Effectiveness of 1-year pemafibrate treatment on steatotic liver disease: the influence of alcohol consumption.

BACKGROUND/AIMS: Pemafibrate is a selective peroxisome proliferator-activated receptor α modulator that improves serum alanine aminotransferase (ALT) in dyslipidemia patients. We previously reported that pemafibrate significantly improves liver function, serum triglyceride (TG) levels and liver stiffness in non-alcoholic fatty liver disease patients, however the influence of alcohol consumption was not considered. Therefore, we explored pemafibrate efficacy in patients with steatotic liver disease (SLD) and alcohol-associated liver disease (ALD). METHODS: We retrospectively evaluated pemafibrate efficacy on liver enzymes and lipids in metabolic dysfunction-associated SLD (MASLD) (n = 93), MASLD plus increased alcohol intake (MetALD; n = 23) and ALD (n = 22) patients who had taken pemafibrate for at least 48 weeks. Liver shear wave velocity (SWV, n = 75) was also evaluated. RESULTS: In MASLD group, ALT, aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GTP) and TG values were significantly decreased from baseline to week 24 and week 48 ( P  < 0.0001). ALT and TG values in MetALD group and ALT and AST values in ALD group were also significantly decreased from baseline to week 24 and week 48. Study participant SWV values decreased from baseline to week 48. We observed no significant difference in changes to ALT, AST, γ-GTP and TG (value at week 24 or week 48 minus value at baseline) among the three groups. CONCLUSION: Pemafibrate improves liver function and liver stiffness thus making it a promising therapeutic agent for SLD, even in patients with excess alcohol consumption (MetALD and ALD groups).

Elevated extracellular particle concentration in plasma predicts in-hospital mortality after severe trauma.

Background: Extracellular particles (EPs), particularly extracellular vesicles, play a crucial role in regulating various pathological mechanisms, including immune dysregulations post-trauma. Their distinctive expression of cell-specific markers and regulatory cargo such as cytokines or micro-ribonucleic acid suggests their potential as early biomarkers for organ-specific damage and for identifying patients at risk for complications and mortality. Given the critical need for reliable and easily assessable makers to identify at-risk patients and guide therapeutic decisions, we evaluated the early diagnostic value of circulating EPs regarding outcomes in severely injured multiple-trauma patients. Methods: Plasma samples were collected from 133 severely injured trauma patients (Injury Severity Score (ISS) ≥16) immediately upon arrival at the emergency department (ED). Patients were categorized into survivors and non-survivors. Injury characteristics and outcomes related to sepsis, pneumonia, or early (<1 day after admission) and late mortality were assessed. Circulating EPs, cytokine profiles, and blood counts of platelets and leukocytes were determined. Receiver operating characteristic analyses were conducted. Results: Despite no significant differences in injury pattern or severity, non-survivors exhibited significantly elevated counts of circulating EPs compared to survivors. The optimal cut-off for EPs <200 nm indicating non-survivors was 17380/µl plasma, with a sensitivity of 77% and a specificity of 61% in predicting in-hospital mortality. Later non-survivors received significantly higher numbers of units of packed red blood cells [8.54 ± 5.45 vs. 1.29 ± 0.36 units], had higher serum lactate [38.00 ± 7.51 vs. 26.98 ± 1.58 mg/dL], significantly lower platelet counts [181.30 ± 18.06 vs. 213.60 ± 5.85 *10³/µL] and lower heart rates [74.50 ± 4.93 vs. 90.18 ± 2.06 beats/minute] upon arrival at the ED compared to survivors. Conclusion: Our results demonstrate the high diagnostic potential of elevated concentrations of circulating EPs <200 nm for identifying patients at risk of mortality after severe trauma. This parameter shows comparable sensitivity to established clinical predictors. Early evaluation of EPs concentration could complement assessment markers in guiding early therapeutic decisions.