Metabolic dysfunction-associated fatty liver disease (MASLD) is a rising global health concern. In addition to direct hepatic complications, extra-hepatic complications, including cardiovascular diseases (CVD), type 2 diabetes (T2D), gastroesophageal reflux disease, chronic kidney disease and some malignancies, are increasingly recognized. CVD, including atrial fibrillation (AF) and heart failure (HF), is the leading cause of death in patients with MASLD. External factors, including excess energy intake, sedentary lifestyle and xenobiotic use, induce inflammation-related complications. MASLD, AF, and HF are associated with immune system activation, including the reprogramming of immune cells and the establishment of immune memory. Emerging evidence suggests that the heart and the liver cross-talk with each other through the diverse spectrum of autocrine, paracrine and endocrine mechanisms. Pro-inflammatory cytokines produced from the liver and the heart circulate systemically to orchestrate metabolic derangements that promote the systematic immune dysregulation in the heart-liver axis and the development of end-organ complications. Cardio-hepatic syndrome describes the clinical and biochemical evidence of hepatic dysfunction and cardiac pathology due to the interaction between the heart and the liver. Activation of inflammatory cascades, oxidative stress and immune system dysregulation underlie key mechanisms in bringing about such pathological changes. This review focuses on the current clinical and molecular evidence about the heart-liver cross-talk. It summarizes the epidemiological and pathophysiological associations of MASLD, AF and HF. In addition, we will discuss how repurposing currently available and emerging pharmacotherapies may help tackle the cardiovascular risks resulting from MASLD.

Epidemiological evidence suggests that non-alcoholic fatty liver disease (NAFLD) may increase the risk of atrial fibrillation (AF). However, the findings are inconsistent, and the causality remains to be established.

We conducted two-step, two-sample Mendelian randomization (MR) analysis to assess the association between genetically predicted NAFLD (i.e. chronically elevated serum alanine aminotransferase levels [cALT], imaging-based and biopsy-confirmed NAFLD) and AF. Subsequently, we further performed Mendelian randomization to investigate the causal relationship between non-alcoholic steatohepatitis (NASH), a subtype of NAFLD, and AF. The inverse variance weighted (IVW) method was used as the primary approach to reveal the potential causation between the exposure and outcome.

There was no significant causal association between NAFLD diagnosed based on cALT, confirmed by imaging, or verified by biopsy, and an increased risk of atrial fibrillation. Furthermore, the results of the IVW method revealed a positive causal effect of NASH on AF (OR=1.113, 95% CI=1.025-1.209, P = 0.011). In the reverse analysis, however, no evidence supported a significant genetic association between AF and NASH (OR=0.974, 95% CI=0.934-1.016, P = 0.214).

A causal relationship existed between NASH and the risk of AF. However, no significant genetic association has been observed between NAFLD and AF risk. This suggests that managing the progression of NAFLD may hold potential value in preventing the onset of AF.

Background: Non-alcoholic fatty liver disease (NAFLD), more recently redefined as metabolic-associated fatty liver disease (MAFLD), is now recognized as the most prevalent cause of chronic liver disease. Its strong association with cardiovascular disease (CVD) underscores its emerging role in global morbidity and mortality. Objective: This review critically examines the pathophysiological mechanisms that link NAFLD/MAFLD with CVD. It focuses on shared metabolic disturbances, inflammatory pathways, and alterations in the gut microbiota that contribute to hepatic and cardiovascular pathology. Review and Gaps: Current evidence highlights insulin resistance, dyslipidemia, systemic inflammation, and gut dysbiosis as pivotal factors connecting NAFLD/MAFLD to CVD. Despite these insights, inconsistencies in diagnostic criteria and a lack of validated non-invasive biomarkers hinder a clear understanding of the causal relationship between liver and cardiovascular diseases. Conclusions: Addressing these knowledge gaps through standardized diagnostic protocols and large-scale longitudinal studies is essential. Improved biomarker validation and clearer delineation of the underlying mechanisms will improve cardiovascular risk stratification and enable more personalized therapeutic strategies for patients with NAFLD/MAFLD.

Studies have reported an association between metabolic dysfunction-associated steatotic liver disease (MASLD) and an increased risk of developing atrial fibrillation (AF). However, the magnitude of the risk and whether this risk varies with the severity of MASLD remains uncertain.

In this systematic review and meta-analysis, we searched three large electronic databases using predefined keywords to identify cohort studies (published up to 30 September 2024) in which MASLD was diagnosed by liver biopsy, imaging methods, International Classification of Diseases (ICD) codes, or blood-based scores. The primary outcome was the occurrence of AF based on ICD codes, medical records, or electrocardiograms. Meta-analysis was performed using random-effects modelling.

We identified 16 retrospective cohort studies with aggregate data on ~19.5 million individuals followed for a median of 7.2 years. MASLD was significantly associated with an increased risk of developing incident AF (random-effects hazard ratio 1.20, 95% CI 1.10-1.32; I2 = 92%). This risk did not appear to further increase with the severity of liver fibrosis (n = 3 studies; random-effects hazard ratio 1.22, 95% CI 1.18-1.26; I2 = 10%). The risk of AF remained significant even after adjusting for age, sex, body mass index, hypertension, Type 2 diabetes or other cardiometabolic risk factors. Sensitivity analyses did not modify these findings. The funnel plot and Egger's test showed no significant publication bias.

This updated and comprehensive meta-analysis provides evidence that MASLD is significantly associated with an increased long-term risk of developing incident AF. Further research is required to better decipher the link between MASLD and increased AF incidence.

The global incidence of pediatric non-alcoholic fatty liver disease (NAFLD) is rising, and it is linked to various potentially dangerous complications such as cardiovascular complications, particularly atrial fibrillation (AF). Atrial electromechanical conduction delay (EMD) has been reported as an early predictor for AF development. This study aimed to explore the link between NAFLD and the increased risk of AF development. This cross-sectional study was performed on 100 newly diagnosed NAFLD children (aged 14-18 years) as the patient group and 100 healthy individuals as a control group. Transthoracic echocardiography and simultaneous electrocardiography (ECG) recording were employed to estimate atrial electromechanical properties. EMD values were calculated for the inter-atrial, left intra-atrial, and right intra-atrial. Our results showed that pediatric patients with NAFLD exhibited significantly prolonged EMD values in the left and right intra-atrial as well as in inter-atrial regions compared to the control group (P = 0.03, P < 0.001, P < 0.01, respectively). Conclusion: Children with NAFLD show atrial electromechanical alterations that may presage AF in adulthood.

Cardiovascular disease (CVD) is a significant global health concern, particularly among Asian, Native Hawaiian, and Pacific Islander (ANHPI) communities that face unique health challenges. Liver cancer disproportionately affects ANHPI populations and has intricate associations with CVD risks due to shared pathophysiological mechanisms and metabolic disturbances. However, the specific CVD risk profile of ANHPI liver cancer patients remains poorly understood.

Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified and matched 1150 ANHPI and 2070 Non-Hispanic White (NHW) liver cancer patients diagnosed between 2000 and 2017. We used the Fine-Gray sub-distribution hazard model to estimate hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) for CVD risks, including ischemic heart disease (IHD), heart failure, and stroke, among ANHPI liver cancer patients compared to NHW counterparts and among ANHPI subgroups.

ANHPI liver cancer patients demonstrated a lower risk of IHD compared to NHW counterparts (HR, 0.65, 95 % CI, 0.50, 0.86), aligning with broader trends. Subgroup analysis revealed notable heterogeneity within ANHPI populations, with Southeast Asian (HR, 0.65, 95 % CI, 0.42, 1.00) and Chinese patients (HR, 0.53, 95 % CI, 0.33-0.83) exhibiting lower IHD risks compared to their NHW counterparts. However, Native Hawaiian and Pacific Islander liver cancer patients showed elevated risks of heart failure (HR, 3.16, 95 % CI, 1.35-7.39) and IHD (HR, 5.64, 95 % CI, 2.19-14.53) compared to their Chinese counterparts.

Our study highlights the complexity of CVD risks among ANHPI liver cancer patients. Addressing these disparities is crucial for improving cardiovascular outcomes and reducing the burden of CVD among ANHPI liver cancer patients.

Background and Objectives: Metabolic syndrome (MetS) is a condition marked by a complex array of physiological, biochemical, and metabolic abnormalities, including central obesity, insulin resistance, high blood pressure, and dyslipidemia (characterized by elevated triglycerides and reduced levels of high-density lipoproteins). The pathogenesis develops from the accumulation of lipid droplets in the hepatocyte (steatosis). This accumulation, in genetically predisposed subjects and with other external stimuli (intestinal dysbiosis, high caloric diet, physical inactivity, stress), activates the production of pro-inflammatory molecules, alter autophagy, and turn on the activity of hepatic stellate cells (HSCs), provoking the low grade chronic inflammation and the fibrosis. This syndrome is associated with a significantly increased risk of developing type 2 diabetes mellitus (T2D), cardiovascular diseases (CVD), vascular, renal, pneumologic, rheumatological, sexual, cutaneous syndromes and overall mortality, with the risk rising five- to seven-fold for T2DM, three-fold for CVD, and one and a half-fold for all-cause mortality. The purpose of this narrative review is to examine metabolic syndrome as a "systemic disease" and its interaction with major internal medicine conditions such as CVD, diabetes, renal failure, and respiratory failure. It is essential for internal medicine practitioners to approach this widespread condition in a "holistic" rather than a fragmented manner, particularly in Western countries. Additionally, it is important to be aware of the non-invasive tools available for assessing this condition. Materials and Methods: We conducted an exhaustive search on PubMed up to July 2024, focusing on terms related to metabolic syndrome and other pathologies (heart, Lung (COPD, asthma, pulmonary hypertension, OSAS) and kidney failure, vascular, rheumatological (osteoarthritis, rheumatoid arthritis), endocrinological, sexual pathologies and neoplastic risks. The review was managed in accordance with the PRISMA statement. Finally, we selected 300 studies (233 papers for the first search strategy and 67 for the second one). Our review included studies that provided insights into metabolic syndrome and non-invasive techniques for evaluating liver fibrosis and steatosis. Studies that were not conducted on humans, were published in languages other than English, or did not assess changes related to heart failure were excluded. Results: The findings revealed a clear correlation between metabolic syndrome and all the pathologies above described, indicating that non-invasive assessments of hepatic fibrosis and steatosis could potentially serve as markers for the severity and progression of the diseases. Conclusions: Metabolic syndrome is a multisystem disorder that impacts organs beyond the liver and disrupts the functioning of various organs. Notably, it is linked to a higher incidence of cardiovascular diseases, independent of traditional cardiovascular risk factors. Non-invasive assessments of hepatic fibrosis and fibrosis allow clinicians to evaluate cardiovascular risk. Additionally, the ability to assess liver steatosis may open new diagnostic, therapeutic, and prognostic avenues for managing metabolic syndrome and its complications, particularly cardiovascular disease, which is the leading cause of death in these patients.

Non-alcoholic fatty liver disease (NAFLD), now known as metabolic-associated steatotic liver disease (MASLD), is the most common liver disease worldwide, with a prevalence of 38%. In these patients, cardiovascular disease (CVD) is the number one cause of mortality rather than liver disease. Liver abnormalities per se due to MASLD contribute to risk factors such as dyslipidemia and obesity and increase CVD incidents. In this review we discuss hepatic pathophysiological changes the liver of MASLD leading to cardiovascular risks, including liver sinusoidal endothelial cells, insulin resistance, and oxidative stress with a focus on glutathione metabolism and function. In an era where there is an increasingly robust recognition of what causes CVD, such as the factors included by the American Heart Association in the recently developed PREVENT equation, the inclusion of liver disease may open doors to how we approach treatment for MASLD patients who are at risk of CVD.

This study review aimed to consolidate current knowledge on the electrocardiographic abnormalities observed in patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), formerly known as Non-Alcoholic Fatty Liver Disease (NAFLD).

This was a systematic review of studies on the association between MASLD and electrocardiographic abnormalities, published between January 1, 1946, and October 31, 2023. Data from eligible studies were extracted, analyzed, synthesized, and summarized.

We evaluated a total of 27 studies with 8,607,500 participants overall and 1,005,101 participants with MASLD. There was a statistically significant association between MASLD and prevalent atrial fibrillation (pooled OR: 1.34 95 % CI: 1.20-1.49, p < 0.001, n = 12), shorter QRS duration (pooled SMD: -0.073, 95 % CI: -0.144 - -0.001, n = 2, p = 0.048, n = 2), QTc prolongation (p < 0.001, n = 2), LVH (pooled OR: 1.48, 95 % CI: 1.25-1.75, p < 0.001, n = 3), low voltage (p < 0.001, n = 1), ST changes (OR: 1.41, 95 % CI: 1.04-1.91, p = 0.027, n = 1), T wave inversion (p < 0.001, n = 1), axis deviation (OR: 3.21, 95 % CI: 1.99-5.17, p < 0.001, n = 1), conduction defect (OR: 2.79, 95 % CI: 1.83-4.26, p < 0.001, n = 1) and bundle branch block (OR: 2.90, 95 % CI: 1.82-4.61, p < 0.001, n = 1), any persistent heart block (p < 0.001, n = 1), fragmented QRS (p < 0.001, n = 1), and p wave dispersion (p < 0.001, n = 1) CONCLUSION: MASLD is associated with multiple ECG abnormalities which are potential markers of early cardiac involvement, highlighting the multisystemic nature of MASLD. These specific ECG abnormalities could be used in screening and management algorithms to improve cardiac risk stratification in MASLD patients.

CRD42023477501.

The gut ecosystem, termed microbiota, is composed of bacteria, archaea, viruses, protozoa, and fungi and is estimated to outnumber human cells. Microbiota can affect the host by multiple mechanisms, including the synthesis of metabolites and toxins, modulating inflammation and interaction with other organisms. Advances in understanding commensal organisms' effect on human conditions have also elucidated the importance of this community for cardiovascular disease (CVD). This effect is driven by both direct CV effects and conditions known to increase CV risk, such as obesity, diabetes mellitus (DM), hypertension, and renal and liver diseases. Cardioactive metabolites, such as trimethylamine N -oxide (TMAO), short-chain fatty acids (SCFA), lipopolysaccharides, bile acids, and uremic toxins, can affect atherosclerosis, platelet activation, and inflammation, resulting in increased CV incidence. Interestingly, this interaction is bidirectional with microbiota affected by multiple host conditions including diet, bile acid secretion, and multiple diseases affecting the gut barrier. This interdependence makes manipulating microbiota an attractive option to reduce CV risk. Indeed, evolving data suggest that the benefits observed from low red meat and Mediterranean diet consumption can be explained, at least partially, by the changes that these diets may have on the gut microbiota. In this article, we depict the current epidemiological and mechanistic understanding of the role of microbiota and CVD. Finally, we discuss the potential therapeutic approaches aimed at manipulating gut microbiota to improve CV outcomes. © 2024 American Physiological Society. Compr Physiol 14:5449-5490, 2024.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to increased cardiovascular (CV) risks, notably congestive heart failure (CHF). We evaluated the influence of MASLD on CHF and mortality among hospitalized cirrhotic patients.

We analyzed the National Inpatient Sample from 2016 to 2020, identifying adult cirrhosis patients. We focused on CHF and in-hospital mortality, plus hospital stay length, costs, and discharge status. Propensity score matching created balanced cohorts for comparison. Poisson and logistic regression provided adjusted CHF risks and mortality odds ratios (ORs) for MASLD patients.

Before matching, 4.1% of 672,625 cirrhotic patients had MASLD. Post-matching, each group had 23,161 patients. Patients with MASLD showed higher CHF risk (OR 1.14, 95% CI 1.10-1.21, p<0.001) but lower in-hospital mortality (OR 0.57, 95% CI 0.52-0.63, p<0.01) and decreased costs (median $24,447 vs. $28,630, OR 0.86, 95% CI 0.85-0.87, p<0.001).

In this nationwide study of patients with cirrhosis, MASLD was associated with a higher prevalence of CHF and lower in-patient mortality. These findings mirror the "adiposity paradox" phenomenon, where obese/overweight individuals with cardiometabolic dysfunction may experience less severe or beneficial health outcomes than those with a normal weight. Further investigation is warranted to decode the intricate interplay between MASLD, cirrhosis, CHF, and in-hospital mortality and its clinical practice implications.

The relationship between liver fibrosis and left atrial (LA) remodeling in atrial fibrillation (AF) remains uncertain. We examined the associations between the fibrosis-4 (FIB4) index, an indicator of liver fibrosis, and both LA low-voltage areas (LVAs) on electroanatomic mapping and AF recurrence postablation.

We recruited 343 patients who underwent radiofrequency catheter ablation (RFCA) or cryoballoon ablation (CBA) for AF. First, the association between the FIB4 index and LA LVAs (<0.5 mV) was evaluated in RFCA using electroanatomic mapping (n = 214). Next, the utility of a FIB4 index ≥1.3, recommended cut-off value of liver fibrosis, was verified to assess the risk for AF recurrence in CBA without additional LVA ablation (n = 129).

Patients with a FIB4 index ≥1.3 had a higher prevalence of LA LVAs (>5 cm2) compared to those without. Additionally, the quantitative size of LVAs showed a positive correlation with the FIB4 index (R = .642, p < .001). In multivariate logistic models, a FIB4 index ≥1.3 was related to the presence of LVAs after adjusting for LA diameter, right atrial end-systolic area, and nonparoxysmal AF (odds ratio 2.508; p = 0.039). In CBA, AF recurrence rate was 13.1% during 3-12 months postablation. In multivariate Cox models, a FIB4 index ≥1.3 was an important predictor of AF recurrence (hazard ratio 3.796; p = .037), suggesting that LVAs might be associated with AF recurrence after CBA.

The FIB4 index was a novel predictor of the existence of LA LVAs on electroanatomic mapping and AF recurrence after CBA.

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 progression of metabolic dysfunction-associated steatotic liver disease (MASLD) has been found to manifest in a series of hepatic and extrahepatic complications. A comprehensive meta-analysis of the longitudinal outcomes associated with MASLD has yet to be conducted.

To investigate the longitudinal outcomes associated with MASLD, Medline and Embase databases were searched to identify original studies that evaluated the longitudinal risks of incident clinical outcomes among MASLD patients compared with non-MASLD individuals. DerSimonian Laird random-effects meta-analysis was performed. Pooled effect estimates were calculated, and heterogeneity among studies was evaluated.

One hundred twenty-nine studies were included in the meta-analysis. Meta-analysis revealed a significant increase in the risk of cardiovascular outcomes (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.27-1.60; P < .01), various metabolic outcomes such as incident hypertension (HR, 1.75; 95% CI, 1.46-2.08; P < .01), diabetes (HR, 2.56; 95% CI, 2.10-3.13; P < .01), pre-diabetes (HR, 1.69; 95% CI, 1.22-2.35; P < .01), metabolic syndrome (HR, 2.57; 95% CI, 1.13-5.85; P = .02), chronic kidney disease (HR, 1.38; 95% CI, 1.27-1.50; P < .01), as well as all cancers (HR, 1.54; 95% CI, 1.35-1.76; P < .01) among MASLD patients compared with non-MASLD individuals. By subgroup analysis, MASLD patients with advanced liver disease (HR, 3.60; 95% CI, 2.10-6.18; P < .01) were also found to be associated with a significantly greater risk (P = .02) of incident diabetes than those with less severe MASLD (HR, 1.63; 95% CI, 1.0-2.45; P = .02) when compared with non-MASLD.

The present study emphasizes the association between MASLD and its clinical outcomes including cardiovascular, metabolic, oncologic, and other outcomes. The multisystemic nature of MASLD found in this analysis requires treatment targets to reduce systemic events and end organ complications.

Liver diseases play an important role in the development and progression of atrial fibrillation (AF). The Fibrosis-4 (FIB-4) index is a non-invasive score recommended for detecting liver fibrosis. Since the association between liver fibrosis and outcomes of AF patients is still not well defined, we aim to analyze prognosis impact of FIB-4 index in those patients.

A retrospective population-based cohort study was performed with 12,870 unselected patients from a single health area in Spain with AF from 2014 to 2019. Cox regression models were used to estimate the association of FIB-4 index with mortality. The association with ischemic stroke (IS), major bleeding (MB), acute myocardial infarction (AMI), and heart failure (HF) was assessed by competing risk analysis.

A total of 61.1%, 22.0%, and 16.9% were classified as low, moderate and high risk of liver fibrosis according to FIB-4 index, respectively. During a mean follow-up of 4.5 ± 1.7 years, FIB-4 index was associated with mortality (adjusted HR 1.04; 95% CI 1.01-1.06; p = 0.002), MB and HF (adjusted sHR 1.03, 95% CI 1.01-1.04; p = 0.004), but not with IS or with AMI. The association between FIB-4 and MB was only found in patients treated with vitamin K antagonists, not in patients on direct oral anticoagulants.

The FIB-4 index, a non-invasive scoring method for evaluating liver fibrosis, is independently associated with all-cause mortality, MB and HF in patients with AF, suggesting that it may be useful as a risk assessment tool to identify adverse outcomes in patients with AF.

Metabolic dysfunction-associated steatotic liver disease (MASLD) was previously known as nonalcoholic fatty liver disease (NAFLD). The main characteristic of the disease is the process of long-term liver inflammation, which leads to hepatocyte damage followed by liver fibrosis and eventually cirrhosis. Additionally, these patients are at a greater risk for developing cardiovascular diseases (CVD). They have several pathophysiological mechanisms in common, primarily lipid metabolism disorders and lipotoxicity. Lipotoxicity is a factor that leads to the occurrence of heart disease and the occurrence and progression of atherosclerosis. Atherosclerosis, as a multifactorial disease, is one of the predominant risk factors for the development of ischemic heart disease. Therefore, CVD are one of the most significant carriers of mortality in patients with metabolic syndrome. So far, no pharmacotherapy has been established for the treatment of MASLD, but patients are advised to reduce their body weight and change their lifestyle. In recent years, several trials of different drugs, whose basic therapeutic indications include other diseases, have been conducted. Because it has been concluded that they can have beneficial effects in the treatment of these conditions as well, in this paper, the most significant results of these studies will be presented.

Prior studies suggest a link between metabolic dysfunction-associated steatotic liver disease (MASLD) and incident arrhythmias, including atrial fibrillation (AF). However, robust data are lacking from cohorts with liver histology, which remains the gold standard for staging MASLD severity.

This population-based cohort included all Swedish adults with histologically-confirmed MASLD and without prior cardiac arrhythmias (1966-2016; n = 11,206). MASLD was defined from prospectively-recorded histopathology, and characterized as simple steatosis, non-fibrotic steatohepatitis (MASH), non-cirrhotic fibrosis, or cirrhosis. MASLD patients were matched to ≤ 5 controls without MASLD or arrhythmias, by age, sex, calendar year and county (n = 51,856). Using Cox proportional hazards modeling, we calculated multivariable-adjusted hazard ratios (aHRs) for incident arrhythmias (including AF, bradyarrhythmias, other supraventricular arrhythmias, ventricular arrhythmias/cardiac arrest).

Over a median follow-up of 10.8 years, incident arrhythmias were confirmed in 1351 MASLD patients (10.3/1000 person-years [PY]) and 6493 controls (8.7/1000PY; difference = 1.7/1000PY; aHR = 1.30, 95%CI 1.22-1.38), and MASLD patients had significantly higher rates of incident AF (difference = 0.9/1000PY; aHR = 1.26, 95%CI 1.18-1.35). Rates of both overall arrhythmias and AF were significantly elevated across all MASLD histological groups, particularly cirrhosis (differences, 8.5/1000PY and 5.3/1000PY, respectively). In secondary analyses, MASLD patients also had significantly higher rates of incident ventricular arrhythmias/cardiac arrest (aHR = 1.53, 95%CI 1.30-1.80), bradyarrhythmias (aHR = 1.26, 95%CI 1.06-1.48), and other supraventricular arrhythmias (aHR = 1.27, 95%CI 1.00-1.62), compared to controls.

Compared to matched controls, patients with biopsy-confirmed MASLD had modest but significantly higher incidence of cardiac arrhythmias, including AF, bradyarrhythmias, other supraventricular arrhythmias and ventricular arrhythmias/cardiac arrest. Excess risk was observed across all stages of MASLD and was highest with cirrhosis.

Non-alcoholic fatty liver disease (NAFLD) is becoming a major cause of liver disease-related morbidity, as well as mortality. Importantly, NAFLD is considered a mediator of systemic diseases including cardiovascular disease. Its prevalence is expected to increase, mainly due to its close association with obesity and type 2 diabetes mellitus (T2D). In addition, T2D and NAFLD share common pathophysiological mechanisms, and one can lead to or worsen the other. Therefore, a close collaboration between primary care physician, endocrinologists and hepatologists is essential to optimize the management of patients with NAFLD and T2D. Here, we summarize relevant aspects about NAFLD and T2D that all clinician managing these patients should know as well as current therapeutic options for the treatment of T2D associated with NAFLD.

Chronic liver disease (CLD) is a highly prevalent condition. There is burgeoning recognition that there are many people with subclinical liver disease that may nonetheless be clinically significant. CLD has a variety of systemic aberrations relevant to stroke, including thrombocytopenia, coagulopathy, elevated liver enzymes, and altered drug metabolism. There is a growing body of literature on the intersection of CLD and stroke. Despite this, there have been few efforts to synthesize these data, and stroke guidelines provide scant guidance on this topic. To fill this gap, this multidisciplinary review provides a contemporary overview of CLD for the vascular neurologist while appraising data regarding the impact of CLD on stroke risk, mechanisms, and outcomes. Finally, the review addresses acute and chronic treatment considerations for patients with stroke-ischemic and hemorrhagic-and CLD.

The association between nonalcoholic fatty liver disease (NAFLD) with cardiovascular and cerebrovascular outcomes, as well as their clinical impact, has yet to be established in the literature. This meta-analysis aims to evaluate the association between the NAFLD patients and the risk of atrial fibrillation (AF), heart failure (HF), stroke, cardiovascular mortality (CVM), and revascularization incidence. We performed a systematic literature search using PubMed, Embase, Scopus, and Cochrane libraries for relevant articles from inception until August 2022. A total of 12 cohort studies with 18,055,072 patients (2,938,753 NAFLD vs 15,116,319 non-NAFLD) were included in our analysis. The mean age of the NAFLD patients group and the non-NAFLD group was comparable (55.68 vs 55.87). The most common comorbidities among the NAFLD patients group included hypertension (38% vs 24%) and diabetes mellitus (14% vs 8%). The mean follow-up duration was 6.26 years. The likelihood of AF (risk ratio (RR), 1.42 (95% CI 1.19, 1.68), p < 0.001), HF (RR, 1.43(95% CI 1.03, 2.00), p < 0.001), stroke (RR, 1.26(95% CI 1.16, 1.36), p < 0.001), revascularization (RR, 4.06(95% CI 1.44, 11.46), p = 0.01), and CVM (RR, 3.10(95% CI 1.43, 6.73), p < 0.001) was significantly higher in the NAFLD patients group compared to that of the non-NAFLD group. However, all-cause mortality was comparable between both the groups of patients (RR, 1.30 (95% CI 0.63, 2.67), p = 0.48). In conclusion, the patients with NAFLD are at increased risk of AF, HF, and CVM.

The association between atrial fibrillation (AF) and non-alcoholic fatty liver disease (NAFLD) or metabolic-associated fatty liver disease (MAFLD) has been explored in recent cohort studies, however, the results have been controversial and inconclusive. This meta-analysis aimed to explore this potential association.

We systematically searched PubMed, Embase, and Web of Science databases to identify all relevant cohort studies investigating the association between NAFLD/MAFLD and AF published from database inception to October 30, 2022. Random-effects models were utilized to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for summary purposes. Additionally, subgroup and sensitivity analyses were performed.

A total of 13 cohort studies with 14 272 735 participants were included. Among these, 12 cohort studies with 14 213 289 participants (median follow-up of 7.8 years) showed a significant association between NAFLD and an increased risk of incident AF (HR = 1.18, 95% CI: 1.12-1.23, P < 0.00001). Our subgroup analyses mostly yielded similar results, and the results of sensitivity analyses remained unchanged. However, meta-analysis of data from 2 cohort studies with 59 896 participants (median follow-up of 2.15 years) showed that MAFLD was not linked to incident AF (HR = 1.36, 95% CI: 0.63-2.92, P = 0.44).

Current evidence shows that NAFLD may be linked to a slightly higher risk of developing AF, particularly among Asian populations and those diagnosed with NAFLD using FLI criteria. Nevertheless, there is not enough evidence to support the proposed association between MAFLD and an increased risk of AF. To better understand this relationship, future studies should consider factors such as specific population, the severity of NAFLD/MAFLD, diagnostic methods of NAFLD and AF, and cardiometabolic risk factors.

https://www.crd.york.ac.uk/prospero, identifier CRD42022371503.

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver condition. In the United States (US), the prevalence of NAFLD in men is higher than that in women. This study aimed to evaluate sex differences in long-term all-cause and cardiovascular (CV) outcomes in patients with NAFLD.

We collected data from participants aged ≥18 years from the National Health and Nutrition Examination Surveys, 2000-2014, which included seven continuous 2-year surveys. A US Fatty Liver Index score of ≥30 was used to define NAFLD. We used a weighted Cox proportional hazards model to compare sex differences in overall and CV mortality. The all-cause and CV mortality rates were obtained from the National Center for Health Statistics. From the selected 2627 participants with NAFLD, 65.4% were males. Men had a significantly higher all-cause mortality than women (12.4% vs. 7.7%; p = 0.005), and the risk of CV death was higher in women with NAFLD aged ≤60 years (adjusted hazard ratio 0.214, 95% confidence interval 0.053-0.869, p = 0.031). Men with a body mass index >30 kg/m² and diabetes showed a higher risk of all-cause mortality. Sex differences in CV events were not apparent in the patients aged >60 years.

Male sex was associated with all-cause mortality in all the age groups. However, CV death is influenced by age, with a higher risk in young and middle-aged women and no apparent difference in older patients.

As a result of the obesity epidemic, Nonalcoholic fatty liver disease (NAFLD) and its complications have increased among millions of people. Consequently, a group of experts recommended changing the term NAFLD to an inclusive terminology more reflective of the underlying pathogenesis; metabolic-associated fatty liver disease (MAFLD). This new term of MAFLD has its own disease epidemiology and clinical outcomes prompting efforts in studying its differences from NAFLD. This article discusses the rationale behind the nomenclature change, the main differences, and its clinical implications.

Whether non-alcoholic fatty liver disease (NAFLD) is a cardiovascular (CV) risk factor is debated. We performed a systematic review and meta-analysis to assess the CV morbidity and mortality related to NAFLD in the general population, and to determine whether CV risk is comparable between lean and non-lean NAFLD phenotypes. We searched multiple databases, including PubMed, Embase, and the Cochrane Library, for observational studies published through 2022 that reported the risk of CV events and mortality. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for all-cause mortality, CV mortality, myocardial infarction (MI), stroke, atrial fibrillation (AF), and major adverse cardiovascular and cerebrovascular events (MACCE) were assessed through random-effect meta-analysis. We identified 33 studies and a total study population of 10,592,851 individuals (mean age 53±8; male sex 50%; NAFLD 2, 9%). Mean follow-up was 10±6 years. Pooled ORs for all-cause and CV mortality were respectively 1.14 (95% CI, 0.78-1.67) and 1.13 (95% CI, 0.57-2.23), indicating no significant association between NAFLD and mortality. NAFLD was associated with increased risk of MI (OR 1.6; 95% CI, 1.5-1.7), stroke (OR: 1.6; 95% CI, 1.2-2.1), atrial fibrillation (OR: 1.7; 95% CI, 1.2-2.3), and MACCE (OR: 2.3; 95% CI, 1.3-4.2). Compared with non-lean NAFLD, lean NAFLD was associated with increased CV mortality (OR: 1.50; 95% CI, 1.1-2.0), but similar all-cause mortality and risk of MACCE. While NAFLD may not be a risk factor for total and CV mortality, it is associated with excess risk of non-fatal CV events. Lean and non-lean NAFLD phenotypes exhibit distinct prognostic profiles and should receive equitable clinical care.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by excess fat accumulation in the liver. It is closely associated with metabolic syndrome, and patients with NAFLD often have comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia. In addition to liver-related complications, NAFLD has been associated with a range of non-liver comorbidities, including cardiovascular disease, chronic kidney disease, and sleep apnea. Cardiovascular disease is the most common cause of mortality in patients with NAFLD, and patients with NAFLD have a higher risk of developing cardiovascular disease than the general population. Chronic kidney disease is also more common in patients with NAFLD, and the severity of NAFLD is associated with a higher risk of developing chronic kidney disease. Sleep apnea, a disorder characterized by breathing interruptions during sleep, is also more common in patients with NAFLD and is associated with the severity of NAFLD. The presence of non-liver comorbidities in patients with NAFLD has important implications for the management of this disease. Treatment of comorbidities such as obesity, type 2 diabetes mellitus, and dyslipidemia may improve liver-related outcomes in patients with NAFLD. Moreover, treatment of non-liver comorbidities may also improve overall health outcomes in patients with NAFLD. Therefore, clinicians should be aware of the potential for non-liver comorbidities in patients with NAFLD and should consider the management of these comorbidities as part of the overall management of this disease.

Accumulating evidence suggests that patients with nonalcoholic fatty liver disease (NAFLD) have a significantly high risk of incident atrial fibrillation (AF). Systemic inflammation, metabolic disorders and oxidative stress could be the potential mechanisms by which NAFLD drives AF. Monocyte-to- high-density lipoprotein ratio (MHR) has emerged as a novel biomarker of inflammation and oxidative stress that has not been studied in AF with NAFLD patients. We aimed to investigate the relationship between MHR and the risk of AF among NAFLD patients.

A retrospective analysis was performed for the clinical data of the patients with NAFLD in the Second Hospital of Shanxi Medical University from January 2019 to October 2022, among whom 204 patients with AF were enrolled as NAFLD+AF group and 613 patients without AF were enrolled as NAFLD control, and 152 patients were selected from each group based on propensity score matching (PSM) at a ratio of 1:1 to balance the covariates between groups. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Logistic regression analysis was performed to identify the independent predictor for occurrence of AF among NAFLD patients. Trend chi-square test to analyze the prevalence of AF among MHR tertiles, and then the correlation between MHR and the risk of AF confirmed by restricted cubic splines (RCS). The receiver operating characteristic (ROC) curve analysis was used to determine the optimum MHR cutoff value to predict AF.

Univariate analysis showed that AF patients had higher MHR than non-AF patients (P < 0.001). Meanwhile, compared with pure NAFLD patients, multivariate logistic regression analysis showed that MHR remained to be an independent risk factor for AF after adjusting for confounding risk factors (OR = 10.67, 95% CI 2.17-52.37, P = 0.004). TC、HDL-C were also independent risk factors for AF. Among them, TC and HDL-C are protective factors for AF. The trend chi-square test showed that the risk of AF increased with an increase in MHR (P < 0.05). However, the RCS showed a nonlinear and J-shaped relationship between MHR and the risk of AF (P for non-linearity = 0.023). The occurrence of AF increased with increasing MHR only when MHR > 0.44. The ROC curve showed that MHR combined with traditional risk factors can improve the ability to predict AF.

MHR is an independently associated with incident AF in patients with NAFLD and show a certain predictive value.

Atrial fibrillation (AF) is an increasingly recognized comorbidity in patients with liver cirrhosis, mainly associated with nonalcoholic fatty liver disease and alcohol-associated liver disease, affecting the quality of life and prognosis. On the other hand, cirrhosis is associated with an elevated risk of both thrombosis and bleeding, making the decision about anticoagulation therapy very challenging. Direct-acting oral anticoagulants (DOACs) are approved for patients with non-valvular AF. However, there is limited clinical experience and scientific evidence about their efficacy and safety in liver cirrhosis. This review article investigates the published literature concerning the administration of DOACs and traditional antithrombotic agents, such as vitamin K antagonists and heparins, in patients with liver cirrhosis and AF.

Fatty liver disease has become the most prevalent chronic liver disease globally and is linked to cardiovascular disease, including arrhythmias. However, there have been inconsistent reports on the association between fatty liver disease and atrial fibrillation, while the role of liver stiffness in this association remains unclear.

Within the Rotterdam Study, a large prospective ongoing cohort, participants attending the abdominal ultrasound program between 2009-2014 were included. Exclusion criteria were no atrial fibrillation data or >20% missing data across analysis variables. Steatosis was assessed by ultrasound, liver stiffness by transient elastography and atrial fibrillation by 12-lead electrocardiograms. Incident atrial fibrillation was based on medical records and complete until 2014. Logistic and Cox-regression were used to quantify associations between fatty liver disease and atrial fibrillation.

We included 5,825 participants (aged 69.5±9.1, 42.9% male), 35.7% had steatosis, liver stiffness measurement was available in 73.3%, and 7.0% had prevalent atrial fibrillation. Steatosis was not associated with prevalent atrial fibrillation in fully adjusted models (odds ratio [OR] 0.80; 95% CI 0.62-1.03), findings were consistent for non-alcoholic or metabolic dysfunction-associated fatty liver disease. Liver stiffness was significantly associated with prevalent atrial fibrillation (OR 1.09 per kPa, 95% CI 1.03-1.16); however, this was only persistent among those without steatosis (OR 1.18 per kPa, 95% CI 1.08-1.29). Lastly, no associations were found between steatosis (hazard ratio 0.88; 95% CI 0.59-1.33; follow-up 2.1 [1.1-3.2] years) and incident atrial fibrillation.

Fatty liver disease was not associated with prevalent or incident atrial fibrillation, while liver stiffness was significantly associated with atrial fibrillation, especially among those without steatosis. This association might be driven by venous congestion instead of fibrogenesis, but this awaits further validation. We recommend assessing cardiovascular health in participants with high liver stiffness, especially in the absence of overt liver disease.

NTR6831.

There have been inconsistent reports about the potential links between fatty liver disease and atrial fibrillation (an irregular and often very fast heart rhythm). Herein, we show that liver stiffness (which is a marker of liver fibrosis), but not fatty liver disease, was associated with a higher prevalence of atrial fibrillation. We hypothesis that atrial fibrillation, rather than fibrosis, may be the cause of increased liver stiffness in participants without overt liver disease.

The epidemiological characteristics of MAFLD and its relationship with atrial fibrillation (AF) are limited in China. Therefore, we explored the epidemiological characteristics of MAFLD from adults along with the association of MAFLD and 12-ECG diagnosed AF in a nationwide population from health check-up centers.

This observational study used cross-sectional and longitudinal studies with 2,083,984 subjects from 2009 to 2017. Age-, sex-, and regional-standardized prevalence of MAFLD was estimated. Latent class analysis (LCA) was used to identify subclusters of MAFLD. Multivariable logistic regression and mixed-effects Cox regression models were used to analyze the relationship between MAFLD and AF.

The prevalence of MAFLD increased from 22.75% to 35.58% during the study period, with higher rates in males and populations with high BMI or resided in northern regions. The MAFLD population was clustered into three classes with different metabolic features by LCA. Notably, a high proportion of MAFLD patients in all clusters had overweight and prediabetes or diabetes. The MAFLD was significantly associated with a higher risk of AF in the cross-sectional study and in the longitudinal study. In addition, the coexistence of prediabetes or diabetes had the largest impact on subsequent AF.

Our findings suggested a high prevalence of MAFLD and a high prevalence of other metabolic diseases in the MAFLD population, particularly overweight and glucose dysregulation. Moreover, MAFLD was associated with a significantly higher risk for existing and subsequent subclinical AF in the Chinese population.

Cardiometabolic disorders are largely responsible for excess mortality in schizophrenia. Non-alcoholic fatty liver disease (NAFLD) is increasingly relevant in the development of metabolic risk factors that have been associated with antipsychotic treatment. We aimed to assess the incidence of NAFLD and metabolic disturbances during the first 3 years of antipsychotic treatment in patients with first episode of psychosis (FEP), and compare it with the incidence in a control group.

Data were obtained from patients with psychosis (n = 160) and healthy controls (n = 66) included in the Cantabria's clinical and research program on FEP (PAFIP) from 2012 to 2018. Fatty Liver Index (FLI) was used to estimate the amount of fat in the liver. FLI has been validated for the diagnosis of NAFLD against different standards such as liver ultrasound and biopsy. FLI and metabolic parameters were registered at baseline, 3 months and then yearly for 3 years.

At the end of the follow-up (3-years), 21.9 % of patients with psychosis developed a FLI ≥ 60, suggestive of liver steatosis, compared to only a 3 % of subjects within the control group (X² = 12.120; p < 0.001). In the FEP patients group, developing a FLI ≥ 60 was statistically associated with significant increments in metabolic parameters, and with Metabolic Syndrome (MetS) (X² = 16.151; p < 0.001) and high blood pressure (X² = 10.654; p = 0.001).

Having a first episode of non-affective psychosis was significantly associated with developing liver steatosis (FLI ≥ 60) in the first three years after initiating antipsychotic treatment. The results highlight the importance of early screening the emergence of NAFLD in schizophrenia patients.

Non-alcoholic fatty liver disease (NAFLD) currently affects more than 25% of the world population and is rising. NAFLD can progress to non-alcoholic steatohepatitis that is associated with hepatic inflammation and fibrosis and can result in cirrhosis with subsequent liver failure. Non-alcoholic steatohepatitis (NASH) has now emerged as one of the leading etiologies for a liver transplant among adults in the United States. Given the rising incidence of liver transplants in patients with NASH-related cirrhosis, it is essential for anesthesiologists to be familiar with this condition as well as with NASH-related comorbidities and perioperative complications. Not only is NASH linked to metabolic syndrome, but it also is independently associated with cardiovascular disease, renal and thyroid dysfunction, obstructive sleep apnea (OSA), and a hypercoagulable state. The association with these conditions can affect the perioperative outcome of these patients, particularly because of increased mortality from major adverse cardiovascular events and sepsis. In order to decrease the perioperative morbidity and mortality of patients with NASH undergoing a liver transplant, a multidisciplinary approach to their perioperative management is essential, along with careful preoperative evaluation and aggressive intraoperative and postoperative monitoring. The focus of this review article is to provide a comprehensive overview of challenges associated with liver transplants in patients with NASH and to provide suggestions for appropriate patient selection and perioperative management.

The emerging issues nowadays are non-alcoholic fatty liver disease (NAFLD) and its advanced stage non-alcoholic steatohepatitis (NASH), which further can be a predisposing factor for chronic liver complications, such as cirrhosis and/or development of hepatocellular carcinoma (HCC). Liver lipotoxicity can influence the accumulation of reactive oxygen species (ROS), so oxidative stress is also crucial for the progression of NASH. Moreover, NASH is in strong connection with metabolic disorders, and supporting evidence shows that insulin resistance (IR) is in a close relation to NAFLD, as it is involved in the progression to NASH and further progression to hepatic fibrosis. The major issue is that, at the moment, NASH treatment is based on lifestyle changes only due to the fact that no approved therapeutic options are available. The development of new therapeutic strategies should be conducted towards the potential NAFLD and NASH treatment by the modulation of IR but also by dietary antioxidants. As it seems, NASH is going to be the leading indication for liver transplantation as a consequence of increased disease prevalence and the lack of approved treatment; thus, an effective solution is needed as soon as possible.