China has a high prevalence rate of Metabolic-associated fatty liver disease (MAFLD), and there is currently limited understanding of the levels of exercise self-efficacy (ESE) among individuals with MAFLD. The objective was to explore the potential ESE patterns in older adults with MAFLD. A cross-sectional study was conducted on 800 older adults with fatty liver disease from five communities from April 20, 2023 to August 15, 2023. Latent profile analysis (LPA) and k-means clustering were used to determine the optimal number of ESE groups. Using univariate analysis and multivariate logistic regression to investigate the factors influencing profiles of ESE. A sample of 775 subjects met the diagnostic criteria for MAFLD. LPA yielded three profiles: the low-ESE, mild-ESE, and high-ESE groups, which comprised 25%, 28%, and 47% of the sample, respectively. K-means clustering further supported the categorization of ESE into three distinct classes. The multivariate logistic regression analysis revealed that diabetes, arthritis and/or arthrosis, as well as companionship during PA were significant influencing factors for the different profiles (p ​< ​0.05). Our findings suggest that the ESE of older patients with MAFLD is primarily at a moderate level or above. There was population heterogeneity in ESE among older patients with MAFLD. Diabetes mellitus, arthritis, and/or arthrosis, as well as companionship during PA were significant factors in influencing the likelihood of having high ESE.

Urinary albumin-to-creatinine ratio (UACR) is an established biomarker for assessing kidney damage, but recent studies suggest it may also reflect broader health risks. This study aimed to investigate the association between UACR and all-cause and cardiovascular disease (CVD)-cause mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

In this prospective cohort study, we included sample of 3,412 MASLD enrolled in the National Health and Nutrition Examination Survey 2001-2018. The study population was divided into three different risk categories based on urinary UACR: low level (<4.67 mg/g), intermediate level (4.67-7.67 mg/g), and high level (7.68-30 mg/g). Cox proportional hazards models were used to estimate the hazard ratios (HR) for the association between UACR level and both all-cause and CVD-cause mortality. Restricted cubic spline (RCS) curve analysis was employed to assess the non-linear association between UACR and mortality. Kaplan-Meier (KM) survival curves were used to evaluate survival rates across UACR groups.

The study found that higher UACR levels, even within the normal range, were independently associated with increased risks of both all-cause and CVD-cause mortality. Each 1 mg/g increase in UACR was associated with a 4% higher risk of all-cause mortality (HR 1.04, 95% CI 1.03-1.05) and a 5% higher risk of cardiovascular mortality (HR 1.05, 95% CI 1.02-1.08). Compared with the low UACR group, high UACR both showed an increased all-cause mortality risk [HR, 2.69 (95% CI, 2.07-3.50)] and CVD-cause mortality risk [HR, 2.97 (95% CI, 1.76-4.99)]. RCS curve analysis revealed a non-linear positive correlation between UACR and both all-cause and CVD-cause mortality, identifying UACR thresholds of 7.467 mg/g for all-cause mortality and 7.195 mg/g for CVD-cause mortality. The KM survival curves confirmed that participants with lower UACR levels had higher survival rates.

Elevated UACR levels within the normal range, are associated with increased all-cause and cardiovascular mortality in patients with MASLD. UACR may serve as a useful early biomarker for identifying individuals at higher risk of mortality, supporting more proactive clinical interventions to manage MASLD-related risks.

The incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) is high among U.S. adults, but studies on its occurrence in different ethnic and age groups are limited. The aim of the present study was to assess MAFLD occurrence among the U.S. adults by considering demographic characteristics, physical indices, and lifestyle conditions.

This study utilized the National Health and Nutrition Examination Survey (NHANES) data 2009-2018 from 23,546 participants aged ≥ 20 years. Variables such as age, sex, race, body mass index (BMI), waist circumference (WC), blood pressure, sedentary behavior, sleep, and depression were analyzed.

Among 9933 participants, 3562 had MAFLD (34.1%), with notably higher percentages of Mexican-Americans (54.1%) and lower percentages of blacks (20.5%). The incidence of MAFLD was significantly greater (P < 0.001) in males (39%) than in females (29.2%), which was particularly evident within the 36-40 years age group. The MAFLD incidence exhibited an age-dependent pattern, initially increasing and subsequently declining (except for whites). Compared to white MAFLD patients, black MAFLD patients exhibited greater BMI, WC, systolic blood pressure (SBP), and diastolic blood pressure (DBP) values, whereas values for these measures were lower among Mexican-American patients. Logistic regression analysis adjusting for age and sex revealed that depression was more common among MAFLD patients (P < 0.001), except for severe depression (P > 0.05). Notably, the MAFLD incidence was not significantly associated with sedentary behavior or sleep duration.

The MAFLD incidence varies across different racial, age, and sex groups, and targeted interventions are essential for reducing the burden of MAFLD. However, further research is necessary to explore the correlations among MAFLD incidence, sleep patterns, and an inactive lifestyle.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a contemporary classification of liver disease linked to metabolic dysfunction. It is recognized as the main form of chronic liver disease and significantly contributes to liver-related morbidity and mortality rates. The epidemiology of MASLD is affected by ethnic background, sex, age, and environmental factors. South Korea is one of the countries that has experienced rapid urbanization. Geographical differences also play a crucial role in the prevalence and progression of the disease. Consequently, it is essential to investigate the prevalence of MASLD; its associated risk factors, particularly in relation to liver fibrosis; and the effectiveness of non-invasive screening techniques within the Korean population. Methods: This review describes the prevalence of MASLD, the risk factors related to MASLD with liver fibrosis, and the non-invasive screening approaches suitable for the Korean general population. Results: This review underscores the rising incidence and implications of MASLD in South Korea. Notably, among younger demographics, there is a swift increase in both the prevalence of MASLD and its associated risk factors, indicating that MASLD is poised to become a significant public health concern. Non-invasive testing methods are increasingly utilized within at-risk groups to determine the presence of advanced fibrosis. Conclusions: Addressing these complex liver diseases necessitates not only ongoing monitoring of MASLD epidemiological patterns but also a unified approach to care that integrates medical interventions with lifestyle changes.

The recent introduction of the term metabolic-dysfunction-associated steatotic liver disease (MASLD) has highlighted the critical role of metabolism in the disease's pathophysiology. This innovative nomenclature signifies a shift from the previous designation of non-alcoholic fatty liver disease (NAFLD), emphasizing the condition's progressive nature. Simultaneously, MASLD has become one of the most prevalent liver diseases worldwide, highlighting the urgent need for research to elucidate its etiology and develop effective treatment strategies. This review examines and delineates the revised definition of MASLD, exploring its epidemiology and the pathological changes occurring at various stages of the disease. Additionally, it identifies metabolically relevant targets within MASLD and provides a summary of the latest metabolically targeted drugs under development, including those in clinical and some preclinical stages. The review finishes with a look ahead to the future of targeted therapy for MASLD, with the goal of summarizing and providing fresh ideas and insights.

Identifying reliable prognostic indicators is essential for the appropriate management of non-alcoholic fatty liver disease (NAFLD). Red blood cell distribution width (RDW) has been established as an inflammatory marker associated with cardiovascular outcomes. This study aimed to evaluate the association between RDW and both cardiovascular and all-cause mortality in individuals with NAFLD.

Data from 7,438 participants with NAFLD were analyzed, collected between 2005 and 2016 through the National Health and Nutrition Examination Survey (NHANES). Mortality data were retrieved from the National Death Index (NDI). Restricted cubic spline (RCS) analysis was used to illustrate the relationship between RDW and mortality risk, Weighted Cox proportional hazards models were used to assess the independent relationship between RDW and mortality risk. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive ability of RDW for survival outcomes.

During a median follow-up period of 124 months, 1,269 deaths were recorded, including 335 from cardiovascular causes. RDW positively correlated with both cardiovascular and all-cause mortality according to the RCS analysis. Participants were categorized into quartiles based on RDW levels. Those in the highest RDW quartile (Q4) demonstrated a significantly higher risk of cardiovascular mortality (HR 3.61, 95% confidence interval [CI]:2.17-6.02, P=0.009) and all-cause mortality (HR 2.29, 95% CI:1.72-3.06, P < 0.0001), according to the weighted Cox hazards models. Additionally, the area under the curve (AUC) for all-cause mortality at 3, 5 and 10 years was, 0.69, 0.67, and 0.66, respectively. For cardiovascular mortality, the AUCs were 0.70, 0.68, and 0.68, respectively.

Among patients with NAFLD, RDW was identified as an independent predictor of increased cardiovascular and all-cause mortality risk.

East Asian populations, which account for approximately 20% of the global population, have become central to the worldwide rise of metabolic diseases over the past few decades. The prevalence of metabolic disorders, including type 2 diabetes mellitus, hypertension and metabolic dysfunction-associated steatotic liver disease, has escalated sharply, contributing to a substantial burden of complications such as cardiovascular disease, chronic kidney disease, cancer and increased mortality. This concerning trend is primarily driven by a combination of genetic predisposition, unique fat distribution patterns and rapidly changing lifestyle factors, including urbanization and the adoption of Westernized dietary habits. Current advances in genomics, proteomics, metabolomics and microbiome research have provided new insights into the biological mechanisms that might contribute to the heightened susceptibility of East Asian populations to metabolic diseases. This Review synthesizes epidemiological data, risk factors and biomarkers to provide an overview of how metabolic diseases are reshaping public health in East Asia and offers insights into biological and societal drivers to guide effective, region-specific strategies.

Metabolic dysfunction-associated fatty liver disease (MAFLD) affects over one-fourth of the global adult population and is the leading cause of liver disease worldwide. To address this, the Asian Pacific Association for the Study of the Liver (APASL) has created clinical practice guidelines focused on MAFLD. The guidelines cover various aspects of the disease, such as its epidemiology, diagnosis, screening, assessment, and treatment. The guidelines aim to advance clinical practice, knowledge, and research on MAFLD, particularly in special groups. The guidelines are designed to advance clinical practice, to provide evidence-based recommendations to assist healthcare stakeholders in decision-making and to improve patient care and disease awareness. The guidelines take into account the burden of clinical management for the healthcare sector.

This study evaluated the predictive value of the APF risk score in East Asian patients undergoing open nephrectomy and its correlation with hypertension and NAFLD.

A retrospective study used the clinical data of 82 patients who underwent ON between January 2010 and December 2022. Per their APF score, patients were categorized into groups A (0-2 points) and B (3-4 points). Logistic regression analyses were used to compare the overall clinical data between the two groups and identify potential risk factors. Intraoperative APF prevalence was significantly higher in group B compared to group A (P < 0.001). Group B patients were older (63.06 ± 8.88 vs. 53.69 ± 15.21 years) and had higher incidences of hypertension (P < 0.001), diabetes (P = 0.002), and NAFLD (P < 0.001). Preoperative CT scans showed significant differences in posterior (P = 0.009) and lateral perinephric fat thickness (P < 0.001), and perinephric stranding (P < 0.001). Group B also had a higher proportion of malignant tumors (P = 0.039). Multivariate logistic regression revealed that NAFLD (OR = 9.053, P = 0.010) and hypertension (OR = 5.181, P = 0.025) were highly correlated with APF risk scores.

In this study, we found that the newly developed APF risk score had significant value in predicting APF in East Asian patients undergoing open nephrectomy. Additionally, NAFLD and hypertension were highly correlated with elevated APF risk scores.

Evidence linked metabolic associated steatotic liver disease (MASLD) to kidney damage with the potential contribution of the I148M variant of the Patatin-like phospholipase containing domain 3 (PNPLA3) gene. We aimed at investigating the relationship of MASLD and of its genetics with kidney function in children with obesity.

A comprehensive evaluation including genotyping for the I148M PNPLA3 polymorphism was performed in 1037 children with obesity. Fatty liver (FL) was assessed by liver ultrasound. According to MASLD criteria, subjects with obesity but without FL were included in group 1, while patients with obesity and FL (encompassing one MASLD criterion) were clustered into group 2. Group 3 included patients with obesity, FL, and metabolic dysregulation (encompassing >1 MASLD criterion).

Alanine transaminase levels significantly increased while estimated glomerular filtration rate (eGFR) significantly reduced from group 1 to 3. Group 3 showed a higher percentage of carriers of the I148M allele of the PNPLA3 gene compared to other groups (p < 0.0001). Carriers of group 2 and of group 3 showed reduced eGFR levels than noncarriers of group 2 (p = 0.04) and of group 3 (p = 0.02), respectively. A general linear model for eGFR variance in the study population showed an inverse association of eGFR with both MASLD and PNPLA3 genotypes (p = 0.011 and p = 0.02, respectively). An inverse association of eGFR with MASLD was also confirmed only in carriers (p = 0.006).

The coexistence of more than 1 MASLD criterion in children with obesity seems to adversely affect kidney function. The PNPLA3 I148M allele further impacts on this association.

Metabolic dysfunction-associated steatotic liver disease (MASLD), which includes the inflammatory subtype metabolic dysfunction-associated steatohepatitis, is a prominent cause of chronic liver disease with systemic effects. Insulin resistance, obesity, and dyslipidaemia produce MASLD in over 30 % of adults. It is a global health issue. From MASLD to MASH, hepatic inflammation and fibrosis grow, leading to cirrhosis, hepatocellular cancer, and extrahepatic complications such CVD, CKD, and sarcopenia. Effects of MASLD to MASH are mediated through mechanisms that include inflammation, oxidative stress, dysbiosis, and predisposition through genetic makeup. Advances in diagnostic nomenclature in the past few years have moved the emphasis away from NAFLD to MASLD, focusing on the metabolic etiology and away from the stigma of an alcoholic-related condition. Epidemiological data show a large geographical variability and increasing prevalence in younger populations, particularly in regions with high carbohydrate-rich diets and central adiposity. Lifestyle modification is considered as the main management of MASLD currently. This may include dietary intervention, exercise, and weight loss management. Pharmaceutical management is primarily aimed at metabolic dysfunction with promising findings for GLP-1 receptor agonists, pioglitazone and SGLT-2 inhibitors, which can correct both hepatic and systemic outcome. However, it still depends on well-integrated multidisciplinary care models by considering complex relationships between MASLD and its effects on extrahepatic organs. Determining complications at an early stage; developing precision medicine strategies; exploring new therapeutic targets will represent crucial factors in improving their outcomes. This review discuss the systemic nature of MASLD and calls for multiple collaborations to reduce its far-reaching health impacts and our quest for understanding its pathological mechanisms. Thus, collective efforts that are required to address MASLD are under the public health, clinical care, and research angles toward effectively containing its rapidly increasing burden.

Sodium-glucose co-transporter type-2 (SGLT2) inhibitors have been identified to have a crucial hepatoprotective role in patients with type 2 diabetes (T2DM) and metabolic-associated steatotic liver disease (MASLD). Thus, we aimed to assess the effect of SGLT2 inhibitors on hepatic steatosis in patients with T2DM and MASLD added to the standard of care (SOC) treatment. Our study was a single-arm clinical trial with trial no ISRCTN85961860. Thirty T2DM patients with MASLD were recruited from the outpatient endocrinology and diabetes clinic of the Internal Medicine Department at Kasr Al-Aini Hospital, Cairo University, Egypt. Our Patients received Empagliflozin 10 mg daily which was added to SOC treatment and followed up for 24 weeks. Magnetic resonance imaging proton density fat fraction (MRI-PDFF) was done at baseline and after 24 weeks to assess the percentage change in hepatic fat mass. Also changes in Fib-4 and NAFLD fibrosis scores were calculated. Our study showed a statistically significant decrease in the mean MRI-PDFF measurement of hepatic steatosis after 24 weeks of adding empagliflozin to SOC treatment (13.297 ± 7.15) compared to the mean at baseline (15.288 ± 8.72), P = 0.006 with overall percentage decrease about 13.16% of liver steatosis. There were significant decreases in BMI, fasting blood glucose, and Alanine transaminase, (P < 0.001, 0.03, 0.01) respectively. There were no significant differences in Fib-4 or NAFLD fibrosis scores. Adding empagliflozin 10 mg to the standard treatment in patients with diabetes and MASLD could reduce hepatic fat mass significantly after 24 weeks of treatment. Thus, adding SGLT2 inhibitors to the clinical practice guidelines could be a therapeutic agent for patients with MASLD and T2DM.

Whether the new standard of metabolic dysfunction-associated fatty liver disease (MAFLD) has more pronounced clinical and population screening diagnostic value than nonalcoholic fatty liver disease (NAFLD) is unclear. This study evaluated the utility of MAFLD and NAFLD for predicting major cardiovascular disease (CVD) risk.

A prospective cohort study approach was utilized to collect 19,399 study participants without CVD at baseline who completed follow-up from the Jinchang cohort platform during 2011-2017. According to clinical ultrasonic diagnosis results and disease diagnosis criteria, the baseline population was divided into MAFLD, NAFLD, Both-FLD and No-FLD groups. Based on the multifactorial Cox proportional risk model to analyze the relationship between three kinds of patients and CVD, the score prediction model of CVD was constructed with reference to the Framingham Risk Score (FRS) and the model was evaluated. Compared with No-FLD, the HRs and 95 % CIs for the risk of CVD development in patients with NAFLD, MAFLD, and Both-FLD were 1.54 (1.34-1.76), 1.57 (1.37-1.79), and 1.62 (1.41-1.87), in that order. The scoring model showed a range of 5.90%-84.59 % risk of CVD in the three groups. As the risk score increased, the risk of developing CVD gradually increased. Evaluation metrics of all three models in the training set and validation set showed that the models have good prediction efficacy.

In terms of CVD risk and prognosis, MAFLD had no advantage over NAFLD. However, Both-FLD was found to predict a higher risk of CVD and to have superior predictive efficacy.

Hepatitis B virus (HBV) infection remains a major global health challenge, affecting approximately 296 million people and causing significant mortality annually. Despite vaccination efforts, HBV prevalence persists, particularly in low- and middle-income regions and endemic areas like China. HBV is closely associated with various kidney diseases, including acute kidney injury, chronic kidney disease, and glomerulonephritis, through mechanisms such as immune complex deposition, direct viral invasion, and chronic inflammation. Patients undergoing hemodialysis or kidney transplantation are at increased risk of HBV infection and reactivation, highlighting the need for effective preventive and therapeutic measures. This review examines the classification and clinical features of HBV-associated nephropathy, focusing on membranous nephropathy and membranoproliferative glomerulonephritis. It explores the pathogenesis, emphasizing immune complex deposition and podocyte apoptosis. Antiviral therapy, particularly with nucleos(t)ide analogs like entecavir and tenofovir (including TAF and TMF), demonstrates superior efficacy and safety compared to older agents such as lamivudine and adefovir. While interferon therapy offers benefits, its use is limited by adverse effects. Additionally, individualized treatment strategies for specific populations, including pregnant women and HIV co-infected patients, are crucial. Addressing HBV-associated nephropathy requires enhanced surveillance, timely antiviral intervention, and tailored therapeutic approaches to improve patient outcomes.

Attenuated insulin-sensitivity (IS) is a characteristic of type 2 diabetes (T2D) and is closely linked to non-alcoholic fatty liver disease (NAFLD). In recent years, many surrogate markers of IS have emerged to predict NAFLD. A natural log transformation of the glucose disposal rate (loge GDR) has been proposed as a new model for IS in patients with T2D. Our aim is to explore the correlation between loge GDR and NAFLD in normoalbuminuric patients with T2D.

A total of 1227 normoalbuminuric patients with T2D were involved in our study. NAFLD was evaluated by ultrasound. Biochemical and clinical data were collected, including parameters essential for calculating the loge GDR (triglycerides, urinary albumin-to-creatinine ratio, γ-glutamyl transferase and body mass index), as well as other relevant covariates required for adjustment. The relationship between the loge GDR and NAFLD was analyzed.

NAFLD patients showed lower loge GDR values than non-NAFLD (P < 0.001). As the loge GDR tertiles increased, the prevalence of NAFLD was decreased (P < 0.001). Multivariate analysis displayed that loge GDR was independently corrected with NAFLD (OR: 0.084; 95% CI: 0.040-0.177). Furthermore, receiver operating characteristic (ROC) analysis showed that loge GDR (area under the curves: 0.797) was superior to other evaluation variables.

The loge GDR was strongly associated with NAFLD and might be a useful predictor in normoalbuminuric patients with T2D.

In recent years, the terms "metabolic associated fatty liver disease-MAFLD" and "metabolic dysfunction-associated steatotic liver disease-MASLD" were introduced to improve the encapsulation of metabolic dysregulation in this patient population, as well as to avoid the negative/stigmatizing terms "non-alcoholic" and "fatty".

There is evidence suggesting links between MASLD and coronary heart disease (CHD), heart failure (HF), atrial fibrillation (AF), stroke, peripheral artery disease (PAD) and chronic kidney disease (CKD), although the data for HF, AF, stroke and PAD are scarcer. Physicians should consider the associations between MASLD and CV diseases in their daily practice. Based on this knowledge and current guidelines, they should also assess and manage CV risk/co-morbidities in such patients. It is important to further investigate the impact of MASLD on CV outcomes, a knowledge that will help to elucidate the clinical implications of this "novel" liver entity.

Metabolic dysfunction-associated fatty liver disease has been linked to negative outcomes in patients with end-stage liver disease following liver transplantation. However, the influence of immunosuppressive regimens on it has not been explored.

A retrospective analysis was conducted using the preoperative and postoperative data from patients with end-stage liver disease. The study compared three different groups: tacrolimus-based group, sirolimus-based group, and combined tacrolimus- and sirolimus-based regimens. Binary logistic regression analysis was employed to identify risk factors for metabolic dysfunction-associated fatty liver disease.

A total of 171 patients participated in the study, consisting of 127 males and 44 females, with a mean age of 49.6 years. The prevalence of posttransplant metabolic dysfunction-associated fatty liver disease was 29.23%. Among the three groups, there were 111 liver transplant recipients in the tacrolimus-based group, 28 in the sirolimus-based group, and 32 in the combination group. A statistically significant difference was observed in the incidence of metabolic dysfunction-associated fatty liver disease (P < 0.05), whereas the other preoperative and postoperative parameters showed no significant differences. Multivariate analysis revealed that a low-calorie diet (95% confidence intervals: 0.15-0.90, P = 0.021) and a combination of tacrolimus- and sirolimus-based immunosuppressive regimen (95% confidence intervals: 1.01-2.77, P = 0.046) were associated with lower risk of posttransplant metabolic dysfunction-associated fatty liver disease.

Our study indicates that implementing a low-calorie diet and utilizing a combination of tacrolimus- and sirolimus-based immunosuppressive regimen can effectively lower the risk of posttransplant metabolic dysfunction-associated fatty liver disease following liver transplantation.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has been used to characterize patients with fatty liver and metabolic dysfunction. The association between MAFLD and chronic kidney disease (CKD) remains undefined. We present high-quality evidence obtained from cohort studies examining if MAFLD leads to an increased risk of CKD.

PubMed, CENTRAL, Embase, Scopus, and Web of Science were searched from the earliest possible date to 17th May 2024 for cohort studies examining the link between MAFLD and CKD.

Eight studies with nine cohorts were included. Pooled analysis of all nine cohorts showed that MAFLD was an independent predictor of CKD (HR: 1.38 95% CI: 1.24, 1.53 I2 = 95%). No change in results was noted on sensitivity analysis. We also noted no change in the significance of effect size on subgroup analysis based on study design (prospective or retrospective), country of origin (China, Korea, Japan, or UK), the incidence of CKD in the cohort (> 10% or ≤ 10%) and if the study adjusted for cardiovascular disease, diabetes, hypertension, and smoking status. Further, meta-analysis showed that MAFLD was still a risk factor for CKD in men (HR: 1.38 95% CI: 1.22, 1.56 I2 = 86%), women (HR: 1.51 95% CI: 1.25, 1.82 I2 = 87%), overweight (HR: 1.41 95% CI: 1.20, 1.66 I2 = 89%) and non-overweight cohorts (HR: 1.35 95% CI: 1.20, 1.53 I2 = 9%).

MAFLD is an independent predictor of CKD. The association seems persistent irrespective of sex, body mass index, and other CKD risk factors.

Recently, Delphi consensus proposed an overarching term steatotic liver disease (SLD), with various subcategories such as MASLD, MetALD and ALD. Our aim was to investigate the association between MASLD/MetALD/ALD and four intrahepatic and extrahepatic diseases (liver diseases, renal diseases, cardiovascular diseases, and cancers) in the UK Biobank cohort.

By defining hepatic steatosis as image-derived phenotype (IDP)-PDFF >5.21%, we used data from the UK Biobank to diagnose MASLD/ MetALD/ALD. The odd ratio (OR) and the hazard ratio (HR) were calculated using the logistic regression modals and Cox regression models, respectively.

Among 39,230 eligible individuals, 6,865 MASLD subjects, 2,379 MetALD subjects and 884 ALD subjects were diagnosed. The last follow-up time was October 13, 2023. Consistent with the logistic analyses, MASLD/MetALD/ALD were significantly associated with a higher risk of liver diseases (HR=3.04 [95%CI:2.60-3.56], HR = 2.69 [95% CI: 2.12-3.42] and HR =3.99 [95%CI:2.92-5.45], respectively). Subjects with MASLD also had an increased higher risk of renal diseases (HR = 1.40 [95%CI:1.20-1.64]) and subjects with ALD had an increased higher risk of cancers (HR = 1.36 [95%CI:1.15-1.60]).

It is the first study to report the association between MASLD, MetALD, ALD and common intrahepatic and extrahepatic diseases based on magnetic resonance imaging data-PDFF. We found that MASLD, MetALD and ALD were risk factors for liver diseases. Meanwhile, MASLD was also a risk factor for renal diseases and ALD was a risk factor for cancers.

Previous research has investigated the hepatotoxicity of single metal exposure. However, there is limited evidence about metal mixture and their association with metabolic dysfunction-associated fatty liver disease (MAFLD), particularly in the Chinese population.

To investigate the individual and combine effects of 20 metals on MAFLD in a large population in China.

This study included 3651 participants from the Medical Physical Examination Center of Tongji Hospital, Wuhan, China. MAFLD was identified based on ultrasonic graphic evidence of hepatic steatosis and the presence of overweight/obese, diabetes mellitus, or metabolic dysregulation. Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine urinary concentrations of 20 metals. Logistic regression was used to assess the relationship between individual metal and MAFLD, with results presented as odds ratios (ORs) and 95 % confidence intervals (CIs). Weighted quantile sum (WQS) regression was performed to evaluate the combine effect of metals.

The prevalence of MAFLD among the participants was 32.1 % (1173/3651). In singe-metal analysis, high exposure to zinc (OR =1.42; 95 % CI = 1.27, 1.59) and selenium (OR = 1.23; 95 % CI = 1.10, 1.39) were positively associated with MAFLD. No significant association was found for other metals. WQS regression analysis showed that urinary metal mixture was positively associated with MAFLD (OR = 1.32, 95 % CI: 1.15, 1.51), with zinc (50.4 %) being the largest contributor, followed by barium (10.8 %).

In conclusion, our finding suggested that exposure to the mixture of metals was positively correlated with MAFLD, with zinc being the major contributor.

In patients with NAFLD, liver fibrosis increases liver-related complications, but there is controversy about the increase in CVD. Based on a prospective cohort study, this study investigated the risk of cardiovascular disease due to liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

This study analyzed KCPS-II prospective cohort that tracked 104,399 people who participated in health check-ups at 18 institutions nationwide from 2004 to 2013. If the fatty liver index was 30 or higher, it was defined as SLD, and participants were classified into No-SLD, MASLD, MetALD, ALD, and Cryptogenic SLD. Liver fibrosis was defined by the FIB-4 index, and the occurrence of cardiovascular disease according to SLD classification was analyzed using Cox proportional model regression analysis. Out study included a total of 6,942 participants (6.6%) had MASLD, 6,694 (6.4%) had MetALD, 4,751 (4.6%) had ALD, and 382 (0.3%) had Cryptogenic SLD. For the cases of FIB-4 index ≥1.3, the multivariable-adjusted HR (95% CI) of cardiovascular disease was 2.27 (1.87-2-76) in MASLD, 1.67 (1.30-2.10) in MetALD, and 2.56 (1.99-3.30) in ALD, but it was 0.78 (0.19-3.10) in Cryptogenic_SLD, which was not significant. The risk of cardiovascular disease according to the fibrosis stage classified by BARD also presented similar results.

This prospective cohort study of Korean patients with newly defined MASLD, MetALD, and ALD with FIB-4 ≥ 1.3 at high risk of developing cardiovascular disease.

The international consensus to revise non-alcoholic fatty liver disease to metabolic (dysfunction)-associated fatty liver disease (MAFLD) in 2020 attracted significant attention. The impact of the MAFLD definition on the research community has not been objectively assessed. We conducted an analysis of systematically collected literature on MAFLD to understand its research impact.

From PubMed, Web of Science, and Scopus, the literature adopting MAFLD, written in English, and published from 2020 to 10 October 2023 was collected. The publication metrics, including publication counts, publishing journals, author countries, author keywords, and citation information, were analyzed to evaluate the research impact and key topics on MAFLD.

1469 MAFLD-related papers were published in 434 journals with a steady increase in the number. The intense publishing and citations activity on MAFLD indicates the large impact of the redefinition. Topic assessment with keyword and citation analysis revealed a transition from the proposal and discussion of the redefinition to clinical characterization of MAFLD with a focus on metabolic dysfunction. Moreover, the diagnostic criteria for MAFLD showed better performance in predicting hepatic and extrahepatic outcomes compared to NAFLD. The publications were from 99 countries with evidence of strong regional and global collaboration. Multiple international societies and stakeholders have endorsed MAFLD for its utility in clinical practice, improving patient management and promoting multidisciplinary care, while alleviating stigma.

This survey provides a quantitative measure of the considerable international impact and contributions of the MAFLD definition towards liver research and as part of the spectrum of cardiometabolic disorders.

Background/Objectives: Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) increases the risk of Type-2 Diabetes (T2DM). The Mediterranean diet (MD) has shown advantages in the management of MAFLD and preventing co-morbidities; however, its relationship with T2DM development in MAFLD has been less investigated. We aimed to evaluate the association of MD adherence with the risk of incident T2DM in the Spanish adult population with MAFLD and according to their weight gain at 7.5 years follow-up. Methods: A cohort of 714 participants (without weight increment: 377; with weight increment: 337) from the Di@bet.es cohort study with MAFLD and without T2DM at baseline were investigated. Anthropometric, sociodemographic, clinical data, and a survey on habits were recorded. OGTT and fasting blood biochemistry determinations were made. Baseline adherence to MD was estimated by the adapted 14-point MEDAS questionnaire and categorized as high and low adherence. Results: In total, 98 people developed T2DM at follow-up. The high adherence to MD was inversely associated with the development of T2DM in both the overall population (0.52 [0.31-0.87]) and subjects without weight gain at follow-up (0.35 [0.16-0.78]). Conclusions: Our results suggest the protective effect of high adherence to MD regarding the risk of T2DM in subjects with MAFLD, with this health benefit being more evident in men with the absence of weight gain. These results support the recommendations for MD use in these patients.

We examined the association of objective measures of cardiometabolic risk with progression to a high-risk for advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) at initially low- and indeterminate-risk for advanced fibrosis.

We performed a retrospective cohort study of primary care patients with MASLD between 2012 and 2021. We evaluated patients with MASLD and low- or indeterminate-risk Fibrosis-4 Index (FIB-4) scores and followed them until the outcome of a high-risk FIB-4 (≥2.67), or the end of the study period. Exposures of interest were body mass index, systolic blood pressure, hemoglobin A1c, cholesterol, estimated glomerular filtration rate, and smoking status. Variables were categorized by the threshold for primary care therapy intensification. Unadjusted and adjusted Cox regression models were developed for the outcome of time to a high-risk FIB-4 value.

The cohort included 1347 patients with a mean follow-up of 3.6 years (SD 2.7). Of the cohort, 258 (19%) had a subsequent FIB-4 > 2.67. In the fully adjusted Cox regression models, mean systolic blood pressure ≥ 150 mm Hg (1.57; 95% confidence interval (CI) 1.02-2.41) and glomerular filtration rate ≤ 59 ml/min (hazard ratio 2.78; 95%CI 2.17-3.58) were associated with an increased hazard of a high-risk FIB-4, while receiving a statin prescription (hazard ratio 0.51; 95%CI 0.39-0.66) was associated with a lower risk.

Nearly 1 in 5 primary care patients with MASLD transitioned to a high-risk FIB-4 score during 3.6 years of follow-up, and uncontrolled blood pressure and reduced kidney function were associated with an increased hazard of a FIB-4 at high-risk for advanced fibrosis.

The recent change in terminology from nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) highlights the link between hepatic steatosis and metabolic dysfunction, taking out the stigmata of alcohol.

We compared the effects of NAFLD and MAFLD definitions on the risk of overall and cardiovascular (CV) mortality, liver-related events (LRE), nonfatal CV events (CVE), chronic kidney disease (CKD), and extra-hepatic cancers (EHC).

We systematically searched four large electronic databases for cohort studies (published through August 2023) that simultaneously used NAFLD and MAFLD definitions for examining the risk of mortality and adverse CV, renal, or oncological outcomes associated with both definitions. In total, 21 eligible cohort studies were identified. Meta-analysis was performed using random-effects modelling.

Compared with those with NAFLD, individuals with MAFLD had significantly higher rates of overall mortality (random-effect OR 1.12, 95% CI 1.04-1.21, p = .004) and CV mortality (random-effect OR 1.15, 95% CI 1.04-1.26, p = .004), and a marginal trend towards higher rates of developing CKD (random-effect OR 1.06, 95% CI 1.00-1.12, p = .058) and EHC events (random-effect OR 1.11, 95% CI 1.00-1.23, p = .052). We found no significant differences in the risk LREs and nonfatal CVE between MAFLD and NAFLD. Meta-regression analyses identified male sex and metabolic comorbidities as the strongest risk factors related to the risk of adverse clinical outcomes in MAFLD compared to NAFLD.

Individuals with MAFLD have higher rates of overall and CV mortality and higher rates of developing CKD and EHC events than those with NAFLD, possibly due to the dysmetabolic risk profile related to MAFLD.

This investigation seeks to explore the correlation between nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVDs), and to to provide evidence for the prevention and treatment of CVDs.

This study utilized data from the Jinchang cohort platform, including 19,399 participants without pre-existing major CVDs. Based on the general population and gender stratification, Cox models were used to analyze the risk of NAFLD for CVDs. The combined effect of NAFLD and different obesity indicators on CVDs was analyzed by additive and multiplicative interaction models and subgroups.

There were 3129 NAFLD patients out of 19399 subjects, and 723 (23.11%) of them had the CVD. After adjusting for multiple confounding factors, the Cox model revealed a 1.17-fold increase in the risk of CVDs among patients with NAFLD compared to those without NAFLD. Moreover, there was no notable disparity in CVDs risk among most NAFLD patients at the same level of obesity. The results indicated no additive interaction between NAFLD and obesity concerning CVDs risk, but rather a positive multiplicative interaction. Using the normal population as a reference, it was found that people with both obesity and NAFLD significantly increased the risk of developing CVDs, with HRs and 95% CIs of 1.790 (1.508, 2.126), 1.356 (1.213, 1.517), and 1.807 (1.503, 2.174), respectively, for BMI, WC, and the combination of BMI and WC.

NAFLD and obesity are independent risk factors for CVDs. The synergy of obesity and NAFLD implies that NAFLD patients should control weight gain. Larger BMI and WC values may increase the CVDs risk for NAFLD patients, especially women.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. In recent years, a new terminology and definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed. Compared to the NAFLD definition, MAFLD better emphasizes the pathogenic role of metabolic dysfunction in the development and progression of this highly prevalent condition. Metabolic disorders, including overweight/obesity, type 2 diabetes mellitus (T2DM), atherogenic dyslipidemia and hypertension, are often associated with systemic organ dysfunctions, thereby suggesting that multiple organ damage can occur in MAFLD. Substantial epidemiological evidence indicates that MAFLD is not only associated with an increased risk of liver-related complications, but also increases the risk of developing several extra-hepatic diseases, including new-onset T2DM, adverse cardiovascular and renal outcomes, and some common endocrine diseases. We have summarized the current literature on the adverse effect of MAFLD on the development of multiple extrahepatic (cardiometabolic and endocrine) complications and examined the role of different metabolic pathways and organ systems in the progression of MAFLD, thus providing new insights into the role of MAFLD as a multisystem metabolic disorder. Our narrative review aimed to provide insights into potential mechanisms underlying the known associations between MAFLD and extrahepatic diseases, as part of MAFLD as a multisystem disease, in order to help focus areas for future drug development targeting not only liver disease but also the risk of extrahepatic complications.

To evaluate the impact of non-alcoholic fatty liver disease (NAFLD) presence and fibrosis risk on adverse outcomes in patients with type 2 diabetes and chronic kidney disease.

Data were sourced from two longitudinal cohorts: 1172 patients from the National Health and Nutrition Examination Survey (NHANES) and 326 patients from the kidney biopsy cohort at the West China Hospital of Sichuan University. Cox regression estimated hazard ratios (HRs) for NAFLD and liver fibrosis concerning adverse clinical outcomes. Subsequently, a two-sample Mendelian randomization study using genome-wide association study statistics explored NAFLD's potential causal link to cardio-cerebrovascular events.

In the NHANES cohort, NAFLD stood as an independent risk factor for various outcomes: overall mortality [HR 1.53 (95% confidence interval, CI 1.21-1.95)], mortality because of cardio-cerebrovascular diseases [HR 1.63 (95% CI 1.12-2.37)], heart disease [HR 1.58 (95% CI 1.00-2.49)], and cerebrovascular disease [HR 3.95 (95% CI 1.48-10.55)]. Notably, advanced liver fibrosis, identified by a fibrosis-4 (FIB-4) score >2.67, exhibited associations with overall mortality, cardio-cerebrovascular disease mortality and heart disease mortality. Within the kidney biopsy cohort, NAFLD correlated with future end-stage kidney disease [ESKD; HR 2.17 (95% CI 1.41-3.34)], while elevated FIB-4 or NAFLD Fibrosis Scores predicted future ESKD, following full adjustment. Liver fibrosis was positively correlated with renal interstitial fibrosis and tubular atrophy in biopsies. Further Mendelian randomization analysis supported a causal relationship between NAFLD and cardio-cerebrovascular events.

In patients with type 2 diabetes and chronic kidney disease, the NAFLD presence and elevated FIB-4 scores link to heightened mortality risk and ESKD susceptibility. Moreover, NAFLD shows a causal relationship with cardio-cerebrovascular events.

Background: This study investigated the association between metabolic dysfunction-associated steatotic liver disease (MASLD) and Kidney Cancer Risk, as the incidence of both diseases gradually increases owing to metabolic health issues. Methods: Participants (aged 20-79) undergoing a national health examination between 2009 and 2010 were monitored for new-onset kidney cancer. The MASLD spectrum was classified as non-MASLD, MASLD, or MASLD with increased alcohol uptake (MetALD). Kidney Cancer Risk associated with the MASLD spectrum was estimated using multivariate Cox proportional hazard models. Age- and sex-stratified analyses were also performed. Results: Among 8,829,510 participants (median follow-up 13.3 years), the proportion of non-MASLD, MASLD, and MetALD was 64.9%, 30.3%, and 4.7%, respectively, with newly developed kidney cancer in 17,555 participants. Kidney cancer was significantly increased with MASLD (adjusted hazard ratio [aHR] 1.51, 95% confidence interval [CI] 1.46-1.56) and MetALD (aHR 1.51, 95% CI 1.42-1.61), compared with the non-MASLD group. Kidney Cancer Risk was the highest among young populations (aHR 1.93, 95% CI 1.77-2.11 for MASLD and aHR 1.91, 95% CI 1.65-2.22 for MetALD), according to stratification analysis. Furthermore, the cumulative relationship between metabolic dysfunction and Kidney Cancer Risk was confirmed across all MASLD spectra. Conclusions: Our study highlights the positive association between MASLD and Kidney Cancer Risk, emphasizing a comprehensive approach to metabolic health. This also serves as a call to devote closer attention to the metabolic health of younger patients.

The rate of incidence of metabolic dysfunction-related fatty liver disease (MAFLD) has rapidly increased globally in recent years, but early diagnosis is still a challenge. The purpose of this systematic review and meta-analysis is to identify visfatin for early diagnosis of MAFLD.

We strictly adhered to the relevant requirements of Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The systematic search was conducted in 7 sources (PubMed, Embase, Cochrane Library, CNKI, Wanfang, CBM, and ClinicalTrials.gov) until February 2024. The meta-analysis was performed using Stata 12. Outcomes were expressed in the form of standardized mean difference (SMD) and 95% confidence interval and were analyzed using meta-analysis.

The results showed that there was no significant difference in circulating visfatin levels between patients with MAFLD and controls (SMD = 0.13 [-0.34, 0.60]). However, the outcomes indicated that the level of circulating visfatin was significantly higher in MAFLD patients in the Middle Eastern subgroup (SMD = 0.45 [0.05, 0.85]) and in the obese patient subgroup (SMD = 1.05 [0.18, 1.92]). No publication bias was detected, and sensitivity analysis confirmed the stability of the outcomes.

The serum visfatin levels of MAFLD patients did not differ significantly from those of controls. However, visfatin concentrations in serum were statistically higher within Middle Eastern or obese MAFLD patients compared to controls. There is a need for further research to investigate visfatin's potential as a biomarker for MAFLD.

Although high-density lipoprotein cholesterol (HDL-C) exerts a significant influence on the development of metabolic dysfunction-associated fatty liver disease (MAFLD), the association of dynamic changes in HDL-C levels with the risk of MAFLD remains unclear. Thus, the aim of the current study was to explore the association between the changing trajectories of HDL-C and new-onset MAFLD. The findings of this study may provide a theoretical basis for future personalized intervention and prevention targeting MAFLD.

A total of 1507 participants who met the inclusion criteria were recruited from a community-based physical examination population in Nanjing, China from 2017 to 2021. Group-based trajectory models were constructed to determine the heterogeneous HDL-C trajectories. The incidence of MAFLD in each group in 2022 was followed up, and the Cox proportional hazards regression model was applied to investigate the associations between different HDL-C trajectories and the risk of new-onset MAFLD.

The incidences of MAFLD in the low-stable, moderate-stable, moderate-high-stable, and high-stable groups of HDL-C trajectory were 26.5%, 13.8%, 7.2% and 2.6%, respectively. The incidence rate of MAFLD in the order of the above trajectory groups exhibited a decreasing trend (χ2 = 72.55, Ptrend<0.001). After adjusting for confounders, the risk of MAFLD onset in HDL-C low-stable group was still 5.421 times (95%CI: 1.303-22.554, P = 0.020) higher than that in the high-stable group. Subgroup analyses of the combined (moderate high-stable and high-stable groups combined), moderate-stable and low-stable groups showed that sex, age, and overweight/obesity did not affect the association between HDL-C trajectory and MAFLD risk.

Persistently low HDL-C level is a risk factor for the onset of MAFLD. Long-term monitoring of HDL-C levels and timely intervention for those experiencing persistent declines are crucial for early prevention of MAFLD.

The cardiometabolic index (CMI) is an emerging and effective indicator for predicting the presence of metabolic-associated fatty liver disease (MAFLD). This study aims to investigate the relationship between CMI and MAFLD using data from NHANES 2017-2020. In this cross-sectional study, a total of 3,749 subjects were included. The study conducted a thorough analysis of CMI with three multivariate logistic regression models, subgroup analyses, and restricted cubic splines (RCS) were utilized. Using multifactorial logistic regression as the primary method of analysis, we found that a higher CMI was also significantly associated with an increased risk of MAFLD (OR = 1.45, 95% CI (1.05-2.01)). This result was further visualized by the RCS curve: There was a non-linear positive correlation between CMI and MAFLD incidence (the turning point is CMI = 0.4554). These findings were strongly reinforced by subsequent subgroup and sensitivity analyses. There is a robust positive relationship between the CMI and the risk of MAFLD, providing valuable clinical benefits for early detection and screening of MAFLD. It is important to highlight the presence of a non-linear association between CMI and MAFLD, with an inflection point identified at CMI = 0.4554.

This study aimed to explore the association between serum uric acid (sUA) levels and metabolic-associated fatty liver disease (MAFLD) in Southeast China.

We performed a cross-sectional study of 2605 subjects who underwent physical examination between 2015 and 2017 in Southeast China. To explore the association between sUA levels and the risk of MAFLD, we employed logistic regression, restricted cubic spline (RCS), subgroups and multiplicative interaction analysis.

Logistic regression analysis showed a positive association between sUA and MAFLD [aOR total population (95% CI)= 1.90 (1.49 ~ 2.42)], [aOR male (95% CI)= 2.01 (1.54 ~ 2.62)], [aOR female (95% CI)= 1.15 (0.62 ~ 2.11)], respectively. The RCS plot presented a significant nonlinear dose-response relationship between sUA levels and MAFLD risk, and the risk of MAFLD increased significantly when sUA> 5.56 mg/dL (P nonlinear< 0.001). Subgroups analysis revealed that the positive association between sUA and MAFLD was consistent across strata of gender, age, BMI, drinking status, smoking status and tea drinking status. Significant associations between sUA and MAFLD were not only found in males but also existed in subjects whose age ≤60, BMI ≥24 kg/m2, drinkers, smokers and tea-drinkers. Adjusted ORs were estimated to be 2.01, 1.95, 2.11, 2.29, 2.64 and 2.20, respectively. Multiplicative interactions were not observed between gender, age, drinking status, smoking status, tea drinking status and sUA (all P interaction> 0.05).

According to our study, sUA was positively associated with the risk of MAFLD. Additionally, the risk of MAFLD increased significantly when sUA levels exceeded 5.56 mg/dL. Our study may help clarify whether sUA plays a diagnostic role in MAFLD.

The incidence density of metabolic dysfunction-associated fatty liver disease (MAFLD) and the effect of a healthy lifestyle on the risk of MAFLD remain unknown. We evaluated the prevalence and incidence density of MAFLD and investigated the association between healthy lifestyle and the risk of MAFLD.

A cross-sectional analysis was conducted on 37,422 participants to explore the prevalence of MAFLD. A cohort analysis of 18,964 individuals was conducted to identify the incidence of MAFLD, as well as the association between healthy lifestyle and MAFLD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) with adjustments for confounding factors.

The prevalence of MAFLD, non-alcoholic fatty liver disease, and their comorbidities were 30.38%, 28.09%, and 26.13%, respectively. After approximately 70 thousand person-years of follow-up, the incidence densities of the three conditions were 61.03, 55.49, and 51.64 per 1,000 person-years, respectively. Adherence to an overall healthy lifestyle was associated with a 19% decreased risk of MAFLD (HR, 0.81; 95% CI, 0.72 to 0.92), and the effects were modified by baseline age, sex, and body mass index (BMI). Subgroup analyses revealed that younger participants, men, and those with a lower BMI experienced more significant beneficial effects from healthy lifestyle.

Our results highlight the beneficial effect of adherence to a healthy lifestyle on the prevention of MAFLD. Health management for improving dietary intake, physical activity, and smoking and drinking habits are critical to improving MAFLD.