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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. [ABSTRACT FROM AUTHOR]

Background: Dysgeusia is a distortion of the sense of taste whose prevalence and relationship with nutritional status in Metabolic dysfunction-associated Steatotic Liver Disease (MASLD)-related advanced chronic liver disease (ACLD) have never been systematically explored. Methods: 200 MASLD patients [60 ≤ F3 fibrosis, 70 compensated ACLD (cACLD), and 70 decompensated (dACLD)] were enrolled. At baseline, the Child–Pugh (CP) score was determined. Dietary habits, body composition, and frailty were evaluated. The European Working Group (EWGSOP2) criteria defined sarcopenia. Dysgeusia was assessed by the Dysgeusia-Total-Score (DTS). A visual analog scale identified appetite impairment (VASAI). During a 6-month follow-up, liver-related decompensation events (LRDEs) were recorded. Results: The prevalence of dysgeusia increased with the liver disease progression, appearing significantly higher in ACLD compared with ≤ F3 (65.7% vs 5%, p:0.003), as well as in dACLD compared to cACLD patients (58.5 vs 7.1% p < 0.0001). On 41 dACLD patients presenting dysgeusia, 37 (90.2%) showed a significant impairment of appetite levels. In dACLD, the CP score was positively correlated with both DTS (R:0.742) and VASAI (R:0.704), as well as DTS was directly correlated with VASAI (R:0.765) (all p < 0.0001). Compared with dACLD patients without dysgeusia, dysgeusia-affected dACLD patients presented a lower daily protein intake (g/kg/die) (1.55 ± 0.192 vs 1.34 ± 0.15, p < 0.0001). Sarcopenia (70.7 vs 41.3%) and frailty (69.29 vs 37.9%) were significantly more prevalent in dysgeusia-affected dACLD individuals (both p < 0.0001). These patients showed a higher risk of LRDEs occurrence during the follow-up [HR:2.205; C.I. 95%:1.186–4.099; p:0.01]. Logistic regression analysis revealed dysgeusia (aOR: 3.32), appetite impairment (aOR:1.32), sarcopenia (aOR: 3.75), and frailty (aOR:3.03) significantly associated with this outcome (all p < 0.0001). Conclusions: Dysgeusia appears predominant in MASLD-dACLD and, via appetite impairment, in a close relationship with malnutrition, sarcopenia, and frailty, negatively influencing patients' outcomes. [ABSTRACT FROM AUTHOR]

Background: Unlike other chronic liver disorders, in primary biliary cholangitis (PBC), systemic oxidative stress (SOS) worsens along with liver disease progression status (DPS), influencing muscle metabolism, muscle quantity (MQ), and itch pathways. Synergistically, cholestasis contributes to reduced vitamin D absorption, with a negative impact on MM and SOS. Despite this evidence, the prevalence of sarcopenia in PBC, and the SOS-MQ relationship comparing PBC with other CLDs, has never been investigated. Moreover, the relationship between vitamin D and MQ-SOS, and the correlation between SOS and pruritus severity, remains unexplored in PBC. Methods: A total of 40 MASLD, 52 chronic HBV infections, 50 chronic HCV infections, and 41 ursodeoxycholic acid/antioxidant-naïve PBC patients were enrolled. Biochemical, nutritional, and liver stiffness (LSM) data were collected, and sarcopenia was assessed after a normalizing 3-month dietetic–physical exercise regimen. The d-ROMs/BAP tests evaluated SOS. The validated "PBC-40 questionnaire" estimated pruritus and quality of life (QoL). Results: Unlike other CLDs, in PBC patients, sarcopenia was more prevalent in initial mild fibrosis (PBC: 57.10% vs. MASLD: 30.76%, HBV: 22.60%, HCV: 20.70%, all p < 0.0001), and SOS significantly correlated with MQ (dROMs-ASM/h2, p: 0.0002; BAP-ASM/h2: p: 0.0092). PBC patients presented lower vitamin D levels and a significant correlation of these with SOS and MQ (all p < 0.0001). SOS also correlated with pruritus severity (dROMs, R: 0.835; BAP, R: −0.775, p < 0.0001). QoL impairment was significantly more represented in PBC individuals with sarcopenia, SOS imbalance, and relevant pruritus (p: 0.0228). Conclusions: In PBC, SOS correlates with MQ impairment and pruritus severity, configuring two independent relationships simultaneously impacting QoL. [ABSTRACT FROM AUTHOR]

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