Non-alcoholic fatty liver disease (NAFLD), one of the most common chronic liver diseases with a prevalence of 23%-25% globally, is an independent risk factor for cardiovascular diseases (CVDs). Growing evidence indicates that the development of NAFLD, ranging from non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), advanced fibrosis to cirrhosis, and even hepatocellular carcinoma, is at substantial risk for CVDs, which clinically contribute to increased cardiovascular morbidity and mortality. Non-invasive serum markers assessing liver fibrosis, such as fibrosis-4 (FIB-4) score, aspartate transaminase-to-platelet ratio index (APRI), and NAFLD fibrosis score (NFS), are expected to be useful tools for clinical management of patients with CVDs. This review aims to provide an overview of the evidence for the relationship between the progression of NAFLD and CVDs and the clinical application of non-invasive markers of liver fibrosis in managing patients with CVDs.

Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels.

Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression.

A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2-31.6%) and 26.2% (23.9-28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively.

The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.

The global burden of non-alcoholic fatty liver disease (NAFLD) is rising. An alternative term, metabolic dysfunction-associated fatty liver disease (MAFLD), instead highlights the associated metabolic risks. This cohort study examined patient classifications under NAFLD and MAFLD criteria and their associations with all-cause mortality.

Participants who attended a paid health check-up (2012-2015) were included. Hepatic steatosis (HS) was diagnosed ultrasonographically. NAFLD was defined as HS without secondary causes, while MAFLD involved HS with overweight/obesity, type 2 diabetes mellitus, or ≥2 metabolic dysfunctions. Mortality was tracked via the Taiwan Death Registry until November 30, 2022.

Of 118,915 participants, 36.9% had NAFLD, 40.2% had MAFLD, and 32.9% met both definitions. Participants with NAFLD alone had lower mortality, and those with MAFLD alone had higher mortality, than individuals with both conditions. After adjustment for potential confounders, the hazard ratios (HRs) for all-cause mortality were 1.08 (95% confidence interval [CI], 0.78 to 1.48) for NAFLD alone and 1.26 (95% CI, 1.09 to 1.47) for MAFLD alone, relative to both conditions. Advanced fibrosis conferred greater mortality risk, with HRs of 1.93 (95% CI, 1.44 to 2.58) and 2.08 (95% CI, 1.61 to 2.70) for advanced fibrotic NAFLD and MAFLD, respectively. Key mortality risk factors for NAFLD and MAFLD included older age, unmarried status, higher body mass index, smoking, diabetes mellitus, chronic kidney disease, and advanced fibrosis.

All-cause mortality in NAFLD and/or MAFLD was linked to cardiometabolic covariates, with risk attenuated after multivariable adjustment. A high fibrosis-4 index score, indicating fibrosis, could identify fatty liver disease cases involving elevated mortality risk.

We conducted a systematic review and meta-analysis to study the association between non-alcoholic fatty liver disease (NAFLD) and incident cardiovascular disease (CVD).

We searched Medline, Embase, Cochrane database and TRIP database. Random-effects model meta-analyses were used to obtain pooled effect sizes and 95% confidence intervals. The certainty in evidence was rated using the GRADE tool.

Altogether 36 studies including a total of 7,068,007 participants were included in the systematic review and meta-analysis. Pooled data from 19 cohort studies demonstrated a significant increase in the risk of non-fatal CVD events in patients with NAFLD (HR 1.57, 95% CI 1.33-1.85, I2 = 95%). Pooled data from eight studies showed a significant increase in fatal CVD (HR 1.40, 95% CI 1.24-1.57, I2 =27%), and eight cohort studies suggested a significant increase in combined non-fatal and fatal CVD (HR 1.41, 95% CI 1.13-1.76, I2 =80%). Meta-analysis of studies reporting adjusted estimates in NAFLD patients with fibrosis revealed a significant increase in CVD events with acceptable level of heterogeneity (HR 1.64, 95% CI 1.25-2.16, I2 = 31%). The anticipated absolute increase in the risk of combined fatal and non-fatal CVD was estimated to be 29 more per thousand with NAFLD; that of fatal CVD events 16 more per thousand and that of non-fatal CVD events 19 more per thousand with NAFLD. The GRADE rating ranged from very low to low for overall and subgroup analyses.

The present systematic review suggests that NAFLD increases the risk of incident CVD. Cohort studies with the ability to analyze subgroup effects based on severity, along with randomized controlled trials that provide experimental evidence demonstrating a decrease in cardiovascular disease events through the treatment of non-alcoholic fatty liver disease, are necessary to validate and reinforce these findings.

The purpose of this study was to investigate the correlation between the severity of fatty liver and factors such as gender, lifestyle, and the risks of metabolic abnormalities, inflammation, and liver dysfunction in the working population. This cross-sectional study included 2936 workers aged 21-64 years. The severity of fatty liver was assessed using ultrasound. A self-administered survey was used to evaluate lifestyle habits. Data on anthropometric measurements, blood pressure, blood tests, and biochemical evaluations was collected. The 45.5% of workers had fatty liver. Males had a higher prevalence of fatty liver and health risks and several unhealthy lifestyle habits compared to females. The health behavior score related to exercise showed notable declines as the severity of fatty liver increased (p < 0.001). Percentages of current alcohol drinkers differed among different levels of fatty liver, with rates of 43.1, 48.4, 44.8, and 63.4% (p = 0.005) observed in the absence, mild, moderate, and severe fatty liver, respectively. Workers with fatty liver showed increased risks related to metabolic anomalies, especially in severe cases. The risk of inflammation and liver dysfunction also significantly increased with elevated fatty liver severity. Overall, fatty liver presents significant health risks, with nearly half of the workers diagnosed with the condition. To improve liver health, it is crucial to have customized strategies for promoting health, taking into account the different levels of severity in fatty liver.

Recently, metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed to replace non-alcoholic fatty liver disease (NAFLD) to emphasize the pathogenic association between fatty liver disease and metabolic dysfunction. Studies have found that MAFLD independently increases the risk of myocardial infarction and stroke. But the relationship between MAFLD and heart failure (HF) is not fully understood.

This study aimed to explore the association between MAFLD and the risk of HF.

The study included 98,685 participants without HF selected from the Kailuan cohort in 2006. All participants were divided into non-MAFLD group and MAFLD group according to MAFLD diagnostic criteria. After follow-up until December 31, 2020, the Cox regression analysis model was used to calculate the effect of MAFLD on the risk of HF.

During the median follow-up of 14.01 years,3260 cases of HF were defined, the HF incidence density of non-MAFLD group and MAFLD group was 2.19/1000pys and 3.29/1000pys, respectively. Compared with the non-MAFLD group, participants with MAFLD had an increased risk of HF (HR: 1.40, 95% CI: 1.30-1.50); in addition, an exacerbation of fatty liver disease was associated with an increased risk of HF in people with MAFLD. We also observed a higher risk of HF among the different metabolic dysfunction of MAFLD in people with both fatty liver disease and type 2 diabetes (HR, 1.95; 95% CI, 1.73-2.20).

Our findings suggest that the risk of HF was significantly increased in participants with MAFLD, and an exacerbation of fatty liver disease was associated with an increased risk of HF in people with MAFLD. In addition, we should pay more attention to people with MAFLD with type 2 diabetes.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is estimated to increase to over half of the adult population by 2040 globally. Since the final diagnosis of NAFLD is made by a liver biopsy, several non-invasive approaches have been developed and validated to define NAFLD and evaluate NAFLD-associated diseases. Presently, NAFLD has been identified as an important and independent risk factor for developing several extrahepatic diseases, including atherosclerosis, cardiovascular disease (CVD), diabetes, and dementia. This review discusses current findings of up-to-date literature regarding the effects of NAFLD on the risk of atherosclerosis and CVD in Asia along with potential underlying biological mechanisms and therapeutic approaches to lower the NAFLD-related CVD risk. We further focus on the difference between NAFLD and metabolic dysfunction-associated fatty liver disease (MAFLD) on the risk of CVD and its implication by comparing the risk of NAFLD and MAFLD.

Fatty liver disease is an emerging contributor to disease burden worldwide. The past decades of work established the heterogeneous nature of non-alcoholic fatty liver disease (NAFLD) etiology and systemic contributions to the pathogenesis of the disease. This called for the proposal of a redefinition in 2020 to that of metabolic dysfunction-associated fatty liver disease (MAFLD) to better reflect the current understanding of the disease. To date, several clinical cohort studies comparing NAFLD and MAFLD hint at the relevancy of the new nomenclature in enriching for patients with more severe hepatic injury and extrahepatic comorbidities. However, the underlying systemic pathogenesis is still not fully understood. Preclinical animal models have been imperative in elucidating key biological mechanisms in various contexts, including intrahepatic disease progression, interorgan crosstalk and systemic dysregulation. Furthermore, they are integral in developing novel therapeutics against MAFLD. However, substantial contextual variabilities exist across different models due to the lack of standardization in several aspects. As such, it is crucial to understand the strengths and weaknesses of existing models to better align them to the human condition. In this review, we consolidate the implications arising from the change in nomenclature and summarize MAFLD pathogenesis. Subsequently, we provide an updated evaluation of existing MAFLD preclinical models in alignment with the new definitions and perspectives to improve their translational relevance.

Gastrodin can reduce neuronal damage through multiple targets and pathways, and can be useful in preventing and treating degenerative lesions of the central nervous system, but the specific mechanism has not been elucidated.

The aging-related genes in the hippocampus and the frontal cortex were detected in adult and aged mice treated with gastrodin or not. In addition, we collected the target genes of gastrodin and aging from a network database, and a Venn diagram was created to obtain the intersection target genes of gastrodin and aging. Then, the String database was used to analyze the protein-protein interactions (PPIs) between aging-related genes and the target genes of gastrodin and aging. The "drug-disease-target-pathway" network was constructed using Cytoscape 3.7.2 software, and the main mechanism and pathway of key genes were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). Finally, the reliability of these key genes was further verified by molecular docking technology.

The results showed that 6 out of 10 genes related to brain aging were differentially expressed after gastrodin intervention. Moreover, there were 11 key genes between gastrodin and differentially expressed genes related to brain aging. GO and KEGG results suggested that material metabolism and carbohydrate digestion and absorption were associated with the pathological mechanism of gastrodin antiaging. Molecular docking results also confirmed the good binding activity of gastrodin to the key genes.

Gastrodin plays a potential role in antiaging by regulating substance metabolism and carbohydrate digestion and absorption.