Non-alcoholic Fatty Liver Disease Status Research Articles

Bone mass, microarchitecture and turnover among young Indian women with non-alcoholic fatty liver disease.

To evaluate comprehensive bone health among young Indian women, including bone mass, microarchitecture, and turnover, in relation to their non-alcoholic fatty liver disease (NAFLD) status. This cross-sectional study (May 2018-November 2019) recruited women with a history of gestational diabetes mellitus (GDM) and normoglycemia in their index pregnancy, who were at least 6 months postpartum. All participants underwent abdominal ultrasonography for determination of NAFLD status (grades 2 and 3: severe NAFLD) and transient elastography (FibroScan) for hepatic fibrosis (LSM >6 kPa). Bone mass was assessed by DXA, bone microarchitecture with trabecular bone score {TBS} (low TBS ≤ 1.310) and bone turnover with markers of bone formation (osteocalcin and P1NP), and resorption (CTX). Bone mineral density (BMD) at femoral neck (p = 0.026) and total hip (p = 0.007) was significantly higher among women with NAFLD (n = 170) compared to those without (n = 124). There was no significant difference in bone turnover markers between the two groups. The presence of NAFLD [adjusted OR: 1.82 (1.07, 3.11)] was associated with low TBS, with a greater strength of association among women with severe NAFLD [adjusted OR: 2.97 (1.12, 7.88)]. However, these associations were attenuated and no longer significant after additionally adjusting for BMI. Women with NAFLD and hepatic fibrosis manifested significantly higher BMD at lumbar spine, femoral neck, and total hip (p < 0.001 for all) and significantly lower bone turnover markers (osteocalcin, p = 0.009 and CTX, p = 0.029), however, the association with low TBS was not observed. Among young Indian women, NAFLD is associated with increased bone mass and impaired bone microarchitecture, and hepatic fibrosis with increased bone mass and reduced bone turnover.

Prevalence of Sarcopenia and Its Defining Components in Non-alcoholic Fatty Liver Disease Varies According to the Method of Assessment and Adjustment: Findings from the UK Biobank

Sarcopenia may increase non-alcoholic fatty liver disease (NAFLD) risk, but prevalence likely varies with different diagnostic criteria. This study examined the prevalence of sarcopenia and its defining components in adults with and without NAFLD and whether it varied by the method of muscle mass assessment [bioelectrical impedance (BIA) versus dual-energy X-ray absorptiometry (DXA)] and adjustment (height2 versus BMI). Adults (n = 7266) in the UK Biobank study (45–79 years) with and without NAFLD diagnosed by MRI, were included. Sarcopenia was defined by the 2018 European Working Group on Sarcopenia in Older People definition, with low appendicular skeletal muscle mass (ASM) assessed by BIA and DXA and adjusted for height2 or BMI. Overall, 21% of participants had NAFLD and the sex-specific prevalence of low muscle strength (3.6–7.2%) and sarcopenia (0.1–1.4%) did not differ by NAFLD status. However, NAFLD was associated with 74% (males) and 370% (females) higher prevalence of low ASM when adjusted for BMI but an 82% (males) to 89% (females) lower prevalence when adjusted for height2 (all P < 0.05). The prevalence of impaired physical function was 40% (males, P = 0.08) to 123% (females, P < 0.001) higher in NAFLD. In middle-aged and older adults, NAFLD was not associated with a higher prevalence of low muscle strength or sarcopenia but was associated with an increased risk of impaired physical function and low muscle mass when adjusted for BMI. These findings support the use of adiposity-based adjustments when assessing low muscle mass and the assessment of physical function in NAFLD.

Integrative metabolomics highlights gut microbiota metabolites as novel NAFLD-related candidate biomarkers in children.

Altered gut microbiota and metabolites are a major cause of non-alcoholic fatty liver disease (NAFLD) in children. This study demonstrated a complete gut metabolic map of children with NAFLD, containing 318 increased and 123 decreased metabolites by untargeted metabolomic. Multiple validation approaches (machine learning and targeted metabolomic) selected five novel gut metabolites for targeted metabolomics, which can distinguish NAFLD status and severity. The gut microbiota (Butyricicoccus and Alistipes) and metabolites (creatinine and dodecanoic acid) were novel biomarkers associated with impaired liver function and inflammation and validated by experiments of hepatocyte cell lines. The data provide a better understanding of the importance of gut microbiota and metabolite alterations in NAFLD, which implies that the altered gut microbiota and metabolites may represent a potential target to prevent NAFLD development.

Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study

ObjectiveTo investigate the risk of non-alcoholic fatty liver disease (NAFLD) for cardiovascular disease and all cause death in patients with type 2 diabetes mellitus (T2DM).DesignNationwide population based study.SettingLongitudinal cohort study...

Beverage consumption in patients with metabolic syndrome and its association with non-alcoholic fatty liver disease: a cross-sectional study.

Previous research has examined the association between coffee and tea consumption and non-alcoholic fatty liver disease (NAFLD). Preclinical studies have indicated the potential hepatoprotective properties of cocoa/chocolate. However, clinical research on the consumption of cocoa/chocolate and soft drinks and their relation to NAFLD, particularly among individuals with metabolic syndrome, is limited. This study primarily aimed to assess the association between beverage consumption and NAFLD in these patients. This cross-sectional study enrolled adult patients with metabolic syndrome visited the Medicine Outpatient Department at Siriraj Hospital, Thailand, from November 2011 to January 2013. The exclusion criteria were secondary causes of hepatic steatosis, such as excessive alcohol use, viral hepatitis, or drug-induced hepatitis. Participants completed a 23-item self-administered questionnaire covering their beverage consumption habits, including type, frequency, volume, duration, and additives in drinks, namely, coffee, tea, cocoa/chocolate, and soft drinks. To ensure accurate responses, these questionnaires were supplemented by face-to-face interviews. Ultrasonography was employed early in the methodology to diagnose NAFLD. Univariable analyses were used to compare the beverage consumption behaviors of participants with and without NAFLD. Multivariable logistic regression was used to adjust for potential confounders, including total beverage energy intake, age, anthropometric data, laboratory results, and comorbidities. This study included 505 patients with metabolic syndrome. Of these, 341 (67.5%, 95%CI: 63.2-71.6%) were diagnosed with NAFLD. The consumption rates of coffee, cocoa/chocolate, and soft drinks were similar between the two groups. However, tea consumption was significantly more common in patients with NAFLD (68.3% vs. 51.8%, p < 0.001). The groups had no significant differences in caffeine intake or total energy intake from beverages. Notably, daily intake of three or more cups of coffee was correlated with a reduced prevalence of NAFLD, with an adjusted odds ratio of 0.35 (95%CI: 0.14-0.89). This study revealed that patients with metabolic syndrome, irrespective of NAFLD status, exhibited similar patterns of beverage consumption. While no definitive associations were identified between the intake of coffee, tea, cocoa/chocolate, or soft drinks and NAFLD, a notable exception was observed. A higher consumption of coffee (≥3 cups daily) was associated with a lower prevalence of NAFLD.

The association between dietary inflammatory index (DII) scores and c-reactive protein (CRP) and nonalcoholic fatty liver disease (NAFLD) in a general population cohort

Although there is extensive literature showing the ability of the dietary inflammation index (DII®) to predict concentrations of plasma inflammatory markers, few studies are testing the association between DII scores and nonalcoholic fatty liver disease (NAFLD). Considering the high prevalence of NAFLD and its complications, we conducted a validation study of DII scores and examined its association with NAFLD in the general adult population of Iran. This cross-sectional study was conducted on 3110 adult participants in the Amol Cohort Study (AmolCS) who underwent abdominal ultrasonography to diagnose NAFLD. DII and energy-adjusted DII (E-DII™) scores were computed using data from a valid semi-quantitative 168-item food frequency questionnaire (FFQ). Multivariable logistic regression adjusting for socio-demographic, lifestyle, and health-related factors was used to assess association. The EDII was associated with CRP inflammatory biomarker. Participants in the highest, i.e., most pro-inflammatory tertile had the highest odds of NAFLD by ultrasound in all models [fully adjusted model: OR (95% CI) tertile3vs.1:1.54 (1.05-2.05); Ptrend=0.04, and 1.63 (1.19-2.21); Ptrend=0.03 in women and men, respectively]. The highest tertile had the highest OR for NAFLD by fatty liver index (FLI) only in men [fully adjusted model OR (95% CI) tertile3vs.1: 1.77 (1.15-2.71); Ptrend=0.01]. Similar results were also obtained for NAFLD by hepatic steatosis index (HSI) in women [fully adjusted model: OR (95% CI) tertile3vs.1: 1.70 (1.12-2.58); Ptrend=0.03]. The results of the fully adjusted multivariable model of liver markers and NAFLD status, stratified by gender and abdominal obesity, revealed that the highest tertiles had the highest OR for NAFLD by ultrasound and NAFLD by FLI only in men without abdominal obesity [fully adjusted model: OR (95% CI) tertile3vs.1: 1.83 (1.17-2.84); Ptrend=0.03, and, respectively]. NAFLD by FLI tended to increase strongly with tertile E-DII scores in men without abdominal obesity in crude and three adjusted models [full-adjusted model: OR (95% CI) tertile3vs.1: 3.64 (1.56-8.46); Ptrend=0.005]. By contrast, women with abdominal obesity in the highest tertile had the highest OR for NAFLD by ultrasound in all models [full-adjusted model: OR (95% CI) tertile3vs.1: 1.67 (1.07-2.62); Ptrend=0.02]. Our results suggest that diet plays a role in regulating inflammation. Additionally, we observed an inflammatory diet predicts the risk of NAFLD in Iranian adults. However, longitudinal studies are required in order to further substantiate the utility of the DII in the development of more effective dietary interventions among populations at risk of chronic disease.

Impact of nonalcoholic fatty liver disease on the risk of gallbladder polyps in lean and non-obese individuals: A cohort study

BackgroundThe association between non-obese or lean nonalcoholic fatty liver disease (NAFLD) and gallbladder polyps (GBPs) has not yet been evaluated. We aimed to determine whether NAFLD is an independent risk factor for the development of GBPs, even in non-obese and lean individuals. MethodsWe analyzed a cohort of 331 208 asymptomatic adults who underwent abdominal ultrasonography (US). The risk of GBP development was evaluated according to the obesity and NAFLD status. ResultsThe overall prevalence of NAFLD and GBPs ≥ 5 mm was 28.5% and 2.9%, respectively. The prevalence of NAFLD among 160 276 lean, 77 676 overweight and 93 256 obese participants was 8.2%, 31.2%, and 61.1%, respectively. Individuals with NAFLD had a significantly higher incidence of GBPs with a size of ≥ 5 mm [adjusted odds ratio (OR) = 1.18; 95% confidence interval (CI): 1.11–1.25]. A higher body mass index and its categories were also significantly associated with an increased risk of GBPs ≥ 5 mm. Moreover, risk of GBPs ≥ 5 mm was significantly increased even in NAFLD individuals who are not obese (lean: adjusted OR = 1.36, 95% CI: 1.19-1.54; overweight: adjusted OR = 1.14, 95% CI: 1.03–1.26, respectively). ConclusionsNon-obese/lean NAFLD is an independent risk factor for GBP development, suggesting that NAFLD may play an important role in the pathogenesis of GBPs regardless of the obesity status. Therefore, a more thorough evaluation for GBPs may be necessary when hepatic steatosis is detected on abdominal US, even in non-obese or lean individuals.

Outcomes of SGLT-2i and GLP-1RA Therapy Among Patients With Type 2 Diabetes and Varying NAFLD Status

Nonalcoholic fatty liver disease (NAFLD) is a cardiovascular risk factor, but whether sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) are associated with reduced cardiovascular risk in patients with type 2 diabetes (T2D) and concomitant NAFLD remains uncertain. To investigate the outcomes of SGLT-2i and GLP-1RA therapy among patients with T2D varied by the presence or absence of NAFLD. This retrospective, population-based, nationwide cohort study used an active-comparator new-user design. Two distinct new-user active-comparator cohorts of patients aged 40 years and older who initiated SGLT-2i or GLP-1RA were propensity score matched to patients who initiated dipeptidyl peptidase-4 inhibitors (DPP-4i). The study was conducted in South Korea from January 2013 to December 2020, and data analysis was conducted from October 2022 to March 2023. The main outcomes were (1) major adverse cardiovascular events (MACE), a composite end point of hospitalization for myocardial infarction, hospitalization for stroke, and cardiovascular death, and (2) hospitalization for heart failure (HHF). Cox proportional hazards models were used to estimate hazard ratios (HRs). The Wald test was applied to assess heterogeneity by NAFLD. After 1:1 propensity score matching, 140 438 patients were retrieved in the first cohort (SGLT-2i vs DPP-4i; mean [SD] age, 57.5 [10.3] years; 79 633 [56.7%] male) and 34 886 patients were identified in the second cohort (GLP-1RA vs DPP-4i; mean [SD] age, 59.5 [10.5] years; 17 894 [51.3%] male). Compared with DPP-4i, SGLT-2i therapy was associated with a lower risk of MACE (HR, 0.78 [95% CI, 0.71-0.85]) and HHF (HR, 0.62 [95% CI, 0.48-0.81]). GLP-1RA therapy was associated with a decreased risk of MACE (HR, 0.49 [95% CI, 0.39-0.62]) but had statistically nonsignificant findings regarding HHF (HR, 0.64 [95% CI, 0.39-1.07]). Stratified analysis by NAFLD status yielded consistent results for SGLT-2i (MACE with NAFLD: HR, 0.73 [95% CI, 0.62-0.86]; without NAFLD: HR, 0.81 [95% CI, 0.72-0.91]; HHF with NAFLD: HR, 0.76 [95% CI, 0.49-1.17]; without NAFLD: HR, 0.56 [95% CI, 0.40-0.78]) and for GLP-1RA (MACE with NAFLD: HR, 0.49 [95% CI, 0.32-0.77]; without NAFLD: HR, 0.49 [95% CI, 0.37-0.65]; HHF with NAFLD: HR, 0.82 [95% CI, 0.38-1.76]; without NAFLD: HR, 0.54 [95% CI, 0.27-1.06]). In this population-based cohort study, SGLT-2i therapy was associated with a decreased risk of MACE and HHF, while GLP-1RA therapy was associated with a decreased risk of MACE among patients with T2D, irrespective of baseline NAFLD status.

Associations of Unhealthy Lifestyle and Nonalcoholic Fatty Liver Disease With Cardiovascular Healthy Outcomes.

The role of nonalcoholic fatty liver disease (NAFLD) as a mediator in the association between various unhealthy lifestyles and major adverse cardiovascular events and all-cause death remains unclear. This study used data from the UK Biobank, with follow-up until the end of 2021. It involved the calculation of unweighted and weighted lifestyle scores using the Cox model to classify participants on the basis of these scores. Additionally, the research assessed the mediation effect proportion of NAFLD using the difference method and examined the interaction and joint effects of lifestyle and NAFLD on health outcomes. Among the 134 616 enrolled participants, 4024 had records of major adverse cardiovascular events, while among the 130 144 participants included in the analysis of all-cause death, 6697 deaths occurred. The proportions of the association between overall lifestyle and major adverse cardiovascular events mediated by NAFLD were 19.4% and 21.7% (95% CI, 16.2-22.6 and 17.8-25.7) for scores 1 and 2, respectively, and those for all-cause death were 14.1% and 10.1% (95% CI, 11.3-17.1 and 7.9-12.2). After fully adjusting for traditional cardiovascular risk factors, the mediating effects declined across both outcomes. The associations between overall lifestyle and outcomes were stronger among those of the non-NAFLD group, and significant interactions were observed between overall lifestyle and NAFLD status. The joint analysis revealed that patients with NAFLD with unhealthy lifestyle had the highest risk of major adverse cardiovascular events and all-cause death. Improving lifestyle and addressing metabolic risk factors are essential for cardiovascular risk management in patients with NAFLD.

Prognostic value of coronary computed tomography angiography parameters, non-alcoholic fatty liver and metabolic syndrome status in symptomatic patients suspected of coronary artery disease

Abstract Background Metabolic syndrome (MetS) is a well-established risk factor for major adverse cardiovascular events (MACE). Previous studies have shown the relationship between MetS, computed tomography derived epicardial fat volume (EFV), non-alcoholic fatty liver disease (NAFLD) status and coronary artery calcium score (CACS) in asymptomatic patients. Objective To assess the prognostic value of coronary computed tomography angiography (CCTA) derived EFV, NAFLD status, CACS and the number of plaques (NoP) in symptomatic patients with and without MetS and to design a new risk score for predicting MACE. Methods We conducted a single-centre, cross-sectional study on 2038 patients with intermediate risk of CAD, which underwent CCTA between March 2019 and May 2022. Data regarding MetS status and other comorbidities were assessed at the moment of the inclusion in the study. CCTA assessment included: CACS, NoP, EFV and NAFLD status. The endpoint was the occurrence of MACE (late revascularization, myocardial infarction, sudden cardiac death). Cox regression was used to assess the relationship between MetS and CCTA derived variables on the occurrence of MACE. Receiver operating characteristic curve analysis was used to determine the prediction value of CCTA derived parameters and of the new risk score. Net reclassification improvement was used to compare the risk score with CACS ability to predict MACE. Results Patients were prospectively followed up during a mean time of 26.9 (standard deviation: 9.5) months. 361 (17.7%) patients developed a MACE (myocardial infarction, n=67; late revascularization, n=282; sudden cardiac death, n=12). More events were seen in MetS+ patients (n=244) versus MetS- patients (n=117) (p&amp;lt;0.001). MetS, age, male gender, CACS, NoP, EFV and NAFLD were all associated with the occurrence of MACE: unadjusted hazard ratios (HR) of: 1.56, 1.25, 1.87, 1.0013, 1.16, 1.053 and 1.67 (p&amp;lt;0.001 for all). However, in the multivariate analysis only the CCTA derived variables showed a significant association with MACE: CCS HR=1.001, NoP HR=1.097, EFV HR=1.035, NAFLD HR=1.843 (p&amp;lt;0.001 for all). Our risk score for predicting MACE included CACS, NoP, EFV and NAFLD. It had an area under the curve (AUC) of 0.948, a sensitivity of 89.7%, a specificity of 92.9% and a negative predicting value of 97.7%. When compared to CCS alone, the risk score correctly reclassified 24 (6.6%) events and 101 (6.2%) non-events, with a net reclassification index of 0.128 (p&amp;lt;0.001). Conclusion MetS is associated with an increased risk for MACE, but not after adjustment for CCS, NoP, EFV, and NAFLD. Adding NoP, EFV and NAFLD to CCS in a risk score further improves the accuracy in predicting MACE, when compared to CCS alone.

Leukocyte cell-derived chemotaxin 2 correlates with pediatric non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD), newly renamed metabolic dysfunction-associated liver disease (MASLD), is a leading cause of liver disease in children and adults. There is a paucity of data surrounding potential biomarkers and therapeutic targets, especially in pediatric NAFLD. Leukocyte cell-derived chemotaxin 2 (LECT2) is a chemokine associated with both liver disease and skeletal muscle insulin resistance. Our aim was to determine associations between LECT2 and common clinical findings of NAFLD in pediatric patients. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum LECT2 concentrations in children (aged 2-17 years) with and without NAFLD. LECT2 concentrations were then correlated to clinical parameters in NAFLD. Mean LECT2 was significantly elevated in children with NAFLD versus healthy controls (n = 63 vs. 42, 5.83 ± 1.98 vs. 4.02 ± 2.02 ng/mL, p < 0.005). Additionally, LECT2 had strong correlations with body mass index (BMI) (Pearson r = 0.301, p = 0.002). A LECT2 concentration of 3.76 mg/mL predicts NAFLD with a sensitivity of 90.5% and specificity of 54.8%. Principal component analysis and logistic regression models further confirmed associations between LECT2 and NAFLD status. This study demonstrates increased serum LECT2 concentrations in pediatric NAFLD, which correlates with BMI and shows strong predictive value within these patients. Our data indicate that LECT2 is a potential diagnostic biomarker of disease and should be further investigated in pediatric as well as adult NAFLD.

Association of energy-adjusted dietary inflammatory index and frailty in older adults with nonalcoholic fatty liver disease

BackgroundEnergy-adjusted dietary inflammatory index (E-DII) can represent daily inflammatory dietary components and chronic inflammatory response is an important pathogenesis of aging, nonalcoholic fatty liver disease (NAFLD) and frailty. Therefore, the purpose of this study is to explore the association of E-DII and frailty in older adults with NAFLD. MethodsThis cross-sectional study utilized data from the National Health and Nutrition Examination Survey (2005–2016) to investigate the association between E-DII and frailty. The NAFLD status was determined using the US Fatty Liver Index (FLI) value ≥30. The relationship between E-DII and frailty was examined through multivariate weighted logistic regression analysis and smooth curve fitting. Subgroup analyses were conducted, considering various demographic and clinical variables. ResultsOur final analysis included 1586 individuals, with an average age of 69.42 years, and 53.15 % of them were males. The overall prevalence of frailty in the study population was 39.42 %. Smooth curve fitting analysis demonstrated a nearly linear relationship between E-DII and H. pylori. Utilizing multivariate weighted logistic regression analysis, we found that the odds ratio (OR) of E-DII for frailty was 1.08 (95%CI, 1.03–1.15). Subgroup analysis further confirmed that E-DII independently increased the risk of frailty. ConclusionHigher E-DII levels were found to be associated with an increased risk of frailty in older adults with NAFLD. However, further studies are required to fully elucidate the precise mechanisms underlying the relationship between E-DII and frailty.

Total Bilirubin Levels in Nonalcoholic Fatty Liver Disease and All- cause and Cause-specific Mortality in US Adults.

Nonalcoholic Fatty Liver Disease (NAFLD) is a chronic progressive illness with a spectrum of disease severity from steatosis to end-stage liver disease. Emerging evidence suggests total serum bilirubin levels are inversely related to the prevalence of metabolic syndrome including NAFLD. We investigated the effects of bilirubin on all-cause and cause-specific mortality stratified by NAFLD status. We used the third National Health and Nutrition Examination Survey Cohort (1988-1994) and linked mortality dataset through 2019. Cox-regression models were constructed to assess the association between bilirubin levels categorized by quartile with all-cause and cause-specific mortality. During the median follow-up of 324 months (n=11,078), higher bilirubin levels were associated with a reduction in risk of all-cause mortality in the multivariate model (hazard ratio [HR]: 0.83, 95% confidence interval [CI]: 0.71-0.97 for quarter 4 [highest bilirubin levels] vs. quarter 1 [lowest bilirubin levels], p for trend=0.033). Higher bilirubin levels were associated with a lower risk for all-cause mortality in individuals with NAFLD (HR; 0.68, 95% CI: 0.55-0.86 for quarter 4, p for trend=0.010); however, this protective association with higher bilirubin levels was not noted in those without NAFLD. Higher bilirubin levels were associated with a lower risk for cardiovascular and cancer-related mortality in individuals with NAFLD. In this large nationally representative sample of American adults, higher bilirubin levels in NAFLD were associated with a lower risk of all-cause mortality, which may be derived from a lower risk of cardiovascular/cancer-related mortality.

Correlation of Nonalcoholic Fatty Liver Disease with Dietary Folate and Serum Folate in U.S. Adults: Cross-Sectional Analyses from National Health and Nutrition Examination Survey 2009-2018.

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is a global health problem, and dietary intervention is still considered one of the primary interventions. This study aimed to examine cross-sectional associations between dietary and serum levels of folate and NAFLD. Methods: We conducted a study of 7543 adults who participated in the National Health and Nutrition Examination Survey, 2009-2018. NAFLD status was determined by a fatty liver index (FLI) value ≥60. Multivariable logistic regression models were used to estimate associations between folate and NAFLD. Results: Almost half (45%) of the patients were classified as having NAFLD based on the FLI. In the fully adjusted model, participants in the highest quartile of dietary total folate and food folate were found to have a lower prevalence of NAFLD than those in the lowest quartile [odds ratio (OR)quartile 4 versus 1 = 0.582; 95% confidence interval (CI) = 0.350-0.968; and ORquartile 4 versus 1 = 0.737; 95% CI = 0.611-0.888, respectively], and the fourth quartile values of serum total folate and 5-methyl-tetrahydrofolate were significantly negatively associated with NAFLD prevalence (ORquartile 4 versus 1 = 0.664; 95% CI = 0.495-0.891; and ORquartile 4 versus 1 = 0.712; 95% CI = 0.532-0.954, respectively). Subgroup analyses revealed that this beneficial association was more significant in women (ORquartile 4 versus 1 = 0.526; 95% CI = 0.329-0.843; pinteraction < 0.001) than in men (ORquartile 4 versus 1 = 0.805; 95% CI = 0.546-1.186). Conclusions: Higher dietary folate intake and serum folate levels are associated with a lower NAFLD prevalence among U.S. adults and the trend is more pronounced among women, indicating opportunities for dietary NAFLD interventions.

Regression of nonalcoholic fatty liver disease is associated with reduced risk of incident diabetes: A longitudinal cohort study.

Non-alcoholic fatty liver disease (NAFLD) is potentially reversible. However, whether improvement of NAFLD leads to clinical benefits remains uncertain. We investigated the association between regression of NAFLD and the risk of incident diabetes in a longitudinal way. A cohort of 11,260 adults who had NAFLD at in an initial exam, had the second evaluation for NAFLD status at 1~2 years from an initial exam were followed up for incident diabetes from 2001 and 2016. NAFLD was diagnosed with abdominal ultrasound. At baseline, NAFLD was regressed in 2,559 participants (22.7%). During 51,388 person-years of follow-up (median 4 years), 1,768 participants developed diabetes. The fully adjusted hazard ratio (HR) for incident diabetes in participants with regressed NAFLD compared to those with persistent NAFLD was 0.81 [95% confidence interval (CI) 0.72-0.92]. When assessed by NAFLD severity, among participants with a low NAFLD fibrosis score (NFS) (< -1.455), participants with regressed NAFLD had a lower risk of incident diabetes than those with persistent NAFLD (HR 0.77, 95% CI 0.68-0.88). However, in participants with an intermediate to high NFS (≥ -1.455), the risk of incident diabetes was not different between NAFLD regression and persistence groups (HR 1.12, 95% CI 0.82-1.51). Regression of NAFLD was associated with decreased risk of incident diabetes compared to persistent NAFLD. However, the benefit was evident only for NAFLD patients with low NFS. This suggests that early intervention for NAFLD, before advanced fibrosis is present, may maximize the metabolic benefit from NAFLD regression.

Transcriptional analysis of the expression and prognostic value of lipid droplet-localized proteins in hepatocellular carcinoma

The accumulation of lipid droplets (LDs) in hepatocytes is the main pathogenesis in nonalcoholic fatty liver disease (NAFLD), which is also the key risk factor for the progression of hepatocellular carcinoma (HCC). LDs behaviors are demonstrated to be associated with HCC advancement, and are tightly regulated by a subset protein localized on the surface of LDs. However, the role of LDs-localized protein in HCC has been rarely investigated. This study is focused on the transcriptional dynamic and prognostic value of LDs-localized protein in HCC. Firstly, we summarized the known LDs-localized proteins, which are demonstrated by immunofluorescence according to previous studies. Next, by the use of GEPIA/UALCAN/The Human Protein Atlas databases, we screened the transcriptional change in tumor and normal liver tissues, and found that 13 LDs-localized proteins may involve in the progression of HCC. Then we verified the transcriptional changes of 13 LDs-localized proteins by the use of HCC samples. Moreover, based on the assays of fatty liver of mice and human NAFLD liver samples, we found that the hepatic steatosis mainly contributed to the transcriptional change of selected LDs-localized proteins, indicating the involvement of these LDs-localized proteins in the negative role of NAFLD in HCC progression. Finally, we focused on the role of PLIN3 in HCC, and revealed that NAFLD status significantly promoted PLIN3 transcription in HCC tissue. Functional studies revealed that PLIN3 knockdown significantly limited the migration and chemosensitivity of hepatoma cells, suggesting the positive role of PLIN3 in HCC progression. Our study not only revealed the transcriptional change and prognostic value of lipid droplet-localized proteins in HCC, but also built the correlation between HCC and hepatic steatosis.

Metabolic dysfunction-associated fatty liver disease and the risk of hepatocellular carcinoma

Background & AimsThe metabolic dysfunction-associated fatty liver disease (MAFLD) is a new inclusive term proposed to replace non-alcoholic fatty liver disease (NAFLD). We analysed whether hepatocellular carcinoma (HCC) risk differs by MAFLD or NAFLD status in a large sample of asymptomatic adults. MethodsA cohort comprising 73,691 adults were followed up for the development of HCC. NAFLD was diagnosed among participants without other liver diseases (n = 65,992). ResultsParticipants with MAFLD showed higher incidence of HCC than those without MAFLD (0.37 and 0.24 per 1,000 person-years, respectively; p = 0.006). However, MAFLD was not an independent factor associated with HCC in multivariable adjusted analysis (hazard ratio [HR] 1.21; 95% CI 0.92–1.60). When stratified according to presence of other liver diseases, MAFLD was not associated with HCC in participants with other liver diseases. In participants without other liver diseases, both MAFLD (adjusted HR 1.84; 95% CI 1.09–3.11) and NAFLD (adjusted HR 1.71; 95% CI 1.01–2.90) were independent factors associated with HCC. When stratified according to NAFLD and MAFLD status, there was no HCC development among participants with NAFLD only during 8,936 person-years of follow-up, but this NAFLD-only group comprised 3.4%, and the majority of participants with hepatic steatosis fulfilled both NAFLD and MAFLD criteria. ConclusionsIn patients with other chronic liver diseases, the presence of MAFLD is not independently associated with an increased risk of HCC. For those without other chronic liver diseases, MAFLD largely overlaps with NAFLD and is associated with an increased risk of HCC. Impact and ImplicationsThis study investigated the usefulness of newly proposed nomenclature, metabolic dysfunction-associated fatty liver disease (MAFLD), over non-alcoholic fatty liver disease (NAFLD), in terms of predicting hepatocellular carcinoma. In patients with other chronic liver diseases, the presence of MAFLD is not independently associated with an increased risk of HCC. However, for those without chronic liver disease, MAFLD largely overlaps with NAFLD and is associated with an increased risk of HCC.

Metabolic-associated fatty liver disease in relation to site-specific and multiple-site subclinical atherosclerosis.

Non-alcoholic fatty liver disease (NAFLD) and the newly proposed metabolic-associated fatty liver disease (MAFLD) were each associated with subclinical atherosclerosis. However, there is limited evidence on risk of atherosclerosis in individuals who meet the criteria for one but not the other. We aimed to investigate the associations of MAFLD or NAFLD status with site-specific and multiple-site atherosclerosis. This is a prospective cohort study involving 4524 adults within the MJ health check-up cohort. Logistic regression model was used to estimate odds ratios (ORs) and confidence intervals (CIs) for subclinical atherosclerosis (elevated carotid intima-media thickness [CIMT], carotid plaque [CP], coronary artery calcification [CAC] and retinal atherosclerosis [RA]) associated with MAFLD or NAFLD status, MAFLD subtypes and fibrosis status. MAFLD was associated with higher risks of elevated CIMT, CP, CAC and RA (OR: 1.41 [95% CI 1.18-1.68], 1.23 [1.02-1.48], 1.60 [1.24-2.08], and 1.79 [1.28-2.52], respectively), whereas NAFLD per se did not increase risk of atherosclerosis except for elevated CIMT. Individuals who met both definitions or the definition for MAFLD but not NAFLD had higher risk of subclinical atherosclerosis. Among MAFLD subtypes, MAFLD with diabetes had the highest risk of subclinical atherosclerosis, but the associations did not differ by fibrosis status. Stronger positive associations were observed of MAFLD with multiple-site than single-site atherosclerosis. In Chinese adults, MAFLD was associated with subclinical atherosclerosis, with stronger associations for multiple-site atherosclerosis. More attention should be paid to MAFLD with diabetes, and MAFLD might be a better predictor for atherosclerotic disease than NAFLD.

Association of serum uric acid with hepatic steatosis detected by controlled attenuation parameter in the United States population

BackgroundThe relationship between serum uric acid (SUA) and nonalcoholic fatty liver disease (NAFLD) has been previously reported. Controlled attenuation parameter (CAP) has better diagnostic performance than ultrasonography for assessing hepatic steatosis. The association of SUA with hepatic steatosis detected by CAP is worth further study.MethodsThe US population aged 20 years or older from the National Health and Nutrition Examination Survey (NHANES) was assessed. Hepatic steatosis was evaluated by the controlled attenuation parameter (CAP). NAFLD status was defined as CAP values of 268 dB/m without hepatitis B or C virus infection or considerable alcohol consumption. Multiple imputations were performed to fill in the missing covariate values. Linear regression, logistic regression, and smooth curve fitting were used to examine the association.ResultsIn total, 3919 individuals participated in this study. There was a positive association between SUA (µmol/L) and CAP (β = 0.14, 95% CI: 0.12-0.17, P < 0.01). After stratification by sex, a significant relationship between SUA and CAP existed in both males (β = 0.12, 95% CI: 0.09-0.16, P < 0.01) and females (β = 0.17, 95% CI: 0.14-0.20, P < 0.01) after multiple imputation. The inflection points of the threshold effect of SUA on CAP were 487.7 µmol/L in males and 386.6 µmol/L in females. There was a positive association between SUA (mg/dL) and NAFLD (OR = 1.30, 95% CI: 1.23-1.37, P < 0.01). After stratification by race, positive relationships were also observed. Meanwhile, a positive relationship existed between hyperuricemia and NAFLD (OR = 1.94, 95% CI: 1.64-2.30, P < 0.01). The positive relationship was more significant in females than in males (P for interaction < 0.01).ConclusionsThere was a positive association between SUA and CAP, as well as between SUA and NAFLD. Subgroup studies stratified by sex and ethnicity demonstrated that the effects were consistent.

Nonalcoholic fatty liver disease and risk of incident young-onset hypertension: Effect modification by sex

Background and aimsAlthough nonalcoholic fatty liver disease (NAFLD) and hypertension are increasingly common among young adults, it is uncertain if NAFLD affects incidence of young-onset hypertension, and if the association is modified by sex. We investigated potential effect modification by sex on the association between NAFLD and incident hypertension in young adults (<40 years). Method and resultsThis cohort study comprised 85,789 women and 67,553 men aged <40 years without hypertension at baseline. Hepatic steatosis was assessed by liver ultrasound and classified as mild or moderate/severe. Hypertension was defined as blood pressure (BP) ≥130/80 mmHg; self-reported history of physician-diagnosed hypertension; or current use of BP-lowering medications. Cox proportional hazard models were used to estimate hazard ratios (HRs; 95% confidence intervals [CIs]) for incident hypertension by NAFLD status (median follow-up 4.5 years). A total of 25,891 participants developed incident hypertension (incidence rates per 103 person-years: 15.6 for women and 63.5 for men). Multivariable-adjusted HRs (95% CIs) for incident hypertension comparing no NAFLD (reference) with mild or moderate/severe NAFLD were 1.68 (1.56–1.80) and 1.83 (1.60–2.09) for women and 1.21 (1.17–1.25) and 1.23 (1.17–1.30) for men, respectively. Stronger associations were consistently observed between NAFLD and incident hypertension in women, regardless of obesity/central obesity (all p-values for interaction by sex <0.001). ConclusionsNAFLD is a potential risk factor for young-onset hypertension with a relatively greater impact in women and in those with more severe hepatic steatosis.