Hot and Cold Fibrosis: The Role of Serum Biomarkers to assess the Immune Mechanisms and ECM-Cell Interactions in Human Fibrosis.

Fibrosis is a pathological condition characterized by excessive accumulation of extracellular matrix (ECM) components, particularly collagens, leading to tissue scarring and organ dysfunction. In fibrosis, an imbalance between collagen synthesis (fibrogenesis) and degradation (fibrolysis) results in the deposition of fibrillar collagens disrupting the structural integrity of the ECM and, consequently, the tissue architecture. Fibrosis is associated with a wide range of chronic diseases, including liver cirrhosis, kidney fibrosis, pulmonary fibrosis, and autoimmune diseases.

Addressing the High and Rising Global Burden of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Steatohepatitis (MASH): From the Growing Prevalence to Payors' Perspective.

Background: The continuum of metabolic syndrome encompasses a spectrum of dysfunctions impacting obesity-linked insulin resistance, glucose homeostasis, lipid metabolism and pro-inflammatory immune responses. The global prevalence of metabolic diseases, including diabetes, chronic liver disease, cardiometabolic disease and kidney disease, has surged in recent decades, contributing significantly to population mortality. Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, is a leading cause of liver disease worldwide.

Precision in Liver Diagnosis: Varied Accuracy Across Subgroups and the Need for Variable Thresholds in Diagnosis of MASLD.

Background And Aims: The performance of non-invasive liver tests (NITs) is known to vary across settings and subgroups. We systematically evaluated whether the performance of three NITs in detecting advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) varies with age, sex, body mass index (BMI), type 2 diabetes mellitus (T2DM) status or liver enzymes.

Methods: Data from 586 adult LITMUS Metacohort participants with histologically characterised MASLD were included.

Hepatic glucose production rises with the histological severity of metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) are associated with a high prevalence of type 2 diabetes (T2D). Individuals with MASLD exhibit insulin resistance (IR) and hyperglycemia, but it is unclear whether hepatic glucose production (HGP) is increased with MASLD severity. We evaluated HGP in a cohort of histologically characterized individuals with MASL/MASH using stable isotope infusion (6,6-H-glucose, U-H-glycerol) and liver-specific genome-scale metabolic models (GEMs).