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21 pages, 434 KB  
Review
The Use of Ultrasound-Based Elastography Techniques in Liver Fibrosis: A Narrative Review
by Arjuna Priyadarsin De Silva, Shashini Madushika Hathurusinghe, Madunil Anuk Niriella and Hithunadura Janaka De Silva
Diagnostics 2026, 16(17), 2694; https://doi.org/10.3390/diagnostics16172694 - 24 Aug 2026
Viewed by 284
Abstract
Liver fibrosis staging plays a key role in the prognosis and management of chronic liver disease. Liver biopsy remains the reference standard for fibrosis assessment but is limited by its invasiveness and risk of complications, while magnetic resonance elastography, though also considered a [...] Read more.
Liver fibrosis staging plays a key role in the prognosis and management of chronic liver disease. Liver biopsy remains the reference standard for fibrosis assessment but is limited by its invasiveness and risk of complications, while magnetic resonance elastography, though also considered a gold standard, is constrained by cost and limited availability. Ultrasound-based elastography techniques—vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), and two-dimensional shear wave elastography (2D SWE)—have emerged as accessible non-invasive alternatives. This narrative review aimed to summarize the principles, diagnostic performance, advantages, and limitations of these three techniques across a range of etiologies. A comprehensive literature search was conducted across Scopus, PubMed, Embase, CINAHL, the Cochrane Library, Informit, and the JBI Database of Systematic Reviews and Implementation Reports, covering January 2015 to February 2026. Search terms included “vibration-controlled transient elastography”, “point shear wave elastography”, “two-dimensional shear wave elastography”, “liver stiffness measurement”, “non-invasive assessment” and “chronic liver disease”. International guidelines, systematic reviews and meta-analyses, large observational cohort studies, and narrative reviews were included in the synthesis. VCTE, pSWE, and 2D SWE all demonstrated good diagnostic performance for detecting advanced fibrosis and cirrhosis across multiple etiologies. VCTE was the most extensively validated technique, with standardized cut-offs endorsed by major international guidelines. pSWE and 2D SWE showed comparable diagnostic accuracy and can be integrated into conventional ultrasound systems, enabling simultaneous structural and stiffness assessment, although validated cut-off values for these two techniques are not yet established in current guidelines, and absolute stiffness values are not directly interchangeable across techniques, manufacturers, or software versions. Obesity, inflammation, steatosis and recent food intake were identified as factors affecting measurement accuracy across all three techniques. Ultrasound-based elastography techniques offer effective, non-invasive alternatives to liver biopsy for fibrosis assessment. VCTE remains the most validated option despite cost and availability constraints, while pSWE and 2D SWE offer comparable accuracy with practical integration advantages. Future research should focus on standardizing cut-off values, addressing confounding factors, and combining elastography with biomarkers and AI-driven models. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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12 pages, 710 KB  
Article
Resting Heart Rate as a Physiologic Marker of Steatosis in MASLD: NHANES 2017–2020 Analysis
by Ethan Shamsian, John Ralph Mack, Mahinaz Mohsen, Anika Makol, Sameer Rao, Rohan Karkra, Michael Bebawy, Muhammad Hassaan Arif Maan, Fariha Ilyas, Ahmed Al-Khazraji and Paul Gaglio
Medicina 2026, 62(8), 1480; https://doi.org/10.3390/medicina62081480 - 1 Aug 2026
Viewed by 446
Abstract
Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked to systemic cardiometabolic dysfunction. Resting heart rate (RHR), a marker of autonomic and metabolic stress, has been associated with metabolic syndrome and cardiovascular disease, though its relationship with MASLD remains [...] Read more.
Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked to systemic cardiometabolic dysfunction. Resting heart rate (RHR), a marker of autonomic and metabolic stress, has been associated with metabolic syndrome and cardiovascular disease, though its relationship with MASLD remains incompletely characterized. We evaluated the association between RHR and liver-related outcomes in a nationally representative U.S. cohort. Materials and Methods: We analyzed adults aged 20–79 years from NHANES 2017–2020 with valid vibration-controlled transient elastography (VCTE) measurements. Participants with significant alcohol use, viral hepatitis, pregnancy, use of heart rate-modifying medications, or missing key data were excluded. Liver outcomes included elevated alanine aminotransferase (ALT), advanced steatosis (CAP ≥ 290 dB/m), FIB-4 fibrosis category, and VCTE-defined fibrosis. Multivariable regression models adjusted for demographic and metabolic covariates were used to evaluate associations between RHR and liver-related outcomes. Results: A total of 3532 adults were included. Each 1 beat-per-minute increase in RHR was independently associated with elevated ALT (OR 1.025, 95% CI 1.002–1.050, p = 0.043) and advanced steatosis (OR 1.036, 95% CI 1.001–1.073, p = 0.048). No significant association was observed between RHR and higher FIB-4 category (OR 1.025, 95% CI 0.992–1.060, p = 0.169) or VCTE-defined fibrosis (OR 0.990, 95% CI 0.961–1.021, p = 0.481). Associations with ALT and steatosis were attenuated after adjustment for glycemic and lipid parameters. Conclusions: Higher RHR was associated with steatosis-related and metabolic liver outcomes, but not fibrosis, in a nationally representative cohort. These findings suggest that RHR may reflect underlying autonomic and metabolic dysfunction relevant to early MASLD pathogenesis rather than advanced fibrotic disease. Full article
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19 pages, 1973 KB  
Review
Ultrasound Elastography in Chronic Liver Disease: From Clinical Applications to Quality Assurance and Future Perspectives
by Rute Santos and Raquel Reis
Diagnostics 2026, 16(15), 2303; https://doi.org/10.3390/diagnostics16152303 - 23 Jul 2026
Viewed by 1144
Abstract
To provide a clinically oriented overview of ultrasound elastography in chronic liver disease, focusing on currently available techniques, their clinical applications, quality assurance, technical pitfalls, and emerging developments that may shape future liver imaging practice. A narrative review of the current literature was [...] Read more.
To provide a clinically oriented overview of ultrasound elastography in chronic liver disease, focusing on currently available techniques, their clinical applications, quality assurance, technical pitfalls, and emerging developments that may shape future liver imaging practice. A narrative review of the current literature was conducted using international guidelines, systematic reviews, and original studies retrieved from major scientific databases. Particular emphasis was placed on the clinical applications of ultrasound elastography, quality assurance procedures, interpretation of liver stiffness measurements, and future technological developments. Vibration-controlled transient elastography (VCTE) and shear wave elastography (SWE) have become established non-invasive techniques for liver fibrosis assessment, demonstrating excellent diagnostic performance, particularly for advanced fibrosis and cirrhosis. Beyond fibrosis staging, ultrasound elastography contributes to prognostic stratification, treatment planning, and longitudinal disease monitoring across a broad spectrum of chronic liver diseases. However, liver stiffness measurements may be influenced by technical and biological confounding factors, including inflammation, cholestasis, hepatic congestion, obesity, and postprandial status, highlighting the importance of standardised acquisition protocols and careful clinical interpretation. Emerging developments, including spleen stiffness assessment, multiparametric ultrasound, and artificial intelligence-assisted image analysis, are expected to further improve diagnostic accuracy and support precision hepatology. Ultrasound elastography has become an essential component of the non-invasive evaluation of chronic liver disease, substantially reducing the need for liver biopsy while improving fibrosis staging, prognostic stratification, and longitudinal patient monitoring. Its optimal clinical implementation requires appropriate patient selection, adherence to quality assurance procedures, and careful interpretation within the broader clinical context. Future advances in multiparametric ultrasound, artificial intelligence, and international standardisation are expected to further strengthen the role of ultrasound elastography within precision hepatology and personalised liver disease management. Ultrasound elastography should be integrated into routine liver imaging as part of a multimodal diagnostic approach. Standardised acquisition protocols, continuous quality assurance, and appropriate operator training are essential to ensure reliable and reproducible liver stiffness measurements. Radiographers play a key role in examination quality, protocol adherence, and multidisciplinary patient care, contributing to accurate diagnosis and improved clinical decision-making. Full article
(This article belongs to the Special Issue Advanced Ultrasound Techniques in Diagnosis)
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10 pages, 684 KB  
Article
Prevalence and Predictors of MASLD and Fibrosis in an Urban Outpatient Setting: A Cross-Sectional Study
by Nicolás Ortiz-López, Daniela Simian, Máximo Cattaneo, Katherine Rojas, Daniel Durán, Martina Contreras, Diego Lizama, María Fernanda Eyssautier, Camila Meza, Catalina Molina, Gerardo Jara and Jaime Poniachik
J. Clin. Med. 2026, 15(12), 4533; https://doi.org/10.3390/jcm15124533 - 11 Jun 2026
Viewed by 393
Abstract
Background/Objectives: This study aims to estimate the prevalence of MASLD in a general outpatient population, describe associated metabolic risk factors, and evaluate liver fibrosis. Methods: We conducted a prospective, cross-sectional study at a tertiary hospital that included adults referred there for [...] Read more.
Background/Objectives: This study aims to estimate the prevalence of MASLD in a general outpatient population, describe associated metabolic risk factors, and evaluate liver fibrosis. Methods: We conducted a prospective, cross-sectional study at a tertiary hospital that included adults referred there for abdominal ultrasound for non-hepatic indications. Exclusion criteria were significant alcohol intake or known liver disease. Hepatic steatosis was assessed by ultrasound in all patients, and vibration-controlled transient elastography (VCTE) was performed in a subgroup. Clinical and laboratory data were collected. Comparisons used the chi-square test, Fisher’s exact test, and the Wilcoxon test, and logistic regression identified associated factors. Results: Hepatic steatosis was identified by ultrasound in 57.6% of the 182 patients, with most (93%) fulfilling the MASLD criteria. MASLD was diagnosed in 58.2% of patients based on ultrasound or VCTE findings of steatosis. Hepatic steatosis by ultrasound was associated with higher BMI (OR 1.30; 95% CI 1.18–1.43), hypertension (OR 1.92; 95% CI 1.04–3.53), glucose disorders (OR 3.33; 95% CI 1.60–6.92), and triglycerides (OR 1.01; 95% CI 1.00–1.03), while physical activity was protective (OR 0.86; 95% CI 0.26–0.99). Among 74 patients evaluated by VCTE, 8% had fibrosis (≥F1), which was more frequent in those with higher BMI and a number of cardiometabolic risk factors. Conclusions: This study reveals a high prevalence of MASLD and fibrosis among outpatients, supporting the use of abdominal ultrasound for opportunistic screening of MASLD and emphasizing the need for early risk stratification and referral. Full article
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26 pages, 1473 KB  
Review
The Evolution of MASLD Management: From Revised Nomenclature to Disease-Modifying Therapies
by Karolina Kornatowska, Szymon Kopciał, Mateusz Wiekiera, Adrianna Wiekiera, Paweł Budzik, Mateusz Tyniec and Kamal Morshed
Gastroenterol. Insights 2026, 17(2), 33; https://doi.org/10.3390/gastroent17020033 - 25 May 2026
Viewed by 2065
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of global chronic liver disease, with a prevalence of approximately 30%. This review outlines the diagnostic transition from the exclusionary non-alcoholic fatty liver disease (NAFLD) framework to the affirmative MASLD nomenclature, which mandates [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of global chronic liver disease, with a prevalence of approximately 30%. This review outlines the diagnostic transition from the exclusionary non-alcoholic fatty liver disease (NAFLD) framework to the affirmative MASLD nomenclature, which mandates the presence of at least one of five specific cardiometabolic risk factors (CMRFs) to prioritize active pathophysiology. Beyond hepatic complications, MASLD drives systemic metabolic failure, significantly elevating risks for type 2 diabetes, hepatocellular carcinoma, and cardiovascular disease, the primary cause of mortality in this cohort. Clinical management relies on a standardized, two-tier risk-stratification pathway for advanced fibrosis. Primary care triage utilizes the Fibrosis–4 (FIB–4) index; a score < 1.3 excludes advanced disease via a high negative predictive value, whereas indeterminate or high scores require secondary validation via vibration-controlled transient elastography (VCTE) or the enhanced liver fibrosis (ELF) test to guide specialist referral. Although lifestyle modifications, principally a 7–10% weight reduction and Mediterranean diet adherence, remain foundational, management has transitioned toward disease-modifying pharmacotherapies. A pivotal breakthrough occurred with the 2024 FDA approval of resmetirom, a selective thyroid hormone receptor-beta (THR-β) agonist, for non-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate-to-advanced fibrosis. Concurrently, the emergence of GLP-1 receptor agonists and multi-incretin mimetics offers a personalized, multi-target approach simultaneously addressing hepatic inflammation, glycemic control, and adiposity. Full article
(This article belongs to the Topic Liver Diseases: From Pathogenesis to Modern Management)
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12 pages, 508 KB  
Article
Intra-Observer Reproducibility of Endoscopic Ultrasound Point Shear-Wave Elastography: A 120-Patient Prospective Cohort Study
by Adrian Burdan, Bogdan Miutescu, Eyad Gadour, Calin Burciu, Mirela Danila, Felix Bende, Moga Tudor, Aymen Almuhaidb, Raluca Lupusoru, Andreea Brasovan, Roxana Sirli and Alina Popescu
Medicina 2026, 62(4), 780; https://doi.org/10.3390/medicina62040780 - 17 Apr 2026
Viewed by 608
Abstract
Background and Objectives: Endoscopic ultrasound point shear-wave elastography (EUS-pSWE) bypasses subcutaneous fat and may provide weight-independent liver stiffness measurements; however, data on reproducibility and quality criteria remain limited. This study aimed to evaluate the intra-observer reproducibility and short-term variability of EUS-pSWE. Materials [...] Read more.
Background and Objectives: Endoscopic ultrasound point shear-wave elastography (EUS-pSWE) bypasses subcutaneous fat and may provide weight-independent liver stiffness measurements; however, data on reproducibility and quality criteria remain limited. This study aimed to evaluate the intra-observer reproducibility and short-term variability of EUS-pSWE. Materials and Methods: In this single-center prospective cohort study (December 2024–February 2025), 120 consecutive adults undergoing diagnostic EUS were enrolled. For each hepatic lobe, 10 consecutive measurements were obtained and grouped into two sequential blocks of five measurements without scope repositioning. Intra-observer reproducibility was assessed using intraclass correlation coefficients (ICC3,1). The agreement between acquisition runs and determinants of short-term variability was also evaluated. Same-day vibration-controlled transient elastography (VCTE) served as an external comparator. Results: Forty-six participants were obese (BMI ≥ 30 kg/m2). The mean VCTE stiffness was 6.24 kPa, while the mean EUS-pSWE stiffness was 9.40 ± 5.64 kPa. Among examinations meeting IQR/Median < 30% quality criteria, reproducibility was excellent (left ICC 0.97 [0.95–0.98]; right ICC 0.92 [0.86–0.95]) and consistent across BMI strata. EUS-pSWE correlated strongly with VCTE (r = 0.81, p < 0.001). In contrast, agreement between consecutive acquisition runs was low, indicating increased short-term variability. EUS-pSWE quality pass rates based on IQR/Median criteria were modest (left 56.7%, right 41.7%, both lobes 23.3%), although all measurements fulfilled device-specific validity criteria (VSN > 60%). Age and BMI were not significant predictors of variability. Conclusions: EUS-pSWE demonstrates excellent intra-observer reproducibility under quality-controlled conditions and shows a strong correlation with VCTE. However, short-term variability between acquisition runs and limited feasibility based on conventional quality thresholds should be considered. EUS-pSWE appears to be a promising modality for liver stiffness assessment, warranting further validation of quality criteria and clinical thresholds. Full article
(This article belongs to the Section Gastroenterology & Hepatology)
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14 pages, 636 KB  
Article
Discordance Between Conventional Ultrasound and Transient Elastography in Hepatic Steatosis Assessment: Clinical Factors Associated with Discrepant Findings
by Mihaela Cristina Brisc, Elena Emilia Babeș, Sabina Florina Călugăr-Șolea, Simona Bota, Laura Maghiar, Ciprian Mihai Brisc and Ciprian Brisc
Diagnostics 2026, 16(8), 1188; https://doi.org/10.3390/diagnostics16081188 - 16 Apr 2026
Viewed by 816
Abstract
Background: Discrepancies are frequently observed between liver steatosis grading assessed by conventional B-mode ultrasonography and vibration-controlled transient elastography (VCTE) with controlled attenuation parameter (CAP). This study aimed to identify factors associated with these differences and to evaluate whether the two imaging methods [...] Read more.
Background: Discrepancies are frequently observed between liver steatosis grading assessed by conventional B-mode ultrasonography and vibration-controlled transient elastography (VCTE) with controlled attenuation parameter (CAP). This study aimed to identify factors associated with these differences and to evaluate whether the two imaging methods provide comparable steatosis classifications. Methods: We conducted a retrospective cross-sectional observational study including 130 hospitalized patients evaluated over a two-year period who underwent laboratory testing, abdominal ultrasonography, and transient elastography. The analyzed variables included demographic characteristics, nutritional status, comorbidities, and biochemical parameters such as alanine aminotransferase (ALAT), total cholesterol, triglycerides, gamma-glutamyl transferase (GGT), and the fibrosis-4 index (FIB-4). Patients were classified into two groups: concordant steatosis grading between the two methods (n = 61) and discordant results (n = 69). Results: Concordant steatosis grading was more frequently observed in patients with serum total cholesterol > 200 mg/dL (45.9%) and FIB-4 values between 1.45–3.25 (44.2%). A trend toward higher concordance was also observed in patients with elevated triglycerides. In contrast, viral liver disease was significantly associated with discordant results (26.2%). Higher fibrosis stages assessed by VCTE (F ≥ 2) and FIB-4 values > 3.25 showed a non-significant trend toward discordance. Conclusions: Several clinical and biochemical factors influence the agreement between ultrasound and VCTE-based CAP in the assessment of hepatic steatosis. Elevated cholesterol and intermediate FIB-4 values were associated with concordant results, whereas viral liver disease was associated with discordance between the two imaging modalities. Full article
(This article belongs to the Special Issue Abdominal Diseases: Diagnosis, Treatment and Management—2nd Edition)
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16 pages, 2002 KB  
Article
Genetic Variants and Molecular Components Associated with Metabolic Dysfunctional-Associated Steatotic Liver Disease and Depression: Shared Association of ADAMTS7 and THRAP3
by Eron G. Manusov, Vincent P. Diego, Marcio Almeida, Jacob A. Galan, Kathryn Herklotz, Edwardo Abrego III, Habiba Sultana, Luis Pena Marquez, Marco A. Arriaga, Marcelo Leandro, Juan Peralta, Ana C. Leandro, Tom E. Howard, Joanne E. Curran, Sandra Laston, John Blangero and Sarah Williams-Blangero
Genes 2026, 17(3), 343; https://doi.org/10.3390/genes17030343 - 19 Mar 2026
Viewed by 1254
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and depression frequently occur together. Identifying the genes that influence both MASLD and depression may facilitate the discovery of biological pathways associated with disease risk. Methods: We recruited 525 participants from Mexican American families [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and depression frequently occur together. Identifying the genes that influence both MASLD and depression may facilitate the discovery of biological pathways associated with disease risk. Methods: We recruited 525 participants from Mexican American families living in the Rio Grande Valley of south Texas. We collected clinical data, biometric measurements, hepatic health assessments using Vibration-Controlled Transient Elastography (VCTE), and depression evaluations determined with the Beck Depression Inventory-II. We estimated the heritability (h2) of MASLD-related measures, depression status, aspartate aminotransferase (AST), alanine aminotransferase (ALT), the AST/ALT ratio, and Vibration-Controlled Transient Elastography measurements. For each gene, we derived a genetic endophenotype representing its expression level. We then performed functional network and gene ontology enrichment analyses to characterize the underlying protein pathways. Results: We observed significant associations between the expression of two genes, Thyroid Hormone Receptor-Associated Protein 3 (THRAP3) (h2 = 0.56 [0.45, 0.67]) and ADAM Metallopeptidase with Thrombospondin Type 1 Motif 7 (ADAMTS7) (h2 = 0.66 [0.55, 0.77]), with depression and multiple MASLD-related phenotypes. We identified 351 genes with expression levels significantly correlated with one or more MASLD phenotypes and depression. Among these, five genes—ADAMTS7, THRAP3, CHPM4A, RAB9A, and PDIA3—were jointly associated with three phenotypes: AST/ALT, ALT, and Controlled Attenuation Parameter (CAP kPa). Based on the Fisher Combined Test, only THRAP3 (p = 3.0 × 10−2) and ADAMTS7 (p = 2 × 10−2) were jointly significant for depression (BDI-II) and AST, ALT, AST/ALT ratio, FAST, and CAP (kPa). We present a protein–protein interaction network comprising nodes (proteins) and edges (interactions), and a gene ontology enrichment analysis of cellular components. Discussion: Our findings highlight pleiotropic genes underlying MASLD and depression. Two genes, ADAMTS7 and THRAP3, warrant further investigation as potential targets for therapeutic interventions to manage MASLD and depression among Mexican Americans. These results may improve our understanding of the pathways involved in these two diseases, advance current research, and contribute to improvements in personalized medicine. Conclusion: We identified possible shared gene expression phenotypes linking MASLD and depression, which may provide insight into a common molecular underpinning. Pathway enrichment and gene analysis were used to help refine networks and enhance our understanding of complex gene-environmental interactions and their implications for precision medicine. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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19 pages, 2413 KB  
Perspective
Primary Biliary Cholangitis—The Changing Biomarker Paradigms for Staging Fibrosis
by Terence N. Moyana
Livers 2026, 6(2), 23; https://doi.org/10.3390/livers6020023 - 16 Mar 2026
Viewed by 3719
Abstract
Primary biliary cholangitis (PBC) is an autoimmune-mediated disease characterized by chronic, non-suppurative, small-duct lymphocytic cholangitis. The prognosis largely depends on early disease recognition and treatment. Suboptimal response to first-line therapy (ursodeoxycholic acid) is associated with risk for disease progression. Reliable biomarkers are also [...] Read more.
Primary biliary cholangitis (PBC) is an autoimmune-mediated disease characterized by chronic, non-suppurative, small-duct lymphocytic cholangitis. The prognosis largely depends on early disease recognition and treatment. Suboptimal response to first-line therapy (ursodeoxycholic acid) is associated with risk for disease progression. Reliable biomarkers are also required to enhance risk stratification. The traditional gold standard for assessing fibrosis is liver biopsy, but it is invasive and unsuitable for serial evaluations. Hence, trends are towards non-invasive surrogate biomarkers (blood-based and imaging biomarkers respectively) which have a much better safety profile. Blood-based biomarkers include: (i) Fibrosis-4 [Fib-4], (ii) Aspartate Aminotransferase to Platelet Ratio Index [APRI], (iii) Enhanced Liver Fibrosis score [ELF], and (iv) total bile acid to platelet ratio [TPR]. They show much potential but are not particularly sensitive tests. Ultrasound-based imaging biomarkers are increasingly being utilized for liver stiffness measurement (LSM), with vibration-controlled transient elastography (VCTE) emerging as the preferred technique. However, despite its growing popularity, VCTE is limited by technical issues. Hence, currently, none of the non-invasive tests fulfill the prerequisites to be the new gold standard as defined by the FDA. Nonetheless, there may be value to combining LSM with various serum biomarkers such as Fib-4, APRI, as aforementioned. The hope is to create nomograms for predicting liver-related events and decision tree algorithms. Newer studies are investigating microbiota in the gut-liver axis, biomolecules such as nanovesicles/nanofibers, and metabolic reprogramming as it pertains to e.g., proteomics and lipidomics. These approaches hold much promise, and if validated, could significantly change the management of PBC. Full article
(This article belongs to the Special Issue Mechanistic and Prognostic Biomarkers in Liver Diseases)
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16 pages, 695 KB  
Article
Vitamin D Sufficiency Revisited: Evidence of a Dose–Response Effect for MASLD in Adults at Risk
by Gediz Dogay Us, Francesco Innocenti, Ozgur Muhammet Koc, Volkan Demirhan Yumuk, Zeynep Banu Gungor and Ger H. Koek
Nutrients 2026, 18(4), 599; https://doi.org/10.3390/nu18040599 - 11 Feb 2026
Cited by 3 | Viewed by 1071
Abstract
Background and Aims: Vitamin D plays a pivotal role in liver health, influencing multiple steps in the development of steatosis, fibrosis, and extrahepatic complications in metabolic dysfunction-associated steatotic liver disease (MASLD). However, serum vitamin D concentrations that confer optimal hepatic protection in MASLD [...] Read more.
Background and Aims: Vitamin D plays a pivotal role in liver health, influencing multiple steps in the development of steatosis, fibrosis, and extrahepatic complications in metabolic dysfunction-associated steatotic liver disease (MASLD). However, serum vitamin D concentrations that confer optimal hepatic protection in MASLD remain unclear. We therefore aimed to investigate the association between vitamin D status and MASLD and to explore whether higher vitamin D concentrations confer incremental protection beyond current sufficiency cut-offs. Method: We conducted a multicenter cross-sectional study of 1039 adults with at least one cardiometabolic risk factor for MASLD diagnosis, recruited between 2022 and 2024. Participants that reported excessive alcohol intake (>30 g/day for men, >20 g/day for women) and other etiologies of liver disease were excluded. Serum vitamin D levels were measured, with ≥20 ng/mL defined as sufficiency. MASLD (controlled attenuation parameter [CAP] ≥ 248 dB/m) and significant fibrosis (liver stiffness measurement [LSM] ≥ 8 kPa) were assessed using vibration-controlled transient elastography. Missing vitamin D values were imputed with multiple imputation. Associations between vitamin D status, MASLD and fibrosis were examined using multivariable logistic regression models adjusted for potential confounders. Results: Participants had a mean age of 52.2 ± 13.0 years; 51.6% were male and mean BMI was 30.1 ± 5.8 kg/m2. Vitamin D sufficiency and obesity were present in 81.2% (95% CI: 78.4–84.9) and 54.7% (95% CI: 51.3–58.0), respectively. Vitamin D sufficiency was associated with lower odds of MASLD (crude OR = 0.47, 95% CI: 0.33–0.67) and significant fibrosis (crude OR = 0.46, 95% CI: 0.28–0.76). After adjusting for potential confounders, the association between Vitamin D sufficiency and MASLD remained clinically relevant but did not reach statistical significance (adjusted OR = 0.60, 95% CI: 0.36–1.03, p = 0.06). In contrast, the association between Vitamin D sufficiency and significant fibrosis was both clinically relevant and statistically significant (adjusted OR = 0.48, 95% CI: 0.246–0.916, p = 0.03). When Vitamin D was categorized into quartiles, participants in the highest quartile (≥44 ng/dL) had 61% lower odds of MASLD in the adjusted model (adjusted OR = 0.39, 95% CI: 0.21–0.71) compared with participants in the lowest quartile (≤22 ng/mL). No significant dose-dependent associations were observed for fibrosis. Conclusions: Vitamin D levels showed a dose-dependent decrease in the odds of MASLD among at-risk adults. While the protective effect on fibrosis was not dose-dependent, these findings collectively suggest vitamin D as a potentially modifiable factor in MASLD prevention and management. Full article
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16 pages, 2240 KB  
Article
Assessment of Liver Fibrosis Stage and Cirrhosis Regression After Long-Term Follow-Up Following Sustained Virological Response
by Lidia Canillas, Dolores Naranjo, Teresa Broquetas, Juan Sánchez, Anna Pocurull, Esther Garrido, Rosa Fernández, Xavier Forns and José A. Carrión
Diagnostics 2026, 16(2), 279; https://doi.org/10.3390/diagnostics16020279 - 15 Jan 2026
Viewed by 2007
Abstract
Background/Objectives: Previous studies have demonstrated that the cessation of liver damage after HCV cure can improve liver function, histological necroinflammation, and portal hypertension. However, scarce data about fibrosis stage or cirrhosis regression have been reported during follow-up. Methods: A prospective study [...] Read more.
Background/Objectives: Previous studies have demonstrated that the cessation of liver damage after HCV cure can improve liver function, histological necroinflammation, and portal hypertension. However, scarce data about fibrosis stage or cirrhosis regression have been reported during follow-up. Methods: A prospective study evaluating hepatic biopsies and liver stiffness measurement by vibration-controlled transient elastography (VCTE-LSM) after the end of treatment (EOT) in patients with compensated advanced chronic liver disease (cACLD). Fibrosis was evaluated according to two semi-quantitative grading systems (METAVIR and Laennec) at 6 years after EOT (LB6) and compared with biopsies at 3 years (LB3). Results: Fifty-four patients with LB6 (34 with paired LB3–LB6) were included. Median (IQR) age was 53.9 (48.5–59.3), 38 (70.4%) were men, and 13 (24.1%) were HIV-coinfected. The VCTE-LSM was >15 kPa in 30 (55.6%). The LB6 (81.4 months after EOT) showed non-advanced fibrosis (F1–F2) in 12 (22.4%) patients, bridging (F3) in 26 (48.2%), and cirrhosis (F4) in 16 (29.6%): F4A in 7 (13.0%), F4B in 4 (7.4%), and F4C in 5 (9.3%). The 1-year post-EOT follow-up VCTE-LSM ≤ 8.6 kPa identifies patients without advanced fibrosis (AUROC = 0.929), with a negative predictive value of 88.9% and a positive predictive value of 95.2%. Paired biopsies showed regression in 9 (47.4%) out of 19 patients with cirrhosis: 8 (61.5%) of 13 with F4A but only 1 (16.7%) of 6 with F4B–F4C. Conclusions: Advanced fibrosis persists in most patients with advanced chronic liver disease after HCV eradication. Regression is possible in mild cirrhosis. However, it is a limited and slow event. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Management of Liver Diseases)
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13 pages, 870 KB  
Article
Use of FibroScan-AST (FAST) Score and Fibrosis-4 Index to Identify Advanced Liver Fibrosis in Patients with Type 2 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease
by Abir Alsaid, Reem J. Al Argan, Yasir A. Elamin, Nora Alshiekh, Amna Hassan, Abdullah Alotaibi, Ihab Gaarour and Mona H. Ismail
J. Clin. Med. 2026, 15(1), 50; https://doi.org/10.3390/jcm15010050 - 21 Dec 2025
Cited by 1 | Viewed by 2113
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent in patients with type 2 diabetes (T2D), and advanced fibrosis is the strongest predictor of liver-related morbidity and mortality. Therefore, early noninvasive risk stratification is critical. While the Fibrosis-4 (FIB-4) index and vibration-controlled [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent in patients with type 2 diabetes (T2D), and advanced fibrosis is the strongest predictor of liver-related morbidity and mortality. Therefore, early noninvasive risk stratification is critical. While the Fibrosis-4 (FIB-4) index and vibration-controlled transient elastography (VCTE) are widely used, the newer FibroScan-AST (FAST) score has shown promise in detecting at-risk metabolic-associated steatohepatitis (MASH) with significant fibrosis. Evidence comparing the FAST and FIB-4 indices in Middle Eastern T2D populations remains limited. We compared the diagnostic performances of these models for advanced fibrosis in Saudi patients with T2D and MASLD. Methods: We conducted a retrospective analysis of 273 patients diagnosed with T2D and MASLD. All patients underwent VCTE. To identify advanced fibrosis, we used liver stiffness measurement (LSM) as a surrogate marker for liver biopsy. We calculated the FAST and FIB-4 indices for each patient. To assess the diagnostic performance of these scores, we evaluated their sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUROC). Results: In this cohort study, 26.4% of participants had a high-risk FAST score (>0.35; median: 0.13). Patients with high-risk FAST scores (>0.35) were younger, had higher BMIs, elevated liver enzyme levels, and poorer glycemic control than those in the lower-risk groups. High-risk FAST scores were strongly correlated with elevated LSM, FIB-4, and controlled attenuation parameter values (p < 0.001). The FAST score demonstrated better performance than the FIB-4 index in detecting advanced fibrosis. It showed higher accuracy (85.4% vs. 77.3%), sensitivity (82.0% vs. 48.0%), and negative predictive value (95.5% vs. 87.8%) while maintaining a similar specificity. The AUROC values were 0.936 (95% CI: 0.901–0.971) for the FAST score compared to 0.711 (95% CI: 0.625–0.797) for the FIB-4 index. Conclusions: The FAST score demonstrated better diagnostic accuracy than the FIB-4 index and identified patients with poor metabolic control and obesity as being at the highest risk among Saudi patients with T2D and MASLD. These findings support the integration of other elastography-based tests into stepwise fibrosis screening pathways for diabetic populations, potentially improving the early detection of advanced fibrosis and patient outcomes. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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11 pages, 407 KB  
Article
Metabolic Syndrome and Methotrexate-Associated Liver Injury: Insights from Elastography and Liver Biopsy Study
by Kaila Fennell, Maya Mahmoud and Kamran Qureshi
Livers 2025, 5(4), 67; https://doi.org/10.3390/livers5040067 - 15 Dec 2025
Viewed by 1666
Abstract
Background: Methotrexate (MTX), a widely used therapeutic agent, is associated with hepatotoxicity. While cumulative MTX dosage has historically been linked to liver injury, recent evidence highlights the potential role of metabolic syndrome (MetS) as a key contributor. Objective: We evaluate the association between [...] Read more.
Background: Methotrexate (MTX), a widely used therapeutic agent, is associated with hepatotoxicity. While cumulative MTX dosage has historically been linked to liver injury, recent evidence highlights the potential role of metabolic syndrome (MetS) as a key contributor. Objective: We evaluate the association between MetS and MTX-associated liver injury using vibration-controlled transient elastography (VCTE) and liver biopsy in patients suspected to have MTX-related liver injury. Design: This retrospective study analyzed 59 patients with chronic MTX use who underwent VCTE in hepatology clinics between 2016 and 2024. Patients with alternative causes of liver injury were excluded. MetS was defined per standard criteria as the presence of ≥3 criteria: diabetes, hypertension, BMI ≥ 30 kg/m2, hypertriglyceridemia, or low HDL levels. Measurements: Liver stiffness measurement (LSM) and steatosis (CAP) were measured via VCTE, and liver biopsy data were reviewed for steatohepatitis. ANCOVA was used to assess the effect of MetS on liver disease while controlling for cumulative MTX dosage. Results: Of the 59 patients (mean age: 62 years; mean BMI: 34.3 kg/m2), 36 (61%) met the criteria for MetS. CAP values were significantly higher in patients with MetS (p < 0.001) independent of cumulative MTX dosage. Transformed LSM values also showed a significant association with MetS (p = 0.028). Logistic regression identified MetS as a significant predictor of biopsy-confirmed steatosis and steatohepatitis (p < 0.001) and higher NAFLD activity score (p = 0.002), whereas cumulative MTX dosage was not (p = 0.47). Conclusions: MetS is strongly associated with liver injury in chronic MTX users, independent of cumulative MTX dosage. These findings suggest metabolic factors as key mediators of MTX-induced hepatotoxicity. Prospective, multicenter studies are needed to confirm these findings and improve non-invasive monitoring strategies. Full article
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17 pages, 3456 KB  
Article
CT-Based Radiomic Models in Biopsy-Proven Liver Fibrosis Staging: Direct Comparison of Segmentation Types and Organ Inclusion
by Andreea Mihaela Morariu-Barb, Tudor Drugan, Mihai Adrian Socaciu, Horia Stefanescu, Andrei Demirel Morariu and Monica Lupsor-Platon
Diagnostics 2025, 15(21), 2671; https://doi.org/10.3390/diagnostics15212671 - 23 Oct 2025
Viewed by 1288
Abstract
Background and Objectives: Liver fibrosis is the key prognostic factor in patients with chronic liver diseases (CLD). Computed tomography (CT) is widely used in clinical practice, but it has limited value in assessing liver fibrosis in precirrhotic stages. Quantitative CT analysis based [...] Read more.
Background and Objectives: Liver fibrosis is the key prognostic factor in patients with chronic liver diseases (CLD). Computed tomography (CT) is widely used in clinical practice, but it has limited value in assessing liver fibrosis in precirrhotic stages. Quantitative CT analysis based on radiomics can provide additional information by extracting hidden image patterns, but the optimal approach remains to be determined. The aims of this study were to evaluate automated CT-based radiomic models for predicting biopsy-proven liver fibrosis, to compare different segmentation strategies and organ inclusions approaches, and to assess its performance against vibration-controlled transient elastography (VCTE). We also examined whether these models could predict liver steatosis. Methods: In this retrospective study, 58 patients with biopsy-proven CLD and 9 controls underwent VCTE and contrast-enhanced abdominal CT within three months of biopsy. Radiomic features were extracted from portal-venous-phase images using both two-dimensional (2D) and three-dimensional (3D) segmentations of the liver, spleen, and combined liver–spleen. Multilayer perceptron neural (MLP) networks were trained to predict fibrosis staging (≥F1, ≥F2, ≥F3, and F4) and steatosis grading (≥S1, ≥S2, and S3). Model performance was assessed using area under the receiver operating characteristic curve (AUROC) and accuracy. Results: The 3D radiomic models outperformed 2D models in predicting liver fibrosis stages. In the 3D radiomic model category, the combined 3D liver–spleen model achieved very good to excellent performance (AUROCs 0.974, 0.929, 0.928, and 0.898, respectively, for ≥F1, ≥F2, ≥F3, and F4), with comparable results to VCTE (AUROCs 0.921, 0.957, 0.968, and 0.909, respectively, for ≥F1, ≥F2, ≥F3, and F4). Radiomic models showed poor predictive ability for steatosis grades (AUROCs 0.44–0.69) compared to controlled attenuation parameter (CAP) (AUROCs 0.798–0.917). Conclusions: CT-based radiomic models showed potential for predicting liver fibrosis stage. The 3D model of liver and spleen had the highest performance, comparable to VCTE. This approach could be valuable in clinical settings where elastography is unavailable or inconclusive and for opportunistic screening in patients already undergoing CT for other medical indications. In contrast, portal-venous-phase radiomics lacked predictive value for steatosis assessment. Larger, multicenter studies are required to validate these results. Full article
(This article belongs to the Special Issue Artificial Intelligence-Driven Radiomics in Medical Diagnosis)
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18 pages, 272 KB  
Review
Racial, Ethnic and Age Disparities in Liver Fibrosis Screening Using Fibrosis Score Measures: A Critical Review of Diagnostic Equity in Liver Disease
by Ethan Shamsian, Michael Bebawy, Zachary Israeli, Mahinaz Mohsen, Rohan Karkra, Steven Rella, Raphael Shankman and Paul Gaglio
Livers 2025, 5(4), 51; https://doi.org/10.3390/livers5040051 - 21 Oct 2025
Viewed by 2585
Abstract
Metabolic-associated steatotic liver disease is currently one of the most common causes of liver disease in the world, affecting a large portion of the global population; these patients are at risk of developing advanced liver fibrosis and cirrhosis. Noninvasive tests (NITs), including lab [...] Read more.
Metabolic-associated steatotic liver disease is currently one of the most common causes of liver disease in the world, affecting a large portion of the global population; these patients are at risk of developing advanced liver fibrosis and cirrhosis. Noninvasive tests (NITs), including lab tests such as FIB-4, NAFLD Fibrosis Score and the Aspartate Aminotransferase-to-Platelet Ratio Index, are widely used for fibrosis risk stratification, but their accuracy across various racial, ethnic, and age groups remains poorly characterized. This review examines disparities in NIT performance across these populations and the need for tailored screening strategies. A comprehensive, narrative literature review highlighted significant variability in NIT performance, with studies in African American, Hispanic and Asian patients all revealing mixed results when the performance of NITs was used to assess fibrosis levels. Additionally, the age of patients may influence fibrosis testing, as older adults tend to have higher false-positive rates due to age-based biases. Although imaging modalities like VCTE and MRE may offer superior accuracy in the noninvasive assessment of hepatic fibrosis, they face accessibility limitations and have rarely been validated in specific racial groups. This review concludes that current NITs for MASLD risk stratification needs to be recalibrated with population-specific and age-adjusted thresholds, and future research should focus on inclusive validation studies and integrating clinical judgment to improve screening accuracy. Full article
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