Nonalcoholic Fatty Liver Disease Cases Research Articles

Identifying potential drug targets for non-alcoholic fatty liver disease: a drug target Mendelian randomization study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): UK Research and Innovation Training Grant: Centre for Doctoral Training in AI-enabled Healthcare Systems Background Non-alcoholic fatty liver disease (NAFLD), a range of conditions caused by the build-up of fat in the liver, is the most common form of chronic liver disease, with an estimated prevalence of ~25% globally. NAFLD is associated with increased risk of all-cause mortality, with CVD emerging as the primary cause of death amongst affected individuals. The aetiology of NAFLD is not yet clearly understood, and currently no drugs exist for its treatment, with therapeutics aimed at symptom management instead. Purpose To identify and prioritise candidate protein drug targets and pathways relevant for therapeutic intervention in NAFLD. Methods To identify plasma proteins causally associated with NAFLD, we analysed genetic associations on 1,561 proteins from 35,559 participants in the deCODE study, and compared these to associations from a GWAS of biopsy confirmed NAFLD cases (1,483 cases, 17,781 controls). We sourced genetic variants from a 400kbp region around each protein-coding gene, pruning variants on an F-statistic of 15, minor allele frequency threshold of 1% and linkage disequilibrium r-squared of 0.4. cis-Mendelian randomization (MR) was used to identify proteins associated with NAFLD. Bias due to pleiotropy was limited by excluding variants with leverage statistic more than 3 times the mean, or outlier statistic larger than 10.83. We used colocalization analysis to identify proteins with a posterior probability of at least 0.8, indicating the presence of common causal variants. We further prioritised proteins by annotating them with information on druggability (i.e. whether a protein is a target for a known drug, or predicted to be a target for a drug), mRNA expression in pathology-relevant tissues, and involvement in known biological pathways. Results We identified 5 proteins with a multiplicity-corrected (p<3.2×10-5) association with NAFLD, and strong evidence of genetic colocalization: CYB5A, NT5C, NCAN, TGFBI, DAPK2. TGFBI and DAPK2 are potentially druggable, with all five found to be expressed in both liver and adipose tissues. Pathway analysis indicated the involvement of NT5C, CYB5A, NCAN in Reactome pathway R-HSA-1430728 reflecting cellular energy metabolism, including mitochondrial lipid metabolism, which is strongly implicated with NAFLD. Conclusion We identified a prioritised set of five plasma proteins influencing NAFLD, including druggable proteins informing de novo and ongoing drug development programs. Figure: MR effect estimates of proteins on NAFLD A: Effect of each protein on NAFLD. Each point represents a protein, effect estimates are reported in log(odds ratio) and statistical significance in -log(p-value). Coloured points represent proteins passing the multiplicity-corrected p-value threshold B: MR effect estimates of prioritised proteins. Estimates are reported in log(odds ratio). Proteins are annotated according to their druggability based on the British National Formulary and ChEMBL

Air pollution, life’s essential 8, and risk of severe non-alcoholic fatty liver disease among individuals with type 2 diabetes

BackgroundThe impacts of long-term exposure to air pollution on the risk of subsequent non-alcoholic fatty liver disease (NAFLD) among participants with type 2 diabetes (T2D) is ambiguous. The modifying role of Life’s Essential 8 (LE8) remains unknown.MethodsThis study included 23,129 participants with T2D at baseline from the UK Biobank. Annual means of nitrogen dioxide (NO2), nitrogen oxides (NOX), and particulate matter (PM2.5, PM2.5–10, PM10) were estimated using the land-use regression model for each participant. The associations between exposure to air pollution and the risk of severe NAFLD were evaluated using Cox proportional hazard models. The effect modification of LE8 was assessed through stratified analyses.ResultsDuring a median 13.6 years of follow-up, a total of 1,123 severe NAFLD cases occurred. After fully adjusting for potential covariates, higher levels of PM2.5 (hazard ratio [HR] = 1.12, 95%CI:1.02, 1.23 per interquartile range [IQR] increment), NO2 (HR = 1.15, 95%CI:1.04, 1.27), and NOX (HR = 1.08, 95%CI:1.01, 1.17) were associated with an elevated risk of severe NAFLD. In addition, LE8 score was negatively associated with the risk of NAFLD (HR = 0.97, 95% CI: 0.97, 0.98 per point increment). Compared with those who had low air pollution and high LE8, participants with a high air pollution exposure and low LE8 had a significantly higher risk of severe NAFLD.ConclusionsOur findings suggest that long-term exposure to air pollution was associated with an elevated risk of severe NAFLD among participants with T2D. A lower LE8 may increase the adverse impacts of air pollution on NAFLD.

Low ankle–brachial index is associated with higher cardiovascular mortality in individuals with nonalcoholic fatty liver disease

Background and aimsAnkle brachial index (ABI) is a risk factor for cardiovascular mortality, but it is unclear whether ABI is associated with cardiovascular mortality in patients with nonalcoholic fatty liver disease (NAFLD). The current study aimed to evaluate the association between ABI with cardiovascular and all-cause mortality in patients with NAFLD.MethodsWe performed a cohort study using the data of the1999–2004 National Health and Nutrition Examination Survey data of adults. Mortality data were followed up to December 2015. NAFLD was defined by the hepatic steatosis index or the US fatty liver index. ABI was classified into three groups: ABI ≤ 0.9 (low value); 0.9 < ABI ≤ 1.1 (borderline value); ABI greater than 1.1 (normal value).ResultsWe found that low ABI was associated with an increased risk of cardiovascular mortality in patients with NAFLD (HR: 2.42, 95% CI 1.10–5.33 for low value ABI vs normal value ABI, P for trend = 0.04), and the relationship was linearly and negatively correlated in the range of ABI < 1.4. However, low ABI was not associated with all-cause mortality in patients with NAFLD. Stratified by cardiovascular disease, ABI remains inversely correlated with cardiovascular mortality in NAFLD patients without cardiovascular disease. Stratified by diabetes, ABI is inversely correlated with cardiovascular mortality in NAFLD patients regardless of diabetes status.ConclusionsLow ABI is independently associated with higher cardiovascular mortality in NAFLD cases. This correlation remains significant even in the absence of pre-existing cardiovascular disease or diabetes.

Association between per- and poly-fluoroalkyl substances and nonalcoholic fatty liver disease: A nested case-control study in northwest China

Per- and poly-fluoroalkyl substances (PFAS) have been reported to have hepatotoxic effects. However, it is unclear whether they are linked to non-alcoholic fatty liver disease (NAFLD). This nested case-control study focused on the epidemiological links between PFAS and the prevalence of NAFLD. We selected 476 new cases of NAFLD and 952 age- and sex-matched controls from the Jinchang cohort population between 2014 and 2019. Serum concentrations of PFAS were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Only PFAS with a detection rate of ≥90 % were included for analysis, which included PFPeA, PFOA, PFNA, PFHxS, PFOS, and 9Cl-PF3ONS. The relationship between single and co-exposure to PFAS and the occurrence of NAFLD was evaluated using conditional logistic regression, Quantile g-computation (QgC), and Bayesian kernel machine regression (BKMR) model. Logistic regression indicated that PFPeA, PFOA, and 9Cl-PF3ONS were positive correlation with the incidence of NAFLD after adjusting for confounders, with odds ratios (OR) and 95 % confidence interval (CI) of 3.13 (95 % CI: 2.53, 3.86), 1.39 (95 % CI: 1.12, 1.73), and 1.41 (95 % CI: 1.20, 1.66), respectively. PFNA, PFHxS, and PFOS were nonlinearly and negatively associated with the incidence of NAFLD, with OR (95 % CI) of 0.53 (0.46, 0.62), 0.83 (0.73, 0.95), and 0.52 (0.44, 0.61), respectively. QgC showed a significant joint effect of PFAS mixture on NAFLD onset (OR: 1.52, 95 % CI: 1.24, 1.88). BKMR showed a weak positive trend between PFAS mixtures and NAFLD incidence. Positive correlations were primarily driven by PFPeA and 9Cl-PF3ONS, while negative correlations were mainly influenced by PFNA and PFOS. The BKMR model also suggested that there was an interaction between PFOS and PFNA and other four PFAS compounds. In conclusion, our findings suggest that individual and co-exposure to PFAS is associated with a risk of NAFLD onset.

Latest Trend and Perspective of Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) as a Novel Nomenclature

Recently, the medical term for nonalcoholic fatty liver disease (NAFLD) has been changed to a novel nomenclature: metabolic dysfunction-associated steatotic liver disease (MASLD). The latest report shows analyses of the National Health and Nutrition Examination Survey (NHANES III) using the fibrosis-4 index (FIB-4) and enhanced liver fibrosis (ELF). Among 6429 NAFLD cases, 99% met MASLD criteria. In another study with 4286 cases, 99% of steatosis cases met the MASLD definition, and 95.4% met the metabolic dysfunction-associated fatty liver disease (MAFLD) definition. Several biomarkers show a relationship with MASLD/MAFLD, such as BMI, T2D, HOMA-IR, central obesity, waist circumference, and CKD.

Non-alcoholic fatty liver modifies associations of body mass index and waist circumference with cardiometabolic risk: The CARDIA study.

Non-alcoholic fatty liver disease (NAFLD) is recognized as a prevalent determinant of cardiometabolic diseases. The association between NAFLD and obesity warrants further research on how NAFLD modifies associations between body mass index (BMI) and Waist circumference (WC) with cardiometabolic risk (CMR). This study assessed whether NAFLD modifies associations between BMI and WC with 5-year changes in CMR in 2366 CARDIA study participants. Non-contrast CT was used to quantify liver attenuation, with ≤51 Hounsfield Units (HU) used to define NAFLD in the absence of secondary causes of excess liver fat. The dependent variable was the average Z score of fasting glucose, insulin, triglycerides [log], (-) high-density lipoprotein cholesterol (HDL-C), and systolic blood pressure(SBP). Multivariable linear regression was used to estimate the associations between BMI and WC with CMR. Effect modification by NAFLD was assessed by an interaction term between NAFLD and BMI or WC. The final sample had 539 (23%) NAFLD cases. NAFLD modified the association of BMI and WC with CMR (interaction p<0.0001 for both). BMI and WC were associated with CMR in participants without NAFLD (p<0.001), but not among those with NAFLD. Participants with NAFLD and normal BMI and WC had CMR estimates that were higher than those without NAFLD in the obese categories. Among those without NAFLD the 5years CMR change estimate was 0.09 (95% CI: 0.062, 0.125) for BMI ≥30kg/m2 compared to -0.06 (-0.092, -0.018) for BMI<25kg/m2, and among those with NAFLD, these estimates were 0.15 (0.108, 0.193) and 0.16 (-0.035, 0.363). NAFLD modifies associations of BMI and WC with CMR. Compared with BMI and WC, NAFLD was more strongly associated with CMR. In the presence of NAFLD, BMI and WC were not associated with CMR. These findings have implications for clinical screening guidelines.

Optimizing lifestyle profiles is potential for preventing nonalcoholic fatty liver disease and enhancing its survival

The aim of this study was to evaluate the association between lifestyle profile and disease incidence/mortality in patients with non-alcoholic fatty liver disease (NAFLD). Lifestyle profiles ascertainment was based on the latent profile analysis. The associations of lifestyle profile and outcomes were analyzed by multivariate logistic or Cox regressions. Four lifestyle profiles (profile 1 and 2 for male, profile 3 and 4 for female) were established for all participants. Compared to profile 1, profile 2 (P = 0.042) and profile 3 (P = 0.013) had lower incidence for NAFLD. In contrast, profile 4 showed similar NAFLD prevalence compared to profile 1 (P = 0.756). Individuals with NAFLD within profile 3 had the best long-term survival, and the HR was 0.55 (95% CI 0.40–0.76) for all-cause mortality (compared to profile 1). Profile 4 (P = 0.098) and profile 2 (P = 0.546) had similar all-cause survival compared to profile 1. We explored the associations of healthy lifestyle score with mortality and incidence of NAFLD stratified by lifestyle profiles. We observed that with the increase of healthy lifestyle score, participants within profile 2 did not display lower NAFLD incidence and better long-term survival in NAFLD cases. In this study, lifestyle profiles were constructed in NHANES participants. The distinct lifestyle profiles may help optimize decision-making regarding lifestyle management in preventing NAFLD development, as well as selection of a more personalized approach for improving NAFLD survival.

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

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

Dietary pattern associated with non-alcoholic fatty liver disease (NAFLD) in non-diabetic adult patients: A case control study

BackgroundDietary intake is an important factor in the development and management of non-alcoholic fatty liver disease (NAFLD) however, optimal food group composition remains unclear. Data on detailed food group intake of NAFLD patients from India is scarce. Methods& Materials: In this study with 320 participants (160 NAFLD cases and 160 controls), dietary habits were assessed using a 24-hour dietary recall for two days and a validated 142-item food frequency questionnaire over the past year. Principal component analysis identified dietary patterns associated with NAFLD among the participants. ResultsCases were having a significantly higher intake of edible oils and fats along with nuts and oilseeds as compared to controls (p<0.05). There was a positive and significant association with edible oils and fats with NAFLD [OR (95 % CI):1.7(1.11-2.49) p=0.013). In dietary pattern analysis western dietary pattern was found to be a risk for NAFLD whereas protective dietary pattern was associated with the decreased risk of NAFLD. ConclusionThe overall food groups intake in NAFLD cases and controls was low suggesting lower diet quality. Protective dietary pattern found to be beneficial for NAFLD. High intake of sugars and edible oils associated with western dietary pattern increases the risk of NAFLD.

Genetically determined circulating micronutrients and the risk of nonalcoholic fatty liver disease

Evidence from epidemiological literature on the association of circulating micronutrients with risk of nonalcoholic fatty liver disease (NAFLD) is inconsistent. We aimed to elucidate the causal relationships using Mendelian randomization (MR). Single-nucleotide polymorphisms associated with 14 circulating micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B6, B12, C, D, K1 and zinc) were employed as instrumental variables. Summary level data for NAFLD were obtained from a genome-wide association study (GWAS) meta-analysis of 8434 cases and 770,180 controls (discovery stage) and another two datasets including 1483 NAFLD cases and 17,781 controls (replication stage 1) and 2134 NAFLD cases and 33,433 controls (replication stage 2). Inverse variance-weighted method (IVW) was used as primary analysis, supplemented with a series of sensitivity analysis. Genetically predicted higher β‑carotene levels were suggestively associated with reduced NAFLD risk [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.66–0.99; P = 0.047], whereas the association did not survive the false discovery rates (FDR) correction (PFDR = 0.164). Genetically predicted circulating iron (OR 1.16, 95% CI 1.05–1.29; P = 0.006, PFDR = 0.028), selenium (OR 1.11, 95% CI 1.03–1.20; P = 0.005, PFDR = 0.028) and vitamin B12 (OR 1.08, 95% CI 1.03–1.13; P = 0.002, PFDR = 0.028) were significantly associated with increased risk of NAFLD. Moreover, the findings were consistent in individual datasets (Pheterogeneity > 0.05) and confirmed in sensitivity analysis. Our study provided evidence that circulating iron, selenium and vitamin B12 might be causally linked to the risk of NAFLD, which deserves further exploration of the potential biological mechanism.

Comparison of Serum C-Reactive Protein (CRP) Level Between Non-Alcoholic Fatty Liver Disease (NAFLD) Cases and Healthy Adults: A Cross-sectional Analytical Study.

Background: Non-alcoholic fatty liver disease (NAFLD) encompasses the simple steatosis to more progressive steatosis with associated hepatitis, fibrosis and cirrhosis. Though accurate diagnosis of simple fatty liver (SFL) and non-alcoholic steatohepatitis (NASH) can be made by liver biopsy, it is not feasible to be done in all NAFLD patients. Relationship of C-reactive protein (CRP) with NAFLD was well documented in many populations, but comprehensive data is lacking in Bangladeshi people. Method: This case-control study was conducted at the Medicine, Gastroenterology and Hepatology departments in Dhaka Medical College Hospital from March to August 2018 involving 30 patients with NAFLD as case and apparently healthy 30 individuals as control. Abdominal ultrasound to detect fatty liver and serum CRP level estimation by nephelometry were performed for each subject to compare between two groups. Result: Majority of the NAFLD cases and healthy controls were female (70% and 60% respectively). Mean age was 47.53±9.69 year in NAFLD group and 46.03±8.44 year in healthy controls. NAFLD cases had significantly higher mean serum CRP concentration (6.27±1.80) mg/dl than that of healthy controls (3.94±2.16) mg/dl (p&lt;0.001). Overweight/obesity and dyslipidaemia were found as significant risk factors for NAFLD compared to the healthy control group (p&lt;0.05). Conclusion: NAFLD cases had significantly higher CRP than the control group. But, to find out the association of increasing CRP level with the severity of NAFLD and to establish it as a diagnostic tool, further extensive studies are recommended. J MEDICINE 2024; 25: 5-10

Estimated small dense low-density lipoprotein cholesterol and nonalcoholic fatty liver disease in nonobese populations.

To explore the association between estimated small dense low-density lipoprotein cholesterol (sdLDL-C) and the risk of incident nonalcoholic fatty liver disease (NAFLD) in nonobese populations. This study included participants who underwent health checkups in 2014 and were followed up until 2019. We carried out Cox proportional hazards regression analyses to evaluate the association of estimated sdLDL-C with NAFLD. Discordance analyses were carried out to estimate the relative NAFLD risk in estimated sdLDL-C versus low-density lipoprotein cholesterol (LDL-C) discordant/concordant groups. Estimated sdLDL-C was calculated by equations based on LDL-C and triglycerides. The diagnosis of NAFLD was based on the presence of abdominal ultrasonography after excluding other causes of chronic liver disease. Over a mean follow-up period of 26,694 person-years, 844 incident NAFLD cases were recorded. Compared with the first quartile of estimated sdLDL-C, the fourth quartile was associated with a 2.933-fold increased risk of NAFLD (95% confidence interval 2.095-4.107). With the increase in estimated sdLDL-C, the risk of NAFLD gradually increased both in participants within the normal range of LDL-C (hazard ratio 2.854, 95% confidence interval 1.650-5.617) and beyond the normal range of LDL-C (hazard ratio 2.636, 95% confidence interval 1.263-5.502). In addition, the inconsistent high estimated sdLDL-C/low LDL-C group was associated with an increased risk of NAFLD, but not the low estimated sdLDL-C/high LDL-C group. Estimated sdLDL-C was positively associated with the risk of incident NAFLD in a nonobese population, independent of LDL-C.

The sulfur microbial diet and risk of nonalcoholic fatty liver disease: a prospective gene–diet study from the UK Biobank

BackgroundThe gut microbiota is closely related to liver diseases. The dietary pattern associated with sulfur-metabolizing bacteria in stool has been found to influence intestinal health. ObjectiveWe aimed to investigate whether consuming the sulfur microbial diet is associated with nonalcoholic fatty liver disease (NAFLD). MethodsWe included 143,918 participants of European descent from the UK Biobank. Information on serving sizes used per diet component was recorded by an online 24-h dietary assessment tool (Oxford WebQ). The total sulfur microbial diet score was constructed by summing the product of β-coefficients and corresponding serving sizes. NAFLD was ascertained using hospital inpatient and death records. Cox proportional hazard models were used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). Mediation analyses were used to investigate underlying mediators including body mass index, waist circumference, glucose, triglyceride, urate, and C-reactive protein. A polygenic risk score for NAFLD was constructed and stratified to assess whether the association is modified by genetic predisposition. ResultsAfter a median follow-up of 11.7 y (interquartile range: 11.3–12.5 y), we documented 1540 incident cases of NAFLD. After adjustment for covariates, we observed an overall J-shaped relationship between the sulfur microbial diet and risk of NAFLD. Those in the highest quartile of sulfur microbial diet score had a 46% increased risk of NAFLD [HRQ4vsQ1 (95% CI): 1.46 (1.26, 1.69)]. We also found that this association is partly mediated by metabolic disorders and systemic inflammation. In addition, the positive association was stronger among individuals at higher genetic risk for NAFLD (Pinteraction = 0.044). ConclusionsThe sulfur microbial diet had adverse associations with incident NAFLD, particularly in those at a higher genetic risk. Our study may provide evidence on the role of sulfur-metabolizing bacteria in the diet–NAFLD association.

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

Iron status and non-alcoholic fatty liver disease: A Mendelian randomization study

ObjectivesThe aim of this study was to assess the association of genetically determined iron status with the risk for non-alcoholic fatty liver disease (NAFLD) using two-sample Mendelian randomization (MR) analysis. MethodsWe applied single nucleotide polymorphisms (SNPs) associated at genome-wide significance with iron status proxied by serum iron, ferritin, transferrin, and transferrin saturation from the Genetics of Iron status Consortium (N = 48 793), in a genome-wide association study of 1664 NAFLD cases and 400 055 controls from the United Kingdom Biobank. A SNP associated with multiple markers of iron status was only applied to one marker with the strongest association in the main analysis. Their effects on NAFLD were calculated using inverse variance weighting after excluding SNPs associated with alkaline phosphatase and lipid metabolism. ResultsThe risk for NAFLD is negatively associated with genetically predicted serum transferrin level with a 20% reduction in NAFLD risk per SD (0.65g/L) increase in transferrin (95% confidence interval [CI], 0.66–0.97), and trending positive association with transferrin saturation (odds ratio [OR], 1.50; 95% CI, 0.96–2.35) but it was not associated with serum iron (OR, 0.90; 95% CI, 0.63–1.29) and ferritin (OR, 1.33; 95% CI, 0.54–3.30). ConclusionsMR analysis provided evidence that genetically predicted higher serum transferrin, indicating lower iron status, may be protective against NAFLD, whereas higher transferrin saturation, indicating higher iron status, might increase the risk for NAFLD and its pathogenesis.

Prevalence, distribution, and hepatic fibrosis burden of the different subtypes of steatotic liver disease in primary care settings.

In relation to the new umbrella terminology for steatotic liver disease (SLD), we aimed to elucidate the prevalence, distribution, and clinical characteristics of the SLD subgroups in the primary care setting. We retrospectively collected data from 2535 individuals who underwent magnetic resonance elastography and MRI proton density fat fraction during health checkups in 5 primary care health promotion clinics. We evaluated the presence of cardiometabolic risk factors according to predefined criteria and divided all the participants according to the new SLD classification. The prevalence of SLD was 39.13% in the total cohort, and 95.77% of the SLD cases had metabolic dysfunction (one or more cardiometabolic risk factors). The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) was 29.51%, with those of metabolic dysfunction and alcohol associated steatotic liver disease (MetALD) and alcohol-associated liver disease (ALD) at 7.89% and 0.39%, respectively. According to the old criteria, the prevalence of NAFLD was 29.11%, and 95.80% of the NAFLD cases fulfilled the new criteria for MASLD. The distribution of SLD subtypes was highest for MASLD, at 75.40%, followed by MetALD at 20.06%, cryptogenic SLD at 3.33%, and ALD at 1.01%. The MetALD group had a significantly higher mean magnetic resonance elastography than the MASLD or ALD group. Almost all the patients with NAFLD met the new criteria for MASLD. The fibrosis burden of the MetALD group was higher than those of the MASLD and ALD groups.

The Surreptitious Burden of Nonalcoholic Fatty Liver Disease in the Elderly in the Asia-Pacific Region: An Insight from the Global Burden of Disease Study 2019.

Nonalcoholic fatty liver disease (NAFLD) represents a significant health threat worldwide. The aging population and a rise in metabolic syndrome in Asia might influence the epidemiology of NAFLD among the elderly. However, there is a lack of understanding of the burden and recommendations for NAFLD in this group. Our study sought to investigate the trends in the NAFLD burden among the elderly in the Asia-Pacific region. We employed data from the Global Burden of Disease 2019 study for an in-depth analysis of the prevalence and disability-adjusted life years (DALYs) along with age-standardized rate (ASR) associated with NAFLD in elderly populations (age 65-89 years) across the Asia-Pacific region, including the Southeast Asia (SEA) and Western Pacific (WP) regions, from 2010 to 2019. This study also examined the trends and disparities in NAFLD burden across different nations and sexes. In 2019, there were over 120 million cases of NAFLD in the elderly in the Asia-Pacific region. The ASR of prevalence was higher in SEA compared to WP (36,995.37 vs. 32,821.78 per 100,000). ASR of prevalence increased with annual percentage change (APC) +0.95% in the WP while it increased by +0.87% in SEA. During the study period, the ASR of DALYs decreased in SEA (APC -0.41%) but remained stable in the WP region. The burden of NAFLD in the elderly population in Asia-Pacific has increased, underscoring the timely intervention to tackle this high and rising burden.

Dietary and lifestyle indices for insulin resistance and nonalcoholic fatty liver disease

PurposeThe aim of the present study was to investigate the association of the empirical dietary index for insulin resistance (EDIR) and empirical lifestyle index for insulin resistance (ELIR) with the risk of nonalcoholic fatty liver disease (NAFLD) in Iranian adults.Design/methodology/approachIn this case-control study, 120 cases of NAFLD and 240 controls aged ≥20 years were included. NAFLD was detected by a gastroenterologist using an ultrasonography test. The food frequency questionnaire was used to collect nutritional data and determine the score of EDIR in participants. ELIR was determined based on body mass index, physical activity and dietary pattern. The odds ratios (ORs) of NAFLD were reported across tertiles of EDIR and ELIR using a logistic regression test.FindingsThe mean±SD age and BMI of subjects were 41.8 ± 7.5 years and 27.4 ± 2.2 kg/m2, respectively. In the age and sex-adjusted model, the odds of NAFLD were increased across tertiles of ELIR (OR = 3.00; 95% CI: 1.63–5.55, Ptrend = 0.001). Also, based on the fully adjusted model, the odds of NAFLD were increased according to tertiles of ELIR (OR = 2.66; 95% CI: 1.38–5.10, Ptrend = 0.006). However, no significant association was found between the higher score of EDIR and odds of NAFLD based on the age and sex-adjusted model (OR = 1.18; 95% CI: 0.68–2.05, Ptrend = 0.52) and the multivariable-adjusted model (OR = 0.91; 95% CI: 0.48–1.70, Ptrend = 0.87).Originality/valueTo the best of the authors’ knowledge, this was the first study to examine the role of the insulinemic potential of diet and lifestyle in predicting NAFLD risk. Our findings suggested that a lifestyle with a higher score of ELIR was positively associated with NAFLD risk. However, a diet with a higher score of EDIR was not related to the odds of NAFLD.

Serum metabolomic profiling unveils distinct sex-related metabolic patterns in NAFLD.

Obesity poses an increased risk for the onset of Nonalcoholic fatty liver disease (NAFLD). The influence of other factors, such as sex in the incidence and severity of this liver disease has not yet been fully elucidated. Thus, we aimed to identify the NAFLD serum metabolic signatures associated with sex in normal, overweight and obese patients and to associate the metabolite fluctuations across the increasing liver steatosis stages. Using nuclear magnetic resonance (NMR) serum samples of 210 NAFLD cases and control individuals diagnosed with liver U/S, our untargeted metabolomics enquiry provided a sex distinct metabolic bouquet. Increased levels of alanine, histidine and tyrosine are associated with severity of NAFLD in both men and women. Moreover, higher serum concentrations of valine, aspartic acid and mannose were positively associated with the progression of NAFLD among the male subjects, while a negative association was observed with the levels of creatine, phosphorylcholine and acetic acid. On the other hand, glucose was positively associated with the progression of NAFLD among the female subjects, while levels of threonine were negatively related. Fluctuations in ketone bodies acetoacetate and acetone were also observed among the female subjects probing a significant reduction in the circulatory levels of the former in NAFLD cases. A complex glycine response to hepatic steatosis of the female subjects deserves further investigation. Results of this study aspire to address the paucity of data on sex differences regarding NAFLD pathogenesis. Targeted circulatory metabolome measurements could be used as diagnostic markers for the distinct stages of NAFLD in each sex and eventually aid in the development of novel sex-related therapeutic options.

Association of single nucleotide polymorphism in patatin like phopholipase domain containing 3 (PNPLA3) gene with paediatric non-alcoholic fatty liver disease

Background: Non-alcoholic fatty liver disease (NAFLD) is the most unabating cause of chronic liver disease in children and adolescents. The aim of this study was to examine the association of paediatric NAFLD and single nucleotide polymorphism in patatin like phopholipase domain containing 3 (PNPLA3) gene. ­Methods:Τhis case-control study was carried out from June 2021 to December 2022. A total of 51 overweight children aged 6  17 years were recruited in this study and divided into NAFLD (cases) and non-NAFLD (controls) groups on the basis of hepatic steatosis detected by liver ultrasonography. We analyzed the rs738409 polymorphism by TaqMan assay and examined its association with NAFLD. ­­­­­Results: A total of 31 (60.7%) children were in case group and 20 children were in control group. Body mass index, waist circumference, total cholesterol and triglycerides levels were statistically higher in NAFLD group. Homogygosity (GG status) and heterogygosity (CG status) for PNPLA3 polymorphism was seen in 2 (6.4%) and 18 (58.1%) children having NAFLD, respectively. PNPLA3 rs738409 genotypes were similar between case and control groups. Conclusion: No association was found between PNPLA3 rs 738409 SNP with the presence of NAFLD in children. Bangabandhu Sheikh Mujib Medical University Journal 2023;16(3): 139-143