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1
Chen, Li. "From metabolic dysfunction-associated fatty liver disease to metabolic dysfunction-associated steatotic liver disease: Controversy and consensus." World Journal of Hepatology 15, no. 12 (December 27, 2023): 1253–57. http://dx.doi.org/10.4254/wjh.v15.i12.1253.
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The newly released nomenclature of metabolic dysfunction-associated steatotic liver disease (MASLD) in the 2023 European Association for the Study of the Liver Congress has raised great clinical concerns. This marks the second instance of significant renaming of non-alcoholic fatty liver disease since the introduction of metabolic dysfunction-associated fatty liver disease (MAFLD) in 2020. The nomenclature and definitions of MASLD and MAFLD exhibit significant disparities as well as substantial consensus. The disparities regarding the framework of nomenclature, the definitions, the clinical management, and the impact on the clinical outcomes between MASLD and MAFLD were comprehensively compared in this editorial. Additionally, the consensus reached by the MASLD and MAFLD definitions also emphasizes positive diagnosis rather than negative diagnosis within the framework of establishing a diagnostic approach. Furthermore, they acknowledged the pivotal role of metabolic dysfunction in the pathogenesis of MAFLD or MASLD and the positive role of increasing the awareness of the disease in public. Fortunately, the non-invasive tests remains effective in the MASLD and MAFLD era. Elucidating these disparities would contribute to a more comprehensive comprehension of the nature of steatotic liver disease and enhance clinical practice. Thus, more efforts are required to reach more consensus about these important topics.
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Bando, Hiroshi. "Latest Trend and Perspective of Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) as a Novel Nomenclature." Asploro Journal of Biomedical and Clinical Case Reports 7, no. 2 (April 6, 2024): 84–87. http://dx.doi.org/10.36502/2024/asjbccr.6341.
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Recently, the medical term for nonalcoholic fatty liver disease (NAFLD) has been changed to a novel nomenclature: metabolic dysfunction-associated steatotic liver disease (MASLD). The latest report shows analyses of the National Health and Nutrition Examination Survey (NHANES III) using the fibrosis-4 index (FIB-4) and enhanced liver fibrosis (ELF). Among 6429 NAFLD cases, 99% met MASLD criteria. In another study with 4286 cases, 99% of steatosis cases met the MASLD definition, and 95.4% met the metabolic dysfunction-associated fatty liver disease (MAFLD) definition. Several biomarkers show a relationship with MASLD/MAFLD, such as BMI, T2D, HOMA-IR, central obesity, waist circumference, and CKD.
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Beygi, Mohammad, Salma Ahi, Samaneh Zolghadri, and Agata Stanek. "Management of Metabolic-Associated Fatty Liver Disease/Metabolic Dysfunction-Associated Steatotic Liver Disease: From Medication Therapy to Nutritional Interventions." Nutrients 16, no. 14 (July 11, 2024): 2220. http://dx.doi.org/10.3390/nu16142220.
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Non-alcoholic fatty liver disease (NAFLD) is a common long-lasting liver disease that affects millions of people around the world. It is best identified with a hepatic fat build-up that ultimately leads to inflammation and damage. The classification and nomenclature of NAFLD have long been a controversial topic, until 2020 when a group of international experts recommended substituting NAFLD with MAFLD (metabolic dysfunction-associated FLD). MAFLD was then terminologically complemented in 2023 by altering it to MASLD, i.e., metabolic dysfunction-associated steatotic liver disease (MASLD). Both the MAFLD and the MASLD terminologies comprise the metabolic element of the disorder, as they offer diagnostic benchmarks that are embedded in the metabolic risk factors that underlie the disease. MASLD (as a multisystemic disease) provides a comprehensive definition that includes a larger population of patients who are at risk of liver morbidity and mortality, as well as adverse cardiovascular and diabetes outcomes. MASLD highlights metabolic risks in lean or normal weight individuals, a factor that has not been accentuated or discussed in previous guidelines. Novel antihyperglycemic agents, anti-hyperlipidemic drugs, lifestyle modifications, nutritional interventions, and exercise therapies have not been extensively studied in MAFLD and MASLD. Nutrition plays a vital role in managing both conditions, where centralizing on a diet rich in whole vegetables, fruits, foods, healthy fats, lean proteins, and specific nutrients (e.g., omega-3 fatty acids and fibers) can improve insulin resistance and reduce inflammation. Thus, it is essential to understand the role of nutrition in managing these conditions and to work with patients to develop an individualized plan for optimal health. This review discusses prevention strategies for NAFLD/MAFLD/MASLD management, with particular attention to nutrition and lifestyle correction.
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Martínez-Montoro, José Ignacio, María Antonia Martínez-Sánchez, Andrés Balaguer-Román, Virginia Esperanza Fernández-Ruiz, José Emilio Hernández-Barceló, Mercedes Ferrer-Gómez, María Dolores Frutos, María Ángeles Núñez-Sánchez, José Carlos Fernández-García, and Bruno Ramos-Molina. "Triglyceride to HDL Cholesterol Ratio for the Identification of MASLD in Obesity: A Liver Biopsy-Based Case-Control Study." Nutrients 16, no. 9 (April 27, 2024): 1310. http://dx.doi.org/10.3390/nu16091310.
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Associations between dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported. Previous studies have shown that the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio may be a surrogate marker of MASLD, assessed by liver ultrasound. However, no studies have evaluated the utility of this ratio according to biopsy-proven MASLD and its stages. Therefore, our aim was to evaluate if the TG/HDL-C ratio allows for the identification of biopsy-proven MASLD in patients with obesity. We conducted a case-control study in 153 patients with obesity who underwent metabolic surgery and had a concomitant liver biopsy. Fifty-three patients were classified as no MASLD, 45 patients as metabolic dysfunction-associated steatotic liver—MASL, and 55 patients as metabolic dysfunction-associated steatohepatitis—MASH. A receiver operating characteristic (ROC) analysis was performed to assess the accuracy of the TG/HDL-C ratio to detect MASLD. We also compared the area under the curve (AUC) of the TG/HDL-C ratio, serum TG, and HDL-C. A higher TG/HDL-C ratio was observed among patients with MASLD, compared with patients without MASLD. No differences in the TG/HDL-C ratio were found between participants with MASL and MASH. The greatest AUC was observed for the TG/HDL-C ratio (AUC 0.747, p < 0.001) with a cut-off point of 3.7 for detecting MASLD (sensitivity = 70%; specificity = 74.5%). However, no statistically significant differences between the AUC of the TG/HDL-C ratio and TG or HDL-C were observed to detect MASLD. In conclusion, although an elevated TG/HDL-C ratio can be found in patients with MASLD, this marker did not improve the detection of MASLD in our study population, compared with either serum TG or HDL-C.
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Bae, Jaehyun, Eugene Han, Hye Won Lee, Cheol-Young Park, Choon Hee Chung, Dae Ho Lee, Eun-Hee Cho, et al. "Metabolic Dysfunction-Associated Steatotic Liver Disease in Type 2 Diabetes Mellitus: A Review and Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association." Diabetes & Metabolism Journal 48, no. 6 (November 30, 2024): 1015–28. http://dx.doi.org/10.4093/dmj.2024.0541.
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Since the role of the liver in metabolic dysfunction, including type 2 diabetes mellitus, was demonstrated, studies on non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) have shown associations between fatty liver disease and other metabolic diseases. Unlike the exclusionary diagnostic criteria of NAFLD, MAFLD diagnosis is based on the presence of metabolic dysregulation in fatty liver disease. Renaming NAFLD as MAFLD also introduced simpler diagnostic criteria. In 2023, a new nomenclature, steatotic liver disease (SLD), was proposed. Similar to MAFLD, SLD diagnosis is based on the presence of hepatic steatosis with at least one cardiometabolic dysfunction. SLD is categorized into metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related/-associated liver disease, alcoholrelated liver disease, specific etiology SLD, and cryptogenic SLD. The term MASLD has been adopted by a number of leading national and international societies due to its concise diagnostic criteria, exclusion of other concomitant liver diseases, and lack of stigmatizing terms. This article reviews the diagnostic criteria, clinical relevance, and differences among NAFLD, MAFLD, and MASLD from a diabetologist’s perspective and provides a rationale for adopting SLD/MASLD in the Fatty Liver Research Group of the Korean Diabetes Association.
6
Kaewdech, Apichat, and Pimsiri Sripongpun. "Navigating the Nomenclature of Liver Steatosis: Transitioning from NAFLD to MAFLD and MASLD - Understanding Affinities and Differences." Siriraj Medical Journal 76, no. 4 (April 1, 2024): 234–43. http://dx.doi.org/10.33192/smj.v76i4.267556.
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The escalating prevalence of non-alcoholic fatty liver disease (NAFLD) represents a significant challenge to public health, with an increasing impact observed across various demographics. This review delivers a comprehensive evaluation of the evolving terminology in steatotic liver disease (SLD), documenting the transition from NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD), and progressing to the latest terms, metabolic dysfunction-associated fatty liver disease (MASLD) and MASLD with increased alcohol intake (MetALD). We conducted a comprehensive review of literature discussing the benefits and drawbacks of these nomenclatural changes. Clinical evidence supporting MASLD and MetALD, including the implications of alcohol consumption thresholds on disease classification and outcomes, was analyzed. The “MAFLD” and “MASLD” labels align with the pathophysiology of metabolic diseases, afford a positive disease connotation, and facilitate the identification of more severe diseases, such as significant fibrosis or advanced liver disease. However, the MAFLD criteria may underdiagnose lean, non-overweight, or non-obese individuals with MAFLD. The review underscores the understanding of liver diseases linked to metabolic dysfunction and alcohol use. The shift in terminology marks progress towards a clinical diagnosis that reflects underlying pathophysiology. However, additional studies are necessary to assess the longterm effects of these changes and their efficacy in enhancing patient care and health outcomes.
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Ahamed, Forkan, Natalie Eppler, Elizabeth Jones, and Yuxia Zhang. "Understanding Macrophage Complexity in Metabolic Dysfunction-Associated Steatotic Liver Disease: Transitioning from the M1/M2 Paradigm to Spatial Dynamics." Livers 4, no. 3 (September 13, 2024): 455–78. http://dx.doi.org/10.3390/livers4030033.
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Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses metabolic dysfunction-associated fatty liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH), with MASH posing a risk of progression to cirrhosis and hepatocellular carcinoma (HCC). The global prevalence of MASLD is estimated at approximately a quarter of the population, with significant healthcare costs and implications for liver transplantation. The pathogenesis of MASLD involves intrahepatic liver cells, extrahepatic components, and immunological aspects, particularly the involvement of macrophages. Hepatic macrophages are a crucial cellular component of the liver and play important roles in liver function, contributing significantly to tissue homeostasis and swift responses during pathophysiological conditions. Recent advancements in technology have revealed the remarkable heterogeneity and plasticity of hepatic macrophage populations and their activation states in MASLD, challenging traditional classification methods like the M1/M2 paradigm and highlighting the coexistence of harmful and beneficial macrophage phenotypes that are dynamically regulated during MASLD progression. This complexity underscores the importance of considering macrophage heterogeneity in therapeutic targeting strategies, including their distinct ontogeny and functional phenotypes. This review provides an overview of macrophage involvement in MASLD progression, combining traditional paradigms with recent insights from single-cell analysis and spatial dynamics. It also addresses unresolved questions and challenges in this area.
8
Guo, Wenying, Ting Weng, and Yufei Song. "Association of serum selenium with MASLD and liver fibrosis: A cross-sectional study." PLOS ONE 19, no. 12 (December 31, 2024): e0314780. https://doi.org/10.1371/journal.pone.0314780.
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Background The evolution of NAFLD, MAFLD, and MASLD underscores significant advancements and nomenclatural shifts in the realm of chronic liver disorders. This study primarily aimed to investigate the possible link between serum selenium levels and the occurrence of MASLD. Methods Utilizing data from NHANES for the years 2017 through 2020, we performed an in-depth analysis. To evaluate the relationship between serum selenium concentrations and the prevalence of MASLD and liver fibrosis, we employed a comprehensive multivariable analysis. This approach accounted for a range of variables to enhance the robustness and reliability of our results by mitigating potential confounding factors. Results Through the application of linear regression models, our comprehensive data analysis revealed significant insights. Elevated serum selenium levels exhibited a distinct positive correlation with CAP, whereas an inverse relationship with LSM was observed. Multivariate logistic regression analysis indicated that higher serum selenium concentrations were significantly associated with an increased likelihood of MASLD, alongside a marked reduction in the probability of liver fibrosis. Conclusion The findings of this study highlight a significant positive association between elevated serum selenium levels, CAP, and the prevalence of MASLD, coupled with an inverse relationship with LSM and liver fibrosis.
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Martínez-Montoro, José Ignacio, Isabel Arranz-Salas, Carolina Gutiérrez-Repiso, Ana Sánchez-García, Luis Ocaña-Wilhelmi, José M. Pinazo-Bandera, Diego Fernández-García, et al. "Weight Loss After Sleeve Gastrectomy According to Metabolic Dysfunction-Associated Steatotic Liver Disease Stage in Patients with Obesity: A Liver Biopsy-Based Prospective Study." Nutrients 16, no. 22 (November 12, 2024): 3857. http://dx.doi.org/10.3390/nu16223857.
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Background: The role of metabolic dysfunction-associated steatotic liver disease (MASLD) in sleeve gastrectomy (SG)-related outcomes remains uncertain. In this study, we aimed to assess the influence of preoperative biopsy-proven MASLD and its stages on weight loss after SG. Methods: One hundred sixty-three patients with obesity undergoing SG with concomitant intraoperative liver biopsy were followed up for 1 year. Fifty-eight participants were categorized as no MASLD, thirty-eight as metabolic dysfunction-associated steatotic liver (MASL), and sixty-seven as metabolic dysfunction-associated steatohepatitis (MASH). Percentage total weight loss (%TWL) and percentage excess weight loss (%EWL) 1 year after SG were calculated for the different groups. We also evaluated the association between preoperative MASLD (and its stages) and weight loss, after adjusting for potential confounders. Results: Significant differences among groups were detected in %EWL (p = 0.004, ANOVA test), but not in %TWL (p = 0.079). However, significant differences in %TWL were found when MASH and no MASH (i.e., participants with MASL and participants without MASLD) groups were compared (27.3 ± 9.9 vs. 30.7 ± 9, respectively, p = 0.025). In the linear regression model for predicting %EWL 1 year after SG, the presence of MASH was independently associated with a lower %EWL, after adjusting for age, sex, baseline body mass index (BMI), and baseline glycated hemoglobin (HbA1c) (Beta −7.1; 95% CI −13.6, −0.5; p = 0.035). The presence of MASLD, liver fibrosis, or advanced liver fibrosis (≥F2) was also associated with lower %EWL after SG in crude models, although they did not remain significant after adjusting for these confounders. The presence of MASH was inversely related to %TWL, although the association did not remain significant after adjustment (Beta −2.7; 95% CI −5.7, 0.2; p = 0.069). Conclusions: MASH may be independently associated with lower %EWL 1 year after SG in patients with obesity.
10
Boccatonda, Andrea, Lorenza Del Cane, Lara Marola, Damiano D’Ardes, Gianfranco Lessiani, Nicoletta di Gregorio, Claudio Ferri, et al. "Platelet, Antiplatelet Therapy and Metabolic-Associated Fatty Liver Disease: A Narrative Review." Life 14, no. 4 (April 4, 2024): 473. http://dx.doi.org/10.3390/life14040473.
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Metabolic-associated fatty liver disease (MASLD) is not only related to traditional cardiovascular risk factors like T2DM and obesity, but it is also an independent risk factor for the development of cardiovascular disease. MASLD has been shown to be independently related to endothelial dysfunction and atherosclerosis. MASLD is characterized by a chronic proinflammatory response that, in turn, may induce a prothrombotic state. Several mechanisms such as endothelial and platelet dysfunction, changes in the coagulative factors, and lower fibrinolytic activity can contribute to induce the prothrombotic state. Platelets are players and aggressors of metabolic dysregulation; obesity and insulin resistance are related to platelet hyperactivation. Furthermore, platelets can exert a direct effect on liver cells, particularly through the release of mediators from granules. Growing data in the literature support the use of antiplatelet agent as a treatment for MASLD. The use of antiplatelets drugs seems to exert beneficial effects on HCC prevention in patients with MASLD, since platelets contribute to fibrosis progression and cancer development. This review aims to summarize the main data on the role of platelets in the pathogenesis of MAFLD and its main complications such as cardiovascular events and the development of liver fibrosis. Furthermore, we examine the role of antiplatelet therapy not only in the prevention and treatment of cardiovascular events but also as a possible anti-fibrotic and anti-tumor agent.
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Ciardullo, Stefano, Michela Vergani, and Gianluca Perseghin. "Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes: Screening, Diagnosis, and Treatment." Journal of Clinical Medicine 12, no. 17 (August 27, 2023): 5597. http://dx.doi.org/10.3390/jcm12175597.
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Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD) affects ~70% of patients with type 2 diabetes (T2D), with ~20% showing signs of advanced liver fibrosis. Patients with T2D are at an increased risk of developing cirrhosis, liver failure, and hepatocellular carcinoma and their liver-related mortality is doubled compared with non-diabetic individuals. Nonetheless, the condition is frequently overlooked and disease awareness is limited both among patients and among physicians. Given recent epidemiological evidence, clinical practice guidelines recommend screening for NAFLD/MASLD and advanced liver fibrosis in patients with T2D. While many drugs are currently being tested for the treatment of NAFLD/MASLD, none of them have yet received formal approval from regulatory agencies. However, several classes of antidiabetic drugs (namely pioglitazone, sodium-glucose transporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and multi-agonists) have shown favorable effects in terms of liver enzymes, liver fat content and, in some occasions, on histologic features such as inflammation and fibrosis. Therefore, diabetologists have the opportunity to actively treat NAFLD/MASLD, with a concrete possibility of changing the natural history of the disease. In the present narrative review, we summarize evidence and clinical recommendations for NAFLD/MAFLD screening in the setting of T2D, as well as on the effect of currently available glucose-lowering drugs on hepatic endpoints.
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Zazueta, Alejandra, Lucía Valenzuela-Pérez, Nicolás Ortiz-López, Araceli Pinto-León, Verónica Torres, Danette Guiñez, Nicolás Aliaga, et al. "Alteration of Gut Microbiota Composition in the Progression of Liver Damage in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)." International Journal of Molecular Sciences 25, no. 8 (April 16, 2024): 4387. http://dx.doi.org/10.3390/ijms25084387.
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Metabolic dysfunction-associated steatotic liver disease (MASLD) is a complex disorder whose prevalence is rapidly growing in South America. The disturbances in the microbiota–gut–liver axis impact the liver damaging processes toward fibrosis. Gut microbiota status is shaped by dietary and lifestyle factors, depending on geographic location. We aimed to identify microbial signatures in a group of Chilean MASLD patients. Forty subjects were recruited, including healthy controls (HCs), overweight/obese subjects (Ow/Ob), patients with MASLD without fibrosis (MASLD/F−), and MASLD with fibrosis (MASLD/F+). Both MASLD and fibrosis were detected through elastography and/or biopsy, and fecal microbiota were analyzed through deep sequencing. Despite no differences in α- and β-diversity among all groups, a higher abundance of Bilophila and a lower presence of Defluviitaleaceae, Lachnospiraceae ND3007, and Coprobacter was found in MASLD/F− and MASLD/F+, compared to HC. Ruminococcaceae UCG-013 and Sellimonas were more abundant in MASLD/F+ than in Ow/Ob; both significantly differed between MASLD/F− and MASLD/F+, compared to HC. Significant positive correlations were observed between liver stiffness and Bifidobacterium, Prevotella, Sarcina, and Acidaminococcus abundance. Our results show that MASLD is associated with changes in bacterial taxa that are known to be involved in bile acid metabolism and SCFA production, with some of them being more specifically linked to fibrosis.
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Cinque, Felice, Rosa Lombardi, Jaqueline Currà, Floriana Santomenna, Dana Kablawi, Annalisa Cespiati, Luca Marchesi, et al. "Metabolic dysfunction-associated steatotic liver disease in people with HIV is associated with lower BMI and more liver fibrosis compared to the uninfected population." European Atherosclerosis Journal 3, no. 1 (April 30, 2024): 27. http://dx.doi.org/10.56095/eaj.v3i1.65.
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Aim: People with HIV (PWH) are at high risk of metabolic dysfunction-associated steatotic liver disease (MASLD), defined by the presence of hepatic steatosis plus any among overweight, diabetes, hypertension, or dyslipidemia. There are limited data whether MASLD in PWH differs in clinical presentation from MASLD in the uninfected population. Aim: to compare the severity of metabolic and hepatic dysfunction between MASLD patients with and without HIV. Methods: 212 consecutive HIV mono-infected patients with MASLD at McGill University in Montreal were compared to a sex and age matched MASLD HIV negative control group at Policlinico Hospital in Milan. Fibroscan with controlled attenuation parameter (CAP) was used to define MASLD (CAP≥248 dB/m), severe MASLD (CAP>280 dB/m), and significant liver fibrosis (liver stiffness measurement>7.0 kPa). Results: PWH with MASLD presented lower median BMI (28[25-31] vs 29[27-32] Kg/m2, p=0.002) and lower prevalence of obesity (26% vs 44%, p<0.001) compared to MASLD uninfected patients, along with a lower prevalence of hypertension (21% vs 38%, p<0.001). The prevalence of dyslipidemia (41% vs 26%, p<0.001), hypertriglyceridemia (26% vs 9%, p<0.001) and low HDL cholesterol (34% vs 15%, p<0.001) was higher in MASLD patients with vs without HIV. No difference in cardiovascular events and diabetes prevalence was observed between the two groups. Regarding liver disease, PWH with MASLD had lower prevalence of severe MASLD (54% vs 74% p<0.001) but higher prevalence of significant liver fibrosis (15 vs 7%, p=0.03) compared to MASLD uninfected patients. After adjustment, HIV positivity was an independent factor associated with significant liver fibrosis (figure). Conclusions: Despite having lower BMI, PWH with MASLD have a more severe hepatic presentation and atherogenic lipid profile than MASLD uninfected patients. HIV positivity seems to be independently associated with significant liver fibrosis. Screening and follow-up for MASLD and liver fibrosis is recommended in PWH, even if they are lean.
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Antentas, Maria, Marina Idalia Rojo-López, Pau Vendrell, Minerva Granado-Casas, Idoia Genua, Berta Fernandez-Camins, Joana Rossell, et al. "Impact of Dietary Niacin on Metabolic Dysfunction-Associated Steatotic Liver Disease in Mediterranean Subjects: A Population-Based Study." Nutrients 16, no. 23 (November 30, 2024): 4178. https://doi.org/10.3390/nu16234178.
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Background: The impact of dietary niacin on metabolic dysfunction-associated steatotic liver disease (MASLD) is elusive. This sub-study aimed to investigate the relationship between dietary niacin intake and the presence of MASLD in participants from two Catalonian cohorts. Methods: A total of 222 subjects with MASLD were age- and sex-matched to 222 non-MASLD subjects. Dietary nutrients were analyzed using a validated food frequency questionnaire (FFQ). Dietary niacin and other nutrients were adjusted for total energy intake. MASLD was defined by a Fatty Liver Index (FLI) of >60 and by having at least one component of metabolic syndrome. The association between niacin intake (distributed into tertiles) and the presence of MASLD was assessed using multivariate logistic regression. Potential non-linear relationships were also analyzed through restricted cubic spline regression (RCS). Results: Our data revealed that subjects with MASLD had worse metabolic profiles. The dietary intake of niacin did not differ between subjects with and without MASLD. Even after adjusting for different confounding variables, i.e., sociodemographic variables, smoking status, physical activity, and cardiometabolic comorbidities, no significant associations were observed between higher intakes of niacin (tertiles 2 and 3) and the presence of MASLD: odds ratio (95% confidence) second tertile: 0.99 (0.89–1.09); third tertile: 0.98 (0.89–1.10). However, RCS analysis uncovered a significant non-linear dose-response association between dietary niacin intake and odds of MASLD. Specifically, such analysis revealed that MASLD risk was decreased in subjects with niacin intake values of <35 mg/day. Conclusions: Our data showed that dietary niacin intake was associated with lower odds of MASLD in a Mediterranean population; however, our logistic regression analysis failed to reveal significant associations between the intake of niacin and the risk of MASLD. Further research is warranted to establish a causal relationship between dietary niacin interventions and MASLD.
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Wang, Shao-Wen, Yu-Wen Chang, Ching Wang, Yu-Ming Cheng, Tsung-Han Hsieh, Chia-Chi Wang, and Jia-Horng Kao. "Clinical profiles and their interaction of concurrent metabolic associated steatotic liver disease and hepatitis B virus infection." World Journal of Hepatology 16, no. 12 (December 27, 2024): 1429–40. http://dx.doi.org/10.4254/wjh.v16.i12.1429.
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BACKGROUND A new nomenclature of metabolic associated steatotic liver disease (MASLD) was proposed in 2023, thus expanding the diagnostic name of “MASLD combined with other etiologies”. AIM To investigate the clinical profiles of patients with concurrent MASLD and chronic hepatitis B virus (HBV) infection. METHODS This study included participants from the Taiwan Bio-bank. The diagnostic criteria of MASLD encompassed hepatic steatosis and any cardio-metabolic risk factors. Positive hepatitis B surface antigen was considered indicative of chronic HBV infection. Dual etiology was defined as MASLD combined with chronic HBV infection (MASLD-HBV). Fibrosis 4 (FIB-4) score determined the severity of liver fibrosis, and atherosclerosis was diagnosed by the presence of carotid plaques on duplex ultrasound. RESULTS In a total of 18980 participants (mean age, 55.18 ± 10.35 years; males, 30.42%), there were 7654 (40.3%) MASLD patients and 2128 (11.2%) HBV carriers. After propensity score matching for age and gender, HBV carriers had a lower percentage of MASLD than healthy controls. Those with dual etiology had higher aspartate aminotransferase, alanine aminotransferase (ALT), and FIB-4 levels, but lower gamma glutamyl transferase (GGT) levels than MASLD patients. In contrast, those with dual etiology had higher ALT and GGT levels, but lower FIB-4 than “HBV alone” patients. The risk of atherosclerosis was similar among these three groups. CONCLUSION MASLD-HBV patients have worse liver fibrosis severity than MASLD patients, but better liver fibrosis stage than “HBV alone” patients, suggesting a complex interaction between MASLD and chronic HBV infection.
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Lee, Jun-Hyuk, JooYong Park, and Sang Bong Ahn. "Different Associations of Coffee Consumption with the Risk of Incident Metabolic Dysfunction-Associated Steatotic Liver Disease and Advanced Liver Fibrosis." Nutrients 16, no. 1 (December 31, 2023): 140. http://dx.doi.org/10.3390/nu16010140.
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Although coffee has a potential hepatoprotective effect, evidence of the relationship between coffee consumption and metabolic dysfunction-associated steatotic liver disease (MASLD) remains conflicting. There is limited evidence regarding the most appropriate coffee intake to prevent advanced liver fibrosis (ALF) in patients with MASLD. We investigated the effect of coffee consumption on MASLD and ALF among 5266 participants without MASLD and 1326 with MASLD but without ALF. Participants were grouped by coffee intake: non-consumers, >0 and <1 cups/day, ≥1 and <2 cups/day, and ≥2 cups/day. Over a median follow-up of 11.6 years for MASLD and 15.7 years for ALF, coffee consumption did not significantly affect the incidence of MASLD, with 2298 new cases observed. However, a notable inverse association was found with ALF risk in patients with MASLD among those consuming coffee ≥2 cups/day (adjusted HR 0.57, 95% CI: 0.37–0.90, p = 0.014), especially among those consuming coffee ≥2 and <3 cups/day (adjusted HR 0.51, 95% CI: 0.30–0.89, p = 0.018). This suggests a potential hepatoprotective effect of coffee, especially in preventing the progression of liver fibrosis in patients with MASLD. These findings propose that coffee consumption could be a simple and effective approach to mitigate the risk of ALF in individuals with MASLD.
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Tatsuta, Miwa, Tsutomu Masaki, Shungo Kimura, Yudai Sato, Akemi Tomida, Ichiro Ishikawa, Yu Nakamura, et al. "Efficiency of Skeletal Muscle Mass/Weight Measurement for Distinguishing Metabolic Dysfunction-Associated Steatotic Liver Disease: A Prospective Analysis Using InBody Bioimpedance Devices." Nutrients 16, no. 24 (December 23, 2024): 4422. https://doi.org/10.3390/nu16244422.
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Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is diagnosed when hepatic steatosis is proven by imaging and one of the five cardiometabolic criteria is present. The relationship between MASLD and body composition components has recently received increased research attention. However, the five cardiometabolic criteria do not include components of body composition. This study aimed to identify significant body composition factors associated with MASLD in patients undergoing health checkups. Methods: This study included a cohort of 6599 examinees who participated in a health check-up conducted between 2022 and 2023, and their data were prospectively analyzed. The inclusion criteria were undergoing abdominal ultrasonography, alcohol consumption <30 g/day for males or <20 g/day for females, and one of the five cardiometabolic criteria. Results: Finally, 3864 examinees were enrolled. In total, 1133 (51.8%) males and 454 (27.1%) females had MASLD. Sarcopenia was present in only 0.62% of males and 0.66% of females with MASLD. The MASLD group had significantly lower skeletal muscle mass/weight (SMM/WT) values than the non-MASLD group. Multivariate analysis revealed that SMM/WT was independently associated with MASLD. Conclusions: SMM/WT was significantly associated with MASLD. Therefore, muscle mass assessment using SMM/WT may be a potential marker for diagnosing MASLD.
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He, Qian-Jun, Yi-Fei Li, Ling-Tong Zhao, Chun-Tong Lin, Chun-Yan Yu, and Dan Wang. "Recent advances in age-related metabolic dysfunction-associated steatotic liver disease." World Journal of Gastroenterology 30, no. 7 (February 21, 2024): 652–62. http://dx.doi.org/10.3748/wjg.v30.i7.652.
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Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 25% of the world's population and has become a leading cause of chronic liver disease. In recent years, an increasing amount of data suggests that MASLD is associated with aging. As the population ages, age-related MASLD will become a major global health problem. Targeting an aging will become a new approach to the treatment of MASLD. This paper reviews the current studies on the role of aging-related factors and therapeutic targets in MASLD, including: Oxidative stress, autophagy, mitochondrial homeostasis, bile acid metabolism homeostasis, and dysbiosis. The aim is to identify effective therapeutic targets for age-related MASLD and its progression.
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Rivera-Esteban, Jesús, Alba Jiménez-Masip, Sergio Muñoz-Martínez, Salvador Augustin, Rafael A. Guerrero, Pablo Gabriel-Medina, Roser Ferrer-Costa, et al. "Prevalence and Risk Factors of MASLD and Liver Fibrosis amongst the Penitentiary Population in Catalonia: The PRISONAFLD Study." Journal of Clinical Medicine 12, no. 23 (November 24, 2023): 7276. http://dx.doi.org/10.3390/jcm12237276.
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Background and Aims: The prevalence of chronic non-communicable diseases, particularly metabolic syndrome (MetS), has increased among the prison population. Nevertheless, we have limited data on metabolic dysfunction-associated steatotic liver disease (MASLD), the hepatic manifestation of this syndrome. We aimed to investigate the prevalence and risk factors of MASLD and MASLD-associated liver fibrosis in the penitentiary population in Catalonia, Spain. Method: A cross-sectional observational study involving eight penitentiary centers. Participants had at least one metabolic disorder and were at a closed-regimen penitentiary. Individuals with concomitant liver diseases and/or alcohol risk consumption were excluded. Significant fibrosis and MASLD were defined as liver stiffness ≥8 kPa and a controlled attenuation parameter ≥275 dB/m by vibration-controlled transient elastography (VCTE), respectively. After exclusions, metabolic inmates with VCTE were analyzed. Logistic regression analysis was performed to identify predictors of MASLD and MASLD-associated significant fibrosis. Results: Out of the 4338 inmates studied, 1290 (29.7%) had metabolic disorders, and 646 (14.9%) underwent VCTE. The mean age was 48.0 years (SD 12.1), and 89.5% were male. MASLD prevalence was 33.9%. Significant fibrosis and MASLD-associated significant fibrosis were found in 16.4% and 9.4% of inmates, respectively. In the multivariate analysis, T2D, waist circumference, MetS, and higher ALT values were identified as independent risk factors for MASLD and MASLD-associated significant fibrosis amongst the prison population. Conclusions: Metabolic disorders including MASLD are highly prevalent among inmates. The prevalence of significant fibrosis seems notably higher than that of the general population, underscoring the need for targeted screening programs and therapeutic interventions in the incarcerated population.
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Scarpellini, Emidio, Marialaura Scarcella, Jan F. Tack, Giuseppe Guido Maria Scarlata, Michela Zanetti, and Ludovico Abenavoli. "Gut Microbiota and Metabolic Dysfunction-Associated Steatotic Liver Disease." Antioxidants 13, no. 11 (November 14, 2024): 1386. http://dx.doi.org/10.3390/antiox13111386.
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Background: The gut microbiota constitutes a complex microorganism community that harbors bacteria, viruses, fungi, protozoa, and archaea. The human gut bacterial microbiota has been extensively proven to participate in human metabolism, immunity, and nutrient absorption. Its imbalance, namely “dysbiosis”, has been linked to disordered metabolism. Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the features of deranged human metabolism and is the leading cause of liver cirrhosis and hepatocellular carcinoma. Thus, there is a pathophysiological link between gut dysbiosis and MASLD. Aims and Methods: We aimed to review the literature data on the composition of the human bacterial gut microbiota and its dysbiosis in MASLD and describe the concept of the “gut–liver axis”. Moreover, we reviewed the approaches for gut microbiota modulation in MASLD treatment. Results: There is consolidated evidence of particular gut dysbiosis associated with MASLD and its stages. The model explaining the relationship between gut microbiota and the liver has a bidirectional organization, explaining the physiopathology of MASLD. Oxidative stress is one of the keystones in the pathophysiology of MASLD and fibrosis generation. There is promising and consolidated evidence for the efficacy of pre- and probiotics in reversing gut dysbiosis in MASLD patients, with therapeutic effects. Few yet encouraging data on fecal microbiota transplantation (FMT) in MASLD are available in the literature. Conclusions: The gut dysbiosis characteristic of MASLD is a key target in its reversal and treatment via diet, pre/probiotics, and FMT treatment. Oxidative stress modulation remains a promising target for MASLD treatment, prevention, and reversal.
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Aggeletopoulou, Ioanna, Efthymios Tsounis, and Christos Triantos. "Vitamin D and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Novel Mechanistic Insights." International Journal of Molecular Sciences 25, no. 9 (April 30, 2024): 4901. http://dx.doi.org/10.3390/ijms25094901.
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Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent condition characterized by abnormal fat accumulation in the liver, often associated with metabolic disorders. Emerging evidence suggests a potential link between vitamin D deficiency and the development and progression of MASLD. The current review provides a concise overview of recent studies uncovering novel mechanistic insights into the interplay between vitamin D and MASLD. Several epidemiological studies have highlighted a significant association between low vitamin D levels and an increased risk of MASLD. Vitamin D, traditionally known for its role in bone health, has now been recognized as a key player in various physiological processes, including immune regulation and inflammation. Experimental studies using animal models have demonstrated that vitamin D deficiency exacerbates liver steatosis and inflammation, suggesting a potential protective role against MASLD. Mechanistically, vitamin D appears to modulate MASLD through multiple pathways. Firstly, the vitamin D receptor (VDR) is abundantly expressed in liver cells, indicating a direct regulatory role in hepatic function. Activation of the VDR has been shown to suppress hepatic lipid accumulation and inflammation, providing a mechanistic basis for the observed protective effects. Additionally, vitamin D influences insulin sensitivity, a critical factor in MASLD pathogenesis. Improved insulin sensitivity may mitigate the excessive accumulation of fat in the liver, thus attenuating MASLD progression. In parallel, vitamin D exhibits anti-inflammatory properties by inhibiting pro-inflammatory cytokines implicated in MASLD pathophysiology. Experimental evidence suggests that the immunomodulatory effects of vitamin D extend to the liver, reducing inflammation and oxidative stress, key drivers of MASLD, and the likelihood of hepatocyte injury and fibrosis. Understanding the complex interplay between vitamin D and MASLD provides a basis for exploring targeted therapeutic strategies and preventive interventions. As vitamin D deficiency is a modifiable risk factor, addressing this nutritional concern may prove beneficial in mitigating the burden of MASLD and associated metabolic disorders.
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Gao, Jingli, Yuhao Li, Yijun Zhang, Xin Zhan, Xue Tian, Junjuan Li, Ru Wang, Yan He, Anxin Wang, and Shouling Wu. "Severity and Remission of Metabolic Dysfunction–Associated Fatty/Steatotic Liver Disease With Chronic Kidney Disease Occurrence." Journal of the American Heart Association, February 23, 2024. http://dx.doi.org/10.1161/jaha.123.032604.
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Background The association of the severity of hepatic steatosis in metabolic dysfunction–associated fatty liver disease (MAFLD)/metabolic dysfunction–associated steatotic liver disease (MASLD) and the remission of MAFLD/MASLD with CKD occurrence is unclear. Methods and Results The study enrolled 79 540 participants from the Kailuan cohort. Hepatic steatosis was diagnosed by ultrasound. MAFLD/MASLD was defined as hepatic steatosis combined with metabolic dysfunction and MASLD further excluded alcohol or other causes of liver disease. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate<60 mL/min per 1.73 m 2 or positive proteinuria (≥1+). Hazard ratio (HR) was calculated by Cox regression models. After a median follow‐up of 12.9 years, CKD occurred in 20 465 participants. After adjusting for potential confounders, MAFLD was associated with a higher risk of CKD compared with non‐MAFLD (HR, 1.12 [95% CI, 1.09–1.16]), and this risk increased with increasing severity of hepatic steatosis ( P ‐trend<0.001). Consistent findings were observed when MASLD was used as the exposure. Compared with persistent non‐MAFLD, no statistical difference was found in the risk of CKD in MAFLD remission (HR, 1.04 [95% CI, 0.95–1.15]); however, MASLD remission still had a higher risk of CKD compared with persistent non‐MASLD (HR, 1.15 [95% CI, 1.03–1.27]). When grouped according to the prior severity of hepatic steatosis, there was no statistically significant difference in risk of CKD in mild‐MAFLD/MASLD remission compared with persistent non‐MAFLD/MASLD, but moderated/severe‐MAFLD/MASLD remission still had a higher risk. Conclusions The risk of CKD in patients with MAFLD/MASLD increased with the severity of hepatic steatosis. Even after remission of the disease, patients with MAFLD/MASLD with prior moderate to severe hepatic steatosis still had a higher risk of CKD.
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Song, Rui, Zhao Li, Yingzhi Zhang, Jiahe Tan, and Zhiwei Chen. "Comparison of NAFLD, MAFLD and MASLD characteristics and mortality outcomes in United States adults." Liver International, January 31, 2024. http://dx.doi.org/10.1111/liv.15856.
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AbstractBackground & AimsFollowing the classification of metabolic dysfunction‐associated fatty liver disease (MAFLD), non‐alcoholic fatty liver disease (NAFLD) has recently been redefined again as metabolic dysfunction‐associated steatotic liver disease (MASLD). However, the distinctions in characteristics and mortality outcomes between NAFLD, MAFLD and MASLD remain unclear.MethodsWe analysed data from 7519 participants in the third National Health and Nutrition Examination Surveys of United States (US) and their linked mortality until 2019. Survey weight‐adjusted multivariable Cox proportional model was used to study the mortality over three terms.ResultsThe prevalence of NAFLD, MAFLD and MASLD was 18.5%, 19.3% and 20.8%, respectively. Most individuals with NAFLD (94.5%) or MAFLD (100%) can be classified as MASLD, while a relatively low percentage of those with MASLD were also diagnosed with either NAFLD (84.1%) or MAFLD (92.7%). During a median follow‐up of 26.9 years, both MAFLD and MASLD were associated with increased risk of all‐cause mortality (adjusted hazard ratio [aHR] 1.18, 95% CI 1.04–1.33 and 1.19, 1.06–1.34, respectively), this association was mainly observed in NAFLD−/MASLD+ subgroups. NAFLD was not associated with all‐cause mortality. However, all three terms were associated with an increased risk of all‐cause mortality in individuals with advanced fibrosis (aHR: 1.71–1.81). Subgroup analyses showed that higher risk of all‐cause mortality for both MAFLD and MASLD were observed among older adults (≥65 year), non‐Hispanic whites and those without diabetes.ConclusionsBoth MASLD and MALFD were linked to higher all‐cause mortality risk, but MASLD identified a greater number of individuals compared to MAFLD.
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Pan, Ziyan, Gamal Shiha, Gamal Esmat, Nahum Méndez‐Sánchez, and Mohammed Eslam. "MAFLD predicts cardiovascular disease risk better than MASLD." Liver International, April 20, 2024. http://dx.doi.org/10.1111/liv.15931.
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AbstractBackground and AimMetabolic dysfunction‐associated steatotic liver disease (MASLD) has been proposed as an alternative for the validated definition of metabolic dysfunction‐associated fatty liver disease (MAFLD). We compared the abilities of MAFLD and MASLD to predict the risk of atherosclerotic cardiovascular disease (ASCVD).MethodsSix thousand and ninety six participants from the 2017 to 2020 National Health and Nutrition Examination Survey cohort who received a thorough medical health check‐up were chosen for the study. The associations between fatty liver status and coronary risk surrogates, such as 10‐year ASCVD risk and self‐reported cardiovascular events, were analysed.ResultsMAFLD and MASLD were identified in 2911 (47.7%) and 2758 (45.2%) patients, respectively. MAFLD (odds ratio [OR]: 2.14, 95% confidence interval [CI], 1.78–2.57, p < .001) was more strongly independently associated with high ASCVD risk than MASLD (OR: 1.82, 95% CI, 1.52–2.18, p < .001) was in comparison with the absence of each condition. However, compared with MAFLD, MASLD alone was not associated with increased ASCVD risk. Multiple logistic regression revealed that MAFLD alone was significantly more strongly associated with a high risk of ASCVD (OR: 2.82; 95% CI: 1.13–7.01; p < .03) than MASLD alone.ConclusionsAlthough both MAFLD and MASLD were associated with different ASCVD risks, MAFLD predicted the ASCVD risk better than MASLD. The higher predictive ability of MAFLD compared to MASLD was attributed to metabolic dysfunction rather than moderate alcohol use.
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Lonardo, Amedeo. "Association of NAFLD/NASH, and MAFLD/MASLD with chronic kidney disease: an updated narrative review." Metabolism and Target Organ Damage 4, no. 2 (April 7, 2024). http://dx.doi.org/10.20517/mtod.2024.07.
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Chronic kidney disease (CKD) and nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) account for substantial financial burden worldwide. These alarming features call for enhanced efforts to prevent and manage the development and progression of CKD. Accumulating evidence supporting a causal role of NAFLD/MAFLD/MASLD-in CKD opens new horizons to achieve this aim. Recent epidemiological studies and meta-analyses exploring the association of NAFLD/MAFLD/MASLD with CKD and the characteristics of NAFLD/MAFLD/MASLD associated with the odds of incident CKD are discussed. The involved pathomechanisms, including the common soil hypothesis, genetics, gut dysbiosis, and portal hypertension, are examined in detail. Finally, lifestyle changes (diet and physical exercise), direct manipulation of gut microbiota, and drug approaches involving statins, renin-angiotensin-aldosterone system inhibitors, GLP-1 Receptor Agonists, Sodium-glucose cotransporter-2, pemafibrate, and vonafexor are examined within the context of prevention and management of CKD among those with NAFLD/MAFLD/MASLD. The evolving NAFLD/MAFLD/MASLD nomenclature may generate confusion among practicing clinicians and investigators. However, comparative studies investigating the pros and contra of different nomenclatures may identify the most useful definitions among NAFLD/MAFLD/MASLD and strategies to identify, prevent, and halt the onset and progression of CKD.
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Rhee, E. J., H. Kwon, S. Park, and W. Y. Lee. "8327 Risk Of Chronic Kidney Disease In Subjects With Metabolic Dysfunction-Associated Fatty Liver Disease Or Metabolic Dysfunction-Associated Steatotic Liver Disease: A Retrospective Study." Journal of the Endocrine Society 8, Supplement_1 (October 2024). http://dx.doi.org/10.1210/jendso/bvae163.917.
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Abstract Disclosure: E. Rhee: None. H. Kwon: None. S. Park: None. W. Lee: None. Background: Recently, the term non-alcoholic fatty liver disease (NAFLD) is replaced by a new term, metabolic dysfunction-associated liver disease (MASLD), with a new definition made by a modified Delphi process led by three large pan-national liver associations. In this study, we aimed to analyze the risk for chronic kidney disease (CKD) development in those with MASLD defined by the new definition and metabolic dysfunction-associated fatty liver disease (MAFLD). Methods: Among 52,606 participants (mean age 35.4 years) in the health checkup program from 2002 to 2019, in whom at least 10 health checkups were performed, after strict exclusion, 48,751 participants were enrolled and analyzed the development of CKD defined by estimated glomeruls filtration lower than 60 mL/min/1.73m2) during a median of 14.7 years of follow-up. The presence of MAFLD was defined by presence of hepatic steatosis plus one of the three criteria of overweight or obese, type 2 diabetes or presence of ≥2 metabolic risk abnormalities. MASLD was defined by presence of hepatic steatosis plus at least 1 of 5 cardiometabolic risk factors. Results: At baseline, 12,773(26.2%) participants had MAFLD and 35,359(74.58%) had MASLD. During the follow-up period, 849(1.7%) participants developed CKD. In participants with MAFLD, 345(2.7%) participants developed CKD, and in participants with MASLD, 609(1.7%) developed CKD. After adjustment for age and sex, the hazard ratio(HR) of CKD was 1.44 (95% confidence interval [CI] 1.25-1.66) for MAFLD, and 1.25(95% CI 1.07-1.47) for MASLD. Both definition predicted development of CKD nicely (Harrell’s C-index: 0.79(0.77-0.81) for MAFL and MASLD) Conclusions: The participants with MAFLD and MASLD showed significantly increased risk for CKD during a median of 15 years of follow-up. Both criteria showed nice predictability for CKD. Presentation: 6/1/2024
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Wu, Tingfeng, Junzhao Ye, Suilin Mo, Miaosheng Ye, Xiaoyi Li, Qing Li, Wengeng Wang, et al. "Impact of nomenclature as metabolic associated steatotic liver disease on steatotic liver disease prevalence and screening: a prospective population survey in Asians." Journal of Gastroenterology and Hepatology, May 2, 2024. http://dx.doi.org/10.1111/jgh.16554.
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AbstractBackground and AimThe introduction of the latest nomenclature, metabolic associated steatotic liver disease (MASLD), proposed by the multi‐society without Asian society consensus statement, aims to redefine the diagnostic criteria for metabolic associated fatty liver disease (MAFLD). However, its effect on the epidemiology in Asia remains unclear.MethodWe conducted a population‐based cross‐sectional survey on fatty liver disease using multistage stratified random sampling of participants from Guangzhou, a representative area in China (ChiCTR2000033376). Demographic, socioeconomic, lifestyle, and laboratory data were collected. Hepatic steatosis and the severity of fibrosis were assessed using FibroScan.ResultsA total of 7388 individuals were recruited, the proportion of which meeting the definitions for nonalcoholic fatty liver disease (NAFLD), MAFLD, and MASLD were 2359 (31.9%), 2666 (36.1%), and 2240 (30.3%), respectively. One hundred and twenty (1.6%) patients had cryptogenic SLD, and 537 (7.3%) patients were diagnosed with MetALD. MASLD did not significantly differ from NAFLD and MAFLD, except that MAFLD patients had a lower proportion of males, hypertension, and diabetes and were less likely to consume tea (P < 0.05). Both cryptogenic SLD and MASLD non‐MAFLD patients exhibited milder hepatic steatosis and a lower frequency of liver injury than NAFLD, MAFLD, or MASLD patients (all P < 0.05). An increased HOMA‐IR (adjusted OR: 1.33, 95% CI: 1.10–2.03) was associated with higher risk of moderate‐to‐severe steatosis for MASLD non‐MAFLD patients, while consuming more cups of tea (P for trend = 0.015) showed inverse associations.ConclusionIrrespective of terminology used is that fatty liver disease is highly prevalent in the Han Chinese population. Differences in insulin resistance and lifestyle risk factors are associated with redefinition disparities.
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Zhou, Xiao-Dong, Giovanni Targher, Christopher D. Byrne, Michael D. Shapiro, Li-Li Chen, and Ming-Hua Zheng. "Metabolic dysfunction-associated fatty liver disease: bridging cardiology and hepatology." Cardiology Plus, December 11, 2024. https://doi.org/10.1097/cp9.0000000000000106.
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Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver diseases, affecting approximately 30% of the global adult population, with a rise largely attributed to increasing rates of obesity and diabetes worldwide. Historically, the term “NAFLD” did not explicitly link the condition to its most common causes, such as obesity and diabetes, or its principal pathophysiological mechanisms, including insulin resistance and low-grade chronic metabolic inflammation. This semantic laxity has potentially reduced attempts at screening, diagnosis, and management. The shift to using the terms metabolic-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) reflects a more accurate understanding of the condition’s metabolic origins and highlights its broader implications, particularly its link to cardiovascular diseases. MAFLD/MASLD represents a convergence point between hepatology and cardiology, with metabolic dysfunction serving as the bridge between liver pathology and increased cardiovascular risk. Growing clinical evidence reveals a strong association between MAFLD/MASLD and cardiovascular morbidity and mortality. Despite this, cardiovascular risks associated with MAFLD/MASLD are often underestimated, especially among cardiologists. This narrative review explores the potential clinical implications of MAFLD/MASLD for cardiology practice, examining diagnostic criteria, cardiovascular risk assessment, adjustments in clinical practice, collaborative care strategies, treatment options, and directions for future research.
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Ortiz-López, Nicolás, Ana María Madrid, Larissa Aleman, Alejandra Zazueta, Gladys Smok, Lucía Valenzuela-Pérez, Jaime Poniachik, and Caroll J. Beltrán. "Small intestinal bacterial overgrowth in obese patients with biopsy-confirmed metabolic dysfunction-associated steatotic liver disease: a cross-sectional study." Frontiers in Medicine 11 (May 24, 2024). http://dx.doi.org/10.3389/fmed.2024.1376148.
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Background/aimsThe metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity are frequent comorbidities with a high prevalence worldwide. Their pathogenesis are multifactorial, including intestinal dysbiosis. The role of small intestinal bacterial overgrowth (SIBO) in MASLD progression in obese patients remains unknown. We aimed to determine the association between SIBO and the severity of MASLD in obese patients.MethodsAn observational and cross-sectional study was conducted in obese patients, diagnosed with or without MASLD by liver biopsy. Metabolic dysfunction-associated steatotic liver (MASL), metabolic dysfunction-associated steatohepatitis without fibrosis (MASH-NF), MASH with fibrosis (MASH-F), or without MASLD (control subjects, CS) were identified by presence of steatosis, portal and lobular inflammation, and fibrosis. SIBO was determined by standardized lactulose breath tests.ResultsA total of 59 patients with MASLD, 16 with MASL, 20 with MASH-NF, 23 with MASH-F, and 14 CS were recruited. Higher percentages of SIBO were observed in MASLD patients (44.2%) compared to CS (14.2%; p = 0.0363). Interestingly, MASH-F showed higher percentages of SIBO (65.2%) in comparison to non-fibrotic MASLD (33.3%; p = 0.0165). The presence of SIBO was not correlated with the level of hepatic steatosis in MASLD patients.ConclusionsA positive correlation between MASLD and SIBO in obese patients was principally explained by the presence of liver fibrosis. Our findings suggest a pathogenic role of intestinal dysbiosis in the progression of MASLD. Future research will elucidate the underlying mechanisms of SIBO in MASLD advancement.
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Zou, Haoxuan, Xiaopu Ma, Wen Pan, and Yan Xie. "Comparing similarities and differences between NAFLD, MAFLD, and MASLD in the general U.S. population." Frontiers in Nutrition 11 (July 8, 2024). http://dx.doi.org/10.3389/fnut.2024.1411802.
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BackgroundRecently, the multisociety Delphi consensus renamed non-alcoholic fatty liver disease (NAFLD) terminology [previously renamed metabolic-associated fatty liver disease (MAFLD)] as metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of this study was to compare the similarities and differences between NAFLD, MAFLD, and MASLD and to clarify the impact of this new name change.MethodsA cross-sectional study of 3,035 general subjects with valid vibration-controlled transient elastography data was conducted based on data from the National Health and Nutrition Examination Survey (NHANES) 2017–2020. NAFLD, MAFLD, and MASLD were defined according to the corresponding consensus criteria.ResultsUsing controlled attenuation parameter (CAP) ≥274 dB/m and liver stiffness measurements (LSM) ≥9.7 kPa as the cutoff values for the presence of hepatic steatosis and advanced liver fibrosis (ALF), the prevalence of NAFLD, MAFLD, and MASLD were 38.01% (95% CI 35.78–40.29%), 41.09% (39.09–43.12%), and 37.9% (35.70–40.14%), respectively, and the corresponding prevalence of ALF was 10.21% (7.09–14.48%), 10.13% (7.06-14.35%), and 10.24% (7.11–14.53%), respectively. The kappa values for the three definitions were above 0.9. The prevalence and severity of the three definitions remained similar when the sensitivity analyses were performed using different CAP thresholds. The prevalence of NAFLD, MAFLD, MASLD, and ALF increased as the number of cardiometabolic risk factors (CMRF) increased.ConclusionsOur findings highlight the consistency among the three definitions, especially between NAFLD and MASLD, so that the new consensus will not disturb the original NAFLD-related findings. Additionally, more attention should be paid to patients with a high number of CMRFs.
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Bao, Xue, Lina Kang, Songjiang Yin, Gunnar Engström, Lian Wang, Wei Xu, Biao Xu, Xiaowen Zhang, and Xinlin Zhang. "Association of MAFLD and MASLD with all-cause and cause-specific dementia: a prospective cohort study." Alzheimer's Research & Therapy 16, no. 1 (June 26, 2024). http://dx.doi.org/10.1186/s13195-024-01498-5.
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Abstract Background Liver disease and dementia are both highly prevalent and share common pathological mechanisms. We aimed to investigate the associations between metabolic dysfunction-associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of all-cause and cause-specific dementia. Methods We conducted a prospective study with 403,506 participants from the UK Biobank. Outcomes included all-cause dementia, Alzheimer’s disease, and vascular dementia. Multivariable Cox proportional hazards models were used for analyses. Results 155,068 (38.4%) participants had MAFLD, and 111,938 (27.7%) had MASLD at baseline. During a median follow-up of 13.7 years, 5,732 participants developed dementia (2,355 Alzheimer’s disease and 1,274 vascular dementia). MAFLD was associated with an increased risk of vascular dementia (HR 1.32 [95% CI 1.18–1.48]) but a reduced risk of Alzheimer’s disease (0.92 [0.84–1.0]). Differing risks emerged among MAFLD subtypes, with the diabetes subtype increasing risk of all-cause dementia (1.8 [1.65–1.96]), vascular dementia (2.95 [2.53–3.45]) and Alzheimer’s disease (1.46 [1.26–1.69]), the lean metabolic disorder subtype only increasing vascular dementia risk (2.01 [1.25–3.22]), whereas the overweight/obesity subtype decreasing risk of Alzheimer’s disease (0.83 [0.75–0.91]) and all-cause dementia (0.9 [0.84–0.95]). MASLD was associated with an increased risk of vascular dementia (1.24 [1.1–1.39]) but not Alzheimer’s disease (1.0 [0.91–1.09]). The effect of MAFLD on vascular dementia was consistent regardless of MASLD presence, whereas associations with Alzheimer’s disease were only present in those without MASLD (0.78 [0.67–0.91]). Conclusions MAFLD and MASLD are associated with an increased risk of vascular dementia, with subtype-specific variations observed in dementia risks. Further research is needed to refine MAFLD and SLD subtyping and explore the underlying mechanisms contributing to dementia risk.
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Kim, Donghee, Karn Wijarnpreecha, George Cholankeril, and Aijaz Ahmed. "Steatotic liver disease‐associated all‐cause/cause‐specific mortality in the United States." Alimentary Pharmacology & Therapeutics, April 22, 2024. http://dx.doi.org/10.1111/apt.18011.
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SummaryBackgroundRecently, a panel of multi‐society experts proposed steatotic liver disease (SLD) as an alternative terminology for metabolic dysfunction‐associated fatty liver disease (MAFLD) or nonalcoholic fatty liver disease (NAFLD).AimsWe compared the impact of SLD, subtype of SLD, MAFLD and NAFLD on all‐cause and cause‐specific mortality.MethodsA total of 7811 individuals in the third National Health and Nutrition Examination Survey and linked mortality through 2019 were analysed. SLD was defined based on ultrasonographic hepatic steatosis. SLD, subtype of SLD and MAFLD were defined using the proposed definitions. The Cox proportional hazard model assessed all‐cause/cause‐specific mortality.ResultsDuring a median follow‐up of 27.1 years, individuals with SLD and MAFLD experienced approximately 13%–23% higher risk of all‐cause mortality (hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 1.02–1.29 for SLD; HR: 1.23, 95% CI: 1.09–1.38 for MAFLD; HR: 1.13, 95% CI: 1.01–1.27 for metabolic dysfunction‐associated steatotic liver disease [MASLD]). Individuals with MetALD demonstrated a higher risk of all‐cause (HR: 1.68, 95% CI: 1.10–2.57) and cancer‐related mortality (HR: 2.40, 95% CI: 1.23–4.66). MASLD with advanced fibrosis had an increased risk of all‐cause mortality compared to MASLD without advanced fibrosis.ConclusionsSLD, especially MASLD and MetALD, is associated with increased all‐cause mortality among adults in the US. Given this significant association between SLD or subtype of SLD (MASLD and MetALD) and all‐cause mortality, adopting the proposed SLD criteria may help identify a sub‐group of individuals with SLD who are at an increased risk for all‐cause mortality.
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Wang, Yumin, Joshua S. Fleishman, Tongda Li, Yulin Li, Zhao Ren, Jichao Chen, and Mingchao Ding. "Pharmacological therapy of metabolic dysfunction-associated steatotic liver disease-driven hepatocellular carcinoma." Frontiers in Pharmacology 14 (January 19, 2024). http://dx.doi.org/10.3389/fphar.2023.1336216.
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In light of a global rise in the number of patients with type 2 diabetes mellitus (T2DM) and obesity, non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD), has become the leading cause of hepatocellular carcinoma (HCC), with the annual occurrence of MASLD-driven HCC expected to increase by 45%–130% by 2030. Although MASLD has become a serious major public health threat globally, the exact molecular mechanisms mediating MASLD-driven HCC remain an open problem, necessitating future investigation. Meanwhile, emerging studies are focusing on the utility of bioactive compounds to halt the progression of MASLD to MASLD-driven HCC. In this review, we first briefly review the recent progress of the possible mechanisms of pathogenesis and progression for MASLD-driven HCC. We then discuss the application of bioactive compounds to mitigate MASLD-driven HCC through different modulatory mechanisms encompassing anti-inflammatory, lipid metabolic, and gut microbial pathways, providing valuable information for future treatment and prevention of MASLD-driven HCC. Nonetheless, clinical research exploring the effectiveness of herbal medicines in the treatment of MASLD-driven HCC is still warranted.
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Byrne, Christopher D., and Giovanni Targher. "MASLD, MAFLD, or NAFLD criteria: have we re-created the confusion and acrimony surrounding metabolic syndrome?" Metabolism and Target Organ Damage 4, no. 2 (February 27, 2024). http://dx.doi.org/10.20517/mtod.2024.06.
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In 1980, there was the first description of patients with nonalcoholic steatohepatitis (NASH), most of whom were overweight and had type 2 diabetes. In the following years, there has been a growing appreciation that metabolic dysfunction underpins this liver disease, and metabolic dysfunction also contributes to the increased risk of extrahepatic complications, manifest in nonalcoholic fatty liver disease (NAFLD) as a multisystem disease. In 2020 & 2023, it was proposed that NAFLD should be renamed and reclassified as metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD), respectively. Despite subtle differences between MAFLD and MASLD, there is excellent congruence between NAFLD, MAFLD, and MASLD definitions, and affected patients usually meet the criteria for all. The following is a perspective of the authors’ views as to the challenges and advantages of the new fatty liver disease terminology and classification.
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Barritt, A. Sidney, Feng Yu, Andrea R. Mospan, Philip Newsome, Michael Roden, Heather L. Morris, Rohit Loomba, and Brent A. Neuschwander-Tetri. "High concordance between nonalcoholic fatty liver disease and metabolic dysfunction associated steatotic liver disease in the TARGET-NASH real world cohort." American Journal of Gastroenterology, April 8, 2024. http://dx.doi.org/10.14309/ajg.0000000000002796.
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Introduction: This study investigates the applicability of the new MASLD nomenclature to the real-world TARGET-NASH US adult cohort. Methods: The new MASLD/MASH nomenclature was applied to patients enrolled with pragmatic diagnoses of NAFL, NASH and NASH cirrhosis and concordance was determined between the definitions. Results: 99% of TARGET-NASH participants met the new MASLD diagnostic criteria. 1484/1541 (96.3%, kappa 0.974) NAFL patients (MASL), 2195/2201 (99.7%, kappa 0.998) NASH patients (MASH), and 1999/2003 (99.8%, kappa 0.999) NASH cirrhosis patients met the new criteria. Conclusion: The new MASLD nomenclature is highly concordant with the prior TARGET-NASH pragmatic definitions.
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Lonardo, Amedeo. "MASLD co-aggregates with HCC in families-names change, fa(c)ts remain." Hepatoma Research, December 29, 2023. http://dx.doi.org/10.20517/2394-5079.2023.110.
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My invited commentary discusses a recent paper published by Ebrahimi et al. [28 ]. To this end, the definitions of nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated fatty liver disease (MAFLD), and the most recently proposed metabolic dysfunction-associated steatotic liver disease (MASLD) are reviewed. For brevity, the overarching definition of metabolic fatty liver syndromes (MFLS) is utilized to allude to NAFLD/MAFLD/MASLD collectively, although each nomenclature identifies different diagnostic criteria and identifies distinct patient populations. Ebrahimi and colleagues conducted an analysis using data from the National Swedish Multigeneration archive, involving 38,018 MASLD first-degree relatives (FDRs) and 9,381 MASLD spouses, alongside 197,303 comparator FDRs and 47,572 comparator spouses. They followed these groups for a median of 17.6 years and reported a definite familial aggregation of adverse liver-related events among families of MASLD individuals. These events comprise increased relative risks of hepatocellular carcinoma (HCC), major chronic liver disease, and mortality owing to hepatic causes. I comment on this study with reference to the ongoing changes in terminology describing MFLS and to sexual dimorphism exhibited by MFLS. It is concluded that the study by Ebrahimi adds another piece to the puzzle of knowledge requested to implement those precision medicine approaches that are eagerly awaited in the field of MFLS.
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Jang, Se Young, Ki Tae Yoon, Young Youn Cho, Hoon Gil Jo, Yang Hyun Baek, Sang Yi Moon, Ae Jeong Jo, et al. "Aspartate aminotransferase‐to‐platelet ratio index outperforms Fibrosis‐4 in 2843 Korean patients with metabolic dysfunction‐associated steatotic liver disease." Hepatology Research, November 29, 2024. http://dx.doi.org/10.1111/hepr.14143.
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AbstractAimThe definition of metabolic dysfunction‐associated steatotic liver disease (MASLD) has recently been proposed. We aim to investigate the diagnostic efficacy of noninvasive fibrosis markers in predicting liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction‐associated fatty liver disease (MAFLD), and MASLD.MethodsThis retrospective study involved 2843 patients diagnosed with steatotic liver disease at six tertiary hospitals in South Korea. Liver fibrosis was assessed using vibration‐controlled transient elastography, and various noninvasive markers, including the aspartate aminotransferase‐to‐platelet ratio index (APRI), Fibrosis‐4 index (FIB‐4), NAFLD fibrosis score (NFS), and serum Mac‐2‐binding protein glycosylation isomer were analyzed.ResultsAmong 1106 patients, 79.9% met criteria for NAFLD, MAFLD, and MASLD. The APRI had area under the receiver operating characteristic curve (AUC) values of 0.819, 0.821, and 0.818 for liver fibrosis ≥F2, and 0.819, 0.824, and 0.884 for liver fibrosis ≥F3, and 0.890, 0.884, and 0.889 for fibrosis ≥F4 in NAFLD, MAFLD, and MASLD, respectively. The FIB‐4 index showed AUC values of 0.776, 0.793, and 0.778 for fibrosis ≥F2, 0.788, 0.814, and 0.79 for fibrosis ≥F3, and 0.846, 0.859, and 0.856 for fibrosis ≥F4. The APRI consistently had the highest AUC values, except in individuals older than 64 years for fibrosis ≥F4.ConclusionsThe APRI was the most effective noninvasive fibrosis marker across NAFLD, MAFLD, and MASLD, particularly in age‐stratified analyses. Further research is needed to establish standardized cut‐off values and enhance the clinical utility of these markers in managing liver fibrosis.
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Sohail, Abdullah, Hassam Ali, Pratik Patel, Subanandhini Subramanium, Dushyant Singh Dahiya, Amir H. Sohail, Manesh Kumar Gangwani, and Sanjaya K. Satapathy. "Impact of metabolic dysfunction-associated steatotic liver disease on COVID-19 hospitalizations: A propensity-matched analysis of the United States." World Journal of Virology 13, no. 1 (March 25, 2024). http://dx.doi.org/10.5501/wjv.v13.i1.91149.
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BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD), formally known as nonalcoholic fatty liver disease, is the most common chronic liver disease in the United States. Patients with MASLD have been reported to be at a higher risk of developing severe coronavirus disease 2019 (COVID-19) and death. However, most studies are single-center studies, and nationwide data in the United States is lacking. AIM To study the influence of MASLD on COVID-19 hospitalizations during the initial phase of the pandemic. METHODS We retrospectively analyzed the 2020 National Inpatient Sample (NIS) database to identify primary COVID-19 hospitalizations based on an underlying diagnosis of MASLD. A matched comparison cohort of COVID-19 hospitalizations without MASLD was identified from NIS after 1: N propensity score matching based on gender, race, and comorbidities, including hypertension, heart failure, diabetes, and cirrhosis. The primary outcomes included inpatient mortality, length of stay, and hospitalization costs. Secondary outcomes included the prevalence of systemic complications. RESULTS A total of 2210 hospitalizations with MASLD were matched to 2210 hospitalizations without MASLD, with a good comorbidity balance. Overall, there was a higher prevalence of severe disease with more intensive care unit admissions (9.5% vs 7.2%, P = 0.007), mechanical ventilation (7.2% vs 5.7%, P = 0.03), and septic shock (5.2% vs 2.7%, P <0.001) in the MASLD cohort than in the non-MASLD cohort. However, there was no difference in mortality (8.6% vs 10%, P = 0.49), length of stay (5 d vs 5 d, P = 0.25), and hospitalization costs (42081.5 $ vs 38614$, P = 0.15) between the MASLD and non-MASLD cohorts. CONCLUSION The presence of MAFLD with or without liver cirrhosis was not associated with increased mortality in COVID-19 hospitalizations; however, there was an increased incidence of severe COVID-19 infection. This data (2020) predates the availability of COVID-19 vaccines, and many MASLD patients have since been vaccinated. It will be interesting to see if these trends are present in the subsequent years of the pandemic.
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Pan, Ziyan, and Mohammed Eslam. "Bringing evidence to the MAFLD‐MASLD debate." Liver International, May 27, 2024. http://dx.doi.org/10.1111/liv.16000.
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Kamal, Enas, Alaa M. Mostafa, and Yasser Fouad. "MAFLD vs. MASLD: Consensus is unlike evidence!" Annals of Hepatology, July 2024, 101527. http://dx.doi.org/10.1016/j.aohep.2024.101527.
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Ramírez-Mejía, Mariana M., Xingshun Qi, Ludovico Abenavoli, Beatriz Barranco-Fragoso, Sandra M. Barbalho, and Nahum Méndez-Sánchez. "NAFLD-MASLD-MAFLD continuum: a swinging pendulum?" Annals of Hepatology, June 2024, 101526. http://dx.doi.org/10.1016/j.aohep.2024.101526.
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Mantovani, Alessandro, Riccardo Morandin, Veronica Fiorio, Maria Giovanna Lando, Salvatore Petta, Pietro Manuel Ferraro, and Giovanni Targher. "Association between metabolic dysfunction-associated steatotic liver disease and risk of urolithiasis: an updated systematic review and meta-analysis." Internal and Emergency Medicine, July 11, 2024. http://dx.doi.org/10.1007/s11739-024-03705-5.
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AbstractEpidemiological studies have reported an association between metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of urolithiasis. However, the magnitude of the risk and whether this risk varies with the severity of MASLD remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between MASLD and urolithiasis. We systematically searched PubMed, Scopus, and Web of Science from database inception to March 31, 2024, using predefined keywords to identify relevant observational studies in which imaging methods or survey questionnaires diagnosed MASLD and urolithiasis. Meta-analysis was performed using random-effects modelling. We identified seven cross-sectional studies and one prospective cohort study with aggregate data on 248,936 adults from different countries. MASLD was significantly associated with an increased risk of prevalent urolithiasis (pooled random-effects odds ratio 1.87, 95% CI 1.34–2.60; I2 = 91%). This association remained significant in those studies whose results were adjusted for age, sex, ethnicity, obesity, diabetes, and other potential confounders. There was a positive graded association between the ultrasonographic severity of MASLD and urolithiasis. Meta-analysis of the single prospective cohort study showed that MAFLD was not associated with risk of developing incident urolithiasis (pooled random-effects hazard ratio 1.08, 95% CI 0.90–1.30), although a significant association was reported in men. Sensitivity analyses did not modify these findings. The funnel plot did not reveal any significant publication bias. This updated meta-analysis provides evidence for a significant association between MASLD and the presence of urolithiasis. Whether MASLD is associated with a higher risk of developing incident urolithiasis remains to be established.
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Mantovani, Alessandro, Riccardo Morandin, Veronica Fiorio, Maria Giovanna Lando, Alberto Gaviraghi, Leonardo Motta, Federico Gobbi, Herbert Tilg, Christopher D. Byrne, and Giovanni Targher. "Association between MASLD and increased risk of serious bacterial infections requiring hospital admission: A meta‐analysis." Liver International, September 11, 2024. http://dx.doi.org/10.1111/liv.16101.
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AbstractBackgroundPrevious studies have reported an association between metabolic dysfunction‐associated steatotic liver disease (MASLD) and the risk of serious bacterial infections. However, the magnitude of the risk and whether this risk varies with the severity of MASLD remains uncertain. We performed a meta‐analysis of observational studies to quantify the association between MASLD and serious bacterial infections requiring hospital admission.MethodsWe systematically searched PubMed, Scopus, Web of Science and Embase from database inception to 1 April 2024, using predefined keywords to identify studies examining the risk of serious bacterial infections among individuals with and without MASLD. MASLD was diagnosed using liver biopsy, imaging or International Classification of Diseases codes. Meta‐analysis was performed using random‐effects modelling.ResultsWe identified six cross‐sectional and two prospective cohort studies with aggregate data on ~26.6 million individuals. MASLD was significantly associated with higher odds of serious bacterial infections (pooled random‐effects odds ratio 1.93, 95% confidence interval [CI] 1.44–2.58; I2 = 93%). Meta‐analysis of prospective cohort studies showed that MAFLD was associated with an increased risk of developing serious bacterial infections (pooled random‐effects hazard ratio 1.80, 95% CI 1.62–2.0; I2 = 89%). This risk further increased across the severity of MASLD, especially the severity of fibrosis (pooled random‐effects hazard ratio 2.42, 95% CI 1.89–2.29; I2 = 92%). These results remained significant after adjusting for age, sex, obesity, diabetes and other potential confounders. Sensitivity analyses did not modify these findings. The funnel plot did not reveal any significant publication bias.ConclusionsThis meta‐analysis shows a significant association between MASLD and an increased risk of serious bacterial infections requiring hospital admission.
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Mori, Kazuma, Yukinori Akiyama, Marenao Tanaka, Tatsuya Sato, Keisuke Endo, Itaru Hosaka, Nagisa Hanawa, Naoya Sakamoto, and Masato Furuhashi. "Deciphering metabolic dysfunction‐associated steatotic liver disease: insights from predictive modeling and clustering analysis." Journal of Gastroenterology and Hepatology, April 17, 2024. http://dx.doi.org/10.1111/jgh.16552.
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AbstractBackground and AimNew nomenclature of steatotic liver disease (SLD) including metabolic dysfunction‐associated SLD (MASLD), MASLD and increased alcohol intake (MetALD), and alcohol‐associated liver disease (ALD) has recently been proposed. We investigated clustering analyses to decipher the complex landscape of SLD pathologies including the former nomenclature of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction‐associated fatty liver disease (MAFLD).MethodsJapanese individuals who received annual health checkups including abdominal ultrasonography (n = 15 788, men/women: 10 250/5538, mean age: 49 years) were recruited.ResultsThe numbers of individuals with SLD, MASLD, MetALD, ALD, NAFLD, and MAFLD were 5603 (35.5%), 4227 (26.8%), 795 (5.0%), 324 (2.1%), 3982 (25.8%), and 4946 (31.3%), respectively. Clustering analyses using t‐distributed stochastic neighbor embedding and K‐means to visually represent interconnections in SLDs uncovered five cluster formations. MASLD and NAFLD mainly shared three clusters including (i) low alcohol intake with relatively low‐grade obesity; (ii) obesity with dyslipidemia; and (iii) dysfunction of glucose metabolism. Both MetALD and ALD displayed one distinct cluster intertwined with alcohol consumption. MAFLD widely shared all of the five clusters. In machine learning‐based analyses using algorithms of random forest and extreme gradient boosting and receiver operating characteristic curve analyses, fatty liver index (FLI), calculated by body mass index, waist circumference, and levels of γ‐glutamyl transferase and triglycerides, was selected as a useful feature for SLDs.ConclusionsThe new nomenclature of SLDs is useful for obtaining a better understanding of liver pathologies and for providing valuable insights into predictive factors and the dynamic interplay of diseases. FLI may be a noninvasive predictive marker for detection of SLDs.
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Sui, Xiaoping, Minqi Wu, Xue Yang, and Yanan Wang. "The Multifaced Roles of Hepatic Macrophages in MASLD." Health and Metabolism, October 29, 2024, 4. https://doi.org/10.53941/hm.2024.100004.
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Review The Multifaced Roles of Hepatic Macrophages in MASLD Xiaoping Sui 1, Minqi Wu 1, Xue Yang 1 and Yanan Wang 1,2,* 1 Med-X Institute, Center for Immunological and Metabolic Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an Jiaotong University, Xi’an, 710061, China 2 Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an Jiaotong University, Xi’an, 710061, China * Correspondence: yanan.wang@xjtu.edu.cn; Tel.: +86-29-8532-3338 Received: 20 September 2024; Revised: 14 October 2024; Accepted: 24 October 2024; Published: 29 October 2024 Abstract: Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming the leading cause of chronic liver disease-related morbidity and mortality globally. It encompasses a spectrum from metabolic dysfunction-associated steatotic liver (MASL) to metabolic dysfunction-associated steatohepatitis (MASH), potentially advancing to cirrhosis and hepatocellular carcinoma. While the pathogenesis of MASLD is complicated and not yet completely elucidated, hepatic macrophages, including liver resident Kupffer cells (Res-KCs) and recruited circulating monocyte-derived macrophages (MoDMs), play a pivotal role in its initiation and progression. Recent advancements in single-cell RNA sequencing have unveiled significant heterogeneity among macrophages and their diverse contributions to MASLD progression. This review delineates the origin and surface markers of hepatic macrophages, emphasizing their multifaceted roles in the pathogenesis of MASLD in steatosis, inflammation and fibrosis. Furthermore, we delve into the latest advancements in pharmacological treatment strategies for patients with MASLD.
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Pan, Ziyan, and Mohammed Eslam. "MAFLD or MASLD: Let the evidence decide again." Annals of Hepatology, June 2024, 101521. http://dx.doi.org/10.1016/j.aohep.2024.101521.
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Chen, Lin, Xuemei Tao, Minghui Zeng, Yuqin Li, Jiaxin Han, Yuekui Wang, Yonggang Liu, et al. "Noninvasive tests maintain high accuracy for advanced fibrosis in chronic hepatitis B patients with different nomenclatures of steatotic liver disease." Journal of Medical Virology 96, no. 4 (April 2024). http://dx.doi.org/10.1002/jmv.29613.
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AbstractMetabolic dysfunction‐associated steatotic liver disease (MASLD) is a new nomenclature proposed in 2023. We aimed to compare the diagnostic efficacy of noninvasive tests (NITs) for advanced fibrosis under different nomenclatures in patients with chronic hepatitis B (CHB). A total of 844 patients diagnosed with CHB and concurrent steatotic liver disease (SLD) by liver biopsy were retrospectively enrolled and divided into four groups. The performances of fibrosis‐4 (FIB‐4), gamma‐glutamyl transpeptidase to platelet ratio index (GPRI), aspartate aminotransferase to platelet ratio index (APRI), and liver stiffness measurement (LSM) were compared among the four groups. The four NITs showed similar diagnostic efficacy for nonalcoholic fatty liver disease (NAFLD), MASLD, and metabolic dysfunction‐associated fatty liver disease (MAFLD) in patients with CHB with advanced fibrosis. LSM showed the most stable accuracy for NAFLD (AUC = 0.842), MASLD (AUC = 0.846), and MAFLD (AUC = 0.863) compared with other NITs (p < 0.05). Among the four NITs, APRI (AUC = 0.841) and GPRI (AUC = 0.844) performed best in patients with CHB & MetALD (p < 0.05). The cutoff value for GPRI in patients with CHB & MetALD was higher than that in the other three groups, while further comparisons of NITs at different fibrosis stages showed that the median GPRI of CHB & MetALD (1.113) at F3‐4 was higher than that in the CHB & MASLD group (0.508) (p < 0.05). Current NITs perform adequately in patients with CHB and SLD; however, alterations in cutoff values for CHB & MetALD need to be noted.
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Copil, Francisca‐Dora, Claudia Campani, Marie Lequoy, Philippe Sultanik, Lorraine Blaise, Mathilde Wagner, Nathalie Ganne‐Carrié, et al. "No correlation between MASLD and poor outcome of Atezolizumab‐Bevacizumab therapy in patients with advanced HCC." Liver International, January 30, 2024. http://dx.doi.org/10.1111/liv.15833.
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AbstractIntroductionIt has been suggested that in patients with hepatocellular carcinoma (HCC) of metabolic aetiology, the efficacy of immunotherapy may be reduced. The aim was to investigate the impact of metabolic‐associated steatotic liver disease (MASLD) and metabolic risk factors (MRF) on the outcomes of Atezolizumab‐Bevacizumab (AtezoBev).MethodsWe collected data from 295 AtezoBev‐treated patients, starting in 2020. MASLD was defined by the current/past presence of MRF, namely BMI ≥ 30 kg/m2, type 2 diabetes, arterial hypertension or dyslipidaemia and no other cause of liver disease (daily alcohol ≤30 g in males and ≤20 g in females). The influence of baseline characteristics on progression (PFS) and overall survival (OS) was assessed by uni/multivariate analysis using the Cox model.ResultsRisk factors for cirrhosis were viral infection in 47%, excessive alcohol consumption in 45% and MASLD in 13%. In the whole cohort, 27% had 1 MRF, 23% had 2 MRF, 15% had 3 MRF and 6% had 4 MRF. Median PFS and OS were 6.5 and 15.6 months, respectively, and similar in patients with or without MASLD in Log rank analysis. The number of MRF or MALSD was not associated with PFS or OS in the univariate analysis. Factors associated with PFS in multivariate analysis included ALBI grade 3 (HR = 1.60, p = .03), AFP (HR = 1.01, p = .01) and metastasis (HR = 1.77, p < .001). During follow‐up, 10% of patients experienced immune‐related adverse events, with age and female gender, but not MRF or MASLD, as independent predictors.ConclusionOur study suggests that the presence of MASLD or the number of MRF did not lead to worse outcomes in advanced HCC patients treated with AtezoBev.
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Abdelhameed, Farah, Chris Kite, Lukasz Lagojda, Alexander Dallaway, Kamaljit Kaur Chatha, Surinderjeet S. Chaggar, Maria Dalamaga, Eva Kassi, Ioannis Kyrou, and Harpal S. Randeva. "Non-invasive Scores and Serum Biomarkers for Fatty Liver in the Era of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD): A Comprehensive Review From NAFLD to MAFLD and MASLD." Current Obesity Reports, May 29, 2024. http://dx.doi.org/10.1007/s13679-024-00574-z.
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Abstract Purpose of Review The prevalence of non-alcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide, making it the leading cause of liver related morbidity and mortality. Currently, liver biopsy is the gold standard for assessing individuals with steatohepatitis and fibrosis. However, its invasiveness, sampling variability, and impracticality for large-scale screening has driven the search for non-invasive methods for early diagnosis and staging. In this review, we comprehensively summarise the evidence on the diagnostic performance and limitations of existing non-invasive serum biomarkers and scores in the diagnosis and evaluation of steatosis, steatohepatitis, and fibrosis. Recent Findings Several non-invasive serum biomarkers and scores have been developed over the last decade, although none has successfully been able to replace liver biopsy. The introduction of new NAFLD terminology, namely metabolic dysfunction-associated fatty liver disease (MAFLD) and more recently metabolic dysfunction-associated steatotic liver disease (MASLD), has initiated a debate on the interchangeability of these terminologies. Indeed, there is a need for more research on the variability of the performance of non-invasive serum biomarkers and scores across the diagnostic entities of NAFLD, MAFLD and MASLD. Summary There remains a significant need for finding valid and reliable non-invasive methods for early diagnosis and assessment of steatohepatitis and fibrosis to facilitate prompt risk stratification and management to prevent disease progression and complications. Further exploration of the landscape of MASLD under the newly defined disease subtypes is warranted, with the need for more robust evidence to support the use of commonly used serum scores against the new MASLD criteria and validation of previously developed scores.
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Jiang, Mingqian, Ziyan Pan, Jacob George, and Mohammed Eslam. "Clinical features and mortality outcomes of patients with MASLD only compared to those with MAFLD and MASLD." Hepatology International, August 28, 2024. http://dx.doi.org/10.1007/s12072-024-10721-2.
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