Explore the vast range of titles available.

Background Fatty liver disease in the absence of excessive alcohol consumption is an increasingly common condition with a global prevalence of ~ 25–30% and is also associated with cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies its pathogenesis, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been proposed for this condition. MAFLD is closely intertwined with obesity, type 2 diabetes mellitus and atherogenic dyslipidemia, which are established cardiovascular risk factors. Unlike CVD, which has received attention in the literature on fatty liver disease, the CVD risk associated with MAFLD is often underestimated, especially among Cardiologists. Methods and results A multidisciplinary panel of fifty-two international experts comprising Hepatologists, Endocrinologists, Diabetologists, Cardiologists and Family Physicians from six continents (Asia, Europe, North America, South America, Africa and Oceania) participated in a formal Delphi survey and developed consensus statements on the association between MAFLD and the risk of CVD. Statements were developed on different aspects of CVD risk, ranging from epidemiology to mechanisms, screening, and management. Conculsions The expert panel identified important clinical associations between MAFLD and the risk of CVD that could serve to increase awareness of the adverse metabolic and cardiovascular outcomes of MAFLD. Finally, the expert panel also suggests potential areas for future research.

Metabolic dysfunction‐associated steatotic liver disease (MASLD) is a major public health concern, largely driven by the high‐fat, high‐sugar and low‐fibre Western diet. The Western diet is often accompanied by binge drinking, or the rapid consumption of alcohol in a short time leading to a blood alcohol concentration of ≥0.08%. Emerging evidence suggests that co‐consumption of a Western diet and binge drinking might converge on shared pathological mechanisms in males, but little is known about the role of sex in this interaction. Given these complex interactions between diet, alcohol, sex and liver health, we sought to investigate how the addition of binge drinking to a Western diet impacts MASLD progression in male and female mice. Young (6‐week‐old) male and female C57BL6/J mice (n = 9–11 per sex per group) were assigned to the following groups: Control, Control/Binge, Western, or Western/Binge. Following 12 weeks of treatment, Western diet, regardless of binge drinking, resulted in increased hepatic lipid accumulation and oxidative damage in both sexes, with males showing more evidence of disease than females. In general, male mice in the Western binge group had the most pronounced evidence of liver damage among males, whereas female mice in the Western diet group tended to have more evidence of disease than all other female groups as measured by histology, serum transaminases and immunohistochemistry. The collective results suggest that addition of binge drinking to a Western diet can result in a more progressive form of liver disease in males and that sex plays a key role in response to the combination of unhealthy diet and binge drinking. What is the central question of this study? Does addition of binge drinking to a Western diet result in a more progressive liver disease than either alone, and how is this modulated by sex? What is the main finding and its importance? In male mice, combining binge drinking and a Western diet resulted in more pronounced detriments in key liver measures than either factor alone, whereas females showed greater liver damage in response to a Western diet alone than to the combined exposure.

We aimed to compare the association of metabolic dysfunction‐associated fatty liver disease (MAFLD), metabolic dysfunction‐associated steatotic liver disease (MASLD), alcohol‐related liver disease (ALD), metabolic dysfunction and ALD (MetALD), and MASLD with viral hepatitis (MASLD‐Viral) with risks of cirrhosis, liver cancer, and mortality. The data of 464,556 adults from the UK Biobank (UKB), 13,526 adults from the National Health and Nutrition Examination Survey (NHANES), and 2554 adults from BeijngFH Health Cohort Study (FHCS) were included. Adjusted hazard ratios (aHR) and odds ratios were calculated using Cox and Logistic regression models, respectively. Compared with non‐SLD, the risk of liver cancer increased from MetALD (aHR 1.70 [95% CI 1.37, 2.09]), MASLD (1.91 [1.66, 2.21]), MAFLD (2.01 [1.76, 2.29]), ALD (3.16 [2.54, 3.93]), to MASLD‐Viral (22.0 [10.8, 44.4]) in a stepwise manner in the UKB; the risk of all‐cause mortality increased from MetALD, MASLD, MAFLD, ALD, to MASLD‐Viral in the NHANES. The odds ratio of liver fibrosis increased from MASLD, MAFLD, to MASLD‐Viral in the FHCS. In patients with diabetes, metformin plus other drugs were associated with higher risks of cirrhosis, liver cancer, and all‐cause mortality in MASLD or MAFLD. Prevention rather than antiglycemic treatment is important for patients with diabetic MASLD or MAFLD. This study analyzed the UK Biobank, NHANES III, and FHCS data to assess the prognostic and associative effects of new steatotic liver disease nomenclatures. It found that MAFLD, MASLD, and MetALD were associated with higher risks of liver‐related conditions and mortality, with diabetes and certain antiglycemic medications further heightening these risks .

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.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated metabolic dysfunction-associated liver disease (MetALD) are significant public health concerns, with diet playing a pivotal role in their pathogenesis. Aims: Using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. This study investigates the associations of the dietary index for gut microbiota (DI-GM), dietary inflammatory index (DII), and their combined effects with MASLD/MetALD, while exploring the mediating roles of inflammation and metabolic dysfunction. Data from the 2007 to 2018 NHANES included 9,529 participants. DI-GM and DII were calculated using 24-hour dietary recalls. Inflammatory and metabolic biomarkers-including triglyceride-glucose (TyG) index, metabolic score (MS), C-reactive protein (CRP), systemic immune inflammation index (SII), and systemic inflammatory response index (SIRI)-were analyzed. Multivariable logistic and linear regression, subgroup analyses, and restricted cubic spline (RCS) models assessed associations and dose-response relationships. Mediation analysis evaluated the roles of inflammatory and metabolic markers. Higher DI-GM scores were significantly associated with reduced MASLD (OR = 0.59, 95% CI: 0.46-0.75) and MetALD (OR = 0.57, 95% CI: 0.46-0.70). Conversely, higher DII scores were positively associated with MASLD (OR = 1.57, 95% CI: 1.23-2.01) and MetALD (OR = 1.40, 95% CI: 1.13-1.75). DI-GM was inversely associated with inflammation and metabolic markers (TyG: β= -0.05, MS: β= -0.11, CRP: β= -0.12, SII: β= -0.08, SIRI: β= -0.09), while DII exacerbated these markers (TyG: β= 0.06, MS: β= 0.18, CRP: β=0.14, SII: β= 0.11, SIRI: β= 0.10). The combined effects of DI-GM and DII further demonstrated that a gut microbiota-healthy and anti-inflammatory diet synergistically reduced MASLD (OR = 0.59, 95% CI: 0.43-0.81) and MetALD risks (OR = 0.58, 95% CI: 0.44-0.76). Mediation analysis confirmed that inflammation and metabolism significantly mediated the diet-disease associations (p < 0.05). Higher DI-GM and lower DII are associated with reduced MASLD/MetALD risks, partially mediated by alleviating systemic inflammation and metabolic dysfunction. These findings highlight dietary interventions targeting gut microbiota and inflammation as strategies for early prevention of MASLD and MetALD.

Background Steatotic liver disease (SLD) was a newly proposed disease category derived from metabolic dysfunction-associated fatty liver disease (MAFLD). MAFLD and sarcopenia were independent risk factors for mortality. We aimed to evaluate the impacts of SLD subtypes, MAFLD, and sarcopenia on mortality. Methods A total of 6543 subjects were identified from the National Health and Nutrition Examination Survey 1999–2006 with the latest Linked Mortality file. Hepatic steatosis, advanced fibrosis, and sarcopenia were determined by the laboratory- and anthropometry- based fatty liver index and fibrosis-4 index, and dual-energy X-ray absorptiometry-based appendicular skeletal muscle mass index, respectively. Associations of SLD subtypes, MAFLD, and sarcopenia with mortality were estimated using the weighted Cox proportional hazards model. Results During a mean follow-up time of 15.7 years, 1567 (16.7%) deaths occurred including 494 (4.9%) deaths from cardiovascular diseases and 372 (4.1%) from cancer. The all-cause mortality rates of MAFLD, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated liver disease (MetALD), other aetiology SLD, MASLD without sarcopenia, and MASLD with sarcopenia were 21.0%, 19.8%, 30.2%, 30.9%, 19.2%, and 75.5%, respectively. MAFLD increased the risk of all-cause mortality (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.00-1.59). MASLD predicted all-cause mortality (HR 1.17, 95% CI 1.03–1.33) but this prediction became insignificant after adjustment for metabolic risks. In contrast, MetALD and other aetiology SLD were significantly associated with all-cause mortality (HR 1.83, 95% CI 1.21–2.76; HR 2.50, 95% CI 1.82–3.44, respectively), predominantly associated with cancer-specific mortality (HR 2.42, 95% CI 1.23–4.74; HR 2.49, 95% CI 1.05–5.90, respectively). MASLD with sarcopenia increased the risk of all-cause mortality by almost twice (HR 2.19, 95% CI 1.37–3.49) and further coexisting advanced fibrosis additively increased mortality (HR 3.41, 95% CI 1.92–6.05). Conclusion SLD definition identified a more homogeneous group with metabolically hepatic steatosis at higher risks of mortality. MASLD or MASLD-related advanced fibrosis and sarcopenia additively increased mortality.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is the most common liver disorder worldwide, with an estimated global prevalence of more than 31%. Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as non-alcoholic steatohepatitis (NASH), is a progressive form of MASLD characterized by hepatic steatosis, inflammation, and fibrosis. This review aims to provide a comprehensive analysis of the extrahepatic manifestations of MASH, focusing on chronic diseases related to the cardiovascular, muscular, and renal systems. A systematic review of published studies and literature was conducted to summarize the findings related to the systemic impacts of MASLD and MASH. The review focused on the association of MASLD and MASH with metabolic comorbidities, cardiovascular mortality, sarcopenia, and chronic kidney disease. Mechanistic insights into the concept of lipotoxic inflammatory “spill over” from the MASH-affected liver were also explored. MASLD and MASH are highly associated (50%–80%) with other metabolic comorbidities such as impaired insulin response, type 2 diabetes, dyslipidemia, hypertriglyceridemia, and hypertension. Furthermore, more than 90% of obese patients with type 2 diabetes have MASH. Data suggest that in middle-aged individuals (especially those aged 45–54), MASLD is an independent risk factor for cardiovascular mortality, sarcopenia, and chronic kidney disease. The concept of lipotoxic inflammatory “spill over” from the MASH-affected liver plays a crucial role in mediating the systemic pathological effects observed. Understanding the multifaceted impact of MASH on the heart, muscle, and kidney is crucial for early detection and risk stratification. This knowledge is also timely for implementing comprehensive disease management strategies addressing multi-organ involvement in MASH pathogenesis.

Diagnosing and managing metabolic dysfunction-associated steatotic liver disease (MASLD) remains a major challenge in primary care due to lack of agreement on diagnostic tools, difficulty in identifying symptoms and determining their cause, absence of approved pharmacological treatments, and limited awareness of the disease. However, prompt diagnosis and management are critical to preventing MASLD from progressing to more severe forms of liver disease. This highlights the need to raise awareness and improve understanding of MASLD among both patients and physicians. The patient perspective is invaluable to advancing our knowledge of this disease and how to manage it, as their perspectives have led to the growing recognition that patients experience subtle symptoms and that patient-reported outcomes should be incorporated into drug development. This review and expert opinion examine MASLD and metabolic dysfunction-associated steatohepatitis from the patient and physician perspective from pre-diagnosis to diagnosis and early care, through to progression to advanced liver damage. Specifically, the paper dives into the issues patients and physicians experience, and, in turn, what is required to improve diagnosis and management, including tips and tools to empower patients and physicians dealing with MASLD.

In recent years, “metabolic dysfunction-associated steatotic liver disease” (MASLD) has been proposed to better connect liver disease to metabolic dysfunction, which is the most common chronic liver disease worldwide. MASLD affects more than 30% of individuals globally, and it is diagnosed by the combination of hepatic steatosis and obesity, type 2 diabetes, or two metabolic risk factors. MASLD begins with the buildup of extra fat, often greater than 5%, within the liver, causing liver hepatocytes to become stressed. This can proceed to a more severe form, metabolic dysfunction-associated steatohepatitis (MASH), in 20–30% of people, where inflammation in the liver causes tissue fibrosis, which limits blood flow over time. As fibrosis worsens, MASH may lead to cirrhosis, liver failure, or even liver cancer. While the pathophysiology of MASLD is not fully known, the current “multiple-hits” concept proposes that dietary and lifestyle factors, metabolic factors, and genetic or epigenetic factors contribute to elevated oxidative stress and inflammation, causing liver fibrosis. This review article provides an overview of the pathogenesis of MASLD and evaluates existing therapies as well as pharmacological drugs that are currently being studied in clinical trials for MASLD or MASH.

Metabolic dysfunction‐associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease globally. Previous studies have shown that MASLD is an independent risk factor for chronic kidney disease (CKD), but the variations in estimated glomerular filtration rate (eGFR) levels across countries with different ethnic backgrounds have not been extensively reported. We enrolled 3308 participants with biopsy‐proven MASLD from 34 centers in this multinational study and analyzed the associations between eGFR and histological severity of liver fibrosis in different countries. European participants had lower eGFR levels (92.2 ± 20.7 vs. 104.7 ± 17.3 mL/min/1.73 m2) and significant liver fibrosis (61.4 vs. 32.4%) than Asian individuals. In Asia, Chinese participants had the highest mean eGFR level at 105.8 mL/min/1.73 m2, while Malaysian participants had the lowest at 87.3 mL/min/1.73 m2 (p < 0.001). In Europe, French participants had the highest mean eGFR level at 95.3 mL/min/1.73 m2, while Romanian individuals had the lowest at 81.1 mL/min/1.73 m2 (p < 0.001). eGFR levels were inversely associated with liver fibrosis in Asian individuals (OR: 0.793, 95%CI: 0.685–0.917, p = 0.002), even after adjusting for traditional renal risk factors, but not in Europeans. Our findings provide the basis for further investigation of the burden of MASLD on CKD risk in different countries. A total of 3308 participants with biopsy‐proven MASLD from 34 centers were enrolled in the study. We collected liver biopsy pathological scores and clinical parameters and conducted correlation analysis. We finally found that eGFR levels are inversely associated with liver fibrosis in Asians, even after adjusting for traditional renal risk factors.