Molecular Mechanisms Involved in MAFLD in Cholecystectomized Patients: A Cohort Study.

Gallstone disease and metabolic dysfunction-associated fatty liver disease (MAFLD) share numerous common risk factors and progression determinants in that they both manifest as organ-specific consequences of metabolic dysfunction. Nevertheless, the precise molecular mechanisms underlying fibrosis development in cholecystectomized MAFLD patients remain inadequately defined. This study aimed to investigate the involvement of farnesoid X receptor 1 (FXR1) and fibroblast growth factor receptor 4 (FGFR4) in the progression of fibrosis in cholecystectomized MAFLD patients. A meticulously characterized cohort of 12 patients diagnosed with MAFLD, who had undergone liver biopsies during programmed cholecystectomies, participated in this study. All enrolled patients underwent a follow-up regimen at 1, 3, and 6 months post-cholecystectomy, during which metabolic biochemical markers were assessed, along with elastography, which served as indirect indicators of fibrosis. Additionally, the hepatic expression levels of FGFR4 and FXR1 were quantified using quantitative polymerase chain reaction (qPCR). Our findings revealed a robust correlation between hepatic FGFR4 expression and various histological features, including the steatosis degree (r = 0.779, p = 0.023), ballooning degeneration (r = 0.764, p = 0.027), interphase inflammation (r = 0.756, p = 0.030), and steatosis activity score (SAS) (r = 0.779, p = 0.023). Conversely, hepatic FXR1 expression did not exhibit any significant correlations with these histological features. In conclusion, our study highlights a substantial correlation between FGFR4 expression and histological liver damage, emphasizing its potential role in lipid and glucose metabolism. These findings suggest that FGFR4 may play a crucial role in the progression of fibrosis in cholecystectomized MAFLD patients. Further research is warranted to elucidate the exact mechanisms through which FGFR4 influences metabolic dysfunction and fibrosis in this patient population.

Identification of Hepatic Dendritic Cells in Liver Biopsies Showing Steatosis in Patients with Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Associated with Obesity.

BACKGROUND Metabolic dysfunction-associated fatty liver disease (MAFLD) is now the term used for hepatic steatosis in patients who are overweight or obese, have type 2 diabetes mellitus (T2DM), or evidence of metabolic dysregulation. The prevalence of MAFLD among morbidly obese subjects is 65-93%. Hepatic dendritic cells (hDCs) are antigen-presenting cells that induce T cell-mediated immunity. MAFLD pathogenesis involves numerous immune cell-mediated inflammatory processes, while the particular role of hDCs is yet to be well defined. This study aimed to identify hDCs in liver biopsies from 128 patients with MAFLD associated with obesity. MATERIAL AND METHODS In this cross-sectional study, 128 liver biopsies from 128 patients with MAFLD (diagnosed as presence of hepatic steatosis, plus T2DM, metabolic dysregulation or overweight/obesity) were collected and assessed for CD11c⁺ immunoreactivity degree (CD11c as dendritic cell biomarker), through antigen retrieval, reaction with CD11c antibodies (primary), and marking with diaminobenzidine chromogen. RESULTS Among the 128 patients with MAFLD, 64 (50%) had MAFLD and fibrosis and 72 (56.2%) positively expressed hDCs (CD11c⁺). Among morbidly obese patients, 49 (64.5%) positively expressed hDCs (CD11c⁺) in liver tissue; from patients with obesity grade I- grade II (GI-II), 18 (54.5%) positively expressed hDCs (CD11c⁺) in liver tissue; and from non-obese patients with MAFLD, 5 (26.3%) positively expressed hDCs (CD11c⁺) in liver tissue. CONCLUSIONS hDC expression increases significantly in morbidly obese patients with MAFLD compared with non-obese patients, independent of the degree of fibrosis, suggesting the role of adaptive changes within hDCs in the perpetuation of inflammatory insults in chronic liver diseases.

A Review of the Increasing Prevalence of Metabolic-Associated Fatty Liver Disease (MAFLD) in Children and Adolescents Worldwide and in Mexico and the Implications for Public Health.

Non-alcoholic fatty liver disease (NAFLD) affects almost a quarter of the world's population and is the most common cause of chronic liver disease in children and adolescents. The recent proposal to replace the terminology of NAFLD with metabolic-associated fatty liver disease (MAFLD) aims to reflect the pathophysiology and risk factors for this disease. Importantly, the risk factors for MAFLD may be prenatal, such as genetic factors, or postnatal, such as obesity and insulin resistance. MAFLD is increasingly recognized in children and adolescents. Early diagnosis and identification of high-risk individuals with type 2 diabetes mellitus and metabolic syndrome is important. The diagnosis and management of MAFLD in children and adolescents should follow international clinical guidelines, such as those from the American Diabetes Association (ADA) and the International Society for Pediatric and Adolescent Diabetes (ISPAD). Current guidelines recommend lifestyle and dietary modifications, exercise, screening, individualized patient assessment, and multidisciplinary patient management. This review assesses the revised terminology and discusses the epidemiology, risk factors, pathophysiology, diagnosis, and prevention of MAFLD in children and adolescents worldwide and in Mexico, and also considers the implications for public health.

Nutraceuticals and microbiota.

Nutraceuticals are defined as products isolated or purified from foods that are generally sold in medicinal or dosage forms not usually associated with food which is demonstrated to have a physiological benefit or provide protection against chronic disease. In this context, the products offered should be rigorously evaluated by international regulatory agencies. More recently, nutraceuticals have been proposed as a potential preventive and therapeutic option in the assessment of chronic diseases, mainly by altering the microbiome composition. However, the current lack of conclusive evidence supporting the "healthy" or "normal" microbiome, along with the dysbiosis concept paradigm, could be both contributing to the lack of homogeneous results. These issues may be solved in the next years with the use of emergent technologies in the individual's microbiome assessment and its fluctuations in time or related to many factors, such as nutraceuticals. Additionally, future research assessing the independent association between the dysbiosis modification and any "potential" nutraceutical product (including bioactive ingredient or chemical compound in food) is going to enlarge the currently reduced "established nutraceuticals" group. In this work we have assessed the nutraceutical's potential role as a microbiome-targeted manipulation therapy, and the gut-liver axis involved in the digestive diseases' pathogenesis and progression, including the chronic liver diseases. Moreover, microbiome targeted nutraceuticals that show consistent results might be further included in clinical research and trials in the therapeutic assessment of chronic diseases. Finally, the indication of these quality microbiome-targeted nutraceuticals will undoubtedly carry health benefits for individuals.