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Biomedicines
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New Insights Into Non-Alcoholic Fatty Liver Diseases
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New Insights Into Non-Alcoholic Fatty Liver Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 9299

Special Issue Editors

Dr. Hazem Ayesh

E-Mail Website
Guest Editor
Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA
Interests: NAFLD; non-alcoholic fatty liver disease; metabolic pathways; molecular mechanisms; genetic polymorphisms; population disparities; risk stratification; clinical challenges; nutritional interventions; triglyceride glucose index
Dr. Robert Schierwagen

E-Mail Website
Guest Editor
Department of Internal Medicine B, University of Münster, 48149 Münster, Germany
Interests: non-alcoholic fatty liver disease; portal hypertension; janus-kinase 2; mas receptor

Special Issue Information

Dear Colleagues,

Non-alcoholic fatty liver disease (NAFLD) poses a significant global health challenge, affecting patients across all age groups, from children to middle-aged and older adults, and is linked to diabetes and cardiovascular diseases. Clinical challenges, including underdiagnosis and the imperative for precise risk stratification, highlight the urgency of comprehending molecular mechanisms, population disparities, and metabolic pathways in the early stages of pathogenesis. This Special Issue delves into essential aspects, focusing on metabolic pathways influencing fatty liver, deciphering genetic contributions to pathogenesis, and exploring population-specific differences. Additionally, we illuminate the crucial role of various metabolic pathways in NAFLD pathogenesis, aiming to deepen our understanding of treatment options. Insights into nutritional interventions, the triglyceride glucose index, and genetic polymorphisms emerge as pivotal elements for addressing NAFLD progression, emphasizing the need for tailored nutritional programs and targeted pharmacological interventions.

Dr. Hazem Ayesh
Dr. Robert Schierwagen
Guest Editors

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Keywords

  • NAFLD
  • non-alcoholic fatty liver disease
  • metabolic pathways
  • molecular mechanisms
  • genetic polymorphisms
  • population disparities
  • risk stratification
  • clinical challenges
  • nutritional interventions
  • triglyceride glucose index

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Published Papers (5 papers)

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Research

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14 pages, 1531 KiB  
Article
Trends and Disparities in Cardiovascular Disease in US Adults with Metabolic Dysfunction-Associated Steatotic Liver Disease
by Yanbing Zhang, Xinge Zhang, Chuiguo Huang and Lei Zhu
Biomedicines 2025, 13(4), 956; https://doi.org/10.3390/biomedicines13040956 - 13 Apr 2025
Viewed by 477
Abstract
Background/Objectives: Recently, the term metabolic dysfunction-associated steatotic liver disease (MASLD) has replaced non-alcoholic fatty liver disease (NAFLD). Through analysis of the trends and disparities regarding cardiovascular disease (CVD) among individuals with MASLD, identifying the leading cause of death in this population is [...] Read more.
Background/Objectives: Recently, the term metabolic dysfunction-associated steatotic liver disease (MASLD) has replaced non-alcoholic fatty liver disease (NAFLD). Through analysis of the trends and disparities regarding cardiovascular disease (CVD) among individuals with MASLD, identifying the leading cause of death in this population is crucial. Methods: We conducted a cross-sectional analysis of National Health and Nutrition Examination Survey (NHANES) III (1988–1994) and NHANES 2017–2020 data. MASLD was identified by using clinical profiles and liver ultrasonography to exclude other liver diseases. We estimated the prevalence of CVD among individuals with MASLD and calculated the prevalence ratios for those with and without MASLD. Results: In 2017–2020, MASLD affected 31.2% or 61.9 million US adults, and 17.0% (95% confidence interval: 13.7–20.3%) of these individuals had CVD. The absolute CVD prevalence in individuals with MASLD doubled from that in the NHANES III cohort, which was 8.7% (6.4%, 10.9%). These increases were especially notable among older adults, non-Hispanic whites, and those with higher education and income. Individuals with MASLD had a higher prevalence of total CVD than those without MASLD, even after adjusting for socioeconomic and metabolic factors. These differences were more pronounced in younger age groups. Conclusions: This study revealed a doubled 30-year trend in CVD prevalence among adults with MASLD in the US. Sociodemographic disparities emphasize the need for tailored screening, prevention, and policy measures to address gaps and promote cardiovascular health in this population. Full article
(This article belongs to the Special Issue New Insights Into Non-Alcoholic Fatty Liver Diseases)
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16 pages, 1782 KiB  
Article
Targeting Insulin Resistance and Liver Fibrosis: CKD Screening Priorities in MASLD
by Tianyuan Yang, Bingqing Yang, Jingya Yin, Chenxue Hou and Qi Wang
Biomedicines 2025, 13(4), 842; https://doi.org/10.3390/biomedicines13040842 - 1 Apr 2025
Viewed by 404
Abstract
Background and Aims: Chronic kidney disease (CKD) is a recognized extra-hepatic disease of nonalcoholic fatty liver disease (NAFLD). With the redefinition of NAFLD as metabolic dysfunction-associated steatotic liver disease (MASLD), the importance of cardiovascular metabolic factors in MASLD has been highlighted. However, whether [...] Read more.
Background and Aims: Chronic kidney disease (CKD) is a recognized extra-hepatic disease of nonalcoholic fatty liver disease (NAFLD). With the redefinition of NAFLD as metabolic dysfunction-associated steatotic liver disease (MASLD), the importance of cardiovascular metabolic factors in MASLD has been highlighted. However, whether MASLD remains independently associated with the prevalence of CKD is yet to be determined. Method: We analyzed data from 6567 non-pregnant adults from the National Health and Nutrition Examination Survey 2017–2020. MASLD was identified using liver ultrasound transient elastography and five cardiovascular risk factors. Multivariate logistic regression, subgroup analysis, and restricted cubic splines were employed to explore the associations and interactions within the data. Results: The prevalence of CKD across MASLD subgroups with different combinations of cardiometabolic risk factors varied. Univariate regression analysis indicated a significant association between MASLD and CKD (OR: 1.68, p < 0.001). This association was not significant after adjusting for diabetes (OR: 0.94, p = 0.74) or insulin resistance (OR: 1.00, p = 0.98) and was not significant in the fully adjusted model (OR: 0.87, p = 0.64). Subgroup analysis confirmed insulin resistance as a modifier in the MASLD-CKD relationship (p for interaction = 0.02). Multivariate analysis revealed that liver stiffness measurements (LSMs) were independently associated with CKD. LSM values showed an S-shaped correlation with CKD, with risk increasing above the 8.612 kPa threshold. Conclusions: This study suggests that the direct relationship between MASLD and CKD diminished when accounting for insulin resistance. Nevertheless, liver fibrosis emerges as an independent CKD risk factor, emphasizing the critical need for targeted CKD screening among MASLD patients, particularly those with insulin resistance or advanced fibrosis. Full article
(This article belongs to the Special Issue New Insights Into Non-Alcoholic Fatty Liver Diseases)
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16 pages, 1878 KiB  
Article
Feasibility of Serum Galectin-1 as a Diagnostic Biomarker for Metabolic Dysfunction-Associated Steatotic Liver Disease: A Study on a Segment of the Chinese Population Using Convenience Sampling
by Ting Zeng, Fang Li, Min Yang, Yao Wu, Wei Cui, Huaming Mou and Xiaohe Luo
Biomedicines 2025, 13(2), 425; https://doi.org/10.3390/biomedicines13020425 - 10 Feb 2025
Viewed by 938
Abstract
Background/Objectives: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is commonly considered as a hepatic manifestation of metabolic syndrome, posing considerable public health and economic challenges due to its high prevalence. This study investigates the diagnostic potential of serum galectin-1 levels in MASLD patients. [...] Read more.
Background/Objectives: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is commonly considered as a hepatic manifestation of metabolic syndrome, posing considerable public health and economic challenges due to its high prevalence. This study investigates the diagnostic potential of serum galectin-1 levels in MASLD patients. Methods: A total of 128 participants were analyzed for this study, comprising 68 healthy controls and 60 MASLD patients. The hepatic steatosis index (HSI) and fatty liver index (FLI) were calculated to evaluate the liver steatosis. Serum galectin-1 levels were measured using an enzyme-linked immunosorbent assay. We additionally conducted a comparative analysis of galectin-1 mRNA and protein expression levels in the liver tissue between the mouse models of MASLD, including ob/ob mice (n = 6), high-fat diet-fed C57 mice (n = 6), and the control group (n = 6). Results: Average serum galectin-1 levels significantly differed between groups, with lower values in the controls (p < 0.01). The frequency of MASLD increased with higher quartiles of galectin-1 levels (p < 0.01). The correlation analysis showed a positive relationship between serum galectin-1 and both HSI and FLI (p < 0.01). The multivariate logistic regression indicated that elevated galectin-1 was associated with an increased risk of MASLD (p < 0.01), yielding an area under the receiver operating characteristic curve for predicting MASLD at 0.745 (95% CI: 0.662–0.829). Hepatic galectin-1 levels were also elevated in the MASLD mouse model at both transcript and protein levels (p < 0.01). Conclusions: Serum galectin-1 can be used as a potential biomarker to help diagnose MASLD. Full article
(This article belongs to the Special Issue New Insights Into Non-Alcoholic Fatty Liver Diseases)
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Review

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22 pages, 524 KiB  
Review
Dietary Interventions and Physical Activity as Crucial Factors in the Prevention and Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease
by Paweł Rajewski, Jakub Cieściński, Piotr Rajewski, Szymon Suwała, Alicja Rajewska and Maciej Potasz
Biomedicines 2025, 13(1), 217; https://doi.org/10.3390/biomedicines13010217 - 16 Jan 2025
Cited by 5 | Viewed by 1933
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and affects nearly 30% of the adult population and 10% of the pediatric population. It is estimated that this number will double by 2030. MASLD is one of the [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and affects nearly 30% of the adult population and 10% of the pediatric population. It is estimated that this number will double by 2030. MASLD is one of the leading causes of hepatocellular carcinoma, cirrhosis, and liver transplantation, as well as a significant risk factor for cardiovascular disease and mortality. Due to the ever-increasing number of patients, the long-term asymptomatic course of the disease, serious complications, and lack of preventive programs, as well as insufficient awareness of the disease among patients and doctors themselves, MASLD is a growing interdisciplinary problem and a real challenge for modern medicine. The main cause of MASLD is an inappropriate lifestyle—inadequate nutrition and insufficient physical activity, which lead to various components of metabolic syndrome. Lifestyle changes—appropriate diet, weight reduction, and systematic physical activity—are also the basis for the prevention and treatment of MASLD. Hence, in recent years, so much importance has been attached to lifestyle medicine, to non-pharmacological treatment as prevention of lifestyle diseases. The narrative review presents possible therapeutic options for non-pharmacological management in the prevention and treatment of MASLD. The best documented and available diets used in MASLD were discussed, focusing on the benefits and drawbacks of the Mediterranean, high-protein, ketogenic, and intermittent fasting diets. In addition, the most recent recommendations regarding physical activity are summarized. Full article
(This article belongs to the Special Issue New Insights Into Non-Alcoholic Fatty Liver Diseases)
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Other

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16 pages, 1970 KiB  
Systematic Review
Comparative Analysis of Resmetirom vs. FGF21 Analogs vs. GLP-1 Agonists in MASLD and MASH: Network Meta-Analysis of Clinical Trials
by Hazem Ayesh, Azizullah Beran, Sajida Suhail, Suhail Ayesh and Kevin Niswender
Biomedicines 2024, 12(10), 2328; https://doi.org/10.3390/biomedicines12102328 - 14 Oct 2024
Cited by 1 | Viewed by 4746
Abstract
Introduction: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic-Dysfunction Associated Steatohepatitis (MASH) are linked to obesity, type 2 diabetes, and metabolic syndrome, increasing liver-related morbidity and cardiovascular risk. Recent therapies, including Resmetirom, FGF21 analogs, and GLP-1 agonists, have shown promise. This network meta-analysis [...] Read more.
Introduction: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic-Dysfunction Associated Steatohepatitis (MASH) are linked to obesity, type 2 diabetes, and metabolic syndrome, increasing liver-related morbidity and cardiovascular risk. Recent therapies, including Resmetirom, FGF21 analogs, and GLP-1 agonists, have shown promise. This network meta-analysis evaluates their comparative efficacy and safety. Methods: A literature search was conducted across PubMed, Scopus, Web of Science, and Cochrane Library. Included clinical trials addressed MASLD or MASH with Resmetirom, FGF21 analogs, or GLP-1 agonists. Statistical analyses used a random-effects model, calculating mean differences (MD) and relative risks (RR), with heterogeneity assessed using τ2, I2, and Q statistics. Results: MASH resolution was significantly higher for FGF21 (RR 4.84, 95% CI: 2.59 to 9.03), Resmetirom showed the most significant reduction in MRI-PDFF (MD −18.41, 95% CI: −23.60 to −13.22) and >30% fat reduction (RR 3.56, 95% CI: 2.41 to 5.26). Resmetirom significantly reduced ALT (MD −15.71, 95% CI: −23.30 to −8.13), AST (MD −12.28, 95% CI: −21.07 to −3.49), and GGT (MD −19.56, 95% CI: −34.68 to −4.44). FGF21 and GLP-1 also reduced these markers. Adverse events were significantly higher with Resmetirom (RR 1.47, 95% CI: 1.24 to 1.74), while GLP-1 and FGF21 showed non-significant trends towards increased risk. Conclusions: Resmetirom and FGF21 show promise in treating MASLD and MASH, with Resmetirom particularly effective in reducing liver fat and improving liver enzymes. GLP-1 agonists also show benefits but to a lesser extent. Further long-term studies are needed to validate these findings and assess cost-effectiveness. Full article
(This article belongs to the Special Issue New Insights Into Non-Alcoholic Fatty Liver Diseases)
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