Metabolic Liver Disease Research Articles

Dietary Interventions and Physical Activity as Crucial Factors in the Prevention and Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and affects nearly 30% of the adult population and 10% of the pediatric population. It is estimated that this number will double by 2030. MASLD is one of the leading causes of hepatocellular carcinoma, cirrhosis, and liver transplantation, as well as a significant risk factor for cardiovascular disease and mortality. Due to the ever-increasing number of patients, the long-term asymptomatic course of the disease, serious complications, and lack of preventive programs, as well as insufficient awareness of the disease among patients and doctors themselves, MASLD is a growing interdisciplinary problem and a real challenge for modern medicine. The main cause of MASLD is an inappropriate lifestyle—inadequate nutrition and insufficient physical activity, which lead to various components of metabolic syndrome. Lifestyle changes—appropriate diet, weight reduction, and systematic physical activity—are also the basis for the prevention and treatment of MASLD. Hence, in recent years, so much importance has been attached to lifestyle medicine, to non-pharmacological treatment as prevention of lifestyle diseases. The narrative review presents possible therapeutic options for non-pharmacological management in the prevention and treatment of MASLD. The best documented and available diets used in MASLD were discussed, focusing on the benefits and drawbacks of the Mediterranean, high-protein, ketogenic, and intermittent fasting diets. In addition, the most recent recommendations regarding physical activity are summarized.

Correlation between metabolic dysfunction-associated steatotic liver disease and subclinical coronary atherosclerosis in eastern China

BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by the presence of at least one cardiovascular disease (CVD) risk factor, underscoring its potential to elevate CVD risk in affected individuals. However, evidence linking MASLD to subclinical coronary atherosclerosis remains scarce, and further investigations are necessary to elucidate the independent role of varying MASLD severities as a CVD risk factor.MethodsThis study analyzed 7,507 participants aged ≥ 40 who underwent comprehensive health evaluations at the Shanghai Health and Medical Center. Logistic regression analysis was utilized to explore the relationship between MASLD severity and the presence of coronary artery calcification (CAC). Correlation analysis was performed to assess the association between MASLD severity and CAC staging.ResultsAfter adjusting for established CVD risk factors, MASLD showed a significant association with CAC, which intensified with increasing MASLD severity. Among individuals with hypertension, MASLD was markedly correlated with CAC. In contrast, in non-hypertensive participants, only moderate and severe MASLD were significantly associated with CAC, while mild MASLD demonstrated no notable link, even after adjustment for CVD risk factors. Moreover, correlation analysis revealed a positive association between MASLD severity and CAC staging, indicating that higher MASLD severity aligned with more advanced CAC stages.ConclusionThis study highlighted that MASLD severity was independently associated with subclinical atherosclerosis, irrespective of traditional CVD risk factors, in an urban eastern Chinese population without a prior history of coronary atherosclerosis. The strongest associations were observed in individuals with severe MASLD, emphasizing the importance of assessing MASLD severity in CVD risk stratification.

Identifying Metabolic Dysfunction Associated Steatotic Liver Disease Using Natural Language Processing in a U.S National Cohort

Background and Aims: Although metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD with increased alcohol intake (MetALD) are identified as clinical entities, tools to identify patients from electronic health records (EHRs) to perform large outcome studies are lacking. Methods: In this retrospective study of participants from the Veterans Analysis of Liver Disease (VALID) cohort assembled from 1/1/2013 to 12/31/2022, a rule-based natural language processing (NLP) algorithm searched EHRs for imaging evidence of hepatic steatosis. This was combined with identification of cardiometabolic risk factors (CMRF) and harmful alcohol use. Algorithm-derived diagnoses of MASLD, MetALD, alcohol-associated steatotic liver disease (ALD), and no steatotic liver disease (SLD) were validated using a blinded review of randomly selected charts. Results: Among 817,657 eligible Veterans, SLD was present in over half (n=438,209, 53.5%), including MASLD in 299,259 (36.5%), 99,163 with MetALD (12.1%), 38,552 (4.7%) with ALD. The NLP algorithm had a high correlation with steatosis on chart review, with a kappa of 0.86 (95% CI 0.82-0.90), sensitivity of 0.96 and specificity of 0.90. Classification of MASLD, MetALD, ALD and no SLD by the algorithm also showed high correlation with chart review, with a kappa of 0.87 (95% CI 0.82-0.91). This algorithm identified 299,259 (36.5%) of the study cohort with MASLD, compared to 23,218 (2.8%) patients identified using ICD 9/10 codes. Conclusions and Relevance: An algorithm combining rule-based NLP with CMRFs and alcohol use from EHRs accurately identifies and classifies SLD and can be applied in large epidemiologic studies of SLD in the VHA.

Publisher Correction: Partitioned polygenic risk scores identify distinct types of metabolic dysfunction-associated steatotic liver disease

Publisher Correction: Partitioned polygenic risk scores identify distinct types of metabolic dysfunction-associated steatotic liver disease

Association Between Sociodemographic Variables, Healthy Habits, and Stress with Risk Scales for Liver Disease Associated with Metabolic Dysfunction

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common cause of chronic liver disease worldwide, with a multifactorial etiology. This study aims to evaluate the associations between various sociodemographic variables, healthy habits, and stress with risk scale values for MAFLD. Materials and Methods: A descriptive, cross-sectional study was conducted on 16,708 Spanish workers to assess how sociodemographic variables (age, gender, and socioeconomic status), healthy habits (smoking, Mediterranean diet adherence, and physical activity), and stress correlate with values from three MAFLD risk scales: fatty liver index (FLI), hepatic steatosis index (HSI), and lipid accumulation product (LAP). Results: All analyzed variables were associated with the values of the three MAFLD risk scales. Among them, the variables showing the strongest associations (represented by odds ratio values) were age and physical activity. Conclusions: The profile of an individual at higher risk of elevated MAFLD risk scale values is a male, aged 50 or older, belonging to lower socioeconomic levels (manual laborers), a smoker, sedentary, with low adherence to the Mediterranean diet, and with high stress scale scores.

Association between neutrophil-to-high-density lipoprotein cholesterol ratio and non-alcoholic fatty liver disease or metabolic dysfunction-associated steatotic liver disease: evidence from NHANES 2017–2020

BackgroundNon-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with chronic inflammation and lipid metabolism disorders. The neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) is an integrative marker reflecting inflammatory responses and lipid metabolism disorders and is associated with various diseases. This cross-sectional study aimed to determine the association between NHR and NAFLD, MASLD, and liver fibrosis.MethodsData for this study were obtained from the 2017–2020 National Health and Nutrition Examination Survey (NHANES), we employed weighted multiple regression and restricted cubic spline (RCS) analysis to assess the relationship between NHR and NAFLD, MASLD, and liver fibrosis. Additionally, we performed stratified analyses based on gender, age, body mass index, diabetes, hypertension, smoking status, and history of cardiovascular disease to evaluate the consistency of these associations across different subgroups.ResultsA total of 6,526 participants were included in the study. 2,839 (weighted 44.1%) participants were diagnosed with NAFLD and 2,813 (weighted 43.7%) participants were diagnosed with MASLD. After adjusting for confounders, NHR was positively associated with the risk of NAFLD/MASLD, and the correlation was particularly significant in the subgroups of females, those without hypertension, and those without diabetes (p < 0.05). By the NHR quartile, the risk of NAFLD/MASLD increased progressively with higher NHR levels (P for trend <0.001). In addition, RCS analysis showed a nonlinear association between NHR and NAFLD/MASLD and liver fibrosis (P-non-linear <0.05).ConclusionNHR may serve as a potential marker for NAFLD/MASLD and liver fibrosis, and lowering NHR levels could help reduce the incidence of these conditions.

Comparison of Referral Rates and Costs Using Fibrosis-4 and Enhanced Liver Fibrosis (ELF) Testing Strategies for Initial Evaluation of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in a Veteran Population.

Global metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is estimated at 30% and projected to reach 55.7% by 2040. In the Veterans Affairs (VA) healthcare system, an estimated 1.8 million veterans have metabolic dysfunction-associated steatohepatitis (MASH). Adult patients at risk for MASLD in a VA healthcare system underwent Fibrosis-4 (FIB-4) and Enhanced Liver Fibrosis (ELF®) testing. Referral rates and cost savings were compared among 6 noninvasive testing (NIT) strategies using these 2 tests independently or sequentially at various cutoffs. Enrolled patients (N = 254) had a mean age of 65.3 ± 9.3 years and mean body mass index (BMI) of 31.7 ± 6, 87.4% male: 78.3% were non-Hispanic/Latino, and 96.5% had type 2 diabetes mellitus (T2DM). Among the 6 evaluated strategies, using FIB-4 followed by ELF at a 9.8 cutoff yielded the highest proportion of patients retained in primary care without need of referral to hepatology clinic (165/227; 72.7%), and was associated with the lowest costs ($407.62). Compared to the FIB-4 only strategy, FIB-4/ELF with a 9.8 cutoff strategy resulted in 26% fewer referrals and 8.47% lower costs. In the subgroup of patients with BMI >32, there were 25.17% fewer referrals and costs were 8.31% lower. Our study suggests that sequential use of ELF with a 9.8 cutoff following indeterminate FIB-4 tests results in lower referral rates and lower care costs in a veteran population at risk of MASLD. Adding ELF as a sequential test after indeterminate FIB-4 might help reduce the number of referrals and overall cost of care.

Circulating Cell-Free DNA in Metabolic Diseases

Abstract Metabolic diseases affect a consistent part of the human population, leading to rising mortality rates. This raises the need for diagnostic tools to monitor the progress of these diseases. Lately, circulating cell-free DNA (cfDNA) has emerged as promising biomarker for various metabolic diseases, including obesity, type 2 diabetes (T2D), and metabolic associated fatty liver disease (MAFLD). CfDNA is released from apoptotic and necrotic cells into the bloodstream and other body fluids, and it retains various molecular signatures of its tissue of origin. Thus, cfDNA load and composition can reflect tissue pathologies and systemic metabolic dysfunctions. In addition to its potential as diagnostic biomarker, interest in cfDNA derives from its recently discovered role in adipose tissue inflammation in obesity. This review discusses detection methods and clinical significance of cfDNA in metabolic diseases.

Association of changes in the type 2 diabetes and MASLD/related SLD status with risk of developing cardiovascular disease.

This study assessed the association of remission of type 2 diabetes mellitus (DM) or metabolic dysfunction-associated steatotic liver disease (MASLD)/related SLD (r-SLD; MASLD with excessive alcohol intake) as defined by the fatty liver index with the risk of cardiovascular disease (CVD). Health examination data at baseline and after 2 years (2-Years) were extracted from a nationwide claims database in Japan. Among participants aged 18-72 years with at least 3 years of follow-up, 9345 participants with DM-associated MASLD/r-SLD and 71 932 participants with non-DM MASLD/r-SLD at baseline were included in the study. The participants were stratified by the achievement of remission of MASLD/r-SLD or DM at 2-Years. In each group after stratification, the risk of new-onset CVD during the observation period was analysed using multivariate Cox proportional hazards models. During a median follow-up of 4.9 years (starting from 2-Years), 1368 cases of CVD were observed. The hazard ratio (95% confidence interval) for CVD was 0.50 (0.31-0.80) for participants with remission of DM, 0.65 (0.47-0.91) for participants with remission of MASLD/r-SLD, and 0.34 (0.15-0.77) for participants with remission of both DM and MASLD/r-SLD. Conversely, remission of MASLD/r-SLD was not linked to a reduced risk of CVD in participants with non-DM MASLD/r-SLD. The association of MASLD/r-SLD remission with CVD risk differs greatly in the presence and absence of DM. In patients with DM-MASLD/r-SLD, MASLD/r-SLD remission can significantly reduce CVD risk similarly as remission of DM.

Triterpenoids from Chios Mastiha Resin Against MASLD—A Molecular Docking Survey

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease without an approved pharmacological approach for its prevention/treatment. Based on the modified Delphi process, NAFLD was redefined as metabolic dysfunction-associated steatotic liver disease (MASLD) to highlight the metabolic aspect of liver pathogenesis. Chios mastiha (Pistacia lentiscus var. Chia, Anacardiaceae) resin demonstrated promising results in MASLD treatment. In this paper, molecular docking was applied to test 16 compounds from Chios mastiha as potential ligands for the receptors GR, LXRα, LXRβ, PPARα PPARγ, MC4R, AMPK, and VEGFR2, whose up- and down-regulation interfere with MASLD development and progression. The observed compounds had moderate and high affinity for LXR, GR, MC4R, and PPARγ in comparison to proven ligands, while their affinity for PPARα, AMPK, and VEGFR was less pronounced. The combination of active compounds from Chios mastiha rather than a single molecule may have a superior ability to control the intertwined MASLD metabolic pathways.

Prospects of elafibranor in treating alcohol-associated liver diseases

Alcohol-related liver disease (ALD), which is induced by excessive alcohol consumption, is a leading cause of liver-related morbidity and mortality. ALD patients exhibit a spectrum of liver injuries, including hepatic steatosis, inflammation, and fibrosis, similar to symptoms of nonalcohol-associated liver diseases such as primary biliary cholangitis, metabolic dysfunction-associated steatotic liver disease, and nonalcoholic steatohepatitis. Elafibranor has been approved for the treatment of primary biliary cholangitis and has been shown to improve symptoms in both animal models and in vitro cell models of metabolic dysfunction-associated steatotic liver disease and nonalcoholic steatohepatitis. However, the efficacy of elafibranor in treating ALD remains unclear. In this article, we comment on the recent publication by Koizumi et al that evaluated the effects of elafibranor on liver fibrosis and gut barrier function in an ALD mouse model. Their findings indicate the potential of elafibranor for ALD treatment, but further experimental investigations and clinical trials are warranted.

Metabolic Dysfunction–Associated Steatotic Liver Disease

Metabolic Dysfunction–Associated Steatotic Liver Disease

Correlation of sarcopenia with progression of liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease: a study from two cohorts in China and the United States

ObjectiveThe objective of this study was to investigate the association between sarcopenia and liver fibrosis in patients aged 18–59 years with metabolic dysfunction-associated steatotic liver disease (MASLD) and to assess the potential of sarcopenia as a risk factor for the progression of liver fibrosis.MethodsThe study included 821 patients with MASLD in the US cohort and 3,405 patients with MASLD in the Chinese cohort. Liver controlled attenuation parameters (CAP) and liver stiffness measurements (LSM) were assessed by vibration-controlled transient elastography (VCTE) to evaluate the extent of hepatic steatosis and fibrosis. Sarcopenia was assessed by measuring appendicular skeletal muscle mass (ASM) and calculating ASMI. To analyze the relationship between sarcopenia, ASMI, and liver fibrosis, logistic regression models, multivariate-adjusted models, and restricted cubic spline (RCS) models were employed, with stratification and interaction analyses.ResultsThe results demonstrated that patients with sarcopenia exhibited a markedly elevated risk of significant liver fibrosis, advanced liver fibrosis, and cirrhosis compared to those without sarcopenia in both cohorts. After adjusting for confounding variables, sarcopenia was identified as an independent risk factor for the progression of liver fibrosis in patients with MASLD. A significant negative correlation was observed between ASMI and the severity of liver fibrosis, with a progressive reduction in the risk of liver fibrosis associated with increasing ASMI. Additionally, a non-linear feature was evident in some liver fibrosis indicators. Subgroup analysis further corroborated the finding that the harmful effect of sarcopenia on liver fibrosis was consistent across all identified subgroups.ConclusionSarcopenia may be associated with the progression of liver fibrosis in patients with MASLD. Monitoring ASMI may assist in identifying individuals at an elevated risk of liver fibrosis in MASLD patients.

Comparative application of MAFLD and MASLD diagnostic criteria on NAFLD patients: insights from a single-center cohort

The diagnostic criteria for Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) and Metabolic Associated Steatotic Liver Disease (MASLD) aim to refine the classification of fatty liver diseases previously grouped under Non-Alcoholic Fatty Liver Disease (NAFLD). This study evaluates the applicability of the MAFLD and MASLD frameworks in NAFLD patients, exploring their clinical utility in identifying high-risk patients. A total of 369 NAFLD patients were assessed using MAFLD and MASLD diagnostic criteria. Baseline characteristics, metabolic profiles, hepatic fibrosis, and cardiovascular risks were compared across the groups. Among NAFLD patients, 97.55% (n = 359) met MASLD criteria, and 97.01% (n = 357) fulfilled MAFLD criteria. Both frameworks MAFLD and MASLD captured overlapping populations, with MASLD encompassing slightly more cases. No significant differences were observed in metabolic risk factors, fibrosis indices (APRI, FIB-4, NAFLD fibrosis score), or cardiovascular risk (10-year ASCVD score). A small subset of lean NAFLD patients (10 cases) with distinct profiles remained uncategorized by either framework. Pure NAFLD cases (n = 10) were with mild insulin resistance (HOMA-IR: 3.07 ± 0.33) and slightly elevated LDL (102.5 ± 42.87 mg/dL), while fibrosis indices indicated low fibrosis risk. Steatosis indices supported the diagnosis of early-stage NAFLD with preserved liver function. These patients do not meet the criteria for inclusion in the MAFLD or MASLD frameworks, highlighting a gap in the current diagnostic systems. MAFLD and MASLD criteria align closely with NAFLD in capturing patients with metabolic risk with MASLD-enhanced inclusivity. Further refinement is required to address heterogeneity, particularly in lean NAFLD patients. Hypertension prevalence was comparable (17.4% in NAFLD, 18.2% in MAFLD, 17.8% in MASLD; p = 0.960), as was diabetes mellitus (36.7%, 37.8%, and 37.6%, respectively; p = 0.945). Body mass index was also similar across groups, with medians of 33.25, 33.6, and 33.4 kg/m2 (p = 0.731). Non-invasive markers of hepatic fibrosis, including APRI, FIB-4, and NAFLD fibrosis scores, did not differ significantly, with median FIB-4 scores around 1.05 (p = 0.953). Similarly, were the results of hepatic steatosis index and ASCVD score.

Predicting colorectal adenomatous polyps in patients with chronic liver disease: A novel nomogram.

Colorectal polyps are commonly observed in patients with chronic liver disease (CLD) and pose a significant clinical concern because of their potential for malignancy. To explore the clinical characteristics of colorectal polyps in patients with CLD, a nomogram was established to predict the presence of adenomatous polyps (AP). Patients with CLD who underwent colonoscopy at Tianjin Second People's Hospital from January 2020 to May 2023 were evaluated. Clinical data including laboratory results, colonoscopy findings, and pathology reports were collected. Key variables for the nomogram were identified through least absolute shrinkage and selection operator regression, followed by multivariate logistic regression. The performance of the model was evaluated using the area under the receiver area under curve, as well as calibration curves and decision curve analysis. The study enrolled 870 participants who underwent colonoscopy, and the detection rate of AP in patients with CLD was 28.6%. Compared to individuals without polyps, six risk factors were identified as predictors for AP occurrence: Age, male sex, body mass index, alcohol consumption, overlapping metabolic dysfunction-associated steatotic liver disease, and serum ferritin levels. The novel nomogram (AP model) demonstrated an area under curve of 0.801 (95% confidence interval: 0.756-0.845) and 0.785 (95% confidence interval: 0.712-0.858) in the training and validation groups. Calibration curves indicated good agreement among predicted and actual probabilities (training: χ 2 = 11.860, P = 0.157; validation: χ 2 = 7.055, P = 0.530). The decision curve analysis underscored the clinical utility of the nomogram for predicting the risk of AP. The AP model showed reasonable accuracy and provided a clinical foundation for predicting the occurrence of AP in patients with CLD, which has a certain predictive value.

Current Treatment Regimens and Promising Molecular Therapies for Chronic Hepatobiliary Diseases

Chronic hepatobiliary damage progressively leads to fibrosis, which may evolve into cirrhosis and/or hepatocellular carcinoma. The fight against the increasing incidence of liver-related morbidity and mortality is challenged by a lack of clinically validated early-stage biomarkers and the limited availability of effective anti-fibrotic therapies. Current research is focused on uncovering the pathogenetic mechanisms that drive liver fibrosis. Drugs targeting molecular pathways involved in chronic hepatobiliary diseases, such as inflammation, hepatic stellate cell activation and proliferation, and extracellular matrix production, are being developed. Etiology-specific treatments, such as those for hepatitis B and C viruses, are already in clinical use, and efforts to develop new, targeted therapies for other chronic hepatobiliary diseases are ongoing. In this review, we highlight the major molecular changes occurring in patients affected by metabolic dysfunction-associated steatotic liver disease, viral hepatitis (Delta virus), and autoimmune chronic liver diseases (autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis). Further, we describe how this knowledge is linked to current molecular therapies as well as ongoing preclinical and clinical research on novel targeting strategies, including nucleic acid-, mesenchymal stromal/stem cell-, and extracellular vesicle-based options. Much clinical development is obviously still missing, but the plethora of promising potential treatment strategies in chronic hepatobiliary diseases holds promise for a future reversal of the current increase in morbidity and mortality in this group of patients.

Prevention of liver cancer in the era of next-generation antivirals and obesity epidemic.

Preventive interventions are expected to substantially improve the prognosis of patients with primary liver cancer, predominantly hepatocellular carcinoma (HCC) and cholangiocarcinoma. HCC prevention is challenging in the face of the evolving etiological landscape, particularly the sharp increase in obesity-associated metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD). Next-generation anti-HCV and HBV drugs have substantially reduced, but not eliminated, the risk of HCC and have given way to new challenges in identifying at-risk patients. The recent development of new therapeutic agents and modalities has opened unprecedented opportunities to refine primary, secondary, and tertiary HCC prevention strategies. For primary prevention (before exposure to risk factors), public health policies, such as universal HBV vaccination, have had a substantial prognostic impact. Secondary prevention (after or during active exposure to risk factors) includes regular HCC screening and chemoprevention. Emerging biomarkers and imaging modalities for HCC risk stratification and detection may enable individual risk-based personalized and cost-effective HCC screening. Clinical studies have suggested the potential utility of lipid-lowering, anti-diabetic/obesity, and anti-inflammatory agents for secondary prevention, and some of them are being evaluated in prospective clinical trials. Computational and experimental studies have identified potential chemopreventive strategies directed at diverse molecular, cellular, and systemic targets for etiology-specific and/or agnostic interventions. Tertiary prevention (in conjunction with curative-intent therapies for HCC) is an area of active research with the development of new immune-based neo/adjuvant therapies. Cholangiocarcinoma prevention may advance with recent efforts to elucidate risk factors. These advances will collectively lead to substantial improvements in liver cancer mortality rates.

Fructose catabolism and its metabolic effects: Exploring host-microbiota interactions and the impact of ethnicity.

Important health disparities are observed in the prevalence of obesity and associated non-communicable diseases (NCDs), including type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD) among ethnic groups. Yet, the underlying factors accounting for these disparities remain poorly understood. Fructose has been widely proposed as a potential mediator of these NCDs, given that hepatic fructose catabolism can result in deleterious metabolic effects, including insulin resistance and hepatic steatosis. Moreover, the fermentation of fructose by the gut microbiota can produce metabolites such as ethanol and acetate, both which serve as potential substrates for de novo lipogenesis (DNL) and could therefore contribute to the development of these metabolic conditions. Significant inter-ethnic differences in gut microbiota composition have been observed. Moreover, fructose consumption varies across ethnic groups, and fructose intake has been demonstrated to significantly alter gut microbiota composition, which can influence its fermenting properties and metabolic effects. Therefore, ethnic differences in gut microbiota composition, which may be influenced by variations in fructose consumption, could contribute to the observed health disparities. This review provides an overview of the complex interactions between host and microbial fructose catabolism, the role of ethnicity in shaping these metabolic processes and their impact on host health. Understanding these interactions could provide insights into the mechanisms driving ethnic health disparities to improve personalized nutrition strategies. KEY POINTS: Dietary fructose consumption has increased substantially over recent decades, which has been associated with the rising prevalence of obesity and non-communicable diseases (NCDs) such as type 2 diabetes and metabolic dysfunction-associated steatotic liver disease. Pronounced disparities among different ethnic groups in NCD prevalence and dietary fructose consumption underscore the need to elucidate the underlying mechanisms of fructose catabolism and its health effects. Together with the well-known toxic effects of hepatic fructose catabolism, emerging evidence highlights a role for the small intestinal microbiota in fermenting sugars like fructose into various bacterial products with potential deleterious metabolic effects. There are significant ethnic differences in gut microbiota composition that, combined with varying fructose consumption, could mediate the observed health disparities. To comprehensively understand the role of the gut microbiota in mediating fructose-induced adverse metabolic effects, future research should focus on the small intestinal microbiota. Future research on fructose - microbiota - host interactions should account for ethnic differences in dietary habits and microbial composition to elucidate the potential role of the gut microbiota in driving the mentioned health disparities.

Association between Healthy Eating Index-2015 total and metabolic associated fatty liver disease in Americans: a cross-sectional study with U.S. National Health and Nutrition Examination Survey

BackgroundUtilizing the National Health and Nutrition Examination Survey (NHANES) dataset to investigate the relationship between dietary quality, as assessed by the Healthy Eating Index-2015 (HEI-2015), and the prevalence of metabolic associated fatty liver disease (MAFLD) among adults in the United States, our analysis revealed that an increased dietary quality was significantly correlated with a reduced risk of MAFLD in the American population.MethodThe NHANES dataset, encompassing the years 2017–2018 and comprising 3,557 participants, was incorporated into our analytical framework. Weighted multivariate linear regression model was performed to assess the linear relationship between the HEI-2015 and MAFLD. Dietary intake data were derived from two 24-h dietary recall interviews conducted as part of NHANES.ResultsFollowing multivariable adjustment, the weighted multivariable linear regression models demonstrated a negative correlation between the HEI-2015 total scores and the risk of MAFLD. The weighted logistic regression models revealed that each unit of increased HEI-2015 total value was associated with a 1.2% (95% CI: 0.9%, 1.5%; P < 0.001) decrease in the risk of f MAFLD. Upon categorization of the HEI-2015 scores into quartiles, the odds ratios (ORs) for the association between the risk of MAFLD and the quartile scores of HEI-2015, in comparison to the baseline quartile, were 0.945 (95% CI: 0.852–1.047; P = 0.279), 0.834 (95% CI: 0.750–0.927; P < 0.001), and 0.723 (95% CI: 0.646–0.811; P < 0.001), respectively. When participants were stratified by age and sex, subgroup analyses showed a similar trend. This pattern was also evident in the smooth curve fitting (SCF) and weighted generalized additive model (GAM).ConclusionElevated dietary quality, as assessed by the total and component food scores of the HEI-2015, was significantly correlated with a diminished risk of MAFLD among participants in the NHANES survey featured in this investigation.

Association between cardiovascular health and metabolic dysfunction-associated steatotic liver disease: a nationwide cross-sectional study

PurposeEvidence concerning the effect of cardiovascular health (CVH) on the risk of metabolic dysfunctional-associated steatotic liver disease (MASLD) is scarce. This study aimed to investigate the association between CVH and MASLD.Methods5680 adults aged ≥ 20 years from the National Health and Nutrition Examination Survey 2017-March 2020 were included. Life’s essential 8 (LE8) was applied to assess CVH. Weighted binary logistic regression was employed to calculate the odds ratio (OR) and 95% confidence interval (CI) to investigate the association of CVH with MASLD. Restricted cubic spline (RCS) was conducted to explore the dose-response association between LE8 and its subscales scores with MASLD.ResultsAmong 5680 participants, 724, 3901, and 1055 had low, moderate, and high CVH levels, respectively, with a MASLD diagnosis prevalence of 36.83%. In the fully adjusted logistic regression model, ORs for MASLD were 0.50 (95% CI, 0.37–0.69) for participants with moderate CVH and 0.21 (95% CI, 0.13–0.34) for those with high CVH, when compared to those with low CVH (P < 0.001 for trend). OR for MASLD was 0.68 (95% CI, 0.61–0.77) for each 10-point increase in LE8 score. RCS model demonstrated a non-linear dose-response relationship between LE8 score and health factors score with MASLD, while a linear relationship was found between health behaviors score and MASLD. Subgroup analysis showed a consistent negative correlation between LE8 score and MASLD, and sensitivity analysis validated the reliability of these findings.ConclusionsHigher LE8 score was associated with a lower risk of MASLD. Encouraging adherence to optimal CVH levels may help mitigate the burden of MASLD.