLD) has not been thoroughly understood, the emerging roles of anthropometric indicators in assessing and predicting the risk of NAFLD have been highlighted by accumulating evidence. AIM To evaluate the causal relationships between five anthropometric indicators and NAFLD employing Mendelian randomization (MR) design. METHODS The Anthropometric Consortium provided genetic exposure data for five anthropometric indicators, including hip circumference (HC), waist circumference (WC), waist-to-hip ratio (WHR), body mass index (BMI), and body fat percentage (BF). Genetic outcome data for NAFLD were obtained from the United Kingdom Biobank and FinnGen Consortium. Genome-wide significant single nucleotide polymorphisms were chosen as instrumental variables. Univariable MR (UVMR) and multivariable MR (MVMR) designs with analytical approaches, including inverse variance weighted (IVW), MR-Egger, weighted median (WM), and weighted mode methods, were used to assess the causal relationships between anthropometric indicators and NAFLD. RESULTS Causal relationships were revealed by UVMR, indicating that a higher risk of NAFLD was associated with a per-unit increase in WC [IVW: odds ratio (OR) = 2.67, 95%CI: 1.42-5.02, P = 2.25 × 10−3], and BF was causally associated with an increased risk of NAFLD (WM: OR = 2.23, 95%CI: 1.07-4.66, P = 0.033). The presence of causal effects of WC on the decreased risk of NAFLD was supported by MVMR after adjusting for BMI and smoking. However, no causal association between BF and NAFLD was observed. In addition, other causal relationships of HC, WHR (BMI adjusted), and BMI with the risk of NAFLD were not retained after FDR correction. CONCLUSION This study establishes a causal relationship, indicating that an increase in WC is associated with a higher risk of NAFLD. This demonstrates that a suitable decrease in WC is advantageous for preventing NAFLD.

Trimethylamine N-oxide, choline and its metabolites are associated with the risk of non-alcoholic fatty liver disease.

It is inconclusive whether trimethylamine N-oxide (TMAO) and choline and related metabolites, namely trimethylamine (TMA), l-carnitine, betaine and dimethylglycine (DMG), are associated with non-alcoholic fatty liver disease (NAFLD). Our objective was to investigate these potential associations. Additionally, we sought to determine the mediating role of TMAO. In this 1:1 age- and sex-matched case-control study, a total of 150 pairs comprising NAFLD cases and healthy controls were identified. According to the fully adjusted model, after the highest tertile was compared with the lowest tertile, the plasma TMAO concentration (OR = 2·02 (95 % CI 1·04, 3·92); P trend = 0·003), l-carnitine concentration (OR = 1·79 (1·01, 3·17); P trend = 0·020) and DMG concentration (OR = 1·81 (1·00, 3·28); P trend = 0·014) were significantly positively associated with NAFLD incidence. However, a significantly negative association was found for plasma betaine (OR = 0. 50 (0·28, 0·88); P trend = 0·001). The restricted cubic splines model consistently indicated positive dose-response relationships between exposure to TMAO, l-carnitine, and DMG and NAFLD risk, with a negative association being observed for betaine. The corresponding AUC increased significantly from 0·685 (0·626, 0·745) in the traditional risk factor model to 0·769 (0·716, 0·822) when TMAO and its precursors were included (l-carnitine, betaine and choline) (P = 0·032). Mediation analyses revealed that 14·7 and 18·6 % of the excess NAFLD risk associated with l-carnitine and DMG, respectively, was mediated by TMAO (the P values for the mediating effects were 0·021 and 0·036, respectively). These results suggest that a higher concentration of TMAO is associated with increased NAFLD risk among Chinese adults and provide evidence of the possible mediating role of TMAO.

Independent associations of serum calcium with or without albumin adjustment and serum phosphorus with nonalcoholic fatty liver disease: results from NHANES 1999-2018.

The associations of serum calcium and phosphorus with nonalcoholic fatty liver disease (NAFLD) remain unclear. In addition, there may be an effect of albumin correction on the association between serum calcium and NAFLD. We aimed to explore these relationships in the National Health and Nutrition Examination Survey (NHANES). Eligible adult individuals from NHANES 1999-2018 were recruited for the study. We explored the associations of serum calcium, albumin-adjusted serum calcium, and serum phosphorus with NAFLD in multivariable-adjusted regression models. In addition, restricted cubic spline (RCS), stratified analysis, and multiple sensitivity analyses were used for further elaboration. The study sample consisted of 20,900 participants, with an observed NAFLD prevalence of 44.65%. Fully adjusted models indicated that serum calcium was inversely associated with NAFLD (odds ratio [OR] and 95% confidence interval [CI] = 0.70 (0.62, 0.78), p<0.0001), whereas albumin-adjusted serum calcium was positively associated with NAFLD (OR and 95% CI=1.59 (1.41, 1.79), p<0.0001). RCS modeling indicated that serum calcium without and with albumin adjustment was linearly(p nonlinear = 0.083) and nonlinearly (p nonlinear < 0.0001) associated with NAFLD, respectively, whereas serum phosphorus showed a U-shaped relationship with NAFLD(p nonlinear < 0.0001). Gender is a significant influence in all associations, and other variables may also have an effect. Sensitivity analyses indicated that these associations were independent of additional significant confounders. Serum calcium and phosphorus were significantly associated with the development of NAFLD. These findings suggest the potential clinical significance of serum calcium/phosphorus and albumin levels in individuals at high risk for NAFLD. Our study supports the potential role of serum calcium/phosphorus homeostasis in the pathophysiology of NAFLD and could serve as NAFLD-related biomarkers.

Effects of dietary supplementation with green lentil (Lens culinaris) hulls on NAFLD: Focus on intestinal and hepatic metabolism

Lentil hulls, a by-product of lentil processing, are rich in polyphenols and dietary fiber. In this study, a mouse model of nonalcoholic fatty liver disease (NAFLD) induced by dextran sulfate sodium (DSS) and high-fat diet (HFD) was used to investigate the intervention effect of green lentil hulls (GLH) from the perspective of intestinal and hepatic metabolism. Results suggest that DSS-induced gut inflammation and barrier disruption aggravate NAFLD; GLH intervention lowered body weight, liver weight gain and lipid deposition. It also inhibited liver fat accumulation and inflammation as well as intestinal inflammation. In addition, it enhanced liver antioxidant capacity, glucose tolerance and intestinal barrier integrity. Analysis of intestinal flora indicated that GLH advanced the abundance of Akkermansia-muciniphila and Verrucomicrobiaceae, which led to increased content of short-chain fatty acids (SCFAs) and inhibited the Firmicutes and Proteobacteria. Moreover, GLH intervention regulated taurine and hypotaurine metabolism, as well as the biosynthesis of unsaturated and saturated fatty acids in the liver. The relief by GLH on NAFLD may be a comprehensive effect of its rich dietary fiber and polyphenols on intestinal and hepatic metabolism via the gut-liver axis. This research also suggests that the low-value lentil hulls can serve as a valuable food supplement for enhanced gut health and reduced risk of NAFLD.

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

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. 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. 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. 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). 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.

Association between weight change, waist circumference change, and the risk of nonalcoholic fatty liver disease in individuals with metabolically healthy overweight or obesity and metabolically unhealthy overweight or obesity

BackgroundThis study aimed to explore and compare the effect of weight change, and waist circumference (WC) change, on the risk of nonalcoholic fatty liver disease (NAFLD) in individuals with metabolically healthy overweight or obesity (MHOW/O) and metabolically unhealthy overweight or obesity (MUOW/O) in a health check-up cohort in China. Methods5625 adults with overweight or obesity, and free from NAFLD at baseline were included. Metabolically healthy was defined as not having any components of metabolic syndrome. Weight/WC changes were calculated as the relative difference between the first and second visits of check-up. NAFLD was assessed based on abdominal ultrasound. ResultsDuring a median follow-up of 2.1 (IQR: 1.1–4.3) years, 1849 participants developed NAFLD. In MHOW/O participants, the multivariable adjusted HRs (95 % CIs) for NAFLD in weight change ≤ −5.0 %, and − 4.9–− 1.0 % were 0.36 (0.23–0.59), 0.59 (0.43–0.80), respectively, compared to the weight stable group (−0.9% to 0.9 %). The corresponding HRs (95 % CIs) for the association between WC change (≤ 6.0 %, - 5.9 to −3.0 %) and NAFLD in MHOW/O participants were 0.41 (0.27–0.62), and 0.74 (0.54–1.01), respectively, compared to the WC stable group (−2.9–2.9 %). Similar patterns were observed in MUOW/O participants. A more marked gradient of cumulative incidence of NAFLD across weight/WC change categories was observed in MHOW/O than in MUOW/O individuals. ConclusionsA more evident association between weight/WC loss and risk of NAFLD was observed in MHOW/O than in MUOW/O individuals. Our findings indicate the practical significance of encouraging all individuals with overweight and obesity to achieve a clinically relevant level of weight/WC loss to prevent NAFLD, even among metabolic healthy groups.

The association of Neuromedin U levels and non-alcoholic fatty liver disease: A comparative analysis

This comprehensive study delves into the potential link between Neuromedin U (NmU) serum levels and the development of non-alcoholic fatty liver disease (NAFLD), a condition of increasing global prevalence and significant public health concern. The research provides a nuanced understanding of the disease's etiology by examining a cohort of 112 participants, including individuals with and without NAFLD. The study meticulously considers a spectrum of variables such as demographic factors, body composition metrics, and blood parameters. Advanced diagnostic tools like Fibroscan® are employed to ascertain NAFLD presence, ensuring accurate and reliable results.The investigation reveals a noteworthy correlation between NAFLD and several risk factors, notably obesity, increased waist and neck circumferences, hypertriglyceridemia, and insulin resistance. These findings underscore the multifactorial nature of NAFLD and its intricate connection with metabolic syndromes. Intriguingly, the study observes lower NmU levels in individuals diagnosed with NAFLD. However, the role of NmU as an independent risk factor for NAFLD remains inconclusive, warranting further investigation. Although triglyceride level was observed to be an independent risk factor for NAFLD, this relationship was not associated with NmU.This research contributes significantly to the existing knowledge on NAFLD, highlighting the disease's complexity and the interplay of various risk factors. It also opens up new avenues for future research, particularly in exploring the role of NmU within the metabolic pathways associated with NAFLD. The insights gained from this study could guide the development of novel diagnostic and therapeutic strategies for NAFLD, addressing a crucial need in contemporary healthcare.In conclusion, the findings of this study not only enhance the understanding of NAFLD's pathophysiology but also emphasize the importance of comprehensive risk factor analysis in the management and prevention of this growing health concern.

Nomogram for predicting the risk of nonalcoholic fatty liver disease in older adults in Qingdao, China: A cross-sectional study.

To explore the risk factors for non-alcoholic fatty liver disease (NAFLD) and to establish a non-invasive tool for the screening of NAFLD in an older adult population. A total of 131,161 participants were included in this cross-sectional study. Participants were randomly divided into training and validation sets (7:3). The least absolute shrinkage and selection operator method was used to screen risk factors. Multivariate logistic regression was employed to develop a nomogram, which was made available online. Receiver operating characteristic curve analysis, calibration plots, and decision curve analysis were used to validate the discrimination, calibration, and clinical practicability of the nomogram. Sex and age subgroup analyses were conducted to further validate the reliability of the model. Nine variables were identified for inclusion in the nomogram (age, sex, waist circumference, body mass index, exercise frequency, systolic blood pressure, fasting plasma glucose, alanine aminotransferase, and low-density lipoprotein cholesterol). The area under the receiver operating characteristic curve values were 0.793 and 0.790 for the training set and the validation set, respectively. The calibration plots and decision curve analyses showed good calibration and clinical utility. Subgroup analyses demonstrated consistent discriminatory ability in different sex and age subgroups. This study established and validated a new nomogram model for evaluating the risk of NAFLD among older adults. The nomogram had good discriminatory performance and is a non-invasive and convenient tool for the screening of NAFLD in older adults.