Non-alcoholic Fatty Liver Disease In Population Research Articles

The role of gut microbiota augmentation in managing non-alcoholic fatty liver disease: an in-depth umbrella review of meta-analyses with grade assessment.

Currently, there are no authorized medications specifically for non-alcoholic fatty liver disease (NAFLD) treatment. Studies indicate that changes in gut microbiota can disturb intestinal balance and impair the immune system and metabolism, thereby elevating the risk of developing and exacerbating NAFLD. Despite some debate, the potential benefits of microbial therapies in managing NAFLD have been shown. A systematic search was undertaken to identify meta-analyses of randomized controlled trials that explored the effects of microbial therapy on the NAFLD population. The goal was to synthesize the existing evidence-based knowledge in this field. The results revealed that probiotics played a significant role in various aspects, including a reduction in liver stiffness (MD: -0.38, 95% CI: [-0.49, -0.26]), hepatic steatosis (OR: 4.87, 95% CI: [1.85, 12.79]), decrease in body mass index (MD: -1.46, 95% CI: [-2.43, -0.48]), diminished waist circumference (MD: -1.81, 95% CI: [-3.18, -0.43]), lowered alanine aminotransferase levels (MD: -13.40, 95% CI: [-17.02, -9.77]), decreased aspartate aminotransferase levels (MD: -13.54, 95% CI: [-17.85, -9.22]), lowered total cholesterol levels (MD: -15.38, 95% CI: [-26.49, -4.26]), decreased fasting plasma glucose levels (MD: -4.98, 95% CI: [-9.94, -0.01]), reduced fasting insulin (MD: -1.32, 95% CI: [-2.42, -0.21]), and a decline in homeostatic model assessment of insulin resistance (MD: -0.42, 95% CI: [-0.72, -0.11]) (P<0.05). Overall, the results demonstrated that gut microbiota interventions could ameliorate a wide range of indicators including glycemic profile, dyslipidemia, anthropometric indices, and liver injury, allowing them to be considered a promising treatment strategy.

Cross-sectional and Mendelian randomization study of fibroblast growth factor 19 reveals causal associations with metabolic diseases.

Fibroblast growth factor 19 (FGF19) is an intestinal-derived factor that plays a role in metabolic diseases. We performed a differential study of circulating FGF19 levels and investigated the causal effects of FGF19 on metabolic diseases using Mendelian randomization (MR). Firstly, 958 subjects were included in the physical examination center of affiliated hospital from January 2019 to January 2021. Dividing the subjects into different subgroups to compare FGF19 levels. We conducted a two-sample MR analysis of genetically predicted circulating FGF19 in relation to alcohol, cardiovascular and metabolic biomarkers and diseases, and liver function biomarkers using publicly available genome-wide association study summary statistics data. The circulating FGF19 levels in nonalcoholic fatty liver disease (NAFLD) patients were lower than those without NAFLD (P<0.001). The FGF19 levels in participants with obese were lower than those without obese (P<0.001). In two-sample MR analyses, genetically predicted higher circulating FGF19 levels was significantly associated with lower aspartate aminotransferase, γ-glutamyltransferase, triglycerides, total cholesterol, low-density lipoprotein, and C-reactive protein concentrations (P<0.05) and a negative correlation with cardiovascular disease and cirrhosis whereas a positive association with type 2 diabetes mellitus (P<0.05). Our study found that circulating FGF19 levels were lower in NAFLD and obese populations. Additionally, our MR research results support the causal effects of FGF19 on improved liver function, lipids, and reduced the occurrence of inflammation, cardiovascular disease, and cirrhosis. We found a positive correlation with diabetes, which may indicate a compensatory increase in regulating above FGF19 resistance states in humans.

The predictive role of the platelet-to-lymphocyte ratio for the risk of non-alcoholic fatty liver disease and cirrhosis: a nationwide cross-sectional study.

The associations between platelet-to-lymphocyte ratio (PLR) and non-alcoholic fatty liver disease (NAFLD) and cirrhosis are unclear, andthere are still no effective means for diagnosing or monitoring disease progression. Data from the National Health and Nutrition Examination Surveys were collected for analysis. Logistic regression and restricted cubic splines were used to evaluate the associations between PLR and NAFLD and cirrhosis in different populations. The Area Under Curve Receiver Operating Characteristic (AUCROC) was used to distinguish the models. Threshold analysis was performed by constructing a two-piecewise linear regression. Correlation analysis was performed separately on either side of the inflection point. A total of 5724 adults were included. Logistic regression analysis revealed that the PLR was associated with NAFLD and cirrhosis (AUCROC of NAFLD: 0.803; AUCROC of cirrhosis: 0.851). The AUCROC of the PLR for predicting NAFLD incidence was 0.762 in the diabetic population and 0.804 in the nondiabetic population. High PLR predicted cirrhosis in the diabetic population, with an AUCROC of 0.824, whereas a high PLR was not associated with cirrhosis in the nondiabetic population. The restricted cubic spline revealed a negative linear correlation between the PLR and NAFLD incidence. The inflection point of the PLR for NAFLD was 180.74.A PLR ≤180.74 was statistically significant (odds ratio=0.997, 95% confidence interval=0.995-0.999). In the NAFLD population, the PLR was negatively correlated with cirrhosis at a PLR ≤130.5 (odds ratio=0.987, 95% confidence interval=0.977-0.996) and positively correlated with cirrhosis at a PLR > 130.5 (odds ratio=1.006, 95% confidence interval=1.001-1.012). The PLR and NAFLD were negatively correlated in the U.S. population. The PLR had a U-shaped relationship with cirrhosis in the NAFLD population. The PLR has potential value in monitoring NAFLD patient progression to cirrhosis.

Noninvasive liver fibrosis markers are independently associated with carotid atherosclerosis risk in patients with nonalcoholic fatty liver disease

Objective Nonalcoholic fatty liver disease (NAFLD) is considered an independent risk factor for cardiovascular disease (CVD). The overall morbidity and mortality of CVD increase with higher fibrosis stage in NAFLD. Carotid atherosclerosis (CAS) is an important predictor of cardiovascular events. However, the relationship between liver fibrosis degree and the risk of CAS in NAFLD patients remains uncertain. We aimed to investigate the relationship between noninvasive liver fibrosis markers and CAS risk in patients with NAFLD. Materials and Methods This study included 3,302 participants with NAFLD. Participants were divided into a CAS group and a non-CAS group based on carotid artery ultrasound results. They were then stratified into quartiles using various noninvasive liver fibrosis markers (fibrosis-4 (FIB-4), modified FIB-4 (mFIB-4), aminotransferase to platelet ratio index (APRI), aminotransferase to alanine aminotransferase ratio (AAR), AAR-to-platelet ratio index (AARPRI), and Forns index) to assess the associations between these markers and the risk of CAS. Results In the NAFLD population, individuals with CAS exhibited elevated levels of blood pressure, glucose, lipids, and noninvasive liver fibrosis markers (p < 0.001). The higher quartiles of noninvasive liver fibrosis markers, including FIB-4, mFIB-4, AAR, AARPRI, and Forns index, were significantly associated with increased risks of CAS, even after adjusting for multiple CVD risk factors. Conclusions In individuals with NAFLD, increased noninvasive liver fibrosis markers were independently associated with elevated CAS risk, which may be beneficial in assessing the risk of CVD in individuals with NAFLD.

Analysis of non-alcoholic fatty liver disease differences from metabolic dysfunction-associated fatty liver disease based on clinical features

Objective: To explore the clinical features of fatty liver disease (FLD) from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MASLD), so as to elucidate its clinical application value under three renames. Methods: Patients who were hospitalized in the Department of Hepatology, Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University, from January 2020 to September 2023 and met the diagnosis of NAFLD, metabolic-associated fatty liver disease (MAFLD), or MASLD were selected as the research subjects. The clinical indicators differences among the three groups of patients were compared, mainly including general information (age, gender, body mass index, past history, etc.), serological indicators (liver and kidney function, blood lipids, blood sugar, coagulation function, etc.), non-invasive liver fibrosis indicators, fat attenuation parameters, etc. Measurement data were analyzed using ANOVA and the rank sum test, while count data were analyzed using the χ(2) test. Results: NAFLD, MAFLD, and MASLD prevalence rates among 536 cases were 64.0%, 93.7%, and 100%, respectively. 318 cases (59.3%) met the three fatty liver names at the same time among them. Male population proportions in NAFLD, MAFLD, and MASLD were 30.9%, 55.8%, and 53.9%, respectively. The alcohol consumption history proportion was 0, 36.7%, and 36.0%, respectively. The smoking history proportion was 7.0%, 31.9%, and 30.6%, respectively. The body mass index was (27.66 ± 3.97), (28.33 ± 3.63), and (27.90 ± 3.89) kg/m(2), respectively. The γ-glutamyltransferase levels were 26.6 (18.0, 47.0) U/L, 31.0 (20.0, 53.0) U/L, and 30.8 (19.8, 30.8) U/L, respectively. The high-density lipoprotein cholesterol levels were 1.07 (0.90, 1.23) mmol/L, 1.02 (0.86, 1.19) mmol/L, and 1.03 (0.87,1.21) mmol/L, respectively. Sequentially measured uric acid was (322.98 ± 84.51) μmol/L, (346.57 ± 89.49) μmol/L, and (344.89 ±89.67) μmol/L, respectively. Sequentially measured creatinine was 69.6 (62.9, 79.0) μmol/L, 73.0 (65.0, 83.5) μmol/L, and 73.0 (65.0, 83.0) μmol/L, respectively. The sequential analysis of obesity proportion was 74.3%, 81.7%, and 76.5%, respectively, with statistically significant differences (P<0.05). Conclusion: Compared with the NAFLD population, the MAFLD and MASLD populations were predominantly male, obese, and had a history of smoking and drinking. The levels of γ-glutamyltransferase, uric acid, and creatinine were slightly higher, while the levels of high-density lipoprotein cholesterol were lower. MASLD appeared in NAFLD and MAFLD on the basis of inheritance and progression, emphasizing once again the important role of metabolic factors in a fatty liver.

Potassium affects the association between dietary intake of vitamin C and NAFLD among adults in the United States.

Although the association between nonalcoholic fatty liver disease (NAFLD) and vitamin C has been well studied, the effects of dietary potassium intake on this relationship are still unclear. Thus, this study aimed to determine the effects of dietary potassium intake on the association between vitamin C and NAFLD. We performed a cross-sectional learn about with 9443 contributors the usage of 2007-2018 NHANES data. Multiple logistic regression evaluation has been utilized to check out the affiliation of dietary vitamin C intake with NAFLD and advanced hepatic fibrosis (AHF). Subsequently, we plotted a smoothed match curve to visualize the association. Especially, the analysis of AHF was conducted among the NAFLD population. In addition, stratified evaluation used to be developed primarily based on demographic variables to verify the steadiness of the results. Effect amendment by way of dietary potassium intake used to be assessed via interplay checks between vitamin C and NAFLD in the multivariable linear regression. In this cross-sectional study, we found that vitamin C was negatively related to NAFLD and AHF. The relationship between vitamin C and NAFLD was different in the low, middle and high potassium intake groups. Furthermore, potassium intake significantly modified the negative relationship between vitamin C and NAFLD in most of the models. Our research showed that potassium and vitamin C have an interactive effect in reducing NAFLD, which may have great importance for clinical medication.

Physiologically Based Pharmacokinetic (PBPK) Model Predictions of Disease Mediated Changes in Drug Disposition in Patients with Nonalcoholic Fatty Liver Disease (NAFLD).

This study was designed to verify a virtual population representing patients with nonalcoholic fatty liver disease (NAFLD) to support the implementation of a physiologically based pharmacokinetic (PBPK) modeling approach for prediction of disease-related changes in drug pharmacokinetics. A virtual NAFLD patient population was developed in GastroPlus (v.9.8.2) by accounting for pathophysiological changes associated with the disease and proteomics-informed alterations in the abundance of metabolizing enzymes and transporters pertinent to drug disposition. The NAFLD population model was verified using exemplar drugs where elimination is influenced predominantly by cytochrome P450 (CYP) enzymes (chlorzoxazone, caffeine, midazolam, pioglitazone) or by transporters (rosuvastatin, 11C-metformin, morphine and the glucuronide metabolite of morphine). PBPK model predictions of plasma concentrations of all the selected drugs and hepatic radioactivity levels of 11C-metformin were consistent with the clinically-observed data. Importantly, the PBPK simulations using the virtual NAFLD population model provided reliable estimates of the extent of changes in key pharmacokinetic parameters for the exemplar drugs, with mean predicted ratios (NAFLD patients divided by healthy individuals) within 0.80- to 1.25-fold of the clinically-reported values, except for midazolam (prediction-fold difference of 0.72). A virtual NAFLD population model within the PBPK framework was successfully developed with good predictive capability of estimating disease-related changes in drug pharmacokinetics. This supports the use of a PBPK modeling approach for prediction of the pharmacokinetics of new investigational or repurposed drugs in patients with NAFLD and may help inform dose adjustments for drugs commonly used to treat comorbidities in this patient population.

Diagnosis of hepatic steatosis and steatohepatitis in people with new-onset type 2 diabetes: a multidisciplinary approach.

Non-Alcoholic-Fatty-Liver-Disease (NAFLD) is the most common cause of chronic liver disease in Western countries; closely linked to obesity and type 2 diabetes (T2DM), it is an additional cardiovascular risk factor. The aim of this study is to investigate the prevalence of NAFLD at T2DM onset. 122 newly diagnosed T2DM patients were enroled; NAFLD was diagnosed using ultrasound and fibrosis risk calculated with an FIB4-score. Intermediate and high-risk patients were referred to a hepatologist and underwent transient elastography (TE). At T2DM diagnosis, 25% of patients were overweight, 47% were obese; ultrasound steatosis was present in 79% of patients; the average FIB-4 score was 1.4 (0.7). The NAFLD population was characterised by higher presence of obesity (60%, p 0.06); hypertension (56%, p 0.00); AST (26.3 (23.6) UI/L; p 0.00); ALT (49.3(41.0) UI/L p 0.00); FIB-4 score (1.6 (0.8); p 0.00). Among patients referred to a hepatologist, at TE, 65% had severe steatosis, 22% significant fibrosis and 25% advanced fibrosis. This is the first proposal of a NAFLD screening model at T2DM diagnosis. The high prevalence of fibrosis found at the early stage T2DM confirms the compelling need for early management of NAFLD through cost-effective screening and long-term monitoring algorithms.

The Integrated Bioinformatic Assay of Genetic Expression Features and Analyses of Traditional Chinese Medicine Specific Constitution Reveal Metabolic Characteristics and Targets in Steatosis of Nonalcoholic Fatty Liver Disease.

In this study, our primary aim is to analyze the genetic expression feature and analyze specific Traditional Chinese medicine (TCM) constitution distribution in non-alcoholic fatty liver disease (NAFLD) and reveal the metabolic characteristic of NAFLD. For revealing genetic features, we obtained the gene expression data from the Gene Expression Omnibus (GEO) database of the National Center for Biotechnology Information(NCBI). The genetic data on NAFLD were analyzed by identifying differentially expressed genes (DEGs), associated pathways, co-expressed genetic networks, and gene set enrichment function. Concurrently, we assessed specific constitution distributions among local NAFLD patients through established TCM constitution models and determined the independent variable, including specific constitution to the NAFLD via the regression analyses. The analyses on GEO datasets showed that simple steatosis in NAFLD is strongly associated with HOMA-insulin resistance (HOMA-IR). Analyses of GEO datasets revealed significantly altered genetic expression profiles between NAFLD and normal populations. For TCM constitution analyses, we demonstrated a decline in yin-yang harmony (YYH) and yang-asthenia (YAAC) constitution, whereas there was an increase in qi-stagnation (QSC) and phlegm-dampness (PDC) in NAFLD. The binary logistic regression analysis indicated that besides other metabolic parameters, YYH, qi asthenia (QAC), YYAC, and yin-asthenia (YAC) were the independent variables of NAFLD, while YAC was the independent variables of T2D. The multilinear regression analyses suggested that NAFLD, DM, BMI, waist, TC, TG, hypertension, ALT, AST, and YAC were the significant determinators of the FPG. This study presents a relatively comprehensive metabolic profile in steatosis of NAFLD, revealed by significant genetic expression feature alterations and different TCM constitution distribution in NAFLD. Through this method, the study intends to associate the genetic feature with the phenotype of TCM constitution. The results could be applied to assist integrative medicine research in exploring the appropriate personalized approaches for NAFLD.

Poor Performance of Non-invasive Tests for Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: A Multicentric Asian Study.

Non-invasive tests (NITs) are useful to assess advanced fibrosis (AF) in nonalcoholic fatty liver disease (NAFLD). Data from Asian countries suggest that these tests have poor performance. We aimed to assess diagnostic accuracy of established thresholds of biomarker-based NITs and Transient Elastography (TE) in identifying AF and evaluated the utility of a two-step test approach. Biopsy-proven 641 NAFLD patients (55.2% males, median age 42years) were included from three different centers of Asia. AF (≥ F3) was identified as per histological staging (24.8%). TE had the highest area under the receiver operating characteristic curve (AUROC) 0.82 (0.79-0.86), and all other biomarker-based NITs had low AUROC (< 0.7). NITs performed poorly at established thresholds. The combination of NITs utilizing liver stiffness measurement (LSM) and biomarkers, Agile 3+ and FAST, demonstrated acceptable diagnostic accuracy (AUROC 0.82 and 0.78, respectively), but none were superior to LSM alone. LSM measured using appropriate M and XL probes remained accurate regardless of body mass index (BMI); NFS and APRI scores were less accurate at higher BMI ranges. A two-step approach using NFS rule-out criteria (< -2.97 to rule out) followed by LSM (< 7.3kPa to rule out and ≥ 12.7kPa to rule in) correctly classified 62.4% of patients, with only 10.2% of patients incorrectly classified. NITs have not been validated to identify AF in the Asian NAFLD population, and internationally accepted thresholds yield high false-negative rates. LSM and LSM-based combination tests remain the most accurate.

Metabolic health phenotype better predicts subclinical atherosclerosis than body mass index-based obesity phenotype in the non-alcoholic fatty liver disease population.

Non-alcoholic fatty liver disease (NAFLD), especially lean NAFLD is associated with an increased risk of atherosclerotic cardiovascular disease (CVD). It is not currently known which clinical phenotypes of NAFLD contribute most to individual subclinical atherosclerosis risk. We examined the relationship between body mass index (BMI), the metabolically healthy status, and subclinical atherosclerosis in the NAFLD population. Data from asymptomatic NAFLD subjects who participated in a routine health check-up examination were collected. Participants were stratified by BMI (cutoff values: 24.0-27.9 kg/m2 for overweight and ≥28.0 kg/m2 for obesity) and metabolic status, which was defined by Adult Treatment Panel III criteria. Subclinical atherosclerosis was evaluated by brachial-ankle pulse wave velocity (baPWV) in 27,738 participants and by carotid plaque in 14,323 participants. Within each BMI strata, metabolically unhealthy subjects had a significantly higher prevalence of subclinical atherosclerosis than metabolically healthy subjects, whereas fewer differences were observed across subjects within the same metabolic category. When BMI and metabolic status were assessed together, a metabolically unhealthy status was the main contributor to the association of clinical phenotypes with the subclinical atherosclerosis burden (all p < 0.001). When BMI and metabolic abnormalities were assessed separately, the incidence of subclinical disease did not increase across BMI categories; however, it increased with an increase in the number of metabolic abnormalities (0, 1, 2 and ≥3). A metabolically healthy status in NAFLD patients was closely correlated with subclinical atherosclerosis, beyond that of the BMI-based obesity phenotype. The application of metabolic phenotyping strategies could enable more precise classification in evaluating cardiovascular risk in NAFLD.

Hepatocellular carcinoma in patients with non-alcoholic fatty liver disease is associated with heterogeneous pattern of fat infiltration in skeletal muscles.

To evaluate the association between fat infiltration in skeletal muscles (myosteatosis) and hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). In a cross-sectional cohort of 72 histologically proven NAFLD patients (n = 38 with non-alcoholic steatohepatitis; NASH), among which 20 had HCC diagnosed on biopsy, we used proton density fat fraction (PDFF) at MRI to evaluate myosteatosis in skeletal muscles (mean fat fraction and first order radiomic-based pattern) at the third lumbar level, namely in erector spinae (ES), quadratus lumborum (QL), psoas, oblique, and rectus muscles. PDFFES was 70% higher in patients with HCC when compared to those without HCC (9.6 ± 5.5% versus 5.7 ± 3.0%, respectively, p < 0.001). In multivariate logistic regression, PDFFES was a significant predictor of the presence of HCC (AUC = 0.72, 95% CI 0.57-0.86, p = 0.002) independently from age, sex, visceral fat area, and liver fibrosis stage (all p < 0.05). The relationship between PDFFES and HCC was exacerbated in patients with NASH (AUC = 0.79, 95% CI 0.63-0.86, p = 0.006). In patients with NASH, radiomics features of heterogeneity such as energy and entropy in any of the paraspinal muscles (i.e., ES, QL, or psoas) were independent predictors of HCC. EnergyES identified patients with HCC (n = 13) in the NASH population with AUC = 0.92 (95% CI 0.82-1.00, p < 0.001). In patients with NAFLD, and more specifically in those with NASH, the degree and heterogeneity of myosteatosis is independently associated with HCC irrespective of liver fibrosis stage. Our data suggest that myosteatosis could be used as a biomarker of HCC in the ever-expanding NAFLD population and pave the way for further investigation in longitudinal studies. • HCC in patients with non-alcoholic fatty liver disease, and more specifically in those with non-alcoholic steatohepatitis, is independently associated with severe fatty infiltration (myosteatosis) of paravertebral skeletal muscles. • Association between myosteatosis and HCC is independent from liver fibrosis stage. • Histogram-based radiomics features of myosteatosis predicts the risk of HCC in patients with non-alcoholic steatohepatitis.

Impact renaming non-alcoholic fatty liver disease to metabolic associated fatty liver disease in prevalence, characteristics and risk factors.

Recently, a group of hepatologists proposed to rename non-alcoholic fatty liver disease (NAFLD) as metabolic associated fatty liver disease (MAFLD) with modified diagnostic criteria. It is important to note, however, that there are some differences between the diagnostic criteria used for NAFLD and MAFLD. Since the research on MAFLD is just beginning, however, evidence on its incidence and prevalence in the general population and in specific subpopulations remains limited. To assess epidemiology of fatty liver in new definition and compare MAFLD with NAFLD. Exploring risk factors of MAFLD individuals. This was a retrospective, cross-sectional study. A total of 85242 adults were selected from the Chinese health management database in 2017-2022. The data of general information, laboratory indicators, lifestyle management and psychological status were obtained. MAFLD was diagnosed as ultrasound diagnosis of fatty liver and at least one between these three conditions: Overweight/obesity, type 2 diabetes mellitus (T2DM) or metabolic dysregulation. Metabolic factors were not considered in NAFLD diagnosis standard. The clinical characteristics of MAFLD and NAFLD were analysed using descriptive statistics. Continuous variables normally distributed were expressed as means ± SD. Categorical variables were expressed as frequencies and proportions. Binary logistic regression was used to determine risk factors of the MAFLD. The prevalence of MAFLD and NAFLD was 40.5% and 31.0%, respectively. The MAFLD or NAFLD population is more likely to be older (M: 47.19 ± 10.82 vs 43.43 ± 11.96; N: 47.72 ± 11.17 vs 43.71 ± 11.66), male (M: 77.21% vs 44.43%; N: 67.90% vs 53.12%) and high body mass index (M: 26.79 ± 2.69 vs 22.44 ± 2.48; N: 26.29 ± 2.84 vs 23.29 ± 3.12) than the non-MAFLD or non-MAFLD population. In multivariate analysis, general information (e.g., ≥ 2 metabolic abnormalities OR = 3.38, (95%CI: 2.99-3.81), P < 0.001; diastolic blood pressure OR = 1.01, (95%CI: 1.00-1.01), P = 0.002), laboratory results [e.g.,total bilirubin (TBIL) OR = 0.98, (95%CI: 0.98-0.99), P < 0.001; serum uric acid(SUA) OR = 1.01, (95%CI: 1.01-1.01), P < 0.001], and lifestyle factors [e.g., drink beverage OR = 0.32, (95%CI: 0.17-0.63), P = 0.001] were influence factors for MAFLD. Our study results offer new insight into potential risk factors associated with fatty liver disease, including SUA, TBIL and creatinine, all of which are related to chronic renal disease (CKD). MAFLD is more prevalent than NAFLD, with two-fifths of individuals meeting the diagnosis criteria. MAFLD and NAFLD populations have different clinical characteristics. CKD may be related with MAFLD.

The impact of gut microbiome-targeted therapy on liver enzymes in patients with nonalcoholic fatty liver disease: an umbrella meta-analysis.

Nonalcoholic fatty liver disease (NAFLD) is considered the leading cause of chronic liver disease worldwide. To date, no confirmed medication is available for the treatment of NAFLD. Previous studies showed the promising effects of gut microbiome-targeted therapies; however, the results were controversial and the strength of the evidence and their clinical significance remained unclear. This umbrella study summarizes the results of meta-analyses investigating the effects of probiotics, prebiotics, and synbiotics on liver enzymes in the NAFLD population. A comprehensive search of the PubMed, Scopus, Web of Science, and Cochrane Library databases was done up to December 20, 2022, to find meta-analyses on randomized control trials reporting the effects of gut microbial therapy on patients with NAFLD. Two independent investigators extracted data on the characteristics of meta-analyses, and any discrepancies were resolved by a third researcher. The AMSTAR2 checklist was used for evaluating the quality of studies. A final total of 15 studies were included in the analysis. Results showed that microbiome-targeted therapies could significantly reduce levels of alanine aminotransferase (ALT; effect size [ES], -10.21; 95% confidence interval [CI], -13.29, -7.14; P < 0.001), aspartate aminotransferase (AST; ES, -8.86; 95%CI, -11.39, -6.32; P < 0.001), and γ-glutamyltransferase (ES, -5.56; 95%CI, -7.92, -3.31; P < 0.001) in patients with NAFLD. Results of subgroup analysis based on intervention showed probiotics could significantly reduce levels of AST (ES, -8.69; 95%CI, -11.01, -6.37; P < 0.001) and ALT (ES, -9.82; 95%CI, -11.59, -8.05; P < 0.001). Synbiotics could significantly reduce levels of AST (ES, -11.40; 95%CI, -13.91, -8.88; P < 0.001) and ALT (ES, -11.87; 95%CI, -13.80, -9.95; P < 0.001). Prebiotics had no significant effects on AST and ALT levels (ES, -2.96; 95%CI, -8.12, 2.18, P = 0.259; and ES, -4.69; 95%CI, -13.53, 4.15, P = 0.299, respectively). Gut microbiome-targeted therapies could be a promising therapeutic approach in the improvement of hepatic damage in patients with NAFLD. However, more studies are needed to better determine the best bacterial strains, duration of treatment, and optimum dosage of gut microbiome-targeted therapies in the treatment of the NAFLD population. PROSPERO registration no. CRD42022346998.

Prevalence and associated factors for non-alcoholic fatty liverdisease among adults in the South Asian Region: a meta-analysis.

Non-alcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease worldwide. We estimated the prevalence and predefined associated factors for NAFLD among South-Asian adults. We searched PubMed and included descriptive, epidemiological studies with satisfactory methodology, reporting the prevalence of NAFLD with ultrasound. Two authors screened and extracted data independently. Gender, urban/rural settings, general population and individuals with metabolic diseases (MetD) stratified the analysis. In addition, a random-effects meta-analysis of the prevalence and effect sizes of associations of NAFLD was performed. Twenty-two publications were included after the quality assurance process. The difference in the NAFLD prevalence between the general population and people with MetD was found to be statistically significant (Q=15.8, DF=1, P<0.001). The pooled overall prevalence of NAFLD in the general population was 26.9% (95% CI: 18.9-35.8%) with high heterogeneity. The prevalence was similar among men and women (Q=0.06, DF=1, P=0.806). The NAFLD prevalence in the rural communities was 22.6% (95% CI: 13.6-33.1%), and the prevalence in urban communities was 32.9% (95% CI: 22.8-43.8%) and the difference was not statistically significant (Q=1.92, DF=1, P=0.166). The pooled overall prevalence of NAFLD in patients with MetD was 54.1% (95% CI: 44.1-63.9%) with high heterogeneity. The pooled overall prevalence of NAFLD in the non-obese population was 11.7% (95% CI: 7.0-17.3%). The pooled prevalence of non-obese NAFLD in the NAFLD population was 43.4% (95% CI: 28.1-59.4%). Meta-analysis of binary variables showed that NAFLD in the South Asian population was associated with diabetes mellitus, hypertension, dyslipidaemia, general obesity, central obesity and metabolic syndrome. Gender was not associated with NAFLD. The overall prevalence of NAFLD among adults in South Asia is high, especially in those with MetD, and a considerable proportion is non-obese. In the South Asian population, NAFLD was associated with diabetes mellitus, hypertension, dyslipidaemia, general obesity, central obesity, and metabolic syndrome. None.

MBOAT7 rs641738 (C>T) is associated with NAFLD progression in men and decreased ASCVD risk in elder Chinese population.

The MBOAT7 rs641738 (C>T) variant has demonstrated an association with non-alcoholic fatty liver disease (NAFLD) in both adult and pediatric patients, while few studies have been conducted in elderly populations. Hence, a case-control study was undertaken to assess their correlation in elderly residents in a Beijing community. A total of 1,287 participants were included. Medical history, abdominal ultrasound, and laboratory tests were recorded. Liver fat content and fibrosis stage were detected by Fibroscan. Genotyping of genomic DNA was performed using the 96.96 genotyping integrated fluidics circuit. Of the recruited subjects, 638 subjects (56.60%) had NAFLD, and 398 subjects (35.28%) had atherosclerotic cardiovascular disease (ASCVD). T allele carriage was associated with higher ALT (p=0.005) and significant fibrosis in male NAFLD patients (p=0.005) compared to CC genotype. TT genotype was associated with reduced risk of metabolic syndrome (OR=0.589, 95%CI: 0.114-0.683, p=0.005) and type 2 diabetes (OR=0.804, 95%CI: 0.277-0.296, p=0.048) in NAFLD population when compared to the CC genotype. In addition, TT genotype was also associated with reduced risk of ASCVD (OR=0.570, 95%CI:0.340-0.953, p=0.032) and less obesity (OR=0.545, 95%CI: 0.346-0.856, p=0.008) in the whole population. MBOAT7 rs641738 (C>T) variant was associated with fibrosis in male NAFLD patients. The variant also reduced risk of metabolic traits and type 2 diabetes in NAFLD and ASCVD risk in Chinese elders.

Sensitivity and specificity of three diabetes diagnostic criteria in people with non-alcoholic fatty liver disease (NAFLD) and otherwise healthy people: Analysis of NHANES III

AimsEstablishing whether fasting plasma glucose (FPG), postprandial glucose (PPG), and HbA1c have the same diagnostic accuracy in NAFLD versus otherwise healthy people could inform T2DM screening recommendations for those with NAFLD. MethodsCross-sectional analysis of the Third National Health and Nutrition Examination Survey (NHANES III) 1989–1994. T2DM was defined as PPG ≥ 200 mg/dL, FPG ≥ 126 mg/dL, or HbA1c ≥ 6.5 %. We estimated sensitivity and specificity between the six pairwise combinations between the three T2DM definitions in people with and without NAFLD. With Poisson regressions, we investigated if people with NAFLD were more likely to have T2DM with two diagnostic criteria yet not with the third one. ResultsThere were 3652 people with mean age 55.6 years and 49.4 % were men; 673 (18.4 %) people had NAFLD. Compared to NAFLD-free individuals, those with NAFLD had lower specificity in all pairwise comparisons except when PPG was the reference vs HbA1c [98.28 % (95 % CI: 97.73 %−98.72 %) in people without NAFLD vs 96.15 % (95 % CI: 94.28 %−97.54 %)]. The sensitivity of FPG was slightly superior to PPG and HbA1c in people without NAFLD; for example, 64.62 % (95 % CI: 55.75 %−72.80 %) for FPG vs 56.58 % (95 % CI: 44.71 %−67.92 %) for HbA1c. People with NAFLD were more likely to be diagnosed with FPG and PPG yet not with HbA1c (PR=2.15; p = 0.020). ConclusionsWhile these T2DM diagnostic criteria may capture different patients both in people with and without NAFLD, in the NAFLD population FPG appears to have the best sensitivity and there were no differences between PPG and HbA1c in terms of specificity.

Examining genetic associations with hepatic steatosis in Mexican-origin adults

Introduction and ObjectivesVarious studies have identified single-nucleotide polymorphisms (SNPs) associated with nonalcoholic fatty liver disease (NAFLD) and related traits, including ones located in or near the LYPLAL1, GCKR, PPP1R3B, TM6SF2, MBOAT7, and PNPLA3 genes. However, these SNPs were identified primarily in populations of European ancestry. This study examined the associations of these previously identified SNPs with hepatic steatosis in a sample of Mexican-origin adults living in Southern Arizona. Materials and MethodsA total of 307 Mexican-origin adults between the ages of 18 and 64 with a body mass index (BMI) of 25 kg/m2 or higher were genotyped at the following SNPs: rs12137855 (LYPLAL1), rs1260326 (GCKR), rs4240624 (PPP1R3B), rs58542926 (TM6SF2), rs641738 (MBOAT7), and rs738409 (PNPLA3). Hepatic steatosis was assessed by transient elastography (FibroScan®) with controlled attenuation parameter. Regression models examined the association between each of the six SNPs and hepatic steatosis. BMI was examined as a potential modifier of the genetic associations. ResultsParticipants were, on average, 45 years old and mostly female (63%) with an overall mean hepatic steatosis of 288.1 dB/m. Models showed no associations between LYPLAL1, GCKR, PPP1R3B, TM6SF2, or MBOAT7 and hepatic steatosis. Only PNPLA3 was statistically significantly associated with hepatic steatosis in both unadjusted and adjusted models (p<0.01). There was no effect modification observed with BMI. ConclusionsSNPs associated with NAFLD in populations of European descent did not strongly contribute to hepatic steatosis in individuals of Mexican-origin, except for rs738409 (PNPLA3). Further efforts are necessary to explore additional SNPs that may be associated with NAFLD in this high-risk population.

The Transition of Cardiovascular Disease Risks from NAFLD to MAFLD.

The increased burden of nonalcoholic fatty liver disease (NAFLD) parallels the increased incidence of overweight and metabolic syndrome worldwide. Because of the close relationship between metabolic disorders and fatty liver disease, a new term, metabolic-related fatty liver disease (MAFLD), was proposed by a group of experts to more precisely describe fatty liver disease resulting from metabolic disorders. According to the definitions, MAFLD and NAFLD populations have considerable discrepancies, but overlap does exist. This new definition has a nonnegligible impact on clinical practices, including diagnoses, interventions, and the risk of comorbidities. Emerging evidence has suggested that patients with MAFLD have more metabolic comorbidities and an increased risk of all-cause mortality, particularly cardiovascular mortality than patients with NAFLD. In this review, we systemically summarized and compared the risk and underlying mechanisms of cardiovascular disease (CVD) in patients with NAFLD or MAFLD.

Effect of Dietary Intervention, with or without Cointerventions, on Inflammatory Markers in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease from simple steatosis to nonalcoholic steatohepatitis, with inflammatory cytokines and adipokines identified as drivers of disease progression. Poor dietary patterns are known to promote an inflammatory milieu, although the effects of specific diets remain largely unknown. This review aimed to gather and summarize new and existing evidence on the effect of dietary intervention on inflammatory markers in patients with NAFLD. The electronic databases MEDLINE, EMBASE, CINAHL, and Cochrane were searched for clinical trials which investigated outcomes of inflammatory cytokines and adipokines. Eligible studies included adults >18 y with NAFLD, which compared a dietary intervention with an alternative diet or control (no intervention) group or were accompanied by supplementation or other lifestyle interventions. Outcomes for inflammatory markers were grouped and pooled for meta-analysis where heterogeneity was allowed. Methodological quality and risk of bias were assessed using the Academy of Nutrition and Dietetics Criteria. Overall, 44 studies with a total of 2579 participants were included. Meta-analyses indicated intervention with an isocaloric diet plus supplement was more effective in reducing C-reactive protein (CRP) [standard mean difference (SMD): 0.44; 95% CI: 0.20, 0.68; P = 0.0003] and tumor necrosis factor-alpha (TNF-α) (SMD: 0.74; 95% CI: 0.02, 1.46; P = 0.03) than an isocaloric diet alone. No significant weighting was shown between a hypocaloric diet with or without supplementation for CRP (SMD: 0.30; 95% CI: -0.84, 1.44; P = 0.60) and TNF-α (SMD: 0.01; 95% CI: -0.43, 0.45; P = 0.97). In conclusion, hypocaloric and energy-restricted diets alone or with supplementation, and isocaloric diets with supplementation were shown to be most effective in improving the inflammatory profile of patients with NAFLD. To better determine the effectiveness of dietary intervention alone on a NAFLD population, further investigations of longer durations, with larger sample sizes are required.