Search Results (588)

Background/objectives: Polycystic ovary syndrome (PCOS) and metabolic dysfunction-associated steatotic liver disease (MASLD) are common co-morbidities in women of reproductive age. PCOS is highly heterogeneous and is, therefore, divided into four phenotypes. MASLD leads to numerous systemic complications. Studies to date have shown an association between PCOS and MASLD. This study was designed to compare the FIB-4 score (based on age, alanine aminotransferase, aspartate aminotransferase and platelet count) and the results of shear wave elastography in assessing the risk of developing MASLD by patients with PCOS divided by phenotypes. Methods: The study enrolled 242 women age 18–35 years with PCOS diagnosed according to Rotterdam criteria, hospitalized at the Department of Gynaecological Endocrinology of the University Clinical Centre in Katowice. The study subjects were assigned to phenotypes A to D. Clinical and biochemical assessments were performed (including androgens and metabolic parameters), and the FIB-4 index was calculated. Liver fibrosis was evaluated by shear wave elastography. To balance the group sizes of phenotypes, oversampling with replacement was applied (PROC SURVEYSELECT, SAS), increasing the number of observations for phenotypes B, C, and D fivefold. Statistical analyses were performed based on data distribution (Shapiro–Wilk test), using ANOVA or the Kruskal–Wallis test with Dunn’s correction. Statistical significance was set at p < 0.05. Results: The FIB-4 score was the highest in phenotype B patients (0.50 ± 0.15), and the lowest in phenotypes A and C (0.42 ± 0.14). The highest rate of positive elastography findings was recorded in phenotype A patients (34.7%) and the lowest in phenotype C group (13.5%). Significant differences between the phenotypes were also found in terms of androgen levels, insulin, HOMA-IR, and the lipid profile. Among patients with positive elastography, the highest FIB-4 scores were recorded in phenotype C group (0.44 ± 0.06), but the differences between the phenotypes were not statistically significant. Conclusions: The FIB-4 score was the highest in phenotype B patients and differed significantly from phenotypes A, C and D. In the elastography exam, the fibrosis index was statistically significantly higher in phenotype A compared to other phenotypes. No correlation was detected between the FIB-4 index and positive elastography. The findings suggest that the FIB-4 index may be used for MASLD screening, but its usefulness as a predictor of eligibility for elastography requires more research. Full article

Background: Restrictive lung disease (RLD) is a potential complication in type 2 diabetes (T2D), but its relationship with insulin resistance and liver-related metabolic dysfunction remains unclear. This study evaluated the association between lung function and metabolic markers in T2D and retrospectively assessed whether metabolic improvements from dietary intervention were accompanied by changes in lung function. Methods: This cross-sectional analysis included 184 individuals (101 with T2D, 33 with prediabetes, and 50 glucose-tolerant individuals). Lung function parameters—vital capacity (VC), total lung capacity by plethysmography (TLC-B), and diffusion capacity for carbon monoxide (TL_CO)—were assessed alongside metabolic markers including HOMA2-IR, fatty liver index (FLI), NAFLD score, and Fibrosis-4 index (FIB-4). In a subset of 54 T2D participants, lung function was reassessed after six months following either a fasting-mimicking diet (FMD, n = 14), Mediterranean diet (n = 13), or no dietary intervention (n = 27). Results: T2D participants had significantly lower VC and TLC-B compared to glucose-tolerant and prediabetic individuals, with 18–21% falling below clinical thresholds for RLD. Lung volumes were negatively correlated with HOMA2-IR, FLI, NAFLD score, and FIB-4 across the cohort and within the T2D group. Although the FMD intervention led to significant improvements in HOMA2-IR and FLI, no corresponding changes in lung function were observed over the six-month period. Conclusions: Restrictive lung impairment in T2D is associated with insulin resistance and markers of liver steatosis and fibrosis. While short-term dietary interventions can improve metabolic parameters, their effect on lung function may require a longer duration or additional interventions and targeted follow-up. These findings highlight the relevance of pulmonary assessment in individuals with metabolic dysfunction. Full article

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

Background: The introduction of cystic fibrosis transmembrane conductance regulator modulators, especially the triple therapy elexacaftor, tezacaftor, ivacaftor (ETI), has improved outcomes in people with cystic fibrosis (pwCF), reducing underweight but increasing overweight rates. Objectives: This study investigates the effect of ETI on appetite control, body composition, and energy balance during a 3-week inpatient rehabilitation programme with regular exercise. Methods: In 54 pwCF (38 on ETI, 16 without ETI), changes in body composition (fat mass index, FMI; fat-free mass index, FFMI) and energy balance (calculated from body composition changes) were assessed. Appetite control was evaluated via plasma peptide YY (PYY) levels and post-exercise meal energy intake. Results: The programme significantly increased BMI (+0.3 ± 0.1 kg/m²; CI 0.1–0.4) and energy balance (+4317 ± 1976 kcal/3 weeks), primarily through FFMI gains (+0.3 ± 0.1 kg/m²; CI 0.1–0.4). Despite higher post-exercise meal energy intake and a tendency towards lower PYY levels in the ETI group, changes in body composition and energy balance did not differ between groups. This is explained by a higher prevalence of exocrine pancreatic insufficiency in the ETI group (92% vs. 50%, p < 0.001). Small sample sizes limit the interpretation of data on appetite control and energy intake. Conclusions: A 3-week inpatient rehabilitation programme improved body composition in pwCF, without resulting in a more positive energy balance with ETI therapy. This is due to a higher prevalence of pancreatic insufficiency in this group. Full article

Background/Objectives: Cystic fibrosis (CF) is a multi-system disorder characterized by chronic respiratory failure, malnutrition, and impaired growth. Achieving linear growth above the 50th percentile is associated with better pulmonary outcomes. Since October 2022, Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been approved in Italy for children aged ≥6 years. However, data on its impact on height velocity (HV) remain lacking. This study aims to evaluate growth patterns by HV and explore differences according to the CFTR variant genotype. Methods: We conducted a prospective single-center study at the CF Unit of Bambino Gesù Children’s Hospital involving 24 children aged 6–11 years eligible for ETI treatment. Baseline assessments included height, weight, body mass index (BMI), bone mineral density (BMD), body composition (via bioelectrical impedance analysis, BIA), and muscle strength (one-minute sit-to-stand test (1STST)). Height, weight, HV, and BMI standard deviation scores (SDS) were calculated for the 6 months before and after ETI initiation. Results: The mean age of the cohort was 8.7 ± 1.9 years (F/M: 12/12), with most patients naïve to CFTR modulators. A significant increase in HV was observed post-ETI: from 4.2 ± 2.0 cm/year (−1.96 ± 2.4 SDS) in the 6 months before treatment to 7.1 ± 3.0 cm/year (+1.5 ± 3.7 SDS) after treatment initiation (p < 0.0001). Patients with F508del/minimal function (F/MF) genotypes (n = 11) showed significantly greater HV compared to those with F508del/F508del (F/F, n = 5) and F508del/residual function (F/RF, n = 8) genotypes (p < 0.0001). No significant differences were observed among genetic groups in baseline BMD or lean mass. Conclusions: ETI treatment significantly and rapidly improves HV in children with CF, particularly in those with F/MF genotypes. These findings underscore the role of CFTR modulator therapy in promoting linear growth, a key indicator of health in pediatric CF populations. Full article

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

Background/Objectives: This study aimed to evaluate the effects of lung injury induced by insoluble uranium oxide particles on gut microbiota and related metabolites in rats. Methods: The rats were randomly divided into six UO₂ dose groups. A rat lung injury model was established through UO₂ aerosol. The levels of uranium in lung tissues were detected by ICP-MS. The expression levels of the inflammatory factors and fibrosis indexes were measured by enzyme-linked immunosorbent assay. Paraffin embedding-based hematoxylin & eosin staining for the lung tissue was performed to observe the histopathological imaging features. Metagenomic sequencing technology and HM700-targeted metabolomics were conducted in lung tissues. Results: Uranium levels in the lung tissues increased with dose increase. The expression levels of Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), Collagen I, and Hydroxyproline (Hyp) in rat lung homogenate increased with dose increase. Inflammatory cell infiltration and the deposition of extracellular matrix were observed in rat lung tissue post-exposure. Compared to the control group, the ratio of Firmicutes and Bacteroides in the gut microbiota decreased, the relative abundance of Akkermansia_mucinphila decreased, and the relative abundance of Bacteroides increased. The important differential metabolites mainly include αlpha-linolenic acid, gamma-linolenic acid, 2-Hydroxybutyric acid, Beta-Alanine, Maleic acid, Hyocholic acid, L-Lysine, L-Methionine, L-Leucine, which were mainly concentrated in unsaturated fatty acid biosynthesis, propionic acid metabolism, aminoacyl-tRNA biosynthesis, phenylalanine metabolism, and other pathways in the UO₂ group compared to the control group. Conclusions: These findings suggest that uranium-induced lung injury can cause the disturbance of gut microbiota and its metabolites in rats, and these changes are mainly caused by Akkermansia_mucinphila and Bacteroides, focusing on unsaturated fatty acid biosynthesis and the propionic acid metabolism pathway. Full article

Cellulite is a widespread aesthetical dermatological condition affecting a significant proportion of postpubertal women, characterized by dimpled skin, primarily on the thighs, buttocks, and hips, which has an important psychological impact. Cellulite, also called lipodystrophy or oedematosclerotic panniculitis, causes an aesthetic change in the skin that affects the epidermis, dermis, hypodermis and subcutaneous fat in different ways. The aim of the present prospective study research was to evaluate the efficacy of electromagnetic field and negative pressure in the treatment of cellulite. Methods: A total of 35 women with an average age of 40, ranging from 18 to 50 (mean 32.2 ± 7.48), with a body mass index between 18.5 and 26.9 (mean 22 ± 3.01), were enrolled in this study. The degree of cellulite of the patients was assessed clinically using the Cellulite Severity Scale (CSS) and Nürnberger–Müller classification. All patients received one session per week for a total 12 treatment sessions with Bi-one^® LifeTouchTherapy medical device (Expo Italia Srl—Florence—Italy), which generates a combination of vacuum and electromagnetic fields (V-EMF). Total treatment time was approximately 20–30 min per patient. The GAIS score, Cellulite Severity Scale (CSS) and Nürnberger–Müller classification for cellulite was evaluated 1 month after the 12 treatments with LifeTouchTherapy. Results: A statistical difference was recorded in cellulite improvement by visual analog scale (VAS) and global aesthetic improvement scale (GAIS). Conclusions: The results of the present prospective clinical study show the efficacy and safety of Bi-one^® LifeTouchTherapy in the treatment of cellulite. Electromagnetic fields combined with negative pressure therapy promote tissue regeneration and reduce fibrosis, which results in visible cosmetic improvements of cellulite. Full article

The therapeutic target of COVID-19 is focused on controlling inflammation and preventing fibrosis. Collagen–polyvinylpyrrolidone (collagen-PVP) and pirfenidone both have the ability to control the cytokine storm observed in rheumatic and fibrotic disorders. In this work, our aim was to understand the benefits of treatment with each of these drugs in patients with severe COVID-19. In total, 36 patients were treated with dexamethasone and enoxaparin, but 26 were allocated collagen-PVP or pirfenidone (n = 15 and 11, respectively); the clinical and metabolic effects were compared among them. Since pirfenidone works via transcriptional mechanisms, we performed a human genome microarray assay using RNA isolated from fibroblast and monocyte cultures treated with the biodrug, with the aim of hypothesising a possible mechanism of action for collagen-PVP. Our results showed that hospital stay duration, quick COVID-19 severity index (qCSI), and admission to the intensive care unit were statistically significantly lower (p < 0.02) in patients treated with collagen-PVP or pirfenidone when compared with the control group, and that only collagen-PVP normalised serum glucose at discharge. Ingenuity Pathway Analysis showed that the cell cycle, inflammation, and cell surface–extracellular matrix interactions could be regulated with collagen-PVP via the downmodulation of proinflammatory cytokines, while Th2 anti-inflammatory response signalling could be upregulated. Furthermore, the downregulation of some of the genes involved in nitric oxide production showed a possible control for JAK in the IFN-γ pathway, allowing for the possibility of controlling inflammation through the JAK/STAT pathway, as has been observed for pirfenidone and other immunomodulators, such as ruxolitinib. Full article

Background/Objectives: Acromegaly is associated with multiple metabolic comorbidities, but the relationship between disease activity and metabolic dysfunction-associated steatotic liver disease (MASLD) or cardiovascular risk remains unclear. This study aimed to assess the prevalence and severity of MASLD and liver fibrosis in patients with acromegaly relative to healthy controls and explore whether disease activity influences these parameters. We also evaluated cardiovascular risk indicators in acromegaly patients. Methods: A retrospective case-control study was conducted between 2000 and 2022, involving 58 acromegaly patients and 58 healthy controls. Patients were classified as active or in biochemical remission. MASLD was assessed using the fibrosis-4 (FIB-4) index, MASLD fibrosis score, body mass index, diabetes (BARD) score, the aspartate aminotransferase-to-platelet index (APRI), and the aspartate aminotransferase-to-alanine aminotransferase ratio. Cardiovascular evaluation included pulse wave velocity (PWV) and carotid intima–media thickness (CIMT). Results: The median age of the acromegaly group was 47.5 (39–57) years, compared to 42 (40–48) years in the control group (p = 0.041). APRI (p < 0.001), FIB-4 (p < 0.001), MASLD fibrosis score (p < 0.001), and BARD score (p < 0.001) were significantly higher in the acromegaly group. The prevalence of hepatic steatosis was also higher in the acromegaly group (p < 0.001). Diastolic blood pressure (p = 0.015) and PWV (p = 0.012) were significantly higher in the acromegaly group. Conclusions: Acromegaly patients have an increased risk of MASLD and fibrosis, but this risk is unassociated with disease activity. Similarly, cardiovascular risk parameters remain elevated regardless of disease activity. These findings suggest that the systemic effects of acromegaly may persist despite biochemical control. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) causes progressive liver fibrosis. Although erythrocyte mean corpuscular volume (MCV) has been shown to have a positive correlation with all-cause mortality, the association between MCV and the development of MASLD has not been fully elucidated. Here, we examined the clinical significance of the association between MCV and MASLD. Methods: A cross-sectional study was carried out in 1009 Japanese individuals (including 186 individuals aged < 60 years and 823 individuals aged ≥ 60 years) with metabolic disorders. The relationships between MCV and noninvasive clinical markers of liver fibrosis, including fibrosis-4 (FIB-4) index, aspartate aminotransferase-to-platelet ratio index (APRI), and non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS), were statistically evaluated. Results: Using multiple and logistic regression analyses in overall subjects, it was found that MCV was positively and independently associated with the values of FIB-4 index, APRI, NFS, and the prevalence of liver fibrosis defined by each index. However, the associations between the MCV value and MASLD indices were found to be positive in subjects aged ≥ 60 years but not in those aged < 60 years. Conclusions: MCV might be a simple and useful biomarker for the development of MASLD in the elderly. Full article

Background/Objectives: Metabolic dysfunction-associated fatty liver disease (MAFLD) is linked to cardiovascular complications, including atrial fibrillation. P-wave indices (PWIs) reflect atrial conduction heterogeneity but have not been fully evaluated in MAFLD. To compare PWIs in MAFLD patients versus controls, assess their association with fibrosis severity, and evaluate their diagnostic performance for MAFLD and fibrosis. Methods: In this retrospective single-center study, 447 subjects were included (noMAFLD: Fatty Liver Index (FLI) < 30 without metabolic dysfunction, n = 205; MAFLD: FLI ≥ 60+ ≥ 1 metabolic risk factor, n = 242). Among MAFLD subjects, the non-alcoholic fatty liver disease (NAFLD) Fibrosis Score (NFS) stratified lower (NFS ≤ −1.455; n = 170), and there was a higher fibrosis risk (NFS > −1.455; n = 72). Standard 12-lead ECGs were digitized for offline PWI measurement. Statistical analyzes included group comparisons, multivariable logistic regression, and ROC curve analysis. Results: MAFLD patients exhibited a longer PWPT-D2 (63 ± 12 vs. 52 ± 10 ms, p = 0.003), PWPT-V1 (68 ± 14 vs. 60 ± 13 ms, p = 0.005), PWdis (55 ± 13 vs. 46 ± 11 ms, p = 0.010), and PTFV₁ (38 [31–46] vs. 28 [22–34] mm·ms, p = 0.021) compared with controls. Within MAFLD, a higher fibrosis risk was associated with a further PWI prolongation (all p < 0.015). Multivariate analysis identified PWPT-D2 (OR 1.05 per ms; 95% CI 1.02–1.08; p = 0.002) and PWDIS (OR 1.03 per ms; 95% CI 1.00–1.06; p = 0.048) as independent MAFLD predictors. ROC curves showed PWPT-D2 had the highest AUC for MAFLD detection (0.78; 95% CI 0.72–0.84) and fibrosis (0.82; 95% CI 0.76–0.88). Combining PWPT-D2 with BMI and waist circumference improved MAFLD discrimination (AUC 0.89; 95% CI 0.85–0.93; p < 0.001 vs. PWPT-D2 alone). Conclusions: PWPT-D2 and PWdis are significantly prolonged in MAFLD and more so with advanced fibrosis. PWPT-D2 may be a simple, noninvasive ECG marker for MAFLD screening and fibrosis staging, particularly when combined with anthropometric measures. Full article

Background and Objectives: Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive interstitial lung disease with an unknown etiology. It is often accompanied by skeletal muscle mass loss. Chest wall muscles play a crucial role in respiratory movements and form part of the skeletal muscles. The aim of this study is to evaluate the relationship between chest wall muscle thickness and pulmonary function test (PFT) results, as well as other prognostic markers, in patients with IPF. Materials and Methods: A retrospective analysis was conducted on 108 patients diagnosed with IPF and 53 control subjects. Chest wall muscle thickness was measured on thoracic computed tomography (CT) images at specific anatomical levels. PFT parameters, the Gender-Age-Physiology (GAP) index, number of acute exacerbations, and mortality data were evaluated in relation to muscle thickness. Results: IPF patients had significantly reduced thickness in the bilateral external scapular muscles at both the aortic and pulmonary trunk levels compared to controls. Bilateral pectoral muscle thickness at the aortic level was positively correlated with forced vital capacity (FVC) and negatively correlated with the number of exacerbations. Internal scapular muscle thickness at the aortic level showed a significant positive correlation with diffusion capacity of the lung for carbon monoxide (DLCO) and a negative correlation with both GAP scores and exacerbation frequency. External scapular muscle thickness at the pulmonary trunk level was positively associated with PFT parameters and inversely correlated with the GAP index, exacerbations, and mortality. Conclusions: In patients with IPF, the bilateral external scapular muscle thickness at the aortic and pulmonary trunk levels was significantly reduced compared to controls. Significant associations were found between some chest wall muscle thicknesses and the GAP index, pulmonary function, acute exacerbations, and mortality, underscoring the prognostic value of baseline muscle measurements. Measurement of chest wall muscle thickness using routine thoracic CT scans may offer additional prognostic value in IPF. Incorporating this parameter into clinical evaluation may help identify patients who could benefit from supportive interventions, such as nutritional therapy or pulmonary rehabilitation. Full article

Objectives: To compare thresholds and accuracies of FIB-4, vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2D shear wave elastography (2D-SWE), and MR elastography (MRE) for detecting hepatic fibrosis in patients with MASLD. Materials and Methods: Systematic searching of MEDLINE, EMBASE, Cochrane Library, Scopus, and the gray literature from inception to March 2024 was performed. Studies evaluating accuracies of FIB-4, VCTE, 2D-SWE, pSWE, and/or MRE for detecting significant (≥F2) and/or advanced (≥F3) hepatic fibrosis in MASLD patients compared to histology were identified. Full-text review and data extraction were performed independently by two reviewers. Multivariate meta-analysis and subgroup analyses were performed using index test and fibrosis grading. Risk of bias was assessed using QUADAS-2. Results: 207 studies with over 80,000 patient investigations were included. FIB-4 1.3 threshold sensitivity was 71% (95% CI 66–75%) for detecting advanced hepatic fibrosis, which improved to 88% (85–91%) using a <0.75 threshold. FIB-4 specificity using a 2.67 threshold was 96% (94–97%). Sensitivities of 88–91% were achieved using thresholds of 3.2 kPa for pSWE, 4.92 kPa for 2D-SWE, 7.18 kPa for VCTE, and 2.32 kPa for MRE. No significant differences were identified for sensitivities in subgroup analysis with thresholds between 7 and 9 kPa. Most imaging-based studies were high risk of bias for the index test. Conclusions: A FIB-4 threshold of <0.75 and modality-dependent thresholds (VCTE < 7 kPa; pSWE <3 kPa; 2D-SWE <5 kPa; and MRE <2.5 kPa) would achieve sensitivities of around 90% when defining low-risk MASLD in population screening. A modified two-tier algorithm aligning with existing Society of Radiologists in Ultrasound guidelines would improve risk stratification accuracies compared to existing guidelines by European and American liver societies. Full article

Background/Objectives: The possibility of progressive liver fibrosis remains even when alanine aminotransferase (ALT) levels are <30 IU/L. Therefore, we aimed to investigate factors that can predict fibrosis progression in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) with ALT levels ≤ 30 U/L. Methods: This multicenter retrospective cohort study was conducted using data collected between December 1994 and December 2021. Among the 1381 patients with MASLD (CLIONE study) who underwent liver biopsy, we performed decision-tree analysis on factors for stage ≥ 3 in 115 with ALT levels ≤ 30 U/L. Of the 818 patients with MASLD (Kawasaki cohort) who underwent liver biopsy, we included 174 with ALT levels ≤ 30 U/L for validation. Results: In the decision-tree analysis of patients with stage ≥ 3 with ALT levels ≤ 30 U/L, 57% of patients with a fibrosis-4 (FIB-4) index ≥ 2.67 and 70% with both FIB-4 index ≥ 2.67 and type-2 diabetes mellitus (DM) were detected. However, no cases of stage ≥ 3 were observed among patients without type-2 DM with ALT ≤ 30 U/L and a FIB-4 index < 2.67. After verifying the decision-tree analysis, the model construction and validation datasets showed a close correlation. Conclusions: Among patients with MASLD with ALT levels ≤ 30 U/L, those with an FIB-4 index ≥ 2.67, particularly with comorbid type-2 DM, should consider consultation with a hepatologist. Full article