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Keywords = transient elastography (TE)

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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 164
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 137
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 195
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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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 300
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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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 859
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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16 pages, 293 KB  
Article
Performance of Blood-Based Indirect Scores Compared to Transient Elastography in Children with Chronic Liver Disease
by Alexandru-Ștefan Niculae, Alina Grama, Monica Lupșor-Platon, Alexandra Mititelu, Gabriel Bența, Sorina Adam and Tudor Lucian Pop
Diagnostics 2026, 16(7), 1102; https://doi.org/10.3390/diagnostics16071102 - 6 Apr 2026
Cited by 1 | Viewed by 531
Abstract
Background: Chronic liver disease (CLD) in children requires long-term monitoring. Liver biopsy and transient elastography (TE) are resource-intensive methods that require specialized equipment and trained personnel. Simple indirect fibrosis scores based on routine laboratory parameters offer a potentially cost-effective alternative but have [...] Read more.
Background: Chronic liver disease (CLD) in children requires long-term monitoring. Liver biopsy and transient elastography (TE) are resource-intensive methods that require specialized equipment and trained personnel. Simple indirect fibrosis scores based on routine laboratory parameters offer a potentially cost-effective alternative but have not been systematically evaluated in pediatric populations with diverse CLD etiologies. Objectives: This study aimed to assess the performance of several indirect fibrosis and cirrhosis scores in predicting significant (≥F2) and advanced (≥F3) fibrosis and cirrhosis (F4) in children with CLD using TE as a comparator. Methods: We retrospectively reviewed medical records of children with CLD evaluated at a tertiary center between January 2023 and June 2025. TE results and routine laboratory data were used to calculate fibrosis scores, including APRI, FIB-4, FibroIndex, FORNS, GPR, GUCI, King’s score, and Lok’s index. ROC analyses were performed to assess each score’s ability to discriminate significant fibrosis, advanced fibrosis and cirrhosis. Optimal cut-offs were established using the Youden index. Results: GPR showed the strongest concordance with TE-based fibrosis classification across both fibrosis thresholds, achieving an AUROC of 0.835 for significant fibrosis and a superior 0.917 for advanced fibrosis. FibroIndex and APRI also demonstrated good discriminatory power for advanced disease. Utilizing mathematically optimized cut-offs, GPR (0.45) and APRI (0.84) achieved good negative predictive values (100% and 95%) and sensitivities (100% and 85%) for advanced fibrosis, establishing them as potentially valuable screening tools. For cirrhosis detection (F4), Lok’s Index performed best (AUROC 0.854). Conclusions: In this diverse pediatric cohort, simple indirect scores—particularly GPR, APRI, and FibroIndex—demonstrated the highest concordance relative to TE findings, with negative predictive values up to 100% for GPR. This indicates that they can serve as reliable first-line screening tools when TE is unavailable. While their good negative predictive values allow for the confident exclusion of severe disease—potentially sparing many children from invasive testing—their low positive predictive values limit their role in definitive diagnosis. The systematic failure of adult-derived, age-dependent formulas in this cohort underscores the critical need for specialized pediatric biomarkers. Full article
16 pages, 414 KB  
Article
From Birth to Midlife—Liver Function, Fibrosis and Mortality in Individuals with Severe Alpha-1-Antitrypsin Deficiency Identified by Neonatal Screening
by Georg Rüdiger Schramm, Mohammed Abdulrasak, Suneela Zaigham, Eeva Piitulainen and Hanan Tanash
J. Clin. Med. 2026, 15(7), 2553; https://doi.org/10.3390/jcm15072553 - 27 Mar 2026
Viewed by 671
Abstract
Background: Severe Alpha-1-Antitrypsin deficiency (AATD), phenotype PiZZ, is a leading cause of liver disease in neonates, children, and adults. Nevertheless, the prevalence of liver disease and mortality within PiZZ adults remains unclear. Between 1972 and 1974, a cohort of 129 individuals with [...] Read more.
Background: Severe Alpha-1-Antitrypsin deficiency (AATD), phenotype PiZZ, is a leading cause of liver disease in neonates, children, and adults. Nevertheless, the prevalence of liver disease and mortality within PiZZ adults remains unclear. Between 1972 and 1974, a cohort of 129 individuals with severe AATD (PiZZ) was identified through the Swedish national screening of 200,000 newborns. The cohort has been followed up regularly since birth. This prospective cohort follow-up study, with a cross-sectional comparison at 50 years of age, aims to characterize the natural history of liver disease and mortality in this cohort in their early fifties, compared with an age-matched control group (PiMM) randomly selected from the population registry. Methods: Study participants completed questionnaires regarding occupation, medical history, medication, and alcohol consumption. They underwent physical examination and measurement of liver stiffness using transient elastography (TE, FibroScan®). Blood samples were obtained for evaluation of liver function, alcohol consumption, calculation of liver fibrosis scores, and detection of viral hepatitis and autoimmune liver disease. Results: Ninety-five PiZZ and 124 PiMM individuals participated in the study, of whom 47 PiZZ and 96 PiMM underwent TE measurement. PiZZ individuals had significantly higher median liver stiffness compared with PiMM individuals (5.9 kPa vs. 4.5 kPa, p < 0.01). No significant differences were found in Fib-4 score or the Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS) between the groups. Since identification of the cohort at birth, 13 (10%) of the 129 PiZZ individuals have died. Of these, liver disease was the main or underlying cause of death in 8 individuals (6%). Conclusions: In their early fifties, PiZZ individuals show a small but significant increase in liver stiffness measured by TE, indicating early liver fibrosis. In contrast, conventional fibrosis scores, such as Fib-4 and NFS, do not differ between PiZZ individuals and PiMM, suggesting that serum-based fibrosis scores may underestimate fibrosis in AATD. In this cohort, liver disease and its complications represented the main cause of death in PiZZ individuals by the age of 50, an observation that is uncommon in the general population at this age. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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14 pages, 967 KB  
Article
Acute Changes in Liver and Spleen Stiffness Following Endoscopic Variceal Ligation in Advanced Liver Disease—A Pilot Study
by Esra Görgülü, Eva Herrmann, Jonel Trebicka, Alexander Queck, Georg Dultz, Vitali Koch, Stefan Zeuzem, Jörg Bojunga, Viola Knop, Florian Alexander Michael and Mireen Friedrich Rust
J. Clin. Med. 2026, 15(2), 816; https://doi.org/10.3390/jcm15020816 - 20 Jan 2026
Viewed by 521
Abstract
Background/Objectives: Endoscopic variceal ligation (EVL) is a common treatment for preventing variceal bleeding in patients with advanced chronic liver disease (ACLD). However, its acute hemodynamic impact is typically assessed using invasive methods, and there is data on short-term spleen stiffness (SS) dynamics are [...] Read more.
Background/Objectives: Endoscopic variceal ligation (EVL) is a common treatment for preventing variceal bleeding in patients with advanced chronic liver disease (ACLD). However, its acute hemodynamic impact is typically assessed using invasive methods, and there is data on short-term spleen stiffness (SS) dynamics are limited. This pilot study aimed to quantify short-interval changes in liver stiffness (LS) and SS following EVL using transient elastography (TE), and to explore their associations with clinical and laboratory parameters. Methods: This prospective observational study enrolled adults with advanced liver disease undergoing esophagogastroduodenoscopy (EGD) with or without EVL at a tertiary center. Liver and spleen TE were performed in a fasted state immediately before endoscopy and repeated within 12 h after EVL. Organ-specific probes and predefined quality criteria were used, and non-parametric methods were applied to assess within-patient changes and correlations. Results: Fifty patients were included in the study: 21 underwent EVL, while the remaining 29 underwent diagnostic endoscopies only. The most common cause was alcohol-related liver disease. Within the EVL subgroup, the median liver stiffness (LSM) increased from 27.6 kPa to 45.1 kPa, and the median spleen stiffness (SSM) increased from 59.9 kPa to 98.3 kPa, both within 12 h. While these increases showed a uniform direction, they did not reach statistical significance. A higher baseline SS predicted a greater LS increase, and stiffness measures correlated with creatinine, disease duration, Child–Pugh class, albumin and ascites. Conclusions: Short-term increases in liver and spleen stiffness following EVL are consistent with acute hemodynamic alterations, such as increased hepatic perfusion and splenic congestion, rather than structural remodeling. These findings, beyond changes in stiffness alone, support the feasibility of integrating TE, particularly the measurement of SS, into early peri-procedural hemodynamic surveillance after EVL. They also justify larger studies with serial time points and direct portal pressure validation. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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16 pages, 953 KB  
Article
MASLD or MetALD? Unveiling the Role of Alcohol in Liver Disease Progression in Diabetic Patients
by Ermina Stratina, Carol Stanciu, Robert Nastasa, Sebastian Zenovia, Remus Stafie, Adrian Rotaru, Stefan Chiriac, Irina Girleanu, Cristina Muzica, Horia Minea, Laura Huiban and Anca Trifan
Biomedicines 2026, 14(1), 82; https://doi.org/10.3390/biomedicines14010082 - 31 Dec 2025
Viewed by 1001
Abstract
Background: The transition from the term non-alcoholic fatty liver disease (NAFLD) to steatotic liver disease (SLD), an umbrella term for several related conditions, offers benefits, particularly in identifying cardiometabolic risk factors more effectively. However, the impact of alcohol consumption on liver disease [...] Read more.
Background: The transition from the term non-alcoholic fatty liver disease (NAFLD) to steatotic liver disease (SLD), an umbrella term for several related conditions, offers benefits, particularly in identifying cardiometabolic risk factors more effectively. However, the impact of alcohol consumption on liver disease progression remains significant, leading to the recognition of a new entity: MetALD (metabolic dysfunction-associated steatotic liver disease with moderate alcohol intake). Aim: This study aimed to compare characteristics associated with liver disease progression in diabetic patients diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD) versus those with MetALD. Materials and Methods: In this prospective study, 286 diabetic patients were followed for 12 months. All patients underwent transient elastography (TE) and ultrasound to assess hepatic steatosis. Participants were classified into MASLD and MetALD groups. The performance of fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) were also evaluated. Results: MASLD was diagnosed in 58.2% (167 patients), of whom 4.9% (7 patients) had TE values suggestive for liver cirrhosis. Among those with MetALD, 17.6% (21 patients) had TE values compatible with advanced fibrosis. MASLD subjects presented a slight decrease in liver fibrosis values from 6.58 ± 2.27 kPa to 6.03 ± 1.57 kPa in the 12 months. On the contrary, MetALD subjects had an increase of liver stiffness measurements (LSM) values from 11.83 ± 6.27 kPa to 12.24 ± 8.66 kPa. Conclusions: in diabetic patients, the coexistence of moderate alcohol intake and cardiometabolic risk factors (MetALD) is associated with more advanced liver fibrosis and impaired long-term glycemic control, compared to MASLD alone. Full article
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18 pages, 1029 KB  
Article
Associations Between Systemic Inflammatory Markers, Metabolic Dysfunction, and Liver Fibrosis Scores in Patients with MASLD
by Ragaey Ahmad Eid, Ahmed Moheyeldien Hamed, Sara O. Elgendy, Khalid M. Orayj, Ahmed R. N. Ibrahim, Ahmed M. Abdel Hamied, Engy A. Wahsh, Maha Youssif, Hoda Rabea, Yasmin M. Madney, Dina Attia and Shaymaa Nafady
Metabolites 2026, 16(1), 25; https://doi.org/10.3390/metabo16010025 - 25 Dec 2025
Cited by 4 | Viewed by 1868
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a global health challenge due to its complex pathophysiological processes. Systemic inflammation may profoundly affect disease progression, but the correlation between inflammatory markers and disease severity remains inadequately explored. This cross-sectional analysis within [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a global health challenge due to its complex pathophysiological processes. Systemic inflammation may profoundly affect disease progression, but the correlation between inflammatory markers and disease severity remains inadequately explored. This cross-sectional analysis within a prospective cohort evaluated associations of inflammatory markers (IL-6, TNF-α, hsCRP) with MASLD severity (five non-invasive scores) and metabolic indices, primarily with early-stage disease (66.7% mild fibrosis by TE). Methods: We recruited 120 patients diagnosed with MASLD. Assessment included anthropometric measurements, laboratory analyses, and non-invasive fibrosis evaluation using five validated scoring systems (APRI, FIB-4, NAFLD fibrosis score, FAST score, and transient elastography). Inflammatory markers were quantified using high-sensitivity ELISA techniques. Medication/comorbidities were recorded (statins 23.3%, diabetes drugs 26.7%), and multivariate regressions and FDR correction were applied. Results: Patients showed remarkably elevated inflammatory markers compared to reference ranges: IL-6 (15.1 ± 9.3 pg/mL), TNF-α (38.8 ± 29.1 pg/mL), and hsCRP (12.3 ± 11.1 mg/L). No correlations were found between inflammatory markers and disease severity across any non-invasive scoring system. However, TNF-α correlated significantly with waist circumference (r = 0.28, p = 0.002) and ALT (r = 0.19, p = 0.03), while showing inverse correlations with total cholesterol (r = −0.27, p = 0.03) and LDL (r = −0.22, p = 0.02). In contrast, hsCRP correlated positively with LDL (r = 0.20, p = 0.02) and WBC count (r = 0.24, p = 0.008). Conclusion: This study reveals a dissociation between systemic inflammatory markers and hepatic fibrosis severity in MASLD. Inflammatory Markers showed stronger metabolic associations than fibrosis, limiting their utility as fibrosis surrogates in early MASLD. These findings support a dual-pathway approach to MASLD management, targeting metabolic and hepatic components independently. The divergent associations of TNF-α and hsCRP with lipid profiles suggest distinct inflammatory mechanisms in MASLD. Full article
(This article belongs to the Special Issue Metabolomics and MASLD: Pathways, Biomarkers, and Clinical Insights)
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12 pages, 797 KB  
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 - 1 Aug 2025
Viewed by 2684
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 KB  
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 - 31 Jul 2025
Cited by 3 | Viewed by 1576
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)
25 pages, 442 KB  
Systematic Review
Ultrasonographic Elastography of the Spleen for Diagnosing Neoplastic Myeloproliferation: Identifying the Most Promising Methods—A Systematic Review
by Mateusz Bilski, Marta Sobas and Anna Zimny
J. Clin. Med. 2025, 14(15), 5400; https://doi.org/10.3390/jcm14155400 - 31 Jul 2025
Cited by 1 | Viewed by 1732
Abstract
Background: The relationship between spleen and bone marrow stiffness, and other features of abnormal myeloproliferation has long been described. However, the scientific knowledge in this area remains very superficial. This review evaluated the diagnostic effectiveness of various ultrasound (US) methods in the [...] Read more.
Background: The relationship between spleen and bone marrow stiffness, and other features of abnormal myeloproliferation has long been described. However, the scientific knowledge in this area remains very superficial. This review evaluated the diagnostic effectiveness of various ultrasound (US) methods in the assessment of neoplastic myeloproliferation using spleen stiffness measurement (SSM). Aim: To explore the diagnostic accuracy of US techniques in assessing spleen stiffness, determining which of them may be suitable for the diagnosis of myeloproliferative diseases in adults. Methods: The review included original retrospective or prospective studies published in the last five years (2019–2024) in peer-reviewed medical journals that reported receiver operating characteristics (ROCs) for SSM and the articles concerning the relation between SSM values and neoplastic myeloproliferation. The studies were identified through PubMed searches on 1 July and 1 December 2024. Quality was assessed using the QUADAS-2 tool. Results were tabulated according to the diagnostic method separately for myeloproliferative neoplasms (MNs) and for other clinical findings. Results: The review included 52 studies providing ROCs for SSM or compatibility between operators, and five studies covering the relation between SSM values and MNs. Conclusions: Acoustic radiation force impulse (ARFI), two-dimensional shear wave elastography (2D-SWE), transient elastography (TE), and point shear wave elastography (p-SWE) are promising methods for measuring SSM that can be incorporated into the diagnosis, screening, and monitoring system in MNs. Full article
(This article belongs to the Special Issue New Insights into Diagnostic and Interventional Radiology)
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14 pages, 1797 KB  
Article
Long-Term Risk of Hepatic and Extrahepatic-Related Events After Direct Antiviral Therapy for Chronic Hepatitis C: A Prospective Long-Term Study Cohort
by Luisa Cavalletto, Eleonora Bertoli, Claudia Mescoli, Camillo Aliberti, Maria Giovanna Quaranta, Loreta Kondili and Liliana Chemello
Cancers 2025, 17(9), 1528; https://doi.org/10.3390/cancers17091528 - 30 Apr 2025
Cited by 2 | Viewed by 2345
Abstract
Novel direct antiviral-acting (DAA) molecules significantly improved efficacy and ameliorated outcomes of patients with chronic hepatitis C (CHC). The extensive use of DAA from 2015, due to large access to therapy, maximized rates of viral eradication with a safety profile in the majority [...] Read more.
Novel direct antiviral-acting (DAA) molecules significantly improved efficacy and ameliorated outcomes of patients with chronic hepatitis C (CHC). The extensive use of DAA from 2015, due to large access to therapy, maximized rates of viral eradication with a safety profile in the majority of cases. Aims: We evaluated risk factors and the incidence of related clinical events and hepatocellular carcinoma (HCC) in cases with sustained virologic response (SVR) after DAA. We also aimed to apply a score assessment to identify the individual patient with unfavorable outcomes during an average follow-up (FU) of five years. Methods: In total, 470 cases consecutively recruited with CHC have been compared by non-invasive tests (NIT), as APRI, FORNS, FIB-4, LSPS, and transient elastography (TE) liver stiffness measurement (LSM), to identify cutoff related to major event onset. Results: Grouping of cases without or with related events development of both types hepatic (HE) (i.e., HCC or further cirrhosis decompensation or/with hospitalized septic state) or extrahepatic (EHE) (i.e., other tumors, bleeding, or thrombotic episodes and other organs pathologic conditions not liver related)allowed us to select the parameters to propose a novel risk stratification system (RISS) for the identification of the remnant individual patient’s risk for HCC occurrence, orthotopic liver transplant (OLT) need, or death during long-term follow-up (FU). Conclusions: Patients with cirrhosis and portal hypertension (PH) maintained a higher LSM mean value (>25 kPa), showed the lowest reduction of NIT scores, and developed events in 80/108 (74%) cases (67 and 13 of HE and EHE type), even after long-term successful DAA therapy. Furthermore, cases with RISS score ≥ 8 demonstrated a significant incidence of HCC (37/46, 80.4%) and a reduction in survival rate to 65.4% at 5-year FU. Full article
(This article belongs to the Special Issue Insights from the Editorial Board Member)
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20 pages, 305 KB  
Review
Liver Elastography Methods for Diagnosis of De Novo and Recurrent Hepatocellular Carcinoma
by Razvan Cerban, Speranta Iacob, Carmen Ester, Mihaela Ghioca, Mirela Chitul, Razvan Iacob and Liana Gheorghe
Diagnostics 2025, 15(9), 1087; https://doi.org/10.3390/diagnostics15091087 - 25 Apr 2025
Cited by 1 | Viewed by 2281
Abstract
Hepatocellular carcinoma (HCC), a common consequence of chronic liver disease, ranks among the most prevalent cancers globally and contributes significantly to cancer-related mortality. Liver fibrosis is intimately associated with hepatic function and the likelihood of future HCC occurrence. Despite the fact that liver [...] Read more.
Hepatocellular carcinoma (HCC), a common consequence of chronic liver disease, ranks among the most prevalent cancers globally and contributes significantly to cancer-related mortality. Liver fibrosis is intimately associated with hepatic function and the likelihood of future HCC occurrence. Despite the fact that liver biopsy continues to be the gold standard for diagnosing fibrosis, its utility is hindered by cost and invasiveness, along with patient unease, procedural rejection, and potential adverse effects. Liver elastography has become a leading noninvasive means of assessing tissue stiffness with considerable diagnostic precision. Malignant tumors generally exhibit higher cellularity in comparison to benign ones, resulting in increased stiffness. Elastography techniques capitalize on alterations in tissue elasticity stemming from specific pathological or physiological processes. Technological innovations, such as advanced ultrasound imaging and artificial intelligence (AI)-integrated systems, are paving the way for enhanced diagnostic accuracy and risk prediction. Recent research underscores the potential of elastography in managing HCC patients, presenting novel clinical applications, including prediction of HCC development, differentiation between malignant and benign liver lesions, evaluating treatment response, and forecasting recurrence post-treatment, though certain findings remain contentious. Therefore, this review aims to sum up the latest advancements in liver elastography for HCC patients, outlining its applications while addressing existing limitations and avenues for future progress. Full article
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