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13 pages, 958 KB  
Article
Liver Stiffness Variability and Limited Performance of Non-Invasive Fibrosis Scores in Hemodialysis: A Prospective Study
by Karem Awad, Fadi Abu Baker, Mahmoud Foqara, Alexander Shtarkman, Abdellatif Zhalka, Tor Regev-Sadeh and Rawi Hazzan
Diagnostics 2026, 16(13), 2080; https://doi.org/10.3390/diagnostics16132080 (registering DOI) - 2 Jul 2026
Viewed by 139
Abstract
Background: Transient elastography (TE) is widely used for noninvasive assessment of liver fibrosis. In patients undergoing hemodialysis, however, liver stiffness measurements (LSM) may be affected by rapid intradialytic changes in volume status, venous congestion, and other non-fibrotic determinants. We prospectively evaluated peridialytic variability [...] Read more.
Background: Transient elastography (TE) is widely used for noninvasive assessment of liver fibrosis. In patients undergoing hemodialysis, however, liver stiffness measurements (LSM) may be affected by rapid intradialytic changes in volume status, venous congestion, and other non-fibrotic determinants. We prospectively evaluated peridialytic variability in liver stiffness and the concordance of serum fibrosis indices with elevated LSM in patients receiving maintenance hemodialysis. Methods: In this prospective paired pilot study, 45 adults on maintenance hemodialysis underwent LSM and controlled attenuation parameter (CAP) assessments immediately before and after a dialysis session; paired data were available for 41 patients. The Fibrosis-4 index (FIB-4) and the aspartate aminotransferase-to-platelet ratio index (APRI) were calculated from routine laboratory values. Paired comparisons, correlation analyses, and receiver operating characteristic curves were used to assess within-patient changes and the ability of serum indices to identify elevated pre-dialysis liver stiffness (LSM ≥ 8 kPa). Because no histologic or imaging reference standard for fibrosis was available, these analyses were interpreted as evidence of concordance with elevated LSM rather than as diagnostic accuracy for liver fibrosis. Results: Median LSM was 7.1 kPa (interquartile range [IQR] 5.2–12.1) pre-dialysis and 7.7 kPa (IQR 5.8–12.2) post-dialysis, with no significant paired change (median ΔLSM −0.2 kPa [IQR −1.1 to 1.2]; p = 0.898). However, the proportion with LSM ≥ 8 kPa increased from 36.6% to 46.3%, with 4 of 41 patients (9.8%) newly exceeding the threshold. CAP values showed no significant paired change (p = 0.511). Intradialytic weight loss was not associated with ΔLSM (rho = −0.13, p = 0.44). FIB-4 and APRI showed poor correlation with LSM and limited concordance with elevated LSM (area under the curve 0.553 and 0.578, respectively, with wide confidence intervals). Conclusions: In this exploratory hemodialysis cohort, cohort-level median LSM did not change significantly after dialysis, but clinically relevant individual-level reclassification occurred in approximately 10% of patients. Measurement timing may alter LSM-based classification, underscoring the need for dialysis-specific validation of LSM thresholds and noninvasive assessment strategies. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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15 pages, 2322 KB  
Article
Diagnostic Performance of Microvascular Imaging for Detecting Histologically Confirmed Liver Fibrosis in Autoimmune Hepatitis: Comparison with Transient Elastography and Serum Biomarkers
by Nazugum Ashimova, Aigul Raissova, Evgeniy Yenin, Rabiga Khozhamkul, Zhamilya Zholdybay, Maigul Shamshidinova, Takhmina Usenova, Andreas Teufel, Aigerim Mustapayeva and Alexander Nersesov
Diagnostics 2026, 16(13), 2072; https://doi.org/10.3390/diagnostics16132072 - 2 Jul 2026
Viewed by 128
Abstract
Background/Objectives: Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease that may progress to cirrhosis and liver failure if not diagnosed early. Although liver biopsy remains the reference standard for fibrosis assessment, its invasive nature limits routine use. This study aimed to [...] Read more.
Background/Objectives: Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease that may progress to cirrhosis and liver failure if not diagnosed early. Although liver biopsy remains the reference standard for fibrosis assessment, its invasive nature limits routine use. This study aimed to compare the diagnostic performance of ultrasound-based microvascular imaging (MVI), transient elastography (TE), and serum fibrosis indices (APRI and FIB-4) in patients with biopsy-confirmed AIH. Methods: Fifty-five patients with probable or definite AIH according to IAIHG criteria were included in the study. All patients underwent liver biopsy, and fibrosis stage was assessed using the METAVIR system. TE and MVI examinations were performed, and APRI and FIB-4 scores were calculated. Diagnostic performance was evaluated using AUROC, sensitivity, and specificity. Spearman correlation and logistic regression analyses were additionally performed. Results: The mean age of the patients was 49.2 years, and most patients were women. Cirrhosis was present in 58.2% of the cohort. TE demonstrated high diagnostic accuracy, whereas FIB-4 showed moderate performance and APRI demonstrated limited utility. MVI achieved the highest diagnostic performance, with AUROC values of 0.99 for significant fibrosis and 0.97 for cirrhosis. MVI showed the strongest correlation with histological fibrosis stage (r = 0.916, p < 0.001), followed by TE (r = 0.907, p < 0.001). MVI was strongly associated with histologically confirmed cirrhosis (OR 16.7, 95% CI 2.36–118.2, p = 0.004). Conclusions: MVI demonstrates diagnostic performance comparable to TE and may represent a promising adjunctive non-invasive imaging biomarker for fibrosis assessment in AIH. Larger multicenter studies are required for external validation before routine clinical implementation. Full article
(This article belongs to the Special Issue Diagnostic Imaging in Gastrointestinal and Liver Diseases)
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14 pages, 876 KB  
Article
Development and Internal Validation of a Novel Pediatric-Adapted Liver (PAL) Score for Predicting Advanced Fibrosis: Comparison with Transient Elastography
by Alexandru-Ștefan Niculae, Alina Grama, Gabriel Bența, Alexandra Mititelu, Sorina Adam and Tudor Lucian Pop
Livers 2026, 6(4), 58; https://doi.org/10.3390/livers6040058 - 26 Jun 2026
Viewed by 190
Abstract
Background & Aims: Accurate assessment of liver fibrosis is important for the management of pediatric chronic liver disease (CLD). Transient Elastography (TE) has emerged as a validated non-invasive method for accurately assessing hepatic fibrosis, yet it remains available only in specialized centers [...] Read more.
Background & Aims: Accurate assessment of liver fibrosis is important for the management of pediatric chronic liver disease (CLD). Transient Elastography (TE) has emerged as a validated non-invasive method for accurately assessing hepatic fibrosis, yet it remains available only in specialized centers and requires specialized equipment. We aimed to develop and internally validate a novel, simple, blood-based scoring system—the pediatric-adapted liver score (PAL score)—to predict advanced fibrosis as defined by liver stiffness, measured using TE across diverse etiologies. Methods: A retrospective study was conducted on 107 pediatric patients with CLD who underwent liver stiffness measurement through TE. Advanced fibrosis was defined as a liver stiffness measurement corresponding to the F3 METAVIR stage or above. Independent predictors of advanced fibrosis were identified using multivariable logistic regression with manual backward elimination. To facilitate bedside utility, the regression model was simplified into a ratio-based index. Performance was assessed via the area under the receiver operating characteristic curve (AUROC) and validated using bootstrap resampling (10,000 iterations). Results: Gamma-glutamyl transferase (GGT), platelets, and albumin were identified as independent predictors of fibrosis. The simplified PAL score demonstrated good discrimination with an AUROC of 0.901 (95% CI: 0.84–0.95). While statistically equivalent to the adult-derived GGT-to-platelet ratio (GPR) and S-Index, the PAL score incorporates parameters of hepatic synthesis and portal hypertension that are absent from other ratios and is easier to calculate at the patient’s bedside. At a clinically practical integer cut-off of 5.0, the score achieved a sensitivity of 95.5% and a negative likelihood ratio of 0.06, effectively ruling out advanced fibrosis. Bootstrap validation confirmed the stability of the model (bootstrap-corrected AUC 0.901). Conclusions: The PAL score is the first simple fibrosis index derived for a diverse pediatric population. Highlighting its primary strength as a highly effective screening tool, the score achieves a sensitivity of 95.5% and a negative likelihood ratio of 0.06 at a user-friendly cut-off of 5. These robust metrics allow clinicians to confidently rule out advanced fibrosis, offering an accessible triage alternative in primary care settings where transient elastography is unavailable. Full article
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14 pages, 788 KB  
Article
Role of Hypoxia-Inducible Factor-1α in the Pathophysiology of Non-Alcoholic Fatty Liver Disease Among Obstructive Sleep Apnea Patients: A Case-Control Study
by Rana Toghan, Tarek A. Salem, Eptehal Dongol, Fatma Rabea A. Hamdan, Omyma Galal Ahmed, Ahlam Mohammed Sabra Ali, Mohammed H. Hassan, Marwa Abdelhady and Rehab H. Abdel-Aziz
J. Clin. Med. 2026, 15(13), 4861; https://doi.org/10.3390/jcm15134861 - 23 Jun 2026
Viewed by 196
Abstract
Background: Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH), which causes numerous metabolic changes, leading to non-alcoholic fatty liver disease (NAFLD). Our study explored the suggested role of hypoxia-inducible factor 1-α (HIF-1α) in the pathophysiological mechanisms linking OSA with NAFLD. [...] Read more.
Background: Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH), which causes numerous metabolic changes, leading to non-alcoholic fatty liver disease (NAFLD). Our study explored the suggested role of hypoxia-inducible factor 1-α (HIF-1α) in the pathophysiological mechanisms linking OSA with NAFLD. Methods: This case-control study was conducted at the Sleep Disorders Unit at Qena University Hospital from March 2022 to October 2023, including 64 subjects (48 OSA patients; in a secondary analysis, OSA patients were further stratified according to the presence or absence of NAFLD–16 controls) who were subjected to a polysomnography (PSG) for apnea hypopnea index (AHI) and transient elastography for controlled attenuation parameter (CAP) score and liver stiffness measurement (LSM). Serum levels of HIF 1-α, fasting blood glucose, and fasting insulin were measured. Results: HIF-1α level showed the highest significant value was in the severe group (p = 0.001). Additionally, the severe group had the highest LSM compared to the other groups (p = 0.032). OSA patients with NAFLD, compared to OSA patients without NAFLD, showed significantly higher BMI (42.74 vs. 29.11 kg/m2, p < 0.001), homeostatic model assessment for insulin resistance (HOMA-IR) mean score (3.92 vs. 1.21, p < 0.0001), HIF-1α level (6.01 vs. 2.14 ng/L, p = 0.045), and the LSM score (5.55 vs. 3.85 kPa, p < 0.001). HIF-1α showed significant positive correlations with AHI (r = 0.515, p < 0.001), waist circumference WC (r = 0.291, p = 0.045), HSI (r = 0.3, p = 0.038), and CAP score (r = 0.288, p = 0.047). Conclusions: Although serum HIF-1α levels were significantly higher in OSA patients with NAFLD and correlated with indices of hepatic steatosis, HIF-1α was not identified as an independent predictor of NAFLD after adjustment for metabolic confounders, suggesting a potential role of hypoxia-responsive pathways in pathophysiology of NAFLD in OSA. Full article
(This article belongs to the Section Respiratory Medicine)
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13 pages, 1499 KB  
Article
A New Ultrasound Method to Study the Relations Between Ileocecal Valve Incontinence and Inflammation in Metabolic Associated Steatotic Liver Disease
by Antonio Salvati, Lorenzo Bertellotti, Francesco Faita, Daniela Campani, Giovanni Petralli, Simone Cappelli, Ferruccio Bonino and Maurizia Rossana Brunetto
Livers 2026, 6(3), 54; https://doi.org/10.3390/livers6030054 - 18 Jun 2026
Viewed by 296
Abstract
Background: Small intestine bacterial overgrowth (SIBO) is associated with steatohepatitis (SH) in subjects with metabolic-associated steatotic liver disease (MASLD). The impact of ileocecal valve (ICV) incontinence, a major cause of SIBO in patients with MASLD, remains unknown because of the unmet need for [...] Read more.
Background: Small intestine bacterial overgrowth (SIBO) is associated with steatohepatitis (SH) in subjects with metabolic-associated steatotic liver disease (MASLD). The impact of ileocecal valve (ICV) incontinence, a major cause of SIBO in patients with MASLD, remains unknown because of the unmet need for a non-X-ray-dependent diagnosis. Methods: Exploiting water as contrast medium and colonic irrigation via a hydro-colon machine (Clean Colon Srl, Monza, Italy), we developed a new abdominal ultrasound (US) procedure for diagnosing and grading ICV incontinence. In a pilot, observational, feasibility and safety study, we correlated a new ICV incontinence parameter with irritable bowel syndrome (IBS, ROMA IV criteria), serum transaminases (AST, ALT), platelet counts, FIB-4, US liver steatosis and stiffness (LS, measured by Shear Wave and Transient Elastography, SWE and TE). Results: We prospectively studied 32 consecutive subjects with IBS who underwent a pre-colonoscopy colon cleansing after informed consent: 19 males (59%), body mass index (BMI) 26.6 ± 2.6 kg/m2, age 57 ± 19 years, 16 (50%) with US liver steatosis. The half-hour (27 min, range 20–35 min) procedure was safe and well tolerated except in two males with prostate hypertrophy. ICV incontinence was graded (after 2500–3000 mL irrigation) according to cecum/right-colon distention with/without (immediate or delayed) reflux into terminal ileum (TI): 0 = cecum distension without TI reflux; 1 = cecum distension with TI reflux; 2 = absence of cecum distension with TI reflux. Cecum/right-colon distention (grade 0 or 1) was perceived by the patients whereas the right colon irrigation with complete ICV incontinence (grade 2) was symptomless. ICV continence associated with LS (p ≤ 0.0001). A histologic diagnosis of non-alcoholic steatohepatitis was confirmed in a 35-year-old obese male with SIBO and LS > 8 kPa (8.7/8.5 kPa by SWE/TE):steatosis (grade S3) with hepatocyte ballooning, lobular inflammation (grade 6/8) without fibrosis (stage 0/4, F0). Conclusions: The new US-based approach provides a feasible, easy-to-perform, mini-invasive tool for the diagnosis and grading of ICV incontinence. Preliminary results prompt prospective studies investigating the impact of ICV incontinence as a possible co-factor of steatohepatitis in patients with MASLD. Full article
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11 pages, 2502 KB  
Review
Summary of Guidelines for Identifying and Risk-Stratifying Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: A Primer for Family Physicians
by Mitchell P. Wilson, Abdel-Aziz Shaheen, Victoria Leung, An Tang, Andreu F. Costa, Casey Hurrell and Gavin Low
Diagnostics 2026, 16(12), 1854; https://doi.org/10.3390/diagnostics16121854 - 15 Jun 2026
Viewed by 216
Abstract
Multiple North American and European societies now endorse a combined serological and imaging-based clinical care pathway for non-invasive risk stratification of patients with metabolic dysfunction-associated steatotic liver disease (MASLD). A multidisciplinary group of Canadian radiologists, hepatologists, family physicians, and other health professionals have [...] Read more.
Multiple North American and European societies now endorse a combined serological and imaging-based clinical care pathway for non-invasive risk stratification of patients with metabolic dysfunction-associated steatotic liver disease (MASLD). A multidisciplinary group of Canadian radiologists, hepatologists, family physicians, and other health professionals have recently published consensus guidelines for identification and risk stratification of patients with suspected MASLD. Screening should be performed with the FIB-4 score, and those with an indeterminate FIB-4 (between 1.32.67) should undergo imaging-based liver stiffness evaluation either with transient elastography (FibroScan), ultrasound shear wave elastography, or magnetic resonance elastography as a second step. While the implementation of these techniques for measuring liver stiffness differ, there is no clinically significant difference in their diagnostic performance. This narrative review, intended for Family Physicians, summarizes recommendations for serological investigations and imaging modalities of liver steatosis and stiffness. Practical guidance includes an algorithm with thresholds. We discuss current challenges and future directions of risk-stratifying patients with MASLD in the community. Full article
(This article belongs to the Special Issue Clinical Diagnosis and Management of Liver Diseases)
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15 pages, 503 KB  
Systematic Review
Prevalence of Liver Fibrosis and Cirrhosis in High-Risk and Hospital-Based Populations in Morocco: A Systematic Review and Narrative Synthesis
by Rahma Ennadi, Hicham Esselmani, Youssef Nadir, Mustapha Najimi and Mohamed Merzouki
Livers 2026, 6(3), 52; https://doi.org/10.3390/livers6030052 - 12 Jun 2026
Viewed by 283
Abstract
Background: Liver diseases are an increasing public health concern in Morocco; reliable national population-based estimates of liver fibrosis and cirrhosis in Morocco are currently unavailable. Existing evidence is largely limited to selected high-risk groups and hospital-based cohorts. Generating reliable prevalence data is crucial [...] Read more.
Background: Liver diseases are an increasing public health concern in Morocco; reliable national population-based estimates of liver fibrosis and cirrhosis in Morocco are currently unavailable. Existing evidence is largely limited to selected high-risk groups and hospital-based cohorts. Generating reliable prevalence data is crucial for designing evidence-based screening pathways, targeting high-risk groups and informing prevention and treatment policies. Objectives: Our aim was to comprehensively review studies on the prevalence of liver fibrosis and cirrhosis in Morocco, focusing on characterizing study populations, specifically high-risk populations and hospital-based cohorts, diagnostic methods and thresholds used. The review also summarizes hospital-based cirrhosis cohorts without merging them with prevalence estimates, and identifies gaps in the literature, particularly the absence of population-based prevalence studies and national epidemiological data in Morocco. Methods: The study systematically reviewed literature up to 26 October 2025, including studies conducted in Morocco among high-risk populations or hospital-based cirrhosis cohorts, using multiple databases. Two reviewers independently screened and extracted data, assessing bias with the Joanna Briggs Institute (JBI) checklist. Due to heterogeneity in study populations and diagnostic approaches, a narrative synthesis was performed. Hospital-based cohorts were analyzed separately to provide contextual information and were not included in prevalence estimates. Results: From 1198 records, four Moroccan studies providing prevalence data on liver fibrosis and cirrhosis were included, primarily involving patients with hepatitis C, HIV, or rheumatoid arthritis. Additionally, three hospital-based cirrhosis cohorts were incorporated for a contextual analysis of disease severity and complications. In total, seven studies were included, with prevalence and hospital-based data analyzed separately to ensure clarity. Conclusions: Current evidence on liver disease in Morocco is limited but suggests a significant burden among high-risk groups. The findings highlight major gaps in national epidemiological data and underscore the urgent need for comprehensive nationwide data and improved diagnostic tools to guide effective screening, prevention, and resource allocation. Full article
(This article belongs to the Special Issue Epidemiology of Chronic Liver Disease and Cirrhosis)
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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 227
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 488
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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24 pages, 2376 KB  
Review
Advances in Diagnostic and Therapeutic Strategies for Metabolic Dysfunction-Associated Steatotic Liver Disease
by Ryan Njeim, Omar Abureesh, Ali Sohail, Ryan Tam and Liliane Deeb
Livers 2026, 6(3), 35; https://doi.org/10.3390/livers6030035 - 6 May 2026
Viewed by 1466
Abstract
The recent redefinition of steatotic liver diseases, introducing metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), reflects a growing consensus among liver societies and marks a paradigm shift in disease classification. MASLD subsumes former categories of nonalcoholic fatty liver disease [...] Read more.
The recent redefinition of steatotic liver diseases, introducing metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), reflects a growing consensus among liver societies and marks a paradigm shift in disease classification. MASLD subsumes former categories of nonalcoholic fatty liver disease (NAFLD) and incorporates metabolic criteria alongside moderate alcohol intake, while MASH replaces nonalcoholic steatohepatitis (NASH), aligning terminology with disease mechanisms. This evolution clarifies the diagnostic criteria and minimizes stigma, facilitating more consistent epidemiological and clinical investigations. Recent advances in noninvasive diagnostics, including vibration-controlled transient elastography, magnetic resonance elastography, shear-wave elastography, and the Enhanced Liver Fibrosis test, have improved the identification and stratification of patients with advanced fibrosis. Current guidelines recommend targeted screening in populations at elevated metabolic risk, enabling earlier intervention and personalized management. Population studies indicate that MASLD affects over one-third of adults and is a major contributor to cardiovascular and metabolic morbidity. Therapeutic progress is highlighted by the approval of novel agents such as resmetirom and semaglutide for the treatment of MASH with fibrosis. Emerging dual and triple agonists, as well as sodium–glucose cotransporter inhibitors, offer additional promise, although further research is required to define their long-term efficacy and safety. As the disease prevalence escalates globally, the integration of multidisciplinary care, the ongoing refinement of diagnostic tools, and the expansion of therapeutic options will remain essential to optimizing outcomes for affected individuals. Full article
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17 pages, 1427 KB  
Article
Small Intestinal Bacterial Overgrowth in Metabolic Dysfunction-Associated Steatotic Liver Disease: Prevalence, Subtypes, and Risk Factors Across Disease Spectrum and Comorbidity Profiles
by Yangjie Li, Huiping He, Limin Chen, Jing Chen, Man Gu, Yueyan Hu, Lirong Guo, Siheng Long, Jiaying Hu, Zhukun Zhou, Yao Xiao, Zihan Wu and Hongju Yang
Biomedicines 2026, 14(5), 1042; https://doi.org/10.3390/biomedicines14051042 - 3 May 2026
Viewed by 1066
Abstract
Background: Small intestinal bacterial overgrowth (SIBO) has been implicated in the pathogenesis of MASLD; however, large-scale clinical data characterizing prevalence patterns, phenotypic subtypes, and disease-specific associations remain limited. Methods: This cross-sectional study enrolled 2549 MASLD patients with gastrointestinal symptoms undergoing lactulose [...] Read more.
Background: Small intestinal bacterial overgrowth (SIBO) has been implicated in the pathogenesis of MASLD; however, large-scale clinical data characterizing prevalence patterns, phenotypic subtypes, and disease-specific associations remain limited. Methods: This cross-sectional study enrolled 2549 MASLD patients with gastrointestinal symptoms undergoing lactulose methane–hydrogen breath testing and transient elastography. Univariate and multivariable analysis identified independent risk factors for SIBO. We also explore the distribution of SIBO subtypes and their associations with comorbidity profiles across the MASLD spectrum. Results: The overall prevalence of SIBO was 66.3%, escalating from 65.9% in MASL to 72.8% in at-risk MASH and 78.9% in cirrhosis, alongside a notable enrichment of the intestinal methanogen overgrowth (IMO) phenotype. Multivariable analysis identified advanced fibrosis (stage F4; OR = 1.75, 95% CI: 1.03–2.96), gastroesophageal reflux disease (GERD; OR = 1.66, 95% CI: 1.22–2.28), and coronary artery disease (CAD; OR = 1.80, 95% CI: 1.06–3.06) as independent predictors of SIBO. Additionally, elevated ALT (OR = 1.01, 95% CI: 1.01–1.13) showed a modest association with SIBO. Subtype analysis revealed that IMO was associated with GERD, alcohol consumption, CAD, and obesity, while a history of cholecystectomy and elevated triglycerides were linked to early-phase hydrogen peaks. Conclusions: SIBO is highly prevalent among patients with MASLD, with its prevalence and phenotypic subtype distribution being closely associated with disease severity. The identification of fibrosis-specific risk factors and subtype–clinical associations suggest consideration of SIBO assessment in advanced MASLD, particularly in patients with cardiometabolic or gastrointestinal comorbidities. Full article
(This article belongs to the Special Issue Small Intestinal Bacterial Overgrowth and Antimicrobial)
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13 pages, 2334 KB  
Article
Cut or Count? Evaluating Advanced Fibrosis Assessment Tools in MASH and Chronic Viral Hepatitis
by Ivana Milošević, Branko Beronja, Nada Tomanović, Marina Đelić, Nikola Mitrović, Dragana Kalajanović and Ankica Vujović
Biomedicines 2026, 14(5), 988; https://doi.org/10.3390/biomedicines14050988 - 25 Apr 2026
Viewed by 857
Abstract
Background/Objectives: Chronic liver diseases, including metabolic dysfunction-associated steatohepatitis (MASH) and chronic viral hepatitis (CVH), are major global health concerns due to their potential progression to cirrhosis, liver failure, and hepatocellular carcinoma. Because liver biopsy, despite meeting the diagnostic gold standard, is invasive [...] Read more.
Background/Objectives: Chronic liver diseases, including metabolic dysfunction-associated steatohepatitis (MASH) and chronic viral hepatitis (CVH), are major global health concerns due to their potential progression to cirrhosis, liver failure, and hepatocellular carcinoma. Because liver biopsy, despite meeting the diagnostic gold standard, is invasive and associated with complications, non-invasive fibrosis assessment tools have been increasingly recommended in clinical practice. This study aimed to compare the diagnostic performance of several non-invasive fibrosis markers (ARR, APRI, FI, FIB-4, API, NFS, BARD) and transient elastography in detecting advanced liver fibrosis (F4) in patients with MASH and CVH. Methods: This retrospective study included 237 adult patients (77 MASH, 160 CVH) who underwent liver biopsy between 2017 and 2025 at the University Clinical Center of Serbia. CVH included chronic hepatitis B (CHB) and C (CHC). Patients were evaluated using serum fibrosis indices and TE, and results were compared to histological staging (F0–F4). ROC analysis assessed diagnostic performance. Results: Cirrhosis (F4) was more common in CVH than MASH (p < 0.001). In MASH, NFS (AUROC 0.931), FIB-4 (0.915), BARD (0.872), and APRI (0.878) showed high diagnostic accuracy for F4. In CHC, APRI (0.931), FIB-4 (0.863), and TE (0.938) had strong performance, while in CHB, TE (0.987) outperformed FIB-4 (0.821). Sensitivity and specificity varied by test and cohort, with TE consistently yielding the best results where available. Conclusions: Non-invasive methods, particularly NFS and FIB-4 for MASH and TE for CVH, effectively identify advanced fibrosis. Their application could significantly reduce the need for biopsy, especially in high-risk groups. TE demonstrated superior accuracy, but access limitations highlight the continued relevance of serum-based scores. Full article
(This article belongs to the Special Issue Viral Hepatitis: From Pathophysiology to Therapeutic Approaches)
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18 pages, 349 KB  
Review
Autoimmune Hepatitis: Emerging Frontiers in Research and Clinical Management
by Armando Curto, Irene Scami, Giulia Gliottone, Rocco G. Iamello, Erica N. Lynch and Andrea Galli
Gastrointest. Disord. 2026, 8(2), 20; https://doi.org/10.3390/gidisord8020020 - 20 Apr 2026
Viewed by 1471
Abstract
Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disorder that, without treatment, can advance to fibrosis and cirrhosis. Although standard regimens with corticosteroids and thiopurines have significantly improved survival, many patients still experience relapses and drug-related toxicity, highlighting the urgent need for alternative [...] Read more.
Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disorder that, without treatment, can advance to fibrosis and cirrhosis. Although standard regimens with corticosteroids and thiopurines have significantly improved survival, many patients still experience relapses and drug-related toxicity, highlighting the urgent need for alternative strategies. Recent studies underscore AIH’s multifactorial nature, revealing intricate interactions among genetic susceptibility, environmental triggers, and dysregulated immune responses. Next-generation diagnostics, ranging from novel biomarkers to high-resolution imaging, are enhancing early detection and more precise disease classification. At the same time, multi-omics analyses and artificial-intelligence-based models are refining predictions of disease trajectory and therapeutic response. On the treatment horizon, investigational options such as targeted immunomodulators, B-cell–depleting therapies, and cell-based interventions aim to achieve durable remission while minimizing adverse effects. This review critically appraises these advances and explores how integrating epidemiological insights with cutting-edge research in pathogenesis, diagnostics, and therapy could pave the way for more personalized and effective management of AIH. Full article
(This article belongs to the Special Issue Feature Papers in Gastrointestinal Disorders in 2025–2026)
19 pages, 944 KB  
Article
Association of Life’s Essential 8 with Hepatic Fibrosis, MASLD, and MetALD in the Framingham Heart Study
by Alejandro Campos, Tianyu Liu, Brenton Prescott, Jiantao Ma, Madeleine G. Haff, Maura E. Walker, Arpan Mohanty and Vanessa Xanthakis
Nutrients 2026, 18(8), 1276; https://doi.org/10.3390/nu18081276 - 17 Apr 2026
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Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated liver disease (MetALD), and related fibrosis are increasingly prevalent conditions. The relation of the American Heart Association’s (AHA) cardiovascular health (CVH) metric Life’s Essential 8 (LE8) with MASLD, MetALD, and hepatic fibrosis [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated liver disease (MetALD), and related fibrosis are increasingly prevalent conditions. The relation of the American Heart Association’s (AHA) cardiovascular health (CVH) metric Life’s Essential 8 (LE8) with MASLD, MetALD, and hepatic fibrosis remains unclear. We aimed to investigate the associations of CVH with MASLD, MetALD, and hepatic fibrosis. Methods: We defined significant hepatic fibrosis as a liver stiffness ≥8.2 kPa measured by vibration-controlled transient elastography. MASLD was defined as steatosis (controlled attenuation parameter of ≥274 dB/m) with ≥1 cardiometabolic risk factor and mild alcohol intake (≤140 g/week [women]; ≤210 g/week [men]). MetALD was defined as steatosis with ≥1 cardiometabolic risk factor and moderate alcohol intake (141–350 g/week [women]; 211–420 g/week [men]). Data from 2962 participants in the Framingham Heart Study (mean age 59 years, 57% women) were used in multivariable-adjusted logistic regression models, accounting for demographic and clinical covariates to relate CVH and liver outcomes. Results: Our study included 2704 participants with mild and 258 with moderate alcohol use. MASLD and MetALD prevalence was 34% and 40%, respectively, and 9% had significant hepatic fibrosis. Each 10-point increase in LE4 score (composite of diet, sleep health, physical activity, and smoking) was associated with 16% lower odds of MASLD (Odds Ratio [OR] 0.84; 95% CI: 0.80–0.90; p < 0.001) but not MetALD. Each 10-point increase in LE8 score was associated with 17% lower odds of hepatic fibrosis (OR 0.83; 95% CI: 0.78–0.89; p < 0.001). Conclusions: Better CVH is related to lower odds of MASLD and significant hepatic fibrosis. Full article
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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
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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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