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Keywords = liver stiffness measurement (LSM)

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12 pages, 257 KiB  
Article
Evaluating the Diagnostic Potential of the FIB-4 Index for Cystic Fibrosis-Associated Liver Disease in Adults: A Comparison with Transient Elastography
by Stephen Armstrong, Kingston Rajiah, Aaron Courtenay, Nermeen Ali and Ahmed Abuelhana
J. Clin. Med. 2025, 14(15), 5404; https://doi.org/10.3390/jcm14155404 - 31 Jul 2025
Viewed by 203
Abstract
Background/Objectives: Cystic fibrosis-associated liver disease (CFLD) is a significant complication in individuals with cystic fibrosis (CF), contributing to morbidity and mortality, with no universally accepted, reliable, non-invasive diagnostic tool for early detection. Current diagnostic methods, including liver biopsy and imaging, remain resource-intensive [...] Read more.
Background/Objectives: Cystic fibrosis-associated liver disease (CFLD) is a significant complication in individuals with cystic fibrosis (CF), contributing to morbidity and mortality, with no universally accepted, reliable, non-invasive diagnostic tool for early detection. Current diagnostic methods, including liver biopsy and imaging, remain resource-intensive and invasive. Non-invasive biomarkers like the Fibrosis-4 (FIB-4) index have shown promise in diagnosing liver fibrosis in various chronic liver diseases. This study explores the potential of the FIB-4 index to predict CFLD in an adult CF population and assesses its correlation with transient elastography (TE) as a potential diagnostic tool. The aim of this study is to evaluate the diagnostic performance of the FIB-4 index for CFLD in adults with CF and investigate its relationship with TE-based liver stiffness measurements (LSM). Methods: The study was conducted in a regional cystic fibrosis unit, including 261 adult CF patients. FIB-4 scores were calculated using an online tool (mdcalc.com) based on patient age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. In parallel, 29 patients underwent liver stiffness measurement using TE (Fibroscan®). Statistical analyses included non-parametric tests for group comparisons and Pearson’s correlation to assess the relationship between FIB-4 scores and TE results. Results: The mean FIB-4 score in patients diagnosed with CFLD was higher (0.99 ± 0.83) compared to those without CFLD (0.64 ± 0.38), although the difference was not statistically significant (p > 0.05). TE results for CFLD patients (5.9 kPa) also did not show a significant difference compared to non-CFLD patients (4.2 ± 1.6 kPa, p > 0.05). However, a positive correlation (r = 0.401, p = 0.031) was found between FIB-4 scores and TE-based LSM, suggesting a potential complementary diagnostic role. Conclusions: The FIB-4 index, while not sufficient as a standalone diagnostic tool for CFLD in adults with CF, demonstrates potential when used in conjunction with other diagnostic methods like TE. This study introduces a novel approach for integrating non-invasive diagnostic markers in CF care, offering a pathway for future clinical practice. The combination of FIB-4 and TE could serve as an accessible, cost-effective alternative to invasive diagnostic techniques, improving early diagnosis and management of CFLD in the CF population. Additionally, future research should explore the integration of these tools with emerging biomarkers and clinical features to refine diagnostic algorithms for CFLD, potentially reducing reliance on liver biopsies and improving patient outcomes. Full article
(This article belongs to the Section Intensive Care)
14 pages, 1004 KiB  
Article
Beyond Weight Loss: Comparative Effects of Tirzepatide Plus Low-Energy Ketogenic Versus Low-Calorie Diet on Hepatic Steatosis and Stiffness in MASLD
by Luigi Schiavo, Biagio Santella, Monica Mingo, Gianluca Rossetti, Marcello Orio and Vincenzo Pilone
Nutrients 2025, 17(15), 2409; https://doi.org/10.3390/nu17152409 - 24 Jul 2025
Viewed by 432
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition globally, strongly linked to obesity, insulin resistance, and type 2 diabetes (T2D). Tirzepatide (TZP), a dual GIP/GLP-1 receptor agonist, improves glycemic control and reduces body weight and the [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition globally, strongly linked to obesity, insulin resistance, and type 2 diabetes (T2D). Tirzepatide (TZP), a dual GIP/GLP-1 receptor agonist, improves glycemic control and reduces body weight and the liver fat content in patients with obesity and T2D. However, its effect on liver-specific outcomes such as steatosis and fibrosis remains incompletely characterized. Low-energy ketogenic therapy (LEKT), a nutritional strategy characterized by carbohydrate restriction and nutritional ketosis, may enhance hepatic β-oxidation and reduce hepatic lipogenesis. To date, however, the combination of TZP and LEKT has not been studied in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to compare the hepatic and metabolic effects of TZP combined with either LEKT or a conventional low-calorie diet (LCD) over a 12-week period. Methods: Sixty adult patients with MASLD undergoing TZP therapy were prospectively assigned to either an LEKT or a conventional LCD, with 30 participants per group. As primary endpoints, the controlled attenuation parameter (CAP, an index of hepatic steatosis) and liver stiffness measurement (LSM, an index of liver fibrosis) were assessed at the baseline and after 12 weeks using FibroScan®. Secondary outcomes included changes in body mass index (BMI), glycated hemoglobin (HbA1c), and liver enzymes. Adherence to both diet and pharmacological treatment, as well as tolerability, were systematically monitored throughout the intervention period. Results: Both groups showed significant reductions in body weight (TZP + LEKT, p = 0.0289; TZP + LCD, p = 0.0278), with no significant intergroup difference (p = 0.665). CAP and LSM improved significantly in both groups, but reductions were greater in the TZP + LEKT group (CAP −12.5%, p < 0.001; LSM −22.7%, p < 0.001) versus LCD (CAP −6.7%, p = 0.014; LSM −9.2%, p = 0.022). Between-group differences were statistically significant for both CAP (p = 0.01) and LSM (p = 0.03). Conclusions: Based on these preliminary findings, we support the hypothesis that the combination of TZP and LEKT may be superior to TZP with an LCD in reducing hepatic steatosis and stiffness in individuals with obesity. Full article
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11 pages, 1176 KiB  
Article
Clinically Important Decrease in Liver Stiffness Following Treatment for Hepatitis C: Outcome of the TraP HepC Nationwide Elimination Program
by Smári Freyr Kristjánsson, Sigurdur Olafsson, Magnús Gottfredsson, Thorvardur Jon Love and Einar Stefán Björnsson
J. Clin. Med. 2025, 14(11), 3982; https://doi.org/10.3390/jcm14113982 - 5 Jun 2025
Viewed by 487
Abstract
Background/Objectives: Direct-acting antiviral (DAA) therapy has been highly successful in treating chronic hepatitis C (CHC). The nationwide Treatment as Prevention of Hepatitis C (TraP HepC) initiative that was launched in Iceland in 2016 utilized liver stiffness measurements (LSM) to assess liver fibrosis at [...] Read more.
Background/Objectives: Direct-acting antiviral (DAA) therapy has been highly successful in treating chronic hepatitis C (CHC). The nationwide Treatment as Prevention of Hepatitis C (TraP HepC) initiative that was launched in Iceland in 2016 utilized liver stiffness measurements (LSM) to assess liver fibrosis at baseline and follow-up. We aimed to determine changes in liver stiffness among patients following treatment with DAAs and evaluate risk factors associated with hepatic fibrosis. Methods: Eligible CHC patients with liver stiffness of >9.5 kilopascals (kPa) before DAA treatment were invited for a follow-up visit in 2024. Risk factors for cirrhosis were registered, LSM performed, and liver enzymes, blood lipids, and glucose levels measured. Changes in liver stiffness were compared to baseline measurements, and correlations with risk factors were analyzed. Results: A total of 96 patients had LSMs > 9.5 kPa at treatment initiation. During the follow-up period, 61 were eligible for participation, 38 consented, and 34 (35%) died. The total follow-up was 258.3 person-years. The median follow-up period between measurements was 7.1 years. The median liver stiffness decreased from 17.2 kPa to 7.3 kPa (p < 0.01), and 80% of those with cirrhosis (>12.5 kPa) regressed to non-cirrhotic values. High BMI and daily alcohol consumption were significantly associated with increased liver stiffness in 8% of patients. Conclusions: In this single-arm, pre-post pilot study, liver stiffness regressed significantly in 92% of patients who were cured of CHC. Patients with other persistent risk factors following cure, such as obesity and alcohol abuse, were the only patients who had increased liver stiffness at the end of follow-up. Full article
(This article belongs to the Special Issue Cirrhosis and Its Complications: Prognosis and Clinical Management)
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11 pages, 710 KiB  
Article
Readily Available Index of Insulin Sensitivity Is Associated with Metabolic Dysfunction-Associated Steatotic Liver Disease and Liver Fibrosis in Patients with Type 2 Diabetes
by Stefano Ciardullo, Alessandro Roberto Dodesini, Emanuele Muraca, Pietro Invernizzi, Roberto Trevisan and Gianluca Perseghin
Diabetology 2025, 6(6), 50; https://doi.org/10.3390/diabetology6060050 - 4 Jun 2025
Viewed by 699
Abstract
Background/Objectives: Insulin resistance is a key factor in the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD), but accurately measuring it in patients with type 2 diabetes (T2D) remains challenging. This study examines the relationship between a recently proposed insulin [...] Read more.
Background/Objectives: Insulin resistance is a key factor in the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD), but accurately measuring it in patients with type 2 diabetes (T2D) remains challenging. This study examines the relationship between a recently proposed insulin resistance index and the presence of liver steatosis and fibrosis in individuals with T2D. Methods: This cross-sectional study utilized data from the 2017–2020 National Health and Nutrition Examination Survey. Patients with T2D who did not have chronic viral hepatitis or significant alcohol intake were included. The insulin sensitivity (IS) index was calculated using a formula incorporating body mass index, urine albumin-to-creatinine ratio, triglycerides, and gamma-glutamyl transferase. Liver stiffness and steatosis were assessed through transient elastography. MASLD was defined as a controlled attenuation parameter (CAP) of ≥274 decibels/meter (dB/m), while significant liver fibrosis was defined as a liver stiffness measurement (LSM) of ≥8 kPa. Multivariable logistic regression models, adjusted for potential confounders, were used to evaluate the association between IS and these liver outcomes. Results: A total of 1084 patients with T2D were analyzed. The prevalence of MASLD and significant liver fibrosis was 74.1% (95% CI 68.7–78.9) and 25.4% (95% CI 21.2–30.2), respectively. After adjusting for age, sex, waist circumference, and race/ethnicity, lower IS scores (indicating higher insulin resistance) were independently associated with increased odds of both MASLD (quartile 1 vs. quartile 4: OR 2.66, 95% CI 1.23–5.71) and significant liver fibrosis (quartile 1 vs. quartile 4: OR 3.30, 95% CI 1.45–7.51). These findings remained consistent across subgroups stratified by age, sex, and obesity status. Conclusions: This novel IS model, derived from commonly available clinical and biochemical markers, is independently associated with liver steatosis and fibrosis. Its application may help identify patients with more advanced MASLD, facilitating early intervention and risk stratification. Full article
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16 pages, 577 KiB  
Article
Liver Fibrosis Is Positively and Independently Associated with Leptin Circulating Levels in Individuals That Are Overweight and Obese: A FibroScan-Based Cross-Sectional Study
by Nicole Cerabino, Martina Di Chito, Davide Guido, Vincenza Di Stasi, Caterina Bonfiglio, Giuseppe Lisco, Endrit Shahini, Marianna Zappimbulso, Raffaele Cozzolongo, Valeria Tutino, Arianna Diciolla, Rosanna Mallamaci, Dolores Stabile, Anna Ancona, Sergio Coletta, Pasqua Letizia Pesole, Gianluigi Giannelli and Giovanni De Pergola
Nutrients 2025, 17(11), 1908; https://doi.org/10.3390/nu17111908 - 1 Jun 2025
Viewed by 708
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly correlated with the severity of obesity, and the extent of liver fibrosis is associated with a higher risk of liver-related complications, cardiovascular events, and overall mortality. Leptin circulating levels are directly correlated with the [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly correlated with the severity of obesity, and the extent of liver fibrosis is associated with a higher risk of liver-related complications, cardiovascular events, and overall mortality. Leptin circulating levels are directly correlated with the amount of adipose tissue. Aims: In the present study, we investigated the association between circulating leptin levels and liver steatosis and fibrosis. Methods: Eighty-six patients (41.7 ± 12.6 yrs, 35 men, 41%), naïve to medications, who attended the Nutrition Center for the Research and Care of Obesity and Metabolic Diseases at the National Institute of Gastroenterology “Saverio de Bellis” for weight management, were cross-sectionally evaluated. Demographic, anthropometric, clinical, and laboratory data were collected and analyzed. All patients underwent liver ultrasonographic assessment by FibroScan to diagnose liver steatosis (controlled attenuation parameter, CAP > 275 dBm) and fibrosis (liver stiffness measurement, LSM > 8.2 kPa). Results: Sixty-three individuals (73.3%) had liver steatosis, and 17 (19.8%) had liver fibrosis. The mean leptin levels were 22.3 ± 14.1 ng/mL, while the BMI and waist circumference were 36.7 ± 7.2 kg/m2 and 114.5 ± 16.4 cm, respectively. CAP values exhibited no correlation with leptin (r = 0.09, p = 0.436), while a significant connection was seen between leptin and LSM (β = 0.065; p = 0.038). Specifically, for each unit increase in leptin, LSM values were varied by +0.065 units (p = 0.038). This association was independent of gender, age, insulin resistance, adiponectin, RBP4, and visfatin. This is the first study showing these results by using FibroScan assessment in patients naïve to medications. Conclusions: Circulating leptin concentrations are independently correlated with hepatic fibrosis in individuals with a BMI ≥ 25 kg/m2. These findings indicate a function for leptin in promoting liver fibrosis; however, longitudinal studies are required to elucidate the causal nature of this interaction. Full article
(This article belongs to the Special Issue Nutrition, Adipose Tissue, and Human Health)
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15 pages, 1797 KiB  
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
Viewed by 1198
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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27 pages, 3509 KiB  
Article
A Comparative Study of N-Acetyl Cysteine, Rosuvastatin, and Vitamin E in the Management of Patients with Non-Alcoholic Steatohepatitis: A Randomized Controlled Trial
by Amr Y. Zakaria, Rehab Badawi, Hasnaa Osama, Mona A. Abdelrahman and Asmaa M. El-Kalaawy
Pharmaceuticals 2025, 18(5), 650; https://doi.org/10.3390/ph18050650 - 29 Apr 2025
Viewed by 2575
Abstract
Background: Non-alcoholic steatohepatitis (NASH) is characterized by increased production of proinflammatory cytokines, fibrosis, and hepatocyte apoptosis. This study aimed to assess the efficacy of N-acetyl cysteine (NAC), rosuvastatin (RSV), and vitamin E (VE) in patients with NASH. Methods: A double-blinded, parallel, [...] Read more.
Background: Non-alcoholic steatohepatitis (NASH) is characterized by increased production of proinflammatory cytokines, fibrosis, and hepatocyte apoptosis. This study aimed to assess the efficacy of N-acetyl cysteine (NAC), rosuvastatin (RSV), and vitamin E (VE) in patients with NASH. Methods: A double-blinded, parallel, randomized, controlled study was conducted and registered on clinicaltrials.gov (Identifier: NCT06105060), involving 135 NASH participants, who were divided into three groups: the control group (group 1), consisting of patients receiving standard therapy VE at a dosage of 400 IU twice daily. In the treated group (group 2), patients were administered NAC at a dosage of 1200 mg twice daily, while treatment (group 3) received RSV at a dosage of 20 mg once daily. FibroScan® examination of liver tissue and fibrosis scores, along with tests for liver aminotransferases, lipid profile, glycemic parameters, and renal and hepatic functions, were assessed before and after six months of treatment. Results: The analyzed groups demonstrated a significant reduction in steatosis and lipid peroxidation (p < 0.05). The NAC group demonstrated greater anti-inflammatory and anti-apoptotic effects compared to the RSV group, although this difference was not significant in the control group. NAC is conceded as the only significant antifibrotic agent in liver stiffness measurement (LSM), biological marker findings, and non-invasive liver fibrosis scores (p < 0.05), in addition to its improvement of several metabolic parameters and health-related quality of life. Conclusions: Patients receiving NAC demonstrated safety and efficacy in enhancing steatosis, fibrosis, and metabolic parameters, representing a novel strategy in the management of NASH. Full article
(This article belongs to the Special Issue New and Emerging Treatment Strategies for Gastrointestinal Diseases)
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19 pages, 1229 KiB  
Article
Effects of Intermittent Fasting on Liver Steatosis and Fibrosis, Serum FGF-21 and Autophagy Markers in Metabolic Dysfunction-Associated Fatty Liver Disease: A Randomized Controlled Trial
by Tugce Ozlu Karahan, Elvan Yilmaz Akyuz, Demet Yilmaz Karadag, Yusuf Yilmaz and Fatih Eren
Life 2025, 15(5), 696; https://doi.org/10.3390/life15050696 - 25 Apr 2025
Viewed by 3731
Abstract
Background: This randomized controlled study sought to determine the effect of intermittent fasting on anthropometric measurements, fibroblast growth factor (FGF)-21, and autophagy markers, as well as on hepatic steatosis and fibrosis levels in overweight or obese patients with metabolic dysfunction-associated fatty liver disease [...] Read more.
Background: This randomized controlled study sought to determine the effect of intermittent fasting on anthropometric measurements, fibroblast growth factor (FGF)-21, and autophagy markers, as well as on hepatic steatosis and fibrosis levels in overweight or obese patients with metabolic dysfunction-associated fatty liver disease (MAFLD). Methods: Patients were randomly assigned into two groups: received a dietary treatment involving 22–25 kcal/kg/day of energy for 8 weeks and followed the same dietary intervention and a 16:8 pattern. The extent of hepatic steatosis and fibrosis was determined using transient elastography on a FibroScan® device. The controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), determined by transient elastography, reflect hepatic steatosis and fibrosis, respectively. In duplicate, serum levels of FGF-21, Beclin-1, and ATG-5 were determined using enzyme-linked immunosorbent assay. Results: The study included 48 patients with a mean age of 48.2 ± 1.4 years (27 female and 21 male). Improvements in anthropometric measurement and CAP and LSM levels and a decrease in serum FGF-21 levels were found in both groups (p < 0.05). Changes in the CAP and FGF-21 levels were higher in the energy + time-restricted diet group (p < 0.05). Autophagy-related protein (ATG)-5 levels increased only in the energy + time-restricted diet group [(0.74 (0.46–1.29) ng/mL vs. 0.95 (0.73–1.32) ng/mL, p = 0.03]. Conclusions: Intermittent fasting was potentially practical in the management of MAFLD. In particular, changes in FGF-21 and ATG-5 levels indicate the potential of intermittent fasting to regulate metabolic processes and autophagy. However, methodological limitations should be taken into consideration when interpreting the study results. Full article
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16 pages, 1782 KiB  
Article
Targeting Insulin Resistance and Liver Fibrosis: CKD Screening Priorities in MASLD
by Tianyuan Yang, Bingqing Yang, Jingya Yin, Chenxue Hou and Qi Wang
Biomedicines 2025, 13(4), 842; https://doi.org/10.3390/biomedicines13040842 - 1 Apr 2025
Viewed by 707
Abstract
Background and Aims: Chronic kidney disease (CKD) is a recognized extra-hepatic disease of nonalcoholic fatty liver disease (NAFLD). With the redefinition of NAFLD as metabolic dysfunction-associated steatotic liver disease (MASLD), the importance of cardiovascular metabolic factors in MASLD has been highlighted. However, whether [...] Read more.
Background and Aims: Chronic kidney disease (CKD) is a recognized extra-hepatic disease of nonalcoholic fatty liver disease (NAFLD). With the redefinition of NAFLD as metabolic dysfunction-associated steatotic liver disease (MASLD), the importance of cardiovascular metabolic factors in MASLD has been highlighted. However, whether MASLD remains independently associated with the prevalence of CKD is yet to be determined. Method: We analyzed data from 6567 non-pregnant adults from the National Health and Nutrition Examination Survey 2017–2020. MASLD was identified using liver ultrasound transient elastography and five cardiovascular risk factors. Multivariate logistic regression, subgroup analysis, and restricted cubic splines were employed to explore the associations and interactions within the data. Results: The prevalence of CKD across MASLD subgroups with different combinations of cardiometabolic risk factors varied. Univariate regression analysis indicated a significant association between MASLD and CKD (OR: 1.68, p < 0.001). This association was not significant after adjusting for diabetes (OR: 0.94, p = 0.74) or insulin resistance (OR: 1.00, p = 0.98) and was not significant in the fully adjusted model (OR: 0.87, p = 0.64). Subgroup analysis confirmed insulin resistance as a modifier in the MASLD-CKD relationship (p for interaction = 0.02). Multivariate analysis revealed that liver stiffness measurements (LSMs) were independently associated with CKD. LSM values showed an S-shaped correlation with CKD, with risk increasing above the 8.612 kPa threshold. Conclusions: This study suggests that the direct relationship between MASLD and CKD diminished when accounting for insulin resistance. Nevertheless, liver fibrosis emerges as an independent CKD risk factor, emphasizing the critical need for targeted CKD screening among MASLD patients, particularly those with insulin resistance or advanced fibrosis. Full article
(This article belongs to the Special Issue New Insights Into Non-Alcoholic Fatty Liver Diseases)
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11 pages, 1952 KiB  
Article
Role of Spleen Stiffness Measurements with 2D Shear-Wave Elastography for Esophageal Varices in Patients with Compensated Advanced Chronic Liver Disease
by Cristina Muzica, Sorina Diaconu, Sebastian Zenovia, Laura Huiban, Carol Stanciu, Horia Minea, Irina Girleanu, Mihaela Muset, Tudor Cuciureanu, Stefan Chiriac, Ana-Maria Singeap, Camelia Cojocariu and Anca Trifan
Diagnostics 2025, 15(6), 674; https://doi.org/10.3390/diagnostics15060674 - 10 Mar 2025
Viewed by 1003
Abstract
Background/Objectives: Esophageal varices (EVs) represent an important portal hypertension complication in patients with compensated advanced chronic liver disease (cACLD). Although upper gastrointestinal endoscopy is currently the gold standard for EV diagnosis, recent guidelines recommend non-invasive approaches to assess EV risk in cACLD [...] Read more.
Background/Objectives: Esophageal varices (EVs) represent an important portal hypertension complication in patients with compensated advanced chronic liver disease (cACLD). Although upper gastrointestinal endoscopy is currently the gold standard for EV diagnosis, recent guidelines recommend non-invasive approaches to assess EV risk in cACLD patients to reduce unnecessary endoscopies. Our study aims to evaluate spleen stiffness measurement (SSM) using 2D shear-wave elastography (2D-SWE) as a non-invasive predictor of EV presence and severity in patients with cACLD. Methods: We included 73 cACLD patients referred to our liver clinic over one year. SSM and liver stiffness measurement (LSM) were performed using 2D-SWE, with specific cut-off values applied to rule in or rule out clinically significant portal hypertension (CSPH) according to Baveno VII consensus criteria. Upper gastrointestinal endoscopy was performed in all patients to confirm EV presence and grade. Results: Among all patients, 49.3% had no EV, while 50.7% presented with different EV grades (15.1% grade I, 13.7% grade II, 9.6% grade III, and 12.3% grade IV). A strong correlation was observed between elevated SSM values and EV presence, with SSM values > 32.8 kPa highly suggestive of EV (AUROC = 0.95, 95% CI: 0.909–0.995, p < 0.001). SSM values exceeding 40.4 kPa were associated with more advanced EV grades. Combining LSM and SSM improved diagnostic accuracy, effectively stratifying EV risk without invasive procedures. Conclusions: SSM via 2D-SWE is a promising, non-invasive tool for EV prediction in cACLD, aligning with Baveno VII recommendations to minimize unnecessary endoscopies. Further validation is required to refine diagnostic thresholds and expand applicability across different chronic liver disease etiologies. Full article
(This article belongs to the Special Issue Diagnosis and Management of Liver Diseases—2nd Edition)
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14 pages, 888 KiB  
Article
Obeticholic Acid Improves Cholestasis, Liver Fibrosis, and Liver Function in Patients with Primary Biliary Cholangitis with Inadequate Response to Ursodeoxycholic Acid
by Matthias Buechter, Paul Manka, Kerem Bulut, Guido Gerken and Alisan Kahraman
J. Pers. Med. 2025, 15(3), 79; https://doi.org/10.3390/jpm15030079 - 21 Feb 2025
Viewed by 1239
Abstract
Background and Aims: Primary biliary cholangitis (PBC) leads to the slow, progressive destruction of the small bile ducts with consecutive cholestasis and intrahepatic cholangitis. If this disease remains untreated, liver parenchyma will be damaged resulting in fibrosis and end-stage liver disease with the [...] Read more.
Background and Aims: Primary biliary cholangitis (PBC) leads to the slow, progressive destruction of the small bile ducts with consecutive cholestasis and intrahepatic cholangitis. If this disease remains untreated, liver parenchyma will be damaged resulting in fibrosis and end-stage liver disease with the need for transplantation. The approval of the Farnesoid X receptor agonist obeticholic acid (Ocaliva; OCA) in early 2017 expanded the drug therapy options of PBC, which previously consisted primarily of the administration of ursodeoxycholic acid (UDCA). Patients and Methods: Included in our prospective pilot study were 16 patients with a confirmed diagnosis of PBC who were treated with an add-on therapy with OCA (5 mg/d). None of the patients had an overlap to autoimmune hepatitis. Patients were investigated between 09/2022 and 09/2023. Results: The majority of patients was female (15/16, 93.75%), and the mean age was 57.63 ± 9.59 (43–77) years. OCA treatment led to a statistically significant decrease in aspartate aminotransferase (AST; AST baseline: 38.50 [26.25; 50.00] IU/L vs. AST 6-month follow-up: 23.50 [21.50; 44.25] IU/L, p = 0.0012), alanine aminotransferase (ALT; ALT baseline: 55.50 [28.75; 97.00] IU/L vs. ALT 6-month follow-up: 36.50 [28.00; 57.25] IU/L, p = 0.0035), and gamma-glutamyl transferase (GGT; GGT baseline: 168.00 [100.30; 328.50] IU/L vs. GGT 6-month follow-up: 88.00 [44.50; 259.80] IU/L, p = 0.0063), while the decrease in alkaline phosphatase (AP) was not statistically significant (AP baseline: 197.00 [170.00; 253.30] IU/L vs. AP 6-month follow-up: 196.00 [134.00; 227.00] IU/L, p = 0.0915). In addition, liver stiffness measurement (LSM) showed a statistically significant decrease after six months of treatment with OCA (LSM baseline: 7.85 [5.55; 10.13] kPa vs. LSM 6-month follow-up: 5.95 [4.55; 8.225] kPa, p = 0.0001). However, the increase in enzymatic liver function measured by LiMAx failed to reach statistical significance, but showed a positive trend (LiMAx baseline: 402.50 [341.50; 469.80] μg/kg/h vs. LiMAx 6-month follow-up: 452.50 [412.50; 562.00] μg/kg/h, p = 0.0625). In none of our patients did therapy with obeticholic acid have to be stopped due to pruritus or poor tolerability. Conclusions: In patients with PBC without adequate response to UDCA, OCA is a promising alternative, which in our group of 16 patients led to a significant improvement of liver enzymes, the amelioration of liver fibrosis, and an increase in liver function capacity in a short-term clinical course. Full article
(This article belongs to the Section Personalized Therapy and Drug Delivery)
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22 pages, 3249 KiB  
Article
FLAME: Training and Validating a Newly Conceived Model Incorporating Alpha-Glutathione-S-Transferase Serum Levels for Predicting Advanced Hepatic Fibrosis and Acute Cardiovascular Events in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
by Marcello Dallio, Mario Romeo, Fiammetta Di Nardo, Paolo Vaia, Carmine Napolitano, Lorenzo Ventriglia, Annachiara Coppola, Alessia Silvestrin, Simone Olivieri and Alessandro Federico
Int. J. Mol. Sci. 2025, 26(2), 761; https://doi.org/10.3390/ijms26020761 - 17 Jan 2025
Cited by 1 | Viewed by 1128
Abstract
Alpha-Glutathione-S-transferase (alphaGST) is a liver enzyme whose serum levels increase with the worsening of fibrosis in alcoholic and viral chronic hepatitis. Its usefulness in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) remains unexplored. From January 2016 to December 2017, 200 patients with MASLD and [...] Read more.
Alpha-Glutathione-S-transferase (alphaGST) is a liver enzyme whose serum levels increase with the worsening of fibrosis in alcoholic and viral chronic hepatitis. Its usefulness in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) remains unexplored. From January 2016 to December 2017, 200 patients with MASLD and 30 controls were enrolled. AlphaGST serum levels were measured. Variables related to advanced fibrosis (AF) were selected via Principal Component Analysis (PCA), and the best cut-off (BCO) was estimated using ROC analysis. Liver stiffness measurement (LSM), NAFLD fibrosis (NFS), Fibrosis-4 (FIB-4), and BMI-AST/ALT Ratio-Diabetes (BARD) scores were determined. The first acute cardiovascular events (ACE) in ACE-naïve subjects were recorded over five years. A validation cohort of 60 MASLD patients was enrolled from January 2018 to May 2019 and followed for five years. AlphaGST levels increased with fibrosis stage (p < 0.0001) in both cohorts, showing high accuracy in predicting AF (TrC: AUC 0.89, VlC: AUC 0.89). PCA-selected variables were HbA1c, HDL, and alphaGST, forming the “FLAME” model. FLAME showed superior predictive performance for AF and ACEs compared to other models and scores. FLAME represents a novel tool that accurately predicts AF and ACEs in MASLD. Full article
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9 pages, 1252 KiB  
Article
Liver Stiffness, Not Steatosis, Predicts Mortality in MASLD Patients: An NHANES Analysis
by Yuting Huang, Yichen Wang, Yan Yan, Samuel O. Antwi, Dilhana S. Badurdeen and Liu Yang
Livers 2024, 4(4), 711-719; https://doi.org/10.3390/livers4040049 - 23 Dec 2024
Viewed by 1019
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has surged as a major cause of liver transplants in the United States. Existing studies have presented conflicting findings regarding the association between liver characteristics (specifically steatosis and fibrosis) and mortality. This study investigates the relationship [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has surged as a major cause of liver transplants in the United States. Existing studies have presented conflicting findings regarding the association between liver characteristics (specifically steatosis and fibrosis) and mortality. This study investigates the relationship between the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) via vibration-controlled transient elastography (VCTE) and all-cause mortality in MASLD patients. Methods: Using the NHANES 2017-2018 database, 3821 individuals representing the United States population with MASLD underwent VCTE for liver stiffness measurement. Exclusion criteria were applied, eliminating ineligible cases, incomplete examinations, underage individuals, and those with hepatitis B or C, along with significant alcohol consumption history. Cox proportional hazard models assessed the hazard ratio (HR) for all-cause mortality in CAP and LSM. Cox regression analysis with interaction terms was employed for deeper exploration. Results: The study unveiled a strong, independent correlation between LSM and all-cause mortality. However, the CAP failed to demonstrate a significant association with mortality in both univariate and adjusted analyses, contrary to recent findings. The analysis underscores the importance of accurately measuring liver stiffness via VCTE in predicting adverse outcomes in MASLD patients, emphasizing the pivotal role of fibrosis in assessing mortality risk. Conclusion: This study reaffirms the robust link between liver fibrosis (measured through VCTE) and mortality among MASLD individuals. The absence of a significant association between steatosis (indicated by CAP) and mortality challenges recent research, urging further comprehensive investigations with larger cohorts to delineate steatosis’ precise impact on MASLD-related mortality. Full article
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12 pages, 702 KiB  
Article
The Role of Liver Stiffness Measurement and Spleen Stiffness Measurement in Predicting the Risk of Developing HCC
by Rui Gaspar, Joana Mota, Maria João Almeida, Marco Silva and Guilherme Macedo
Diagnostics 2024, 14(24), 2867; https://doi.org/10.3390/diagnostics14242867 - 20 Dec 2024
Viewed by 1044
Abstract
Background/Objectives: Hepatocellular carcinoma (HCC) is the sixth most common cause of cancer worldwide. More than 90% of cases occur in cirrhotic patients, with the degree of fibrosis being the main risk factor for the development of HCC. Liver biopsy is the gold-standard for [...] Read more.
Background/Objectives: Hepatocellular carcinoma (HCC) is the sixth most common cause of cancer worldwide. More than 90% of cases occur in cirrhotic patients, with the degree of fibrosis being the main risk factor for the development of HCC. Liver biopsy is the gold-standard for fibrosis assessment, but it is an invasive procedure. Liver stiffness measurement (LSM) has shown high accuracy for diagnosing liver cirrhosis, as well as for predicting decompensation and HCC development. More recently, spleen stiffness measurement (SSM) has presented excellent results for ruling in/out high-risk varices and the presence of clinical significant portal hypertension. The aim of our study was to evaluate the relationship between LSM and SSM and the risk of hepatocellular carcinoma. Methods: A prospective study on cirrhotic patients was performed in a tertiary center from January 2020 to May 2024. All patients were submitted to liver and spleen elastography (with a new probe of 100 Hz) by the same blinded operator and were treated in the same institution for the development of hepatocellular carcinoma. Results: We included 299 cirrhotic patients, 75.9% male, with a mean age of 61.8 years (±10.0). The median value of LSM was 25.7 kPa [4.5–75.0] and that of SSM was 44.6 kPa [7.9–100.0]. The median follow-up time was 505 days [114.0–1541.0]. During this period, 18 patients developed HCC, with a median time to HCC diagnosis after LSM and SSM of 321 days [63.0–1227.0]. LSM was the only factor associated with the development of HCC (p = 0.002) with an AUC of 0.715. On the other hand, SSM was not associated with the development of HCC. Conclusions: We found that the risk of developing HCC is associated with liver fibrosis but not with portal hypertension (assessed using SSM). Full article
(This article belongs to the Special Issue Diagnosis and Management of Liver Diseases—2nd Edition)
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13 pages, 2908 KiB  
Article
Two-Dimensional and Point Shear-Wave Elastography to Predict Esophageal Varices and Clinically Significant Portal Hypertension in Patients with Chronic Liver Disease
by Myriam W. Heilani, Max Bolender, Victoria T. Mücke, Katharina M. Schwarzkopf, Alica Kubesch-Grün, Nada Abedin, Georg Dultz, Stefan Zeuzem, Christoph Welsch, Mireen Friedrich-Rust, Jörg Bojunga, Eva Herrmann and Marcus M. Mücke
J. Clin. Med. 2024, 13(24), 7719; https://doi.org/10.3390/jcm13247719 - 18 Dec 2024
Viewed by 1163
Abstract
Introduction: The non-invasive assessment of disease severity remains pivotal in patients with chronic liver disease (CLD) as it has wide implications in predicting liver-related complications or death. Shear-wave elastography (SWE) is an emerging ultrasound-based method to non-invasively measure liver stiffness. The aim of [...] Read more.
Introduction: The non-invasive assessment of disease severity remains pivotal in patients with chronic liver disease (CLD) as it has wide implications in predicting liver-related complications or death. Shear-wave elastography (SWE) is an emerging ultrasound-based method to non-invasively measure liver stiffness. The aim of our study was to evaluate two-dimensional (2D) and point (p) SWE to predict the presence of esophageal varices (EV) or clinically significant portal hypertension (CSPH). Methods: This was a retrospective analysis of a prospectively performed cohort study of patients with CLD treated in the outpatient clinic of the Frankfurt University Hospital. PSWE using the Hitachi HI Vision ASCENDUS system and the Siemens ACUSON S2000TM system or 2D-SWE using the Toshiba APLIO500 system were analyzed at baseline and during follow-up to predict EV or surrogate parameters of CSPH. ROC curves were calculated for pooled liver stiffness measurements (LSMs) using a bootstrap approach. A combined model of SWE and platelet count was created and a mixed-effect logistic regression analysis using log-transformed values was performed. Results: Overall, 511 patients with CLD and 919 consecutive LSMs were included and 315 patients (61.6%) had signs of CSPH. 2D-SWE performed best to predict EV and CSPH, and the addition of platelet count to the predictive model significantly increased test results for EV (AUC 0.83, 95%-CI: 0.76–0.89; difference in AUC 0.11, 95%-CI: 0.03–0.19, p = 0.004), but only marginally for CSPH (AUC 0.75, 95%-CI: 0.64–0.85; difference in AUC 0.06, 95%-CI: 0.02–0.14, p = 0.150). LSM > 18.5 and >20 kPa were indicative of CSPH and EV, while LSM < 10 kPa and <11 kPa ruled out CSPH and EV, respectively. Conclusions: Our study found that 2D-SWE in combination with platelet count performed best (in comparison to the other SWE methods) to predict EV or CSPH in patients with CLD. Future prospective trials are needed to validate our results. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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