Independent Dose-Response Associations between Fetuin-A and Lean Nonalcoholic Fatty Liver Disease.
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ABSTRACT:
SUBMITTER: Lu CW
PROVIDER: S-EPMC8468081 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Nonalcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in the world. The risk factor for NAFLD is often considered to be obesity, but it can also occur in people with lean type, which is defined as lean NAFLD. Lean NAFLD is commonly associated with sarcopenia, a progressive loss of muscle quantity and quality. The pathological features of lean NAFLD such as visceral obesity, insulin resistance, and metabolic inflammation are inducers of sarcopenia, whereas loss of muscle mass and function further exacerbates ectopic fat accumulation and lean NAFLD. Therefore, we discussed the association of sarcopenia and lean NAFLD, summarized the underlying pathological mechanisms, and proposed potential strategies to reduce the risks of lean NAFLD and sarcopenia in this review.
| S-EPMC10327437 | biostudies-literature
Project description:Adipocyte hypertrophy and expression of adipokines in subcutaneous adipose tissue (SAT) have been linked to steatosis, nonalcoholic steatohepatitis (NASH) and fibrosis in morbidly obese (BMI ≥ 40 kg/m2) subjects. It is unknown if this is also true for subjects with NAFLD with lesser degrees of obesity (BMI < 35 kg/m2). Thirty-two subjects with biopsy-proven NAFLD and 15 non-diabetic controls matched for BMI underwent fine-needle biopsies of SAT. Adipocyte volume was calculated. RNA-sequencing of SAT was performed in a subset of 20 NAFLD patients. Adipocyte volume and gene expression levels were correlated to the presence of NASH or significant fibrosis. Subjects with NAFLD had larger adipocyte volume compared with controls, (1939 pL, 95% CI 1130-1662 vs. 854 pL, 95% CI 781-926, p < 0.001). There was no association between adipocyte volume and the presence of NASH. Gene expression of adipokines previously described to correlate with NASH in morbid obesity, was not associated with NASH or fibrosis. Our results suggest that persons with NAFLD have larger SAT adipocytes compared with controls and that adipocytes are involved in the pathophysiology of hepatic steatosis in NAFLD. However, adipocyte volume was not associated with NASH or fibrosis in NAFLD subjects with varying degrees of obesity.
| S-EPMC9705525 | biostudies-literature
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.
| S-EPMC7673972 | biostudies-literature
Project description:ImportanceThe diagnostic performance of the fibrosis-4 index (FIB-4) and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) for advanced fibrosis in lean patients with NAFLD is limited.ObjectiveTo evaluate the diagnostic performance of the FIB-4 and NFS in lean individuals with NAFLD.Design, setting, and participantsThis diagnostic study included adults with biopsy-proven NAFLD from 6 referral centers in Asia from 1995 to 2019. Cohorts were matched by age and sex between the lean and nonlean groups. All statistical analyses were executed from October 2022 to March 2023.Main outcomes and measuresThe diagnostic performance of the FIB-4 and NFS at the current cutoff for advanced hepatic fibrosis in lean (body mass index [BMI] below 23 [calculated as weight in kilograms divided by height in meters squared]) and nonlean (BMI above 23) patients were evaluated.ResultsA total of 1501 patients were included in analysis (mean [SD] age, 46.1 [16.4] years); 788 male (52.5%), 115 lean (7.7%), 472 (30.2%) Korean, 821 (48.7%) Japanese, and 341 (21.3%) Taiwanese. Among the age- and sex-matched cohort, the mean (SD) age was 52.3 (15.1) years and 41.2% (47 of 114) were male. The diagnostic performance and areas under the operating characteristic curve of the FIB-4 (lean, 0.807 vs nonlean, 0.743; P = .28) and NFS (lean, 0.790 vs nonlean, 0.755; P = .54) between the 2 groups were comparable in the age- and sex-matched cohort. The sensitivity and specificity of the NFS showed increasing and decreasing tendency according to the BMI quartiles (P for trend < .001), while those of the FIB-4 did not (P for trend = .05 and P = .20, respectively). Additionally, although the areas under the operating characteristic curve of the FIB-4 and NFS were not significantly different in the lean group (0.807 vs 0.790; P = .09), the sensitivity of the current NFS cutoff values was lower in the lean group than in that of FIB-4 (54.4% vs 81.8%; P = .03).Conclusions and relevanceIn this cohort study, the performance of the FIB-4 and NFS in diagnosing advanced fibrosis did not differ significantly between the 2 groups overall. However, in lean NAFLD, while the sensitivity for diagnosing advanced hepatic fibrosis remained reasonable at the current cutoff level, the sensitivity of NFS at the current cutoff was too low to be an adequate screening tool.
| S-EPMC10436134 | biostudies-literature
Project description:Background/aims: Nonalcoholic fatty liver disease (NAFLD) and obesity are independently associated with an increased risk for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality in patients with NAFLD. Many NAFLD patients are lean, but their ASCVD risk compared to obese subjects with NAFLD is unclear.MethodsData from the 2008 to 2011 Korea National Health and Nutrition Examination Surveys database were analyzed (n=4,786). NAFLD was defined as a comprehensive NAFLD score ≥40 or a liver fat score ≥-0.640. ASCVD risk was evaluated using the American College of Cardiology/ American Heart Association guidelines.ResultsThe frequency of subjects without NAFLD, with obese NAFLD, and with lean NAFLD was 62.4% (n=2,987), 26.6% (n=1,274), and 11.0% (n=525), respectively. Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of a high ASCVD risk (mean 15.6±14.0, 51.6%) than those with obese NAFLD and without NAFLD (mean 11.2±11.4, 39.8%; mean 7.9±10.9, 25.5%; all p<0.001). Subjects with lean NAFLD and significant liver fibrosis showed a significantly higher odds ratio for a high risk for ASCVD than those with obese NAFLD with or without significant liver fibrosis (odds ratio, 2.60 vs 1.93; p=0.023).ConclusionsSubjects with lean NAFLD had a significantly higher ASCVD score and prevalence of high risk for ASCVD than those with obese NAFLD. Similarly, lean subjects with significant liver fibrosis had a higher probability of ASCVD than obese subjects in the subpopulation with NAFLD.
| S-EPMC8924809 | biostudies-literature
Project description:Background/aimsThis study aimed to examine the independent and synergistic association of aerobic physical activity and resistance exercise with nonalcoholic fatty liver disease (NAFLD) using a nationwide representative database.MethodsThis was a cross-sectional study using data from the Korea National Health and Nutritional Examination Survey between 2007 and 2010. Multiple logistic regression models were used to examine the independent and synergistic (additive interaction) associations of aerobic physical activity and resistance exercise with NAFLD after adjusting for multiple covariates.ResultsThe prevalence of NAFLD was 26.2% for men and 17.6% for women. In the fully adjusted multiple logistic regression model to examine the independent association of aerobic physical activity or resistance exercise with NAFLD, the odds ratios for NAFLD were significantly decreased in both men (p=0.03) and women (p<0.01) who had highly active aerobic physical activity. Regarding the frequency of resistance exercise, the odds ratio for NAFLD was decreased in men who did resistance exercise ≥5 days per week (p=0.04), but not in women (p=0.19). However, when investigating the synergistic associations of aerobic physical activity and resistance exercise, the odds ratios for NAFLD significantly decreased when the frequency of both exercises increased together in both men (p for interaction <0.01) and women (p for interaction<0.01).ConclusionsCombining aerobic physical activity and resistance exercise had a synergistic preventive association for NAFLD in Korean men and women.
| S-EPMC10352066 | biostudies-literature
Project description:IntroductionAlthough a milder metabolic phenotype of nonalcoholic fatty liver disease (NAFLD) in lean patients (body mass index [BMI] <25 kg/m2) compared to overweight/obese patients with NAFLD is assumed, the relevance of NAFLD among lean subjects remains a matter of debate. We aimed to characterize the metabolic/cardiovascular phenotype of lean patients with NAFLD.MethodsIn total, 3,043 subjects (cohort I) and 1,048 subjects (cohort II) undergoing screening colonoscopy between 2010 and 2020 without chronic liver disease other than NAFLD were assigned to one of the following groups: lean patients without NAFLD, lean NAFLD, overweight NAFLD (BMI 25-30 kg/m2), and obese NAFLD (BMI >30 kg/m2). Diagnosis of NAFLD was established using ultrasound (cohort I) and controlled attenuation parameter (cohort II).ResultsThe prevalence of lean patients with NAFLD was 6.7%/16.1% in the overall cohort I/II and 19.7%/40.0% in lean subjects of cohort I/II. Compared with lean subjects without NAFLD, lean patients with NAFLD had a higher prevalence of dyslipidemia, dysglycemia, and the metabolic syndrome, together with a higher median Framingham risk score in both cohorts (all P < 0.001). On multivariable analyses, NAFLD in lean subjects was associated with higher odds of metabolic syndrome (adjusted odds ratio cohort I: 4.27 [95% confidence interval (CI): 2.80-6.51], P < 0.001; cohort II: 2.97 [95% CI: 1.40-6.33], P < 0.001), and higher Framingham risk score (regression coefficient B cohort I: 1.93 [95% CI: 0.95-2.92], P < 0.003; cohort II: 1.09 [95% CI: 0.81-2.10], P = 0.034), among others. Only 69.8% of lean patients with NALFD in cohort I and 52.1% in cohort II fulfilled the novel criteria for metabolic associated fatty liver disease.DiscussionNAFLD in lean patients is associated with the metabolic syndrome and increased cardiovascular risk. Novel metabolic associated fatty liver disease criteria leave a considerable proportion of patients unclassified.
| S-EPMC8345908 | biostudies-literature
Project description:Methods:A cross-sectional study was performed among 6285 lean Chinese adults (body mass index?<?24?kg/m2) who took their annual health checkups. NAFLD was diagnosed based on hepatic ultrasound examination, with exclusion of other etiologies. Results:Of 6285 lean participants enrolled, 654 NAFLD cases were diagnosed. The overall NAFLD prevalence was 10.41%, and the prevalence was 15.45% and 7.16% in men and women, respectively. UHR was significantly higher in NAFLD patients than in controls (14.25?±?5.33% versus 10.09?±?4.23%, P < 0.001). UHR quintiles were positively associated with NAFLD prevalence, which was 1.91% in the first UHR quintile and increased to 3.58%, 7.81%, 14.17%, and 24.54% in the second, third, fourth, and fifth quintile groups, respectively (P < 0.001 for trend). Multivariate logistic regression analysis showed that UHR was independently associated with an increased risk of NAFLD (odds ratio: 1.105; 95% CI: 1.076-1.134; P < 0.001). Sensitivity analysis showed that UHR remained significantly associated with NAFLD in lean participants with normal range of serum uric acid and HDL-cholesterol levels. Conclusions:UHR was significantly associated with NAFLD and may serve as a novel and reliable marker for NAFLD in lean adults.
| S-EPMC7125489 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of liver disease worldwide and has emerged as a significant public health concern in China. A better understanding of the etiology of NAFLD can inform effective management strategies for this disease. We examined factors associated with NAFLD in two districts of Hangzhou, China, focusing on the relationship of regional body fat distribution, muscle mass, and NAFLD. We used baseline data to carry out a cross-sectional analysis among 3,589 participants from the Wellness Living Laboratory (WELL) China study, a longitudinal population-based study that aims to investigate and promote well-being among the Chinese population. NAFLD was defined using the widely validated fatty liver index (FLI). Multivariate logistic regressions were performed to assess independent associations between NAFLD and metabolic risk factors (e.g., insulin resistance) and dual x-ray absorptiometry (DXA)-derived measures (e.g., android fat ratio [AFR] and skeletal muscle index [SMI]). Of the 3,589 participants, 476 (13.3%) were classified as having FLI-defined NAFLD (FLI ≥60). Among those, 58.0% were men. According to our analysis, AFR (odds ratio [OR], 10.0; 95% confidence interval [CI], 5.8-18.5), insulin resistance (OR, 4.0; 95% CI, 3.0-5.3), high alanine aminotransferase levels (OR, 7.6; 95% CI, 5.8-10.0), smoking (OR, 2.0; 95% CI, 1.4-3.0), and male sex (OR, 2.9; 95% CI, 2.0-4.2) were positively associated with NAFLD risk, while SMI (OR, 0.1; 95% CI, 0.07-0.13) was inversely associated with NAFLD risk. Conclusion: In addition to known metabolic risk factors, DXA-derived AFR and SMI may provide additional insights to the understanding of NAFLD. Interventions that aim to decrease AFR and increase SMI may be important to reduce the burden of NAFLD in this population.
| S-EPMC6671685 | biostudies-literature
Project description:BackgroundPrevious studies have suggested an association between Helicobacter pylori (H pylori) and nonalcoholic fatty liver disease (NAFLD). The aim of the current study was to examine the association in Guatemala, a region with elevated prevalences of both H pylori and NAFLD. Associations between H pylori and other metabolic conditions were also examined, as were associations between H hepaticus and H bilis and the metabolic conditions.Materials & methodsThe analysis included 424 participants from a cross-sectional study in Guatemala. H pylori seropositivity was defined as positivity for ≥ 4 antigens. Seropositivities for H bilis and H hepaticus were defined as positivity for ≥ 2 antigens. NAFLD was estimated using the Fatty Liver Index and the Hepatic Steatosis Index. Other conditions examined were obesity, central obesity, hypercholesterolemia, low HDL, diabetes and metabolic syndrome (MetSyn). Prevalence odds ratios (POR) and 95% confidence intervals (CIs) were estimated.ResultsNo overall associations between H pylori,H hepaticus, or H bilis and NAFLD or related metabolic conditions were found. Seropositivity for H pylori antigens CagA and VacA and H hepaticus antigen HH0713 was each significantly associated with NAFLD, however. In addition, associations were observed between the H pylori antigens HyuA, HP1564, and UreA and specified metabolic conditions.ConclusionsWhile no overall associations between H pylori or Helicobacter species with NAFLD or related conditions were observed, some selected Helicobacter spp. antigens were associated with NAFLD. Further research is warranted to examine whether H. species are associated with any metabolic condition.
| S-EPMC7688101 | biostudies-literature