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12 pages, 797 KiB  
Article
Comparison Between Transient Elastography and Point Shear Wave Elastography in the Assessment of Liver Fibrosis According to the Grade of Liver Steatosis
by Giuseppe Losurdo, Antonino Castellaneta, Claudia Di Nuccio, Paola Dell’Aquila, Ilaria Ditonno, Domenico Novielli, Antonio Continisio, Margherita De Bellis, Alfredo Di Leo, Mariabeatrice Principi and Michele Barone
J. Clin. Med. 2025, 14(15), 5417; https://doi.org/10.3390/jcm14155417 (registering DOI) - 1 Aug 2025
Abstract
Background: Transient elastography (TE), using Fibroscan® and point shear wave elastography (pSWE), are two techniques used to estimate liver fibrosis. The aim of our study was to compare, for the first time, these two techniques in Metabolic Dysfunction-Associated Steatotic Liver Disease [...] Read more.
Background: Transient elastography (TE), using Fibroscan® and point shear wave elastography (pSWE), are two techniques used to estimate liver fibrosis. The aim of our study was to compare, for the first time, these two techniques in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), stratifying the analysis on the basis of the grades of steatosis. Methods: We recruited 85 consecutive MAFLD patients who underwent liver stiffness (LS) measurement performed by Fibroscan® and pSWE on the same day. Severity of steatosis was estimated by Fibroscan® and expressed as controlled attenuation parameter (CAP), ranging from S0 to S3. Spearman’s “r” coefficient was used to calculate the correlation and Bland–Altman graphs was used to evaluate the agreement. Results: In general, the correlation and agreement between Fibroscan® and pSWE were substantial (r = 0.66, p < 0.001 and bias= −0.64 ± 2.48, respectively). When data were analyzed according to the grade of steatosis, an increasing significant correlation was observed going from S0 to S2 (r = 0.79, r = 0.81, and r = 0.85, respectively), whereas a low correlation and agreement were observed for S3 patients (r = 0.48, p = 0.003, bias= −0.95 ± 2.51). Conclusions: Fibroscan® and pSWE are equivalent techniques to estimate liver fibrosis in patients with mild to moderate steatosis, while in presence of severe steatosis their agreement is low. Full article
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12 pages, 257 KiB  
Article
Evaluating the Diagnostic Potential of the FIB-4 Index for Cystic Fibrosis-Associated Liver Disease in Adults: A Comparison with Transient Elastography
by Stephen Armstrong, Kingston Rajiah, Aaron Courtenay, Nermeen Ali and Ahmed Abuelhana
J. Clin. Med. 2025, 14(15), 5404; https://doi.org/10.3390/jcm14155404 (registering DOI) - 31 Jul 2025
Abstract
Background/Objectives: Cystic fibrosis-associated liver disease (CFLD) is a significant complication in individuals with cystic fibrosis (CF), contributing to morbidity and mortality, with no universally accepted, reliable, non-invasive diagnostic tool for early detection. Current diagnostic methods, including liver biopsy and imaging, remain resource-intensive [...] Read more.
Background/Objectives: Cystic fibrosis-associated liver disease (CFLD) is a significant complication in individuals with cystic fibrosis (CF), contributing to morbidity and mortality, with no universally accepted, reliable, non-invasive diagnostic tool for early detection. Current diagnostic methods, including liver biopsy and imaging, remain resource-intensive and invasive. Non-invasive biomarkers like the Fibrosis-4 (FIB-4) index have shown promise in diagnosing liver fibrosis in various chronic liver diseases. This study explores the potential of the FIB-4 index to predict CFLD in an adult CF population and assesses its correlation with transient elastography (TE) as a potential diagnostic tool. The aim of this study is to evaluate the diagnostic performance of the FIB-4 index for CFLD in adults with CF and investigate its relationship with TE-based liver stiffness measurements (LSM). Methods: The study was conducted in a regional cystic fibrosis unit, including 261 adult CF patients. FIB-4 scores were calculated using an online tool (mdcalc.com) based on patient age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. In parallel, 29 patients underwent liver stiffness measurement using TE (Fibroscan®). Statistical analyses included non-parametric tests for group comparisons and Pearson’s correlation to assess the relationship between FIB-4 scores and TE results. Results: The mean FIB-4 score in patients diagnosed with CFLD was higher (0.99 ± 0.83) compared to those without CFLD (0.64 ± 0.38), although the difference was not statistically significant (p > 0.05). TE results for CFLD patients (5.9 kPa) also did not show a significant difference compared to non-CFLD patients (4.2 ± 1.6 kPa, p > 0.05). However, a positive correlation (r = 0.401, p = 0.031) was found between FIB-4 scores and TE-based LSM, suggesting a potential complementary diagnostic role. Conclusions: The FIB-4 index, while not sufficient as a standalone diagnostic tool for CFLD in adults with CF, demonstrates potential when used in conjunction with other diagnostic methods like TE. This study introduces a novel approach for integrating non-invasive diagnostic markers in CF care, offering a pathway for future clinical practice. The combination of FIB-4 and TE could serve as an accessible, cost-effective alternative to invasive diagnostic techniques, improving early diagnosis and management of CFLD in the CF population. Additionally, future research should explore the integration of these tools with emerging biomarkers and clinical features to refine diagnostic algorithms for CFLD, potentially reducing reliance on liver biopsies and improving patient outcomes. Full article
(This article belongs to the Section Intensive Care)
14 pages, 267 KiB  
Article
Impact of Short-Term Liraglutide Therapy on Non-Invasive Markers of Liver Fibrosis in Patients with MASLD
by Aleksandra Bołdys, Maciej Borówka, Łukasz Bułdak and Bogusław Okopień
Metabolites 2025, 15(8), 510; https://doi.org/10.3390/metabo15080510 (registering DOI) - 31 Jul 2025
Abstract
Background/Objectives: Affecting close to one-third of the global population, metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disorder linked to metabolic risk factors such as obesity and insulin resistance. Liver fibrosis is a key determinant of prognosis, and [...] Read more.
Background/Objectives: Affecting close to one-third of the global population, metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disorder linked to metabolic risk factors such as obesity and insulin resistance. Liver fibrosis is a key determinant of prognosis, and its progression increases the risk of liver-related and overall mortality. This exploratory research evaluated the potential impact of a 3-month intervention involving dietary counseling and liraglutide therapy on liver fibrosis and related metabolic markers in patients with MASLD and obesity without diabetes. Methods: In this prospective, single-arm exploratory intervention, 28 adult patients with MASLD and obesity received structured dietary counseling and daily subcutaneous liraglutide for 12 weeks. Liver fibrosis was assessed using non-invasive indices (FIB-4, APRI, BARD, ELF) and transient elastography performed with the FibroScan® device (Echosens, Paris, France). Results: After 3 months, a significant reduction in liver stiffness (−7.14%, p < 0.05) and ELF score (from 6.71 to 6.63; −1.2%, p < 0.05) was observed. APRI (p = 0.06) and FIB-4 (p = 0.09) showed trends toward improvement, while the BARD score and AST/ALT ratio remained unchanged. Conclusions: Short-term liraglutide therapy combined with lifestyle modification may improve early-stage liver fibrosis in patients with MASLD and obesity, as indicated by reductions in liver stiffness and ELF score. These preliminary findings highlight the potential of advanced non-invasive fibrosis markers in monitoring treatment response. However, as an exploratory study, results should be interpreted with caution, and larger, long-term trials are needed to confirm these observations and evaluate efficacy in patients with more advanced fibrosis stages. Full article
14 pages, 1004 KiB  
Article
Beyond Weight Loss: Comparative Effects of Tirzepatide Plus Low-Energy Ketogenic Versus Low-Calorie Diet on Hepatic Steatosis and Stiffness in MASLD
by Luigi Schiavo, Biagio Santella, Monica Mingo, Gianluca Rossetti, Marcello Orio and Vincenzo Pilone
Nutrients 2025, 17(15), 2409; https://doi.org/10.3390/nu17152409 - 24 Jul 2025
Viewed by 343
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition globally, strongly linked to obesity, insulin resistance, and type 2 diabetes (T2D). Tirzepatide (TZP), a dual GIP/GLP-1 receptor agonist, improves glycemic control and reduces body weight and the [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition globally, strongly linked to obesity, insulin resistance, and type 2 diabetes (T2D). Tirzepatide (TZP), a dual GIP/GLP-1 receptor agonist, improves glycemic control and reduces body weight and the liver fat content in patients with obesity and T2D. However, its effect on liver-specific outcomes such as steatosis and fibrosis remains incompletely characterized. Low-energy ketogenic therapy (LEKT), a nutritional strategy characterized by carbohydrate restriction and nutritional ketosis, may enhance hepatic β-oxidation and reduce hepatic lipogenesis. To date, however, the combination of TZP and LEKT has not been studied in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to compare the hepatic and metabolic effects of TZP combined with either LEKT or a conventional low-calorie diet (LCD) over a 12-week period. Methods: Sixty adult patients with MASLD undergoing TZP therapy were prospectively assigned to either an LEKT or a conventional LCD, with 30 participants per group. As primary endpoints, the controlled attenuation parameter (CAP, an index of hepatic steatosis) and liver stiffness measurement (LSM, an index of liver fibrosis) were assessed at the baseline and after 12 weeks using FibroScan®. Secondary outcomes included changes in body mass index (BMI), glycated hemoglobin (HbA1c), and liver enzymes. Adherence to both diet and pharmacological treatment, as well as tolerability, were systematically monitored throughout the intervention period. Results: Both groups showed significant reductions in body weight (TZP + LEKT, p = 0.0289; TZP + LCD, p = 0.0278), with no significant intergroup difference (p = 0.665). CAP and LSM improved significantly in both groups, but reductions were greater in the TZP + LEKT group (CAP −12.5%, p < 0.001; LSM −22.7%, p < 0.001) versus LCD (CAP −6.7%, p = 0.014; LSM −9.2%, p = 0.022). Between-group differences were statistically significant for both CAP (p = 0.01) and LSM (p = 0.03). Conclusions: Based on these preliminary findings, we support the hypothesis that the combination of TZP and LEKT may be superior to TZP with an LCD in reducing hepatic steatosis and stiffness in individuals with obesity. Full article
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40 pages, 1040 KiB  
Systematic Review
Comparing FIB-4, VCTE, pSWE, 2D-SWE, and MRE Thresholds and Diagnostic Accuracies for Detecting Hepatic Fibrosis in Patients with MASLD: A Systematic Review and Meta-Analysis
by Mitchell Patrick Wilson, Ranjit Singh, Shyam Mehta, Mohammad Hassan Murad, Christopher Fung and Gavin Low
Diagnostics 2025, 15(13), 1598; https://doi.org/10.3390/diagnostics15131598 - 24 Jun 2025
Viewed by 1827
Abstract
Objectives: To compare thresholds and accuracies of FIB-4, vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2D shear wave elastography (2D-SWE), and MR elastography (MRE) for detecting hepatic fibrosis in patients with MASLD. Materials and Methods: Systematic searching of MEDLINE, [...] Read more.
Objectives: To compare thresholds and accuracies of FIB-4, vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2D shear wave elastography (2D-SWE), and MR elastography (MRE) for detecting hepatic fibrosis in patients with MASLD. Materials and Methods: Systematic searching of MEDLINE, EMBASE, Cochrane Library, Scopus, and the gray literature from inception to March 2024 was performed. Studies evaluating accuracies of FIB-4, VCTE, 2D-SWE, pSWE, and/or MRE for detecting significant (≥F2) and/or advanced (≥F3) hepatic fibrosis in MASLD patients compared to histology were identified. Full-text review and data extraction were performed independently by two reviewers. Multivariate meta-analysis and subgroup analyses were performed using index test and fibrosis grading. Risk of bias was assessed using QUADAS-2. Results: 207 studies with over 80,000 patient investigations were included. FIB-4 1.3 threshold sensitivity was 71% (95% CI 66–75%) for detecting advanced hepatic fibrosis, which improved to 88% (85–91%) using a <0.75 threshold. FIB-4 specificity using a 2.67 threshold was 96% (94–97%). Sensitivities of 88–91% were achieved using thresholds of 3.2 kPa for pSWE, 4.92 kPa for 2D-SWE, 7.18 kPa for VCTE, and 2.32 kPa for MRE. No significant differences were identified for sensitivities in subgroup analysis with thresholds between 7 and 9 kPa. Most imaging-based studies were high risk of bias for the index test. Conclusions: A FIB-4 threshold of <0.75 and modality-dependent thresholds (VCTE < 7 kPa; pSWE <3 kPa; 2D-SWE <5 kPa; and MRE <2.5 kPa) would achieve sensitivities of around 90% when defining low-risk MASLD in population screening. A modified two-tier algorithm aligning with existing Society of Radiologists in Ultrasound guidelines would improve risk stratification accuracies compared to existing guidelines by European and American liver societies. Full article
(This article belongs to the Special Issue Diagnostic Imaging in Gastrointestinal and Liver Diseases)
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14 pages, 267 KiB  
Article
Liraglutide Reduces Liver Steatosis and Improves Metabolic Indices in Obese Patients Without Diabetes: A 3-Month Prospective Study
by Aleksandra Bołdys, Łukasz Bułdak, Michał Nicze and Bogusław Okopień
Int. J. Mol. Sci. 2025, 26(12), 5883; https://doi.org/10.3390/ijms26125883 - 19 Jun 2025
Viewed by 577
Abstract
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a leading cause of liver cirrhosis, with its global prevalence rising due to obesity, insulin resistance, and type 2 diabetes mellitus. While bariatric surgery remains effective for weight loss, Glucagon-Like Peptide-1 analogs such as liraglutide are [...] Read more.
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a leading cause of liver cirrhosis, with its global prevalence rising due to obesity, insulin resistance, and type 2 diabetes mellitus. While bariatric surgery remains effective for weight loss, Glucagon-Like Peptide-1 analogs such as liraglutide are emerging as promising pharmacological treatments. This study aimed to evaluate the effects of a 3-month liraglutide treatment on liver steatosis, subclinical markers, and insulin resistance in non-diabetic, obese patients with MASLD. Twenty-eight obese adults (BMI ≥ 30 kg/m2) were treated with daily subcutaneous liraglutide injections for three months. Liver steatosis was assessed using FibroScan® (CAP score) and non-invasive indices (Hepatic Steatosis Index—HSI, and NAFLD Liver Fat Score—NLFS). Insulin resistance was measured with conventional markers (HOMA-IR, QUICKI) and triglyceride-based indices (METS-IR, TyG). Liraglutide significantly reduced liver steatosis (CAP score: 305 to 268 dB/m, p < 0.05) and improved HSI, while NLFS remained unchanged. Despite significant weight loss, traditional insulin resistance markers remained unchanged, while METS-IR and TyG improved. Liraglutide therapy improved liver steatosis and triglyceride-based insulin resistance markers in non-diabetic obese patients with MASLD. These findings support the use of liraglutide, highlighting the value of personalized approaches and alternative insulin resistance assessments in MASLD management. Full article
(This article belongs to the Special Issue Molecular Pharmacology of Human Metabolism Diseases)
13 pages, 960 KiB  
Article
Immunological and Virological Responses in Patients with Monoinfection and Coinfection with Hepatitis B and C Viruses in the Brazilian Amazon
by Joseane R. Silva, Regiane M. A. Sampaio, Patrícia F. Nunes, Vanessa S. Guimarães, Camila Carla da Silva Costa, Evelen da Cruz Coelho, Micheline Vale de Souza, Luana Wanessa Cruz Almeida, Hellen T. Fuzii, Aldemir Branco Oliveira Filho and Luisa C. Martins
Trop. Med. Infect. Dis. 2025, 10(6), 166; https://doi.org/10.3390/tropicalmed10060166 - 13 Jun 2025
Viewed by 811
Abstract
Infections with the Hepatitis B (HBV) and Hepatitis C (HCV) viruses share some transmission routes, which is why coinfection with these viruses becomes common, especially in endemic areas. This study evaluated the immunological response profile, viral load, and liver damage in groups monoinfected [...] Read more.
Infections with the Hepatitis B (HBV) and Hepatitis C (HCV) viruses share some transmission routes, which is why coinfection with these viruses becomes common, especially in endemic areas. This study evaluated the immunological response profile, viral load, and liver damage in groups monoinfected with HBV or HCV and in those co-infected with HBV/HCV. The groups were composed of 22 patients monoinfected by HCV, 22 patients monoinfected by HBV, and 34 co-infected by HBV/HCV, according to serological markers and molecular biology tests. The study was carried out from December 2017 to October 2019. Virus detection employed enzyme immunoassay, Enzyme-Linked Immunosorbent Assay (ELISA), and real-time PCR, while liver function and fibrosis were assessed using biochemical tests and Fibroscan. To research the immunological profile, cytokines were quantified using the BIO-Plex Pro Human Cytokine. Comparing the groups, both mono- and co-infected patients exhibited a Th1 immune response profile. HCV monoinfection notably showed significantly elevated serum levels of INF-γ (p < 0.01) and TNF-α (p < 0.01). The viral load was significantly higher in the HCV monoinfected group when compared to the other groups. Regarding liver damage, patients with a high level of fibrosis (F4) presented significant levels of cytokines INF-γ (p < 0.001), IL-17 (p < 0.0001), and TNF-α (p < 0.0001). Full article
(This article belongs to the Section Infectious Diseases)
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19 pages, 1427 KiB  
Article
Exploring the Potential of Oral Butyrate Supplementation in Metabolic Dysfunction-Associated Steatotic Liver Disease: Subgroup Insights from an Interventional Study
by Miloš Mitrović, Verica Stanković Popović, Sanja Erceg, Milena Perišić Mitrović, Ana Dobrosavljević, Andrej Stupar, Petra Vuković, Dušan Zlatković and Petar Svorcan
Int. J. Mol. Sci. 2025, 26(12), 5561; https://doi.org/10.3390/ijms26125561 - 10 Jun 2025
Viewed by 943
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common cause of chronic liver disease and is closely associated with metabolic abnormalities and cardiovascular risks. Butyrate, a short-chain fatty acid produced by gut microbiota, has the potential to enhance liver health by modulating inflammation [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common cause of chronic liver disease and is closely associated with metabolic abnormalities and cardiovascular risks. Butyrate, a short-chain fatty acid produced by gut microbiota, has the potential to enhance liver health by modulating inflammation and supporting gut barrier integrity. This study aimed to investigate and compare the effects of sodium butyrate and calcium butyrate in patients with MASLD. In this single-center, randomized clinical trial, 181 patients with MASLD were enrolled and assigned to receive either sodium butyrate (n = 121) or calcium butyrate (n = 60) supplementation at a daily dose of 1000 mg. The primary endpoint was the change in liver steatosis, measured using the Controlled Attenuation Parameter (CAP) via FibroScan®. Secondary endpoints included liver stiffness, biochemical parameters, hepatic steatosis and fatty liver indices, fecal calprotectin levels, stool short-chain fatty acid levels, and microbiome composition. A subgroup analysis compared responders (a ≥ 5% reduction in CAP) to non-responders. There were no significant changes in CAP values for either group (ΔCAP: sodium butyrate, 0.84; calcium butyrate, −0.23; p = 0.70). Sodium butyrate significantly reduced serum trimethylamine N-oxide and fatty liver index, while calcium butyrate led to a decrease in fecal calprotectin levels. Responders demonstrated a lower body mass index, higher levels of high-sensitivity C-reactive protein and HbA1c, and distinct microbiome profiles, characterized by lower abundance of Subdoligranulum and higher abundance of Catenibacterium. Although butyrate supplementation did not significantly improve liver steatosis as measured by CAP, the differing effects on metabolic and inflammatory markers suggest that there may be potential benefits for specific subgroups of patients with MASLD. Full article
(This article belongs to the Special Issue Current Advances in Gut Microbiota in Human Diseases and Health)
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11 pages, 710 KiB  
Article
Readily Available Index of Insulin Sensitivity Is Associated with Metabolic Dysfunction-Associated Steatotic Liver Disease and Liver Fibrosis in Patients with Type 2 Diabetes
by Stefano Ciardullo, Alessandro Roberto Dodesini, Emanuele Muraca, Pietro Invernizzi, Roberto Trevisan and Gianluca Perseghin
Diabetology 2025, 6(6), 50; https://doi.org/10.3390/diabetology6060050 - 4 Jun 2025
Viewed by 690
Abstract
Background/Objectives: Insulin resistance is a key factor in the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD), but accurately measuring it in patients with type 2 diabetes (T2D) remains challenging. This study examines the relationship between a recently proposed insulin [...] Read more.
Background/Objectives: Insulin resistance is a key factor in the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD), but accurately measuring it in patients with type 2 diabetes (T2D) remains challenging. This study examines the relationship between a recently proposed insulin resistance index and the presence of liver steatosis and fibrosis in individuals with T2D. Methods: This cross-sectional study utilized data from the 2017–2020 National Health and Nutrition Examination Survey. Patients with T2D who did not have chronic viral hepatitis or significant alcohol intake were included. The insulin sensitivity (IS) index was calculated using a formula incorporating body mass index, urine albumin-to-creatinine ratio, triglycerides, and gamma-glutamyl transferase. Liver stiffness and steatosis were assessed through transient elastography. MASLD was defined as a controlled attenuation parameter (CAP) of ≥274 decibels/meter (dB/m), while significant liver fibrosis was defined as a liver stiffness measurement (LSM) of ≥8 kPa. Multivariable logistic regression models, adjusted for potential confounders, were used to evaluate the association between IS and these liver outcomes. Results: A total of 1084 patients with T2D were analyzed. The prevalence of MASLD and significant liver fibrosis was 74.1% (95% CI 68.7–78.9) and 25.4% (95% CI 21.2–30.2), respectively. After adjusting for age, sex, waist circumference, and race/ethnicity, lower IS scores (indicating higher insulin resistance) were independently associated with increased odds of both MASLD (quartile 1 vs. quartile 4: OR 2.66, 95% CI 1.23–5.71) and significant liver fibrosis (quartile 1 vs. quartile 4: OR 3.30, 95% CI 1.45–7.51). These findings remained consistent across subgroups stratified by age, sex, and obesity status. Conclusions: This novel IS model, derived from commonly available clinical and biochemical markers, is independently associated with liver steatosis and fibrosis. Its application may help identify patients with more advanced MASLD, facilitating early intervention and risk stratification. Full article
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16 pages, 577 KiB  
Article
Liver Fibrosis Is Positively and Independently Associated with Leptin Circulating Levels in Individuals That Are Overweight and Obese: A FibroScan-Based Cross-Sectional Study
by Nicole Cerabino, Martina Di Chito, Davide Guido, Vincenza Di Stasi, Caterina Bonfiglio, Giuseppe Lisco, Endrit Shahini, Marianna Zappimbulso, Raffaele Cozzolongo, Valeria Tutino, Arianna Diciolla, Rosanna Mallamaci, Dolores Stabile, Anna Ancona, Sergio Coletta, Pasqua Letizia Pesole, Gianluigi Giannelli and Giovanni De Pergola
Nutrients 2025, 17(11), 1908; https://doi.org/10.3390/nu17111908 - 1 Jun 2025
Viewed by 679
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly correlated with the severity of obesity, and the extent of liver fibrosis is associated with a higher risk of liver-related complications, cardiovascular events, and overall mortality. Leptin circulating levels are directly correlated with the [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly correlated with the severity of obesity, and the extent of liver fibrosis is associated with a higher risk of liver-related complications, cardiovascular events, and overall mortality. Leptin circulating levels are directly correlated with the amount of adipose tissue. Aims: In the present study, we investigated the association between circulating leptin levels and liver steatosis and fibrosis. Methods: Eighty-six patients (41.7 ± 12.6 yrs, 35 men, 41%), naïve to medications, who attended the Nutrition Center for the Research and Care of Obesity and Metabolic Diseases at the National Institute of Gastroenterology “Saverio de Bellis” for weight management, were cross-sectionally evaluated. Demographic, anthropometric, clinical, and laboratory data were collected and analyzed. All patients underwent liver ultrasonographic assessment by FibroScan to diagnose liver steatosis (controlled attenuation parameter, CAP > 275 dBm) and fibrosis (liver stiffness measurement, LSM > 8.2 kPa). Results: Sixty-three individuals (73.3%) had liver steatosis, and 17 (19.8%) had liver fibrosis. The mean leptin levels were 22.3 ± 14.1 ng/mL, while the BMI and waist circumference were 36.7 ± 7.2 kg/m2 and 114.5 ± 16.4 cm, respectively. CAP values exhibited no correlation with leptin (r = 0.09, p = 0.436), while a significant connection was seen between leptin and LSM (β = 0.065; p = 0.038). Specifically, for each unit increase in leptin, LSM values were varied by +0.065 units (p = 0.038). This association was independent of gender, age, insulin resistance, adiponectin, RBP4, and visfatin. This is the first study showing these results by using FibroScan assessment in patients naïve to medications. Conclusions: Circulating leptin concentrations are independently correlated with hepatic fibrosis in individuals with a BMI ≥ 25 kg/m2. These findings indicate a function for leptin in promoting liver fibrosis; however, longitudinal studies are required to elucidate the causal nature of this interaction. Full article
(This article belongs to the Special Issue Nutrition, Adipose Tissue, and Human Health)
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18 pages, 607 KiB  
Article
The Role of Global Physical Capacity Score in Key Parameters of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
by Nicola Verrelli, Caterina Bonfiglio, Isabella Franco, Claudia Beatrice Bagnato, Dolores Stabile, Endrit Shahini and Antonella Bianco
J. Clin. Med. 2025, 14(11), 3821; https://doi.org/10.3390/jcm14113821 - 29 May 2025
Viewed by 455
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to metabolic syndrome, type 2 diabetes, and obesity. This study investigates the relationship between physical capacity, assessed by the Global Physical Capacity Score (GPCS), and MASLD-related parameters, including hepatic steatosis (CAP score), insulin resistance [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to metabolic syndrome, type 2 diabetes, and obesity. This study investigates the relationship between physical capacity, assessed by the Global Physical Capacity Score (GPCS), and MASLD-related parameters, including hepatic steatosis (CAP score), insulin resistance (HOMA-IR), and body mass index (BMI). Methods: A cross-sectional analysis was performed on 204 individuals with MASLD (mean age: 50 years; 57.6% males). Participants underwent physical tests to determine their GPCS. Hepatic steatosis was assessed using FibroScan® (Echosens, Paris, France), and metabolic markers were collected from fasting blood samples. Statistical analyses included linear and logistic regression models adjusted for potential confounders. Results: A higher GPCS was inversely associated with CAP (β = −5.30; p < 0.05), HOMA-IR (β = −0.28; p < 0.001), and BMI (β = −0.96; p < 0.001). Logistic regression analysis confirmed a lower risk of severe hepatic steatosis (OR = 0.44; p < 0.05), obesity (OR = 0.39; p < 0.05), and insulin resistance (OR = 0.32; p < 0.001) in individuals with higher GPCS values. Conclusions: The GPCS may indicate MASLD severity and reflect metabolic and hepatic health. Our findings support the promotion of physical activity and suggest a potential role for GPCS in risk stratification and personalized interventions for patients with MASLD. Full article
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26 pages, 5471 KiB  
Article
A Defective Circulating Mitochondrial Bioenergetics Profile Reflects the Hepatic One and Outlines Genetic MASLD
by Erika Paolini, Miriam Longo, Marica Meroni, Paola Podini, Marco Maggioni, Angelo Quattrini, Anna Ludovica Fracanzani and Paola Dongiovanni
Antioxidants 2025, 14(6), 618; https://doi.org/10.3390/antiox14060618 - 22 May 2025
Viewed by 494
Abstract
Genetics and mitochondrial (mt) dysfunction contribute to metabolic dysfunction-associated steatotic liver disease (MASLD). Recently, we demonstrated that the co-presence of PNPLA3, TM6SF2 and MBOAT7 polymorphisms predisposes to disease progression in MASLD patients and that their deletion triggers mt maladaptation in vitro. Here, [...] Read more.
Genetics and mitochondrial (mt) dysfunction contribute to metabolic dysfunction-associated steatotic liver disease (MASLD). Recently, we demonstrated that the co-presence of PNPLA3, TM6SF2 and MBOAT7 polymorphisms predisposes to disease progression in MASLD patients and that their deletion triggers mt maladaptation in vitro. Here, we deepened the impact of the silencing of these genes on mt dynamism and respiration by reintroducing TM6SF2 and/or MBOAT7 wild-type proteins in deleted cells through lentiviral infection. Since hepatic mt bioenergetics is impaired in MASLD, in the attempt to identify a non-invasive signature, we then compared the enzymatic mt activity of seahorses, which was assessed in liver biopsies and peripheral blood mononuclear cells (PBMCs) of biopsy-proven MASLD patients (n = 44; Discovery cohort) stratified according to the number of the three at-risk variants (3NRV). Concerning the in vitro results, the rescue of MBOAT7 and/or TM6SF2 wild-type proteins resulted in the assembly of spaghetti-shaped mitochondria with improved oxidative phosphorylation (OXPHOS) capacity. In the Discovery cohort, the hepatic bioenergetic profile fully reflected that in PBMCs and was impaired especially in 3NRV carriers. A lowered serum respiration rate was confirmed in noninvasively assessed MASLD (n = 45; Fibroscan-MASLD cohort), while it did not change in unrelated liver disease patients (n = 45). In summary, we firstly demonstrated that mt circulating respirometry reflects that in liver and is specific in defining genetic MASLD. Full article
(This article belongs to the Special Issue Oxidative Stress and Liver Disease)
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10 pages, 390 KiB  
Article
Prevalence and Risk Factors of Metabolic-Associated Fatty Liver Disease in Children with Down Syndrome at a Tertiary Care Center
by Maria D. Karaceper, Maria-Jose Villegas, Sanathan Sadh, Sierra Kawesa, Jamie Strain, Asha Nair, Alissa Dupuis, Mary Pothos, Ming-Hua Zheng and Mohit Kehar
J. Clin. Med. 2025, 14(9), 3239; https://doi.org/10.3390/jcm14093239 - 7 May 2025
Viewed by 755
Abstract
Background: The global rise of metabolic-associated fatty liver disease (MAFLD) in children is particularly concerning in high-risk groups such as those with Down Syndrome (DS), who have an elevated risk of obesity and insulin resistance. Despite increasing recognition of MAFLD in pediatric populations, [...] Read more.
Background: The global rise of metabolic-associated fatty liver disease (MAFLD) in children is particularly concerning in high-risk groups such as those with Down Syndrome (DS), who have an elevated risk of obesity and insulin resistance. Despite increasing recognition of MAFLD in pediatric populations, data on its prevalence and risk factors among children with DS in Canada remain limited. Method: This retrospective study reviewed medical records of children with DS at the CHEO Down Syndrome Clinic (2013–2023). A diagnosis of MAFLD required evidence of hepatic steatosis on imaging, lab markers, or biopsy, along with the presence of metabolic risk features. Demographic, laboratory, and diagnostic data were analyzed. Results: Among 503 children with DS (231 females, 271 males; median age: 172 months), 54 (10.7%) had MAFLD. The MAFLD group was older (median age: 205 vs. 163 months, p = 0.0002) and had higher BMI (31.39 vs. 20.5, p < 0.0001). Most cases (47/54) were diagnosed via ultrasound, and 49/54 met MAFLD criteria due to excessive adiposity. Lab results showed a median ALT of 35 U/L, triglycerides of 4.4 mmol/L, and LDL cholesterol of 2.59 mmol/L. FibroScan in 13 children revealed a median transient elastography of 5.3 kPa. BMI was the strongest predictor of MAFLD (OR: 1.2, 95% CI: 1.1–1.2). Conclusions: The DS clinic-based prevalence of MAFLD underscores the need for proactive screening and early intervention. BMI was the strongest predictor, emphasizing targeted management strategies. Further research is needed to refine diagnostic approaches and improve outcomes. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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12 pages, 232 KiB  
Article
Diagnosis and Monitoring of Metabolic Dysfunction Associated with Fatty Liver Disease in Primary Care Patients with Risk Factors—EsteatoGal Study
by Nerea Sánchez-Varela, Sergio Cinza-Sanjurjo, Tatiana Danif-Ferreira, Liseth I. Medina Araujo, Diego G. Mosteiro Miguéns, Daniel Rey-Aldana, Manuel Portela-Romero and on behalf of the EsteatoGal Researchers
J. Clin. Med. 2025, 14(9), 3089; https://doi.org/10.3390/jcm14093089 - 29 Apr 2025
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Abstract
Objective: The objective of this study was to calculate the epidemiological impact of metabolic dysfunction associated with fatty liver disease (MAFLD) and hepatic fibrosis in primary care (PC). Secondarily, we assessed the correlation between serological markers (FIB-4, ELF test), abdominal ultrasound, and [...] Read more.
Objective: The objective of this study was to calculate the epidemiological impact of metabolic dysfunction associated with fatty liver disease (MAFLD) and hepatic fibrosis in primary care (PC). Secondarily, we assessed the correlation between serological markers (FIB-4, ELF test), abdominal ultrasound, and transient elastography in the early detection of MAFLD. Methods: An observational prospective study was designed to determine the prevalence of MAFLD and to assess the correlation between complementary tests. Patients were recruited from five health centres. Eligible participants were adults aged between 18 and 70 years with at least one metabolic risk factor, including being overweight (BMI 25–29.9 kg/m2) or obese (BMI > 30 kg/m2), or diagnosed with type 2 diabetes mellitus (T2DM), dyslipidemia, or metabolic syndrome. The prevalence of MAFLD was calculated. Correlations between diagnostic tests were evaluated using Pearson’s correlation coefficient. Results: A total of 98 patients was included. Using CAP (controlled attenuation parameter) measurements, the prevalence of MAFLD was found to be 67.7%, and the prevalence of hepatic fibrosis was 6.5%. The correlation between conventional ultrasound and CAP from FibroScan® for the diagnosis of MAFLD was low and not statistically significant (0.160 [95% CI: −0.100; 0.400], p = 0.226). In contrast, the diagnosis of hepatic fibrosis using FibroScan® in PC showed a high correlation with diagnoses performed in gastroenterology department (0.942 [95% CI: 0.844; 0.979], p < 0.001). The correlation with biochemical markers was low and not statistically significant for both FIB-4 (0.125 [95% CI: −0.129; 0.363], p = 0.334) and the ELF test (0.159 [95% CI: −0.111; 0.407], p = 0.246). Conclusions: Two out of three patients with metabolic risk factors were diagnosed with MAFLD, while hepatic fibrosis diagnoses were uncommon. These results reinforce the validity of using FibroScan® in PC. Full article
(This article belongs to the Special Issue Metabolic Syndrome and Its Burden on Global Health)
27 pages, 3509 KiB  
Article
A Comparative Study of N-Acetyl Cysteine, Rosuvastatin, and Vitamin E in the Management of Patients with Non-Alcoholic Steatohepatitis: A Randomized Controlled Trial
by Amr Y. Zakaria, Rehab Badawi, Hasnaa Osama, Mona A. Abdelrahman and Asmaa M. El-Kalaawy
Pharmaceuticals 2025, 18(5), 650; https://doi.org/10.3390/ph18050650 - 29 Apr 2025
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Abstract
Background: Non-alcoholic steatohepatitis (NASH) is characterized by increased production of proinflammatory cytokines, fibrosis, and hepatocyte apoptosis. This study aimed to assess the efficacy of N-acetyl cysteine (NAC), rosuvastatin (RSV), and vitamin E (VE) in patients with NASH. Methods: A double-blinded, parallel, [...] Read more.
Background: Non-alcoholic steatohepatitis (NASH) is characterized by increased production of proinflammatory cytokines, fibrosis, and hepatocyte apoptosis. This study aimed to assess the efficacy of N-acetyl cysteine (NAC), rosuvastatin (RSV), and vitamin E (VE) in patients with NASH. Methods: A double-blinded, parallel, randomized, controlled study was conducted and registered on clinicaltrials.gov (Identifier: NCT06105060), involving 135 NASH participants, who were divided into three groups: the control group (group 1), consisting of patients receiving standard therapy VE at a dosage of 400 IU twice daily. In the treated group (group 2), patients were administered NAC at a dosage of 1200 mg twice daily, while treatment (group 3) received RSV at a dosage of 20 mg once daily. FibroScan® examination of liver tissue and fibrosis scores, along with tests for liver aminotransferases, lipid profile, glycemic parameters, and renal and hepatic functions, were assessed before and after six months of treatment. Results: The analyzed groups demonstrated a significant reduction in steatosis and lipid peroxidation (p < 0.05). The NAC group demonstrated greater anti-inflammatory and anti-apoptotic effects compared to the RSV group, although this difference was not significant in the control group. NAC is conceded as the only significant antifibrotic agent in liver stiffness measurement (LSM), biological marker findings, and non-invasive liver fibrosis scores (p < 0.05), in addition to its improvement of several metabolic parameters and health-related quality of life. Conclusions: Patients receiving NAC demonstrated safety and efficacy in enhancing steatosis, fibrosis, and metabolic parameters, representing a novel strategy in the management of NASH. Full article
(This article belongs to the Special Issue New and Emerging Treatment Strategies for Gastrointestinal Diseases)
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