Advances in Non-Alcoholic Fatty Liver Disease: Pathophysiology, Diagnosis, and Emerging Therapies

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 2236

Special Issue Editors


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Guest Editor
First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
Interests: general surgery; surgical oncology; hepato-pancreato-biliary (HPB) surgery; non-alcoholic fatty liver disease (NAFLD)
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Special Issue Information

Dear Colleagues,

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, correlating strongly with the increasing prevalence of metabolic syndrome. First recognized in the 1980s, NAFLD encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma. Despite its widespread impact, the pathophysiological mechanisms and optimal management strategies for NAFLD are not yet fully understood, necessitating ongoing research and clinical innovation.

This Special Issue aims to provide a platform for the dissemination of the latest research findings and clinical advancements in NAFLD. Our goal is to enhance our understanding of the disease’s etiology, improve diagnostic accuracy, and explore novel therapeutic options. By fostering a multidisciplinary dialogue, this Special Issue seeks to bridge gaps between basic science, clinical practice, and public health approaches to tackle NAFLD comprehensively.

We are particularly interested in studies elucidating the molecular and genetic underpinnings of NAFLD, the role of the gut–liver axis, and the impact of comorbid conditions such as diabetes and cardiovascular disease. Advances in non-invasive diagnostic techniques, including imaging and biomarkers, are also a key focus. Additionally, we seek submissions focused on innovative therapeutic approaches, encompassing lifestyle interventions, pharmacotherapy, and surgical treatments.

We invite original research articles, comprehensive reviews, and meta-analyses addressing the aforementioned topics. Submissions should offer new insights into the mechanisms of NAFLD, present data on novel diagnostic and therapeutic strategies, or provide critical evaluations of current knowledge and future directions.

Dr. Ioannis Katsaros
Dr. Dimitrios Schizas
Guest Editors

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Keywords

  • non-alcoholic fatty liver disease (NAFLD)
  • metabolic dysfunction-associated fatty liver disease (MAFLD)
  • steatohepatitis
  • metabolic syndrome
  • insulin resistance
  • apoptosis/cell death

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Published Papers (2 papers)

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Research

19 pages, 1229 KiB  
Article
Effects of Intermittent Fasting on Liver Steatosis and Fibrosis, Serum FGF-21 and Autophagy Markers in Metabolic Dysfunction-Associated Fatty Liver Disease: A Randomized Controlled Trial
by Tugce Ozlu Karahan, Elvan Yilmaz Akyuz, Demet Yilmaz Karadag, Yusuf Yilmaz and Fatih Eren
Life 2025, 15(5), 696; https://doi.org/10.3390/life15050696 - 25 Apr 2025
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Abstract
Background: This randomized controlled study sought to determine the effect of intermittent fasting on anthropometric measurements, fibroblast growth factor (FGF)-21, and autophagy markers, as well as on hepatic steatosis and fibrosis levels in overweight or obese patients with metabolic dysfunction-associated fatty liver disease [...] Read more.
Background: This randomized controlled study sought to determine the effect of intermittent fasting on anthropometric measurements, fibroblast growth factor (FGF)-21, and autophagy markers, as well as on hepatic steatosis and fibrosis levels in overweight or obese patients with metabolic dysfunction-associated fatty liver disease (MAFLD). Methods: Patients were randomly assigned into two groups: received a dietary treatment involving 22–25 kcal/kg/day of energy for 8 weeks and followed the same dietary intervention and a 16:8 pattern. The extent of hepatic steatosis and fibrosis was determined using transient elastography on a FibroScan® device. The controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), determined by transient elastography, reflect hepatic steatosis and fibrosis, respectively. In duplicate, serum levels of FGF-21, Beclin-1, and ATG-5 were determined using enzyme-linked immunosorbent assay. Results: The study included 48 patients with a mean age of 48.2 ± 1.4 years (27 female and 21 male). Improvements in anthropometric measurement and CAP and LSM levels and a decrease in serum FGF-21 levels were found in both groups (p < 0.05). Changes in the CAP and FGF-21 levels were higher in the energy + time-restricted diet group (p < 0.05). Autophagy-related protein (ATG)-5 levels increased only in the energy + time-restricted diet group [(0.74 (0.46–1.29) ng/mL vs. 0.95 (0.73–1.32) ng/mL, p = 0.03]. Conclusions: Intermittent fasting was potentially practical in the management of MAFLD. In particular, changes in FGF-21 and ATG-5 levels indicate the potential of intermittent fasting to regulate metabolic processes and autophagy. However, methodological limitations should be taken into consideration when interpreting the study results. Full article
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17 pages, 1329 KiB  
Article
Lean MASLD and IBD: Exploring the Intersection of Metabolic Dysfunction and the Gut–Liver Axis
by Adrian Rotaru, Remus Stafie, Ermina Stratina, Sebastian Zenovia, Robert Nastasa, Horia Minea, Laura Huiban, Tudor Cuciureanu, Cristina Muzica, Stefan Chiriac, Irina Girleanu, Ana-Maria Singeap, Catalin Sfarti, Carol Stanciu and Anca Trifan
Life 2025, 15(2), 288; https://doi.org/10.3390/life15020288 - 12 Feb 2025
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Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) challenges traditional paradigms by manifesting in lean individuals. The link between MASLD and inflammatory bowel disease (IBD) underscores the importance of the gut–liver axis in disease progression and chronic inflammation. This study evaluates MASLD prevalence, clinical characteristics, [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) challenges traditional paradigms by manifesting in lean individuals. The link between MASLD and inflammatory bowel disease (IBD) underscores the importance of the gut–liver axis in disease progression and chronic inflammation. This study evaluates MASLD prevalence, clinical characteristics, and diagnostic predictors in lean individuals with and without IBD. This prospective study included 387 lean patients. Hepatic steatosis and fibrosis were assessed using vibration-controlled transient elastography (VCTE). Anthropometric, clinical and biological data were compared. The subgroup analyses focused on MASLD patients with and without IBD. MASLD was present in 34.1% of lean individuals and 46.3% of those who were lean with IBD. MASLD patients had increased visceral adiposity (CUN-BAE: 31.21 ± 5.42 vs. 24.57 ± 6.49, p < 0.001) and metabolic dysfunction, including dyslipidemia and elevated fasting glucose. IBD-MASLD patients exhibited greater hepatic steatosis and systemic inflammation. CUN-BAE outperformed FLI and HSI in predicting liver steatosis, especially in IBD patients (AUC = 0.806). Lean MASLD, particularly in IBD patients, highlights the need for tailored diagnostic and management strategies. The gut–liver axis plays a key role in disease progression, and the CUN-BAE index demonstrates superior accuracy for identifying liver steatosis. Full article
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