Project description:Psychological stress may have adverse metabolic effects and induce unhealthy behaviors, but the role of stress in the development of non-alcoholic fatty liver disease (NAFLD) is largely unexplored. We investigated the association between perceived stress and the prevalence of NAFLD in a large sample of apparently healthy men and women. We performed a cross-sectional study of 171,321 adults who underwent health screening examination between 2011 and 2013 in one health screening center. Perceived stress was assessed using the short version of the Perceived Stress Inventory (PSI). NAFLD was assessed using ultrasonography in the absence of excessive alcohol use or any other identifiable cause of liver disease. The prevalence of NAFLD was 27.8%. In fully-adjusted multivariable models, the odds ratio (95% confidence intervals) for NAFLD comparing participants in the 5<sup>th</sup> quintile of PSI score (?23) with those in the lowest quintile (<12) was 1.17 (1.11, 1.22), with a moderately increased prevalence of NALFD across quintiles of PSI score. The positive association between PSI score and NAFLD was observed in all subgroups analyzed, although the association was stronger in men compared to women (p interaction <0.001), and in obese compared to non-obese (p interaction 0.005). In this large study of apparently healthy men and women, higher perceived stress was independently associated with an increased prevalence of NAFLD, supporting a possible relationship between perceived stress and NAFLD. Prospective study is needed to elucidate mediating mechanisms to warrant stress management to reduce NAFLD.
Project description:Data on prevalence and profile of nonalcoholic fatty liver disease (NAFLD) among individuals who are lean (normal body mass index) is unclear. Published data from studies comparing lean with obese NAFLD or with healthy subjects on prevalence, comorbidities, liver chemistry and histology, and metabolic/inflammatory markers were analyzed. Data were reported as odds ratio and 95% confidence interval for categorical variables and difference of means for continuous variables. Analysis of 53 studies on 65,029 subjects with NAFLD (38,084 lean) and 249,544 healthy subjects showed a prevalence of lean NAFLD at 11.2% in the general population. Among individuals with NAFLD, the prevalence of lean NAFLD was 25.3%. Lean NAFLD versus healthy subjects had higher odds for abnormalities on metabolic profile, including metabolic syndrome and its components, renal and liver function, and patatin-like phospholipase domain-containing protein 3 (PNPLA3) G allele; and inflammatory profile, including uric acid and C-reactive protein. The abnormalities were less severe among lean versus obese NAFLD on metabolic syndrome with its components, renal and liver chemistry, liver stiffness measurement, PNPLA3 and transmembrane 6 superfamily member 2 polymorphisms, and uric acid levels as markers of inflammation. Lean NAFLD had less severe histologic findings, including hepatocyte ballooning, lobular inflammation, NAFLD activity score, and fibrosis stage. Limited data also showed worse outcomes between obese versus lean NAFLD. Conclusion: Lean NAFLD is a distinct entity with metabolic, biochemical, and inflammatory abnormalities compared to healthy subjects and a more favorable profile, including liver histology of steatohepatitis and fibrosis stage, compared to obese NAFLD. We suggest that prospective multicenter studies examine long-term hepatic and extrahepatic outcomes in individuals with lean NAFLD.
Project description:OBJECTIVES:Some metabolic factors and noninvasive markers, including fatty liver index (FLI), are used to predict nonalcoholic fatty liver disease (NAFLD) in obese patients. Despite the increasing prevalence of NAFLD in lean patients (lean-NAFLD), the risk factors and predictors are not well determined in this population. We investigated factors associated with lean-NAFLD and validated their predictive ability. METHODS:From 9,293 examinees who underwent routine health checkups, we enrolled 4,000, aged ?20 years, with a body mass index <24 kg/m in our lean-NAFLD study population. NAFLD diagnoses were made according to the patients' histories, laboratory values, and sonographic criteria. Clinical variables, serum sugar, lipid, and liver profiles were evaluated using multiple logistic regression analysis. The predictive ability and optimal cutoff values for NAFLD were determined according to the area under the receiver operating characteristic curve. RESULTS:Overall, 18.5% (n = 740) of the lean population had NAFLD. Male sex, body mass index, body fat mass, fasting plasma glucose, uric acid, alanine aminotransferase, triglyceride, and FLI values were associated with NAFLD. FLI had the best discriminative ability to predict lean-NAFLD compared to the other biochemical markers. We further used the Youden index test and found an optimum cut-off value for FLI of 15 with the highest discriminant ability than other values. DISCUSSION:The prevalence of lean-NAFLD was not low. FLI was superior to other predictors including sex, liver function, and other metabolic factors, in the prediction of lean-NAFLD. FLI may be considered an easy to use, noninvasive marker to screen for lean-NAFLD.
Project description:Background and aim:Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases with simple steatosis on one end and hepatocellular carcinoma on the other. Although obesity is a known risk factor for NAFLD, individuals with normal body mass index (BMI) also have hepatic fatty infiltration, now termed "lean-NAFLD". It represents a distinct entity with a strong underlying genetic component. The present study aimed to sequence the complete exonic regions of individuals with lean-NAFLD to identify germline causative variants associated with disrupted hepatic fatty acid metabolism, thereby conferring susceptibility to NAFLD. Methods:Whole blood was collected from patients with lean-NAFLD (n = 6; BMI < 23.0 kg/m2) and matched lean controls (n = 2; discovery set). Liver fat was assessed using acoustic radiation force impulse (ARFI) imaging. Patients with ultrasound-detected NAFLD (n = 191) and controls (n = 105) were part of validation set. DNA was isolated, and whole-exome sequencing (WES) was performed in the discovery cohort (Ion Proton™; Ion AmpliSeq™ Exome RDY Kit). Data were analyzed (Ion Reporter software; Life Technologies), and variants identified. Validation of variants was carried out (Taqman probes; Real time-PCR). Student's t test and Fisher's exact test were used to analyze the statistical significance. Results:Although WES identified ?74,000 variants in individual samples, using various pipelines. variants in genes namely phosphatidylethanolamine N-methyltransferase (PEMT) and oxysterol-binding protein-related protein10 (OSBPL10) that have roles in dietary choline intake and regulation of cholesterol homeostasis, respectively, were identified (discovery set). Furthermore, significant differences were noted in BMI (p = 0.006), waist/hip circumference (p > 0.001), waist/hip ratio (p > 0.001), aspartate aminotransferase (p > 0.001), alanine aminotransferase (p > 0.001), and triglycerides (p = 0.002) between patients and controls. Validation of variants (rs7946-PEMT and rs2290532-OSBPL10) revealed that variant in PEMT but not OSBPL10 gene was associated (p = 0.04) with threefold increased risk of NAFLD in lean individuals. Conclusion:Our results demonstrate the association of rs7946 with lean-NAFLD. WES may be an effective strategy to identify causative variants underlying lean-NAFLD.
Project description:Non-alcoholic fatty liver disease (NAFLD) is commonly diagnosed in obese subjects; however, it is not rare among lean individuals. Given the absence of traditional risk factors, it tends to remain under-recognised. The metabolic profiles of lean NAFLD patients are frequently comparable to those of obese NAFLD patients. Though results from several studies have been mixed, it has been generally revealed that lean subjects with NAFLD have minor insulin resistance compared to that in obese NAFLD. Several genetic variants are associated with NAFLD without insulin resistance. Some data suggest that the prevalence of steatohepatitis and advanced fibrosis do not differ significantly between lean and obese NAFLD; however, the former tend to have less severe disease at presentation. The underlying pathophysiology of lean NAFLD may be quite different. Genetic predispositions, fructose- and cholesterol-rich diet, visceral adiposity and dyslipidaemia have potential roles in the pathogenic underpinnings. Lean NAFLD may pose a risk for metabolic disturbances, cardiovascular morbidity or overall mortality. Secondary causes of hepatic steatosis are also needed to be ruled out in lean subjects with NAFLD. The effectiveness of various treatment modalities, such as exercise and pharmacotherapy, on lean NAFLD is not known. Weight loss is expected to help lean NAFLD patients who have visceral obesity. Further investigation is needed for many aspects of lean NAFLD, including mechanistic pathogenesis, risk assessment, natural history and therapeutic approach.
Project description:Nonalcoholic fatty liver disease (NAFLD) accounts for most cases of chronic liver disease worldwide, with an estimated global prevalence of approximately 25% and ranges from simple steatosis to nonalcoholic steatohepatitis and cirrhosis. NAFLD is strongly connected to metabolic syndrome, and for many years, fatty liver was considered to be an exclusive feature of obese patients. However, recent studies have highlighted the presence of NAFLD in non-obese subjects, with or without increased visceral fat or even in lean subjects without increased waist circumference. "Lean NAFLD" is a relatively new concept and there is significant scientific interest in understanding the differences in pathophysiology, prognosis and management compared with NAFLD in overweight/obese patients. In the present editorial, we discuss the clinical and metabolic profiles and outcomes of lean NAFLD compared with both obese NAFLD and lean healthy individuals from Asian and Western countries. Moreover, we shed light to the challenging topic of management of NAFLD in lean subjects since there are no specific guidelines for this population. Finally, we discuss open questions and issues to be addressed in the future in order to categorize NAFLD patients into lean and non-lean cohorts.
Project description:Nonalcoholic fatty liver disease (NAFLD) is a common form of chronic liver disease, and serum uric acid is observed to be significantly elevated in NAFLD patients. However, whether this elevation is causal, a bystander, or a consequence of NAFLD remains unclear. We performed a population-based prospective study among the employees of Zhenhai Refining & Chemical Company Ltd., Ningbo, China to investigate whether the elevation of serum uric acid has a casual role for NAFLD. A total of 6890 initially NAFLD-free subjects were followed up for 3 years. Overall, 11.80% (813/6890) subjects developed NAFLD over 3 years of follow-up. The cumulative incidence of NAFLD increased with progressively higher baseline serum uric acid levels (the cumulative incidence was 7.2%, 9.5%, 11.5%, 13.8%, and 17.2% in quintile 1, quintile 2, 3, 4 and 5, respectively; P value for trend <0.001). Cox proportional hazards regression analyses showed that serum uric acid levels were independently and positively associated with the risk for incident NAFLD; the age-, gender- and metabolic syndrome adjusted hazard ratio (95% CI) for the subjects in quintile 2, 3, 4 and 5 versus quintile 1 was 1.18 (0.91-1.54), 1.32 (1.03-1.70), 1.39 (1.09-1.78) and 1.50 (1.18-1.92), respectively. Taken together, our prospective observational study showed that elevation of serum uric acid levels independently predicts increase risk for incident NAFLD.
Project description:BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic diseases in the world. Nowadays, the percentage of non-obese or lean patients with NAFLD is increasing. NAFLD in non-obese populations, especially the lean subgroup with a normal waist circumference (WC), might lead to more problems than obese individuals, as these individuals may not visit clinics for NAFLD diagnosis or ignore the diagnosis of NAFLD. If the precise characteristics of these populations, especially the lean subgroup, are identified, the clinicians would be able to provide more appropriate advice and treatment to these populations. AIM:To investigate the prevalence, clinical characteristics, risk factors, and possible indicators for NAFLD in lean Chinese adults with a normal WC. METHODS:People without diabetes mellitus or significant alcohol consumption who underwent routine health examinations were included. Their fatty liver index (FLI), abdominal ultrasonography results, and controlled attenuation parameter were all assessed. Genotyping for single-nucleotide polymorphisms associated with NAFLD was performed in another small group consisting of biopsy-proven NAFLD subjects and healthy controls. RESULTS:A total of 2715 subjects who underwent routine health examinations were included in the study. Among 810 lean participants with a normal WC, 142 (17.5%) fulfilled the diagnostic criteria for NAFLD. Waist-height ratio, hemoglobin, platelets, and triglycerides were significant factors associated with the presence of NAFLD in these participants. The appropriate cut-off value of the FLI score in screening for NAFLD in the lean subjects with a normal WC was 25.15, which had a 77.8% sensitivity and 75.9% specificity. There was no significant difference in the single-nucleotide polymorphisms in the SIRT1, APOC3, PNPLA3, AGTR1, and PPARGC1A genes between lean subjects with and without NAFLD (P < 0.05). CONCLUSION:NAFLD is not uncommon in lean Chinese adults even with a normal WC. Metabolic factors, rather than genetic factors, may play important roles in the development of NAFLD in this population. A lower cut-off value of the FLI score in screening for NAFLD should be used for lean Chinese adults with a normal WC.
Project description:The aim was to test the association between dietary iron intake and the prevalence of nonalcoholic fatty liver disease (NAFLD) in a large sample of middle-aged and elderly Chinese population.The data included in this analysis were collected from a population-based cross-sectional study, that is, the Xiangya Hospital Health Management Center Study. Dietary iron intake was assessed using a validated semiquantitative food frequency questionnaire. The relationship between dietary iron intake and the prevalence of NAFLD was examined using logistic and spline regressions.A cross-sectional study including 5445 subjects was conducted. The prevalence of NAFLD was 36.9%. Compared with the lowest quintile, the energy-adjusted odds ratios (ORs) of NAFLD were 1.33 (95% confidence interval [CI]: 1.07-1.64), 1.80 (95% CI: 1.41-2.29) and 2.11 (95% CI: 1.60-2.80) in the 3rd, 4th, and 5th quintile of iron intake, respectively (P-value for trend <.001). In addition, dietary iron intake was positively associated with the OR of NAFLD in a dose-response relationship manner (test for trend P?<?.001). However, after stratifying the data by gender, such association only remained in the male, but not in the female population. With adjustment of additional potential confounders, the results did not change materially.Subjects with higher dietary iron intake were subject to a higher prevalence of NAFLD in a dose-response relationship manner. However, such association probably only exists in males, but not in females.