Nonalcoholic Fatty Liver Disease Participants Research Articles

Newly identified single-nucleotide polymorphism associated with the transition from nonalcoholic fatty liver disease to liver fibrosis: results from a nested case-control study in the UK biobank.

Genetic factors may have a significant influence on the likelihood of liver fibrosis in individuals with nonalcoholic fatty liver disease (NAFLD). The present study was conducted to explore how single-nucleotide polymorphism (SNP) impacts the development of fibrosis in those suffering from NAFLD. Utilizing the UK Biobank dataset, we conducted a nested case-control analysis among NAFLD participants, defining the case group as those with liver fibrosis and cirrhosis during follow-up. For our in vitro investigations, we employed the LX-2 human hepatic stellate cell line. Our procedures included cultivating these cells, employing SAMM50-rs2073080 plasmid techniques to enhance the expression of recently discovered SNPs, and conducting biochemical assays. To quantify gene expression, we used real-time PCR with fluorescence detection. The study analyzed data from 5467 participants (1094 cases and 4373 controls). Genome-wide association analysis identified nine significant loci, including the novel rs2073080 variant, strongly associated with NAFLD-associated hepatic fibrosis. In vitro TGF-β modeling revealed significant upregulation of α-SMA and COL1A1, confirming model effectiveness. Oxidative stress markers like elevated malondialdehyde (MDA) and reduced catalase (CAT) and superoxide dismutase (SOD) levels indicated liver damage in the TGF-β group. SAMM50-rs2073080 was upregulated in the NAFLD-associated fibrosis model. In vitro experiments on LX-2 cells showed that SAMM50-rs2073080 overexpression led to increased fibrosis, as indicated by higher cellular MDA levels and lower CAT and SOD levels, compared to the vector group. Our research highlights a significant association of SAMM50-rs2073080 with the progression of NAFLD to hepatic fibrosis, and the in vitro experiments further corroborated these findings.

Association between serum vitamin D and depression among non-alcoholic fatty liver disease.

While previous population-based studies have suggested a link between serum vitamin D levels and depression in individuals with non-alcoholic fatty liver disease (NAFLD), the exact correlation between serum vitamin D and depression among NAFLD patients remains controversial and disputed. Thus, we conducted this study to evaluate the relationship between serum vitamin D and depression in NAFLD participants diagnosed via transient elastography. This cross-sectional study was extracted from the latest NHANES 2017-2018 dataset. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9) score of ≥10. NAFLD phenotype was identified by vibration-controlled transient elastography (VCTE) examination based on diagnostic criteria. Binary logistic regression models were applied to estimate the impact of increased serum vitamin D on the reduced risk of depression based on sample weights. A total of 1339 participants with NAFLD were included in this investigation, of which 127 (8.58%) were diagnosed with depression according to PHQ-9 scores. Binary logistic regression analysis presented that high serum vitamin D level was a protective factor for depression in NAFLD (OR=0.61, 95% CI: 0.37-0.99, p=0.048) after adjusting for all confounding factors. In subgroup analyses, these associations were more pronounced among men (OR=0.32, 95% CI: 0.13-0.81, p=0.024) and obese population (OR=0.53, 95% CI: 0.33-0.86, p=0.019). Increased serum vitamin D was negatively associated to the prevalence of depression in males and obese individuals with NAFLD diagnosed by VCTE.

Overlapping group between non-alcoholic fatty liver disease and metabolic associated fatty liver disease better for liver research.

Metabolic associated fatty liver disease (MAFLD) was proposed to replace "non-alcoholic fatty liver disease (NAFLD) with new diagnostic criteria." The group meeting these two diagnostic criteria is called "Overlapping Fatty Liver Disease (FLD)." Its clinical characteristics remain unknown. This study included participants from the Taiwan Bio-Bank database, where NAFLD was defined as hepatic steatosis in liver ultrasound, with exclusion of other known chronic liver diseases. MAFLD was defined as the presence of hepatic steatosis plus metabolic dysfunction, defined as having any of following three criteria: overweight/obesity, type 2 diabetes mellitus (DM), or ≥2 metabolic risk abnormalities in lean/normal weight subjects. According to these two diagnostic criteria, three groups were identified: "overlapping FLD", "NAFLD alone", and "MAFLD alone." NAFLD fibrosis score (NFS) >0.675 was defined as advanced liver fibrosis. Eight thousand thirty-eight NAFLD participants (age 55.86 ± 10.12; males 41.07%) were included in the final analysis. Of them, "overlapping FLD" was diagnosed in 7377 (91.8%) and "NAFLD alone" in 661 (8.2%) participants. "Overlapping FLD" patients were older and had a higher percentage of male, worse metabolic profiles, higher NFS, and the percentage of carotid plaques was higher than those with "NAFLD alone." Multivariate analysis showed age, hypertension, DM, and BMI were positively associated with advanced liver fibrosis in "overlapping FLD" patients. "Overlapping FLD" is better for liver research due to identifying a high-risk population among NAFLD patients. NAFLD definition introduces the heterogeneity through "NAFLD alone" group and MAFLD criteria overcome this limitation.

Impact of silymarin-supplemented cookies on liver enzyme and inflammatory markers in non-alcoholic fatty liver disease patients.

Nonalcoholic fatty liver disease (NAFLD) is a growing public health concern characterized by fat accumulation and severe disorders like nonalcoholic steatohepatitis (NASH), which are influenced by obesity, inflammatory processes, and metabolic pathways. This research investigates the potential of silymarin-supplemented cookies in managing NAFLD by evaluating their impact on liver enzyme activity, inflammatory markers, and lipid profiles. A clinical trial in Lahore, Pakistan, involved 64 NAFLD patients. Participants were divided into placebo and three treatment groups, with the latter receiving silymarin-supplemented cookies for 3 months. The study assessed liver enzyme levels and inflammatory markers, at baseline and after the intervention, utilizing statistical analyses to evaluate differences. The lipid profile and renal function test (RFT) were also measured at baseline and after 3 months in each group for safety assessment. After 3 months, the treatment groups indicated more significant decreases in liver enzymes compared to the placebo group (p ≤ .05). Treatment 3 showed significant reductions in alanine aminotransferase (ALT) (64.39-49.38 U/L) and aspartate aminotransferase (AST) (61.53-45.38 U/L). Treatment 3 also showed improvements in alkaline phosphatase (ALP) levels and the AST/ALT ratio. Additionally, the treatment group demonstrated a significant reduction in inflammatory markers. Treatment 3 showed a significant decrease in C-reactive protein (CRP) (6.32-3.39 mg/L) and erythrocyte sedimentation rate (ESR) (38.72-23.86 mm/h), indicating that individuals with NAFLD may benefit from the intervention's potential benefits in lowering inflammation. The study revealed that an intervention significantly improved the inflammatory markers, liver enzymes, and lipid profiles of NAFLD participants, suggesting potential benefits for liver health.

Association between Lifestyle Modification and All-Cause, Cardiovascular, and Premature Mortality in Individuals with Non-Alcoholic Fatty Liver Disease.

This study is designed to explore the correlation between multiple healthy lifestyles within the framework of "lifestyle medicine", and the mortality risk of nonalcoholic fatty liver disease (NAFLD). The National Health and Nutrition Examination Survey (NHANES) database was employed. The analysis consisted of 5542 participants with baseline NAFLD and 5542 matched non-NAFLD participants from the database. Lifestyle information, including five low risk factors advocated by lifestyle medicine (healthy diet, vigorous physical activity, healthy sleep duration, avoiding smoking, and maintaining a non-depressed psychological status), was collected through a baseline questionnaire. Cox proportional hazards regression models and Kaplan-Meier survival curve were used to evaluate risk of mortality. In addition, subgroups were analyzed according to gender, age, body mass index and waist circumference. In total, 502 deaths (n = 181 deaths from cardiovascular disease (CVD)) were recorded among NAFLD participants after the median follow up duration of 6.5 years. In the multivariate-adjusted model, compared to participants with an unfavorable lifestyle (scoring 0-1), NAFLD participants with a favorable lifestyle (scoring 4-5) experienced a 56% reduction in all-cause mortality and a 66% reduction in CVD mortality. Maintaining an undepressed psychological state and adhering to vigorous exercise significantly reduced CVD mortality risk in NAFLD participants (HR, 0.64 [95% CI, 0.43-0.95]; HR, 0.54 [95% CI, 0.33-0.88]) while maintaining healthy sleep reduced premature mortality due to CVD by 31%. Healthy lifestyle, characterized by maintaining an undepressed mental state and healthy sleep, significantly mitigates the risk of all-cause, CVD, and premature mortality risk among NAFLD patients, with a particularly pronounced effect observed in female and obese subpopulations.

Do Hepatic Fibrosis and Steatosis Measured by Hepatic Transient Elastography (FibroScan) Predict Cardiovascular Risk in Patients with Non-alcoholic Fatty Liver Disease: An Observational Cross-sectional Study

Objectives: Non-alcoholic fatty liver disease (NAFLD) has been associated with increased cardiovascular risk (CVR) in the previous studies. In the majority, ultrasonography has been used to diagnose and stage NAFLD, which lacks sensitivity and is non-quantitative. Other more sensitive, comprehensive, and quantitative diagnostic tools such as vibration-controlled transient elastography (TE) have largely been underused in research work. TE-driven liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) provide an accurate and simplified estimation of liver fibrosis and steatosis, respectively. Therefore, we aimed to analyze the association between these two objective, robust parameters and CVR. Materials and Methods: In this observational cross-sectional study, NAFLD participants were divided into two distinct categories of steatosis (CAP <290 and ≥290 dB) and fibrosis (LSM <10 and ≥10 kPa). Their CVR assessment was done by calculating Framingham risk score (FRS), American College of Cardiology/American Heart Association Pooled Cohort Equation Score (ACC/AHA PCES), and carotid intimal medial thickness (CIMT). Results: A greater number of participants presented with mild-moderate fibrosis (n = 41, 62.1%) as compared to severe fibrosis (n = 25, 37.8%) whereas severe steatosis participants predominated (n = 52, 78%) as compared to mild-moderate steatosis. The presence of significant fibrosis (LSM ≥10 kPa) was independently and significantly associated with FRS, ACC/AHA PCES, and CIMT. On the other hand, the presence of significant steatosis (CAP ≥290 dB/m) was not significantly associated with any CVR marker (FRS, ACC/AHA PCES, or CIMT), though a greater number of participants with CIMT >0.7 belonged to severe steatosis group. Conclusion: Subjects with severe fibrosis (LSM ≥10) had a significantly higher CVR, whereas severe steatosis (CAP ≥290) alone failed to predict CVR. Therefore, CVR reduction strategies can be targeted primarily in NAFLD subjects with fibrosis, particularly in resource-limited healthcare settings.

Analysis of the association between non-alcoholic fatty liver disease and mortality in United States adults.

Non-alcoholic Fatty Liver Disease (NAFLD) is a prevalent condition characterized by the accumulation of fat in the liver, often linked with increased risk for multi-systemic diseases. This study aims to investigate the relationship between NAFLD and mortality, particularly all-cause and cardiovascular mortality, among United States adults. Data from the National Health and Nutrition Examination Survey (NHANES) were utilized, encompassing 80,312 participants from 2003-2004 to 2017-2018. After exclusions for incomplete data, potential other liver diseases, and significant alcohol consumption, the final analytical cohort included 32,698 participants. The Fatty Liver Index (FLI), a non-invasive diagnostic tool, was used to identify NAFLD. Covariates included demographic characteristics, lifestyle factors, and biochemical parameters. Survival analysis was conducted using a weighted Cox proportional hazards regression model to quantify the impact of NAFLD on mortality. The study revealed that NAFLD was significantly associated with increased risks of all-cause and cardiovascular disease (CVD) mortality. The hazard ratios (HRs) from the survival analysis consistently indicated a higher risk among participants with NAFLD compared to those without. Subgroup analyses further confirmed the association, with notable exceptions in certain subgroups such as those with high school education and diabetes. Additionally, a nonlinear relationship between serum uric acid (SUA) levels and mortality risk was identified among NAFLD participants. Non-alcoholic Fatty Liver Disease is a significant risk factor for all-cause and CVD mortality in US adults. The findings underscore the importance of early detection and intervention for NAFLD to mitigate its impact on public health. Further research is needed to explore the complex interactions between NAFLD, SUA levels, and mortality, particularly in high-risk subgroups.

The Glutamate-Serine-Glycine Index as a Biomarker to Monitor the Effects of Bariatric Surgery on Non-alcoholic Fatty Liver Disease.

Bariatric surgery effectively treats non-alcoholic fatty liver disease (NAFLD). The glutamate-serine-glycine (GSG) index has emerged as a non-invasive diagnostic marker for NAFLD, but its ability to monitor treatment response remains unclear. This study investigates the GSG index's ability to monitor NAFLD's response to bariatric surgery. Ten NAFLD participants were studied at baseline and 6 months post-bariatric surgery. Blood samples were collected for serum biomarkers and metabolomic profiling. Hepatic steatosis [proton density fat fraction (PDFF)] and fibroinflammation (cT1) were quantified with multiparametric magnetic resonance imaging (mpMRI), and hepatic stiffness with magnetic resonance elastography (MRE). Amino acids and acylcarnitines were measured with mass spectrometry. Statistical analyses included paired Student's t-test, Wilcoxon-signed rank test, and Pearson's correlation. Eight participants provided complete data. At baseline, all had hepatic steatosis (BMI 39.3 ± 5.6 kg/m2, PDFF ≥5%). Post-surgery reductions in PDFF (from 12.4 ± 6.7% to 6.2 ± 2.8%, p = 0.013) and cT1 (from 823.3 ± 85.4 ms to 757.5 ± 41.6 ms, p = 0.039) were significant, along with the GSG index (from 0.272 ± 0.03 to 0.157 ± 0.05, p = 0.001). The GSG index can potentially be developed as a marker for monitoring the response of patients with NAFLD to bariatric surgery.

Different dietary carbohydrate component intakes and long-term outcomes in patients with NAFLD: results of longitudinal analysis from the UK Biobank

BackgroundThis study aimed to investigate the association between the intake of different dietary carbohydrate components and the long-term outcomes of non-alcoholic fatty liver disease (NAFLD).MethodsWe used prospective data from 26,729 NAFLD participants from the UK Biobank cohort study. Dietary information was recorded by online 24-hour questionnaires (Oxford WebQ). Consumption of different carbohydrate components was calculated by the UK Nutrient Databank Food Composition Table. Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). A substitution model was used to estimate the associations of hypothetical substitution for free sugars.ResultsDuring a median of 10.5 (IQR: 10.2–11.2) years and a total of 280,135 person-years of follow-up, 310 incident end-stage liver disease (ESLD) and 1750 deaths were recorded. Compared with the lowest quartile, the multi-adjusted HRs (95% CI) of incident ESLD in the highest quartile were 1.65 (1.14–2.39) for free sugars, 0.51 (0.35–0.74) for non-free sugars, and 0.55 (0.36–0.83) for fiber. For overall mortality, the multi-adjusted HRs (95% CI) in the highest quartile were 1.21 (1.04–1.39) for free sugars, 0.79 (0.68–0.92) for non-free sugars, and 0.79 (0.67–0.94) for fiber. Substituting free sugars with equal amounts of non-free sugars, starch or fiber was associated with a lower risk of incident ESLD and overall mortality.ConclusionsA lower intake of free sugars and a higher intake of fiber are associated with a lower incidence of ESLD and overall mortality in NAFLD patients. These findings support the important role of the quality of dietary carbohydrates in preventing ESLD and overall mortality in NAFLD patients.

HbA1c of 5.8% or higher as the most useful indicator for recommendation of ultrasonography to detect nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is closely associated with metabolic syndrome. This study was performed to examine the association between NAFLD and each factor of metabolic syndrome and to identify the factors that are most strongly associated with NAFLD in participants undergoing health checkups. We studied 6538 participants who underwent a health checkup from 2017 to 2018 in our institution. Participants with alcohol intake exceeding 20 g/day or with other chronic liver diseases were excluded. Fatty liver was detected by ultrasonography. In total, 4310 participants were enrolled, and 28.4% had fatty liver (NAFLD). The prevalence of NAFLD was highest in the diabetes mellitus (DM)-only group than in the dyslipidemia-only or hypertension-only group. The DM-only group was the only group whose prevalence of NAFLD was >50% in the overall study and in males. The prevalence of NAFLD was higher in males than in females in the DM-only, hypertension-only, and dyslipidemia-only groups. The prevalence of NAFLD was >70% in the dyslipidemia and DM combined group. Multivariate analysis showed that gender and HbA1c were the independent factors most strongly associated with NAFLD. The cutoff value for HbA1c by receiver operating characteristic curve analysis was 5.8% (sensitivity, 57.9%; specificity, 72.6%; area under the curve, 0.70). NAFLD was most strongly associated with DM, among the various components of metabolic syndrome. We strongly recommend abdominal ultrasonography to detect NAFLD in patients with an HbA1c of ≥5.8% in general practice and during health checkups.

Impact of smoking cessation on non-alcoholic fatty liver disease prevalence: a systematic review and meta-analysis

ObjectivesThe negative effects of smoking on numerous cardiovascular and metabolic diseases have been widely acknowledged. However, the potential effect of smoking cessation is relatively unelucidated. The objective of this study...

Non-alcoholic fatty liver degree and long-term risk of incident inflammatory bowel disease: A large-scale prospective cohort study.

Non-alcoholic fatty liver disease (NAFLD) and inflammatory bowel disease (IBD) have shown similar worsening epidemic patterns globally and shared various overlapping pathophysiological mechanisms. However, evidence on the relationship between NAFLD and IBD risk is lacking. We aimed to investigate the associations between long-term risk of incident IBD and NAFLD in a large prospective cohort. Participants from the United Kingdom Biobank cohort ( https://biobank.ndph.ox.ac.uk/ ) who were free of IBD and alcoholic liver disease at baseline were enrolled. Baseline non-alcoholic fatty liver degree was measured by the well-established fatty liver index (FLI). The outcomes of interest included incident IBD, ulcerative colitis (UC), and Crohn's disease (CD). Multivariable Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Among 418,721 participants (mean FLI: 48.11 ± 30.11), 160,807 (38.40%) participants were diagnosed as NAFLD at baseline. During a median of 12.4 years' follow-up, 2346 incident IBD cases (1545 UC, 653 CD, and 148 IBD-unclassified) were identified. Due to limited events, those IBD-unclassified were combined in UC or CD when examining the associated risk of UC or CD, separately. Compared with the lowest quartile of FLI, the highest quartile showed a separately 36.00%, 25.00%, and 58.00% higher risk of incident IBD (HR Q4 vs.Q1 = 1.36, 95% CI: 1.19-1.55, Ptrend <0.001), UC (HR Q4 vs.Q1 = 1.25, 95% CI: 1.07-1.46, Ptrend = 0.047), and CD (HR Q4 vs.Q1 = 1.58, 95% CI: 1.26-1.97, Ptrend <0.001) after multivariable adjustment. Compared with non-NAFLD, NAFLD participants had a significantly higher risk of incident IBD (HR = 1.13, 95% CI: 1.04-1.24) and CD (HR = 1.36, 95% CI: 1.17-1.58). Higher degree of non-alcoholic fatty liver is associated with increased risk of incident IBD. Interventions aimed at improving NAFLD may be a potential targeted strategy for the detection and treatment of IBD.

The association between telomere length and non-alcoholic fatty liver disease: a prospective study

BackgroundResearch on the association between telomere length (TL) and incident non-alcoholic fatty liver disease (NAFLD) is limited. This study examined this association and further assessed how TL contributes to the association of NAFLD with its known risk factors.MethodsQuantitative PCR (polymerase chain reaction) was employed to assess leucocyte telomere length. Polygenic risk score (PRS) for NAFLD, air pollution score, and lifestyle index were constructed. Cox proportional hazard models were conducted to estimate the hazard ratios (HRs) and 95% confidence intervals.ResultsAmong 467,848 participants in UK Biobank, we identified 4809 NAFLD cases over a median follow-up of 12.83 years. We found that long TL was associated with decreased risk of incident NAFLD, as each interquartile range increase in TL resulted in an HR of 0.93 (95% CI 0.89, 0.96). TL partly mediated the association between age and NAFLD (proportion mediated: 15.52%). When assessing the joint effects of TL and other risk factors, the highest risk of NAFLD was found in participants with low TL and old age, low TL and high air pollution score, low TL and unfavorable lifestyle, and low TL and high PRS, compared to each reference group. A positive addictive interaction was observed between high PRS and low TL, accounting for 14.57% (2.51%, 27.14%) of the risk of NAFLD in participants with low telomere length and high genetic susceptibility.ConclusionsLong telomere length was associated with decreased risk of NAFLD incidence. Telomere length played an important role in NAFLD.Graphical

Sex Differences in the Association Between AST/ALT and Incidence of Type 2 Diabetes in Japanese Patients with Nonalcoholic Fatty Liver Disease: A Retrospective Cohort Study

ABSTRACT Objectives/Introduction The purpose of the current study was to investigate the association between Aspartate Transaminase (AST)/Alanine transaminase(ALT) and type 2 diabetes (T2DM) in nonalcoholic fatty liver disease (NAFLD) patients and to determine whether there were sex differences. Methods In the retrospective study, we collected data on NAFLD patients (1, 896 men and 465 women) at Murakami Memorial Hospital from 2004 to 2015. Data were stratified by sex to investigate the association between AST/ALT and T2DM incidence by sex. Multiple regression analysis, smooth curve fitting model and subgroup analysis were used to determine the correlation, non-linear relationship and threshold effect between AST/ALT and T2DM. Results In our study, 157 men and 40 women developed T2DM at follow-up. After adjusting for risk factors, AST/ALT was significantly associated with T2DM in men with NAFLD but not in women with NAFLD. The risk of T2DM increased as the AST/ALT ratio decreased. Besides, in male NAFLD patients, AST/ALT showed a non-linear relationship with T2DM, with an inflection point value of 0.964. When the AST to ALT ratio was below the threshold (AST/ALT <0.964), AST/ALT was significantly negatively associated with T2DM (HR = 0.177, 95% CI 0.055–0.568; P = 0.0036). In contrast, when AST/ALT >0.964, no significant association was found (HR = 3.174, 95% CI 0.345–29.167; P = 0.3074). Moreover, subgroup analysis showed that GGT could alter the relationship between AST/ALT and T2DM. In the group with GGT ≤ 40, AST/ALT was strongly associated with T2DM (HR = 0.24, 95% CI 0.09–0.66; P = 0.0059). Conclusions These results suggested that there were sex differences in the association between AST/ALT and T2DM in NAFLD participants. A non-linear association between AST/ALT and T2DM was observed in males. AST/ALT in the normal GGT group (GGT ≤40) might better facilitate the early screening of T2DM.

The association of healthy lifestyle score and risk of non-alcoholic fatty liver disease

BackgroundThe combined role of important environmental factors as a single lifestyle index in predicting non-alcoholic fatty liver disease (NAFLD) risk is not fully assessed. Therefore, we aimed to investigate the association of healthy lifestyle factor score (HLS) with the odds of NAFLD in Iranian adults.MethodsThis case-control study was conducted on 675 participants, aged ≥ 20–60 years, including 225 new NAFLD cases and 450 controls. We measured dietary intake information using a validated food frequency questionnaire and determined diet quality based on the alternate healthy eating index-2010(AHEI-2010). The score of HLS was calculated based on four lifestyle factors, including a healthy diet, normal body weight, non-smoking, and high physical activity. An ultrasound scan of the liver was used to detect NAFLD in participants of the case group. Logistic regression models were used to determine the odds ratios(ORs) and 95% confidence interval(CI) of NAFLD across tertiles of HLS and AHEI.ResultsMean ± SD age of the participants were 38.13 ± 8.85 years. The Mean ± SD HLS in the case and control groups was 1.55 ± 0.67 and 2.53 ± 0.87, respectively. Also, the Mean ± SD AHEI in the case and control groups was 48.8 ± 7.7 and 54.1 ± 8.1, respectively. Based on the age and sex-adjusted model, the odds of NAFLD were decreased across tertiles of AHEI (OR:0.18;95%CI:0.16–0.29,Ptrend<0.001) and HLS(OR:0.03;95%CI:0.01–0.05,Ptrend<0.001). Also, in the multivariable model, the odds of NAFLD were decreased across tertiles AHEI (OR:0.12;95%CI:0.06–0.24,Ptrend<0.001) and HLS(OR:0.02;95%CI:0.01–0.04,Ptrend<0.001).ConclusionsOur findings reported that higher adherence to lifestyle with a higher score of HLS was associated with decreased odds of NAFLD. Also, a diet with a high AHEI score can reduce the risk of NAFLD in the adult population.

Dietary advanced glycation end products are associated with an increased risk of non-alcoholic fatty liver disease in Iranian adults

BackgroundDietary advanced glycation end products(AGEs) may contribute to increased inflammation and oxidative stress as risk factors for chronic diseases such as liver disease. In the current study, we aimed to examine the possible association of dietary AGEs with the odds of non-alcoholic fatty liver disease (NAFLD) in Iranian adults.MethodsA total of 675 participants (225 newly diagnosed NAFLD cases and 450 controls), aged 20–60 years, were recruited for this case-control study. Nutritional data were measured using a validated food frequency questionnaire, and dietary AGEs were determined for all participants. An ultrasound scan of the liver performed the detection of NAFLD in participants of the case group without alcohol consumption and other causes of hepatic disorders. We used logistic regression models, adjusted for potential confounders, to estimate the odds ratios(ORs) and 95% confidence interval(CI) of NAFLD across tertiles of dietary AGEs.ResultsMean ± SD age and body mass index of the participants were 38.13 ± 8.85 years and 26.85 ± 4.31 kg/m2, respectively. The median(IQR) of dietary AGEs in participants was 3262(2472–4301). In the sex and age-adjusted model, the odds of NAFLD were increased across tertiles of dietary AGEs intake(OR:16.48;95%CI:9.57–28.40, Ptrend<0.001). Also, in the final model, after controlling for confounding effects of BMI, smoking, physical activity, marital status, socio-economic status, and energy intake, the odds of NAFLD were increased across tertiles of dietary AGEs intake(OR:12.16; 95%CI:6.06–24.39, Ptrend<0.001).ConclusionOur results showed that greater adherence to dietary pattern with high dietary AGEs intake was significantly related to increased odds of NAFLD.

Relevance of vitamin D on NAFLD and liver fibrosis detected by vibration controlled transient elastography in US adults: a cross-sectional analysis of NHANES 2017–2018

Background The connection between vitamin D to non-alcoholic fatty liver disease (NAFLD) is still unclear. Herein, the relationship of vitamin D with NAFLD and liver fibrosis (LF) detected by vibration controlled transient elastography was investigated in US adults. Methods The National Health and Nutrition Examination Survey of 2017–2018 was employed for our analysis. Participants were categorized as having either vitamin D deficiency (<50 nmol/L) or vitamin D sufficiency (≥50 nmol/L). A controlled attenuation parameter score of ≥ 263 dB/m was employed to define NAFLD. Significant LF was identified by the liver stiffness measurement value of ≥ 7.9 kPa. Multivariate logistic regression was adopted to explore the relationships. Results Among the 3407 participants, the prevalence of NAFLD and LF was 49.63% and 15.93% respectively. Compared to participants without NAFLD, no significant difference in serum vitamin D was observed in NALFD participants (74.26 vs. 72.24 nmol/L; p = 0.21). Using multivariate logistic regression analysis, no obvious connection of vitamin D status to NAFLD (sufficiency vs. deficiency, OR 0.89, 95%CI 0.70–1.13) was discovered. However, among NAFLD participants, the sufficiency of vitamin D represents a lower LF risk (OR 0.56, 95%CI 0.38–0.83). When evaluated in quartiles, in comparison to the lowest quartile, high vitamin D represents low LF risk in a dose-dependent manner (Q2 vs. Q1, OR 0.65, 95%CI 0.37–1.14; Q3 vs. Q1, OR 0.64, 95%CI 0.41–1.00; Q4 vs. Q1, OR 0.49, 95%CI 0.30–0.79). Conclusions No relationship was found between vitamin D and CAP-defined NAFLD. However, a positive connection of the high serum vitamin D to the reduced LF risk was found among NAFLD subjects. Key messages: Our study found no relationship between vitamin D and CAP-defined NAFLD in US adults. High serum vitamin D was inversely associated with liver fibrosis in a dose-dependent manner among NAFLD participants.

Effectiveness and safety analysis of Danggui Shaoyao Powder for the treatment of non-alcoholic fatty liver disease: study protocol for a randomized, double-blind, placebo-controlled clinical trial

BackgroundThe incidence of non-alcoholic fatty liver disease (NAFLD) has been on the rise in recent years, and there are no effective drugs to treat NAFLD; therefore, effective prevention and treatment of NAFLD have become a new challenge. Danggui Shaoyao Powder (DGSY) is a classic prescription commonly used in clinical practice and has been shown to reduce hepatic steatosis in patients with NAFLD. In addition, previous studies have shown that DGSY can alleviate hepatic steatosis and inflammation in NAFLD mice. Although clinical practice and basic studies have shown that DGSY is effective in NAFLD, high levels of clinical evidence are lacking. Therefore, a standardized RCT study protocol is required to evaluate its clinical efficacy and safety.Methods and analysisThis study will be a randomized, double-blind, placebo-controlled, and single-center trial. According to the random number table, NAFLD participants will be randomly divided into the DGSY or placebo group for 24 weeks. The follow-up period will be 6 weeks after drug withdrawal. The primary outcome is the relative change in MRI-proton density fat fraction (MRI-PDFF) from baseline to 24 weeks. Absolute changes in serum alanine aminotransferase (ALT), liver stiffness measurement (LSM), body mass index (BMI), blood lipid, blood glucose, and insulin resistance index will be selected as secondary outcomes to comprehensively evaluate the clinical efficacy of DGSY in the treatment of NAFLD. The safety of DGSY will be evaluated by renal function, routine blood and urine tests, and electrocardiogram.DiscussionThis study will provide evidence-based medical corroboration for the clinical application of DGSY and promote the development and application of this classic prescription.Trial registrationhttp://www.chictr.org.cn. Trial number: ChiCTR2000029144. Registered on 15 Jan 2020.

The systemic immune-inflammation index was non-linear associated with all-cause mortality in individuals with nonalcoholic fatty liver disease

Objective Systemic immune-inflammation index (SII), a novel inflammatory indicator based on platelets, neutrophils and lymphocytes, has been shown to be associated with prognostic value in several solid tumors. However, its prognostic value in nonalcoholic fatty liver disease (NAFLD) has not been reported yet. Therefore, the present study aimed to investigate the prognostic value of SII in individuals with NAFLD. Methods Data was collected from the 2005 to 2014 National Health and Nutrition Examination Survey (NHANES, https://www.cdc.gov/nchs/nhanes/index.htm), and vital status was derived from the National Death Index (NDI) up to 31 December 2015. NAFLD was diagnosed based on Hepatic Steatosis Index (HSI). Multivariate Cox regression and Kaplan–Meier survival curves were performed to measure the hazard ratios (HRs) and 95% confidence interval (CI). Our study investigated the relationship between SII and all-cause mortality by using two-part linear regression models with penalized splines, as well as Cox models with penalized splines. Results A total of 10,787 NAFLD participants (44.14% men) aged ≥20 years old were enrolled. There were 776 deaths from all causes after a mean follow-up period of 5.6 years. According to the full adjusted Cox regression analysis, the low log2-SII group (quartile 1) and the highest log2-SII group (quartile 4) were significantly associated with increased mortality from all causes (aHR =1.86; 95% CI: 1.47–2.37; p < 0.0001). After controlling for confounders, an increase in log2-SII was associated with an increased all-cause mortality risk of 41% for every unit raised (aHR = 1.41; 95% CI: 1.26–1.57; p < 0.0001). After adjusting for multiple potential confounders, the association between log2-SII and all-cause mortality was nonlinear, and the threshold value was 8.8. There was no association between an increase of one unit in log2-SII and all-cause mortality below the threshold (aHR = 0.90, 95% CI: 0.71–1.15, p = 0.419). However, a higher log2-SII was associated with a higher risk of death from any cause when it exceeded the threshold (aHR = 1. 73, 95% CI: 1.49–2.02, p < 0.001). Conclusion Based on a study of US NAFLD patients, it was found that the baseline log2-SII is associated with all-cause mortality. Elevated SII is associated with poor survival among NAFLD patients. KEY MESSAGES Using a large nationally representative survey of individuals among US adults, the study demonstrated that log2-SII was J-shaped and associated with all-cause death among individuals with NAFLD. Spline analyses demonstrated that the association between log2-SII and all-cause mortality was non-linear after adjusting for multiple potential confounders, and the threshold value was 8.8. Higher log2-SII associated with poor survival in NAFLD.

Association between Regional Body Muscle Mass and Non-Alcoholic Fatty Liver Disease: An Observational Study Using Data from the REACTION Study

Background and aims: Regional muscle distribution is associated with abdominal obesity and metabolic syndrome. However, the relationship between muscle distribution and nonalcoholic fatty liver disease (NAFLD) remains unclear. This study was to determine the relationship between regional muscle distribution and the risk and severity of NAFLD. Methods: This cross-sectional study ultimately included 3161 participants. NAFLD diagnosed by ultrasonography was classified into three groups (non, mild, and moderate/severe). We estimated the regional body muscle mass (lower limbs, upper limbs, extremities, and trunk) through multifrequency bioelectrical impedance analysis (BIA). The relative muscle mass was defined as the muscle mass adjusted for the body mass index (BMI). Results: NAFLD participants accounted for 29.9% (945) of the study's population. Individuals with a higher lower limb, extremity, and trunk muscle mass had a lower risk of NAFLD (p < 0.001). Patients with moderate/severe NAFLD had a lower muscle mass of the lower limbs and trunk than patients with mild NAFLD (p < 0.001), while the muscle mass of the upper limbs and extremities did not differ significantly between the two groups. Moreover, similar results were found for both sexes and among different age groups. Conclusions: A higher muscle mass of the lower limbs, extremities, and trunk was negatively associated with the risk of NAFLD. A lower muscle mass of the limbs and trunk was inversely associated with the severity of NAFLD. This study provides a new theoretical basis for the development of individualized exercise prescriptions for the prevention of NAFLD in non-NAFLD patients.