Leisure-Time Physical Activity in Subjects with Metabolic-Dysfunction-Associated Steatotic Liver Disease: An All-Cause Mortality Study.

Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) affects 30% of adults worldwide and is associated with obesity and cardiovascular risk factors. If left untreated, it can progress to severe liver disease. Lifestyle changes such as physical activity and weight loss help to reduce the severity and risk of mortality. This study estimated the impact of MASLD and leisure-time physical activity (LTPA) on mortality and examined how gender mediates this effect in a Southern Italian population. Methods: This work is a population-based prospective cohort study of inhabitants of Castellana Grotte (>30 years old) in Southern Italy, which began in 1985. Participants provided general health information, underwent anthropometric measurements and ultrasonography, and completed a validated questionnaire on their food intake and LTPA. The vital status was tracked through local municipalities Results: In total, 1826 participants (39% with MASLD) were enrolled in this study, drawn from 2970 eligible subjects; the mean age was 51.91 (±14.76) years and 56.2% were men. Subjects with MASLD who practiced low LTPA had a significantly higher risk of death than those who did not have MASLD and practiced high LTPA. In addition, subjects with MASLD who practiced low LTPA were about 19% less likely to survive to the age of 82 years. As regards gender, both men and women with MASLD and low LTPA showed a significant risk of death, but this was higher in women. Conclusions: The presence of MASLD, especially in women, increases the risk of death from all causes. LTPA plays a key role in the disease and reduces mortality in these individuals.

Effect of a 12-Week Walking Program Monitored by Global Physical Capacity Score (GPCS) on Circulating Cell-Free mtDNA and DNase Activity in Patients with Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) involves low-grade mucosal inflammation. Among the various approaches capable of managing the symptoms, physical activity is still under investigation. Despite its benefits, it promotes oxidative stress and inflammation. Mitochondria impacts gut disorders by releasing damage-associated molecular patterns, such as cell-free mtDNA (cf-mtDNA), which support inflammation. This study evaluated the effects of a 12-week walking program on the cf-mtDNA and DNase in 26 IBS and 17 non-IBS subjects. Pro- and anti-inflammatory cytokines were evaluated by ELISA. Digital droplet PCR was used to quantify cf-mtDNA; DNase activity was assessed using a single radial enzyme diffusion assay. PCR-RFLP was used to genotype DNASE1 rs1053874 SNP. Significantly lower IL-10 levels were found in IBS than in non-IBS individuals. Exercise reduced cf-mtDNA in non-IBS subjects but not in IBS patients. DNase activity did not correlate with the cf-mtDNA levels in IBS patients post-exercise, indicating imbalanced cf-mtDNA clearance. Different rs1053874 SNP frequencies were not found between groups. The study confirms the positive effects of regular moderate-intensity physical activity in healthy subjects and its role in cf-mtDNA release and clearance. Walking alone might not sufficiently reduce subclinical inflammation in IBS, based on imbalanced pro- and anti-inflammatory molecules. Prolonged programs are necessary to investigate their effects on inflammatory markers in IBS.

Development and Internal Validation of a Model for Predicting Overall Survival in Subjects with MAFLD: A Cohort Study.

Background & Aims: Fatty liver disease with metabolic dysfunction (MAFLD) is a new concept proposed to replace the previous concept of Non-Alcoholic Hepatic Steatosis (NAFLD). We developed and internally validated a prognostic model to predict the likelihood of death in a cohort of subjects with MAFLD. Methods: Our work involved two steps: the first was the construction of a bootstrapped multivariable Cox model for mortality risk prognosis and the second was its validation. Results: The study cohort included 1506 subjects, of which 907 were used for internal validation. Discriminant measures for the final model were R2D 0.6845 and Harrell's C 0.8422 in the development and R2D 0.6930 and Harrell's C 0.8465 in the validation. We used the nine independent prognostic factors selected by the LASSO Cox procedure and fitted by the bootstrap Cox survival model, and observed ß were: Gender 0.356 1.42 (p < 0.008), Age 0.146 (p < 0.001), Glycemia 0.004 (p < 0.002), Total Cholesterol -0.0040 (p < 0.009), Gamma Glutamyl Transpeptidase 0.009 (p < 0.001), SBP 0.009 (p < 0.036), DBP -0.016 (p < 0.041), ALP 0.008 (p < 0.071) and Widowhood 0.550 (p < 0.001). Conclusions: We produced and validated a model to estimate the probability of death in subjects with MAFLD. The instruments we used showed satisfactory predictive capabilities.