Inflammatory bowel diseases (IBDs), encompassing Crohn’s disease and ulcerative colitis, are complex chronic disorders characterized by an intricate interplay between genetic predisposition, immune dysregulation, gut microbiota alterations, and environmental exposures. This review aims to synthesize recent advances in IBD pathogenesis, exploring key mechanisms and potential avenues for prevention and personalized therapy. A comprehensive literature search was conducted across major bibliographic databases, selecting the most recent and impactful studies on IBD pathogenesis. The review integrates findings from multi-omics analyses, single-cell transcriptomics, and longitudinal cohort studies, focusing on immune regulation, gut microbiota dynamics, and environmental factors influencing disease onset and progression. Immune dysregulation, including macrophage polarization (M1 vs. M2) and Th17 activation, emerges as a cornerstone of IBD pathogenesis. Dysbiosis, as a result of reduced alpha and beta diversity and overgrowth of harmful taxa, is one of the main contributing factors in causing inflammation in IBD. Environmental factors, including air and water pollutants, maternal smoking, and antibiotic exposure during pregnancy and infancy, significantly modulate IBD risk through epigenetic and microbiota-mediated mechanisms. While recent advances have supported the development of new therapeutic strategies, deeply understanding the complex dynamics of IBD pathogenesis remains challenging. Future efforts should aim to reduce the burden of disease with precise, personalized treatments and lower the incidence of IBD through early-life prevention and targeted interventions addressing modifiable risk factors.

Background/Objectives: Liver fibrosis is a progressive consequence of chronic liver injury that can evolve into cirrhosis, liver failure, or hepatocellular carcinoma, representing a major global health burden. Fibrogenesis is driven by hepatic stellate cell (HSC) activation, excessive extracellular matrix deposition, and structural disruption of liver tissue, with transforming growth factor-β (TGF-β) signaling and inflammatory mediators as central pathways. Current therapies primarily target the underlying causes, which may halt disease progression but rarely reverse established fibrosis. This review aims to outline current and emerging therapeutic strategies for liver fibrosis, informing both clinical practice and future research directions. Methods: A narrative synthesis of preclinical and clinical evidence was conducted, focusing on pharmacological interventions, microbiota-directed strategies, and innovative modalities under investigation for antifibrotic activity. Results: Bile acids, including ursodeoxycholic acid and derivatives, modulate HSC activity and autophagy. Farnesoid X receptor (FXR) agonists, such as obeticholic acid, reduce fibrosis but are limited by adverse effects. Fatty acid synthase inhibitors, exemplified by denifanstat, show promise in metabolic dysfunction-associated steatohepatitis (MASH). Additional strategies include renin–angiotensin system inhibitors, omega-3 fatty acids, and agents targeting the gut–liver axis. Microbiota-directed interventions—probiotics, prebiotics, symbiotics, antibiotics (e.g., rifaximin), and fecal microbiota transplantation—are emerging as potential modulators of barrier integrity, inflammation, and fibrogenesis, though larger clinical trials are required. Reliable non-invasive biomarkers and innovative trial designs, including adaptive platforms, are essential to improve patient selection and efficiently evaluate multiple agents and combinations. Conclusions: Novel modalities such as immunotherapy, gene editing, and multi-targeted therapies hold additional potential for fibrosis reversal. Continued translational efforts are critical to establish safe, effective, and accessible treatments for patients with liver fibrosis.

The expression “lung–gut–liver axis” refers to the interconnected processes occurring in the lungs, gastrointestinal tract, and liver, particularly in relation to immune function, microbial regulation, and metabolic responses. Over the past decade, growing concern has emerged regarding the detrimental impact of air pollution on liver disease. Air pollutants, including particulate matter (PM) and chemical gases such as nitrogen oxides (NOx), can influence the microbiome in the lungs and gut by generating reactive oxygen species (ROS), which induce oxidative stress and local inflammation. This redox imbalance leads to the production of altered secondary microbial metabolites, potentially disrupting both the alveolar–capillary and gut barriers. Under these conditions, microbes and their metabolites can translocate to the liver, triggering inflammation and contributing to liver diseases, particularly metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, and hepatocellular carcinoma (HCC). This manuscript aims to review recent findings on the impact of air pollution on liver disease pathogenesis, exploring the molecular, genetic, and microbiome-related mechanisms underlying lung–gut–liver interactions, providing insights into potential strategies to prevent or mitigate liver disease progression.

The advent of Janus kinase (JAK) inhibitors, including tofacitinib, filgotinib, and upadacitinib, has significantly widened the therapeutic options for patients with inflammatory bowel disease (IBD). These agents offer the advantage of oral administration and have demonstrated efficacy in inducing and maintaining remission. However, concerns regarding their safety have emerged, particularly concerning cardiovascular and infectious complications, which appear more pronounced in patients with pre-existing risk factors such as older age, smoking, or comorbidities. While these risks are better understood, the potential association between JAK inhibitors and malignancies remains a subject of ongoing investigation. Current data from randomised controlled trials, pooled and integrated analyses, and real-world studies provide conflicting evidence regarding cancer risk. Notably, studies in patients with rheumatologic diseases treated with JAK inhibitors have contributed additional insights into long-term safety outcomes. Despite the uncertainty surrounding malignancy risks, it is likely that predisposing factors, including older age, smoking history, and long-standing IBD with chronic inflammation, play a more substantial role in cancer development than JAK inhibitor therapy alone. This paper reviews safety data from clinical trials, meta-analyses, and observational studies, focusing on cancer risk in patients treated with JAK inhibitors for IBD. We also review evidence from rheumatology studies, highlighting the need for individualised risk assessment and close monitoring to optimise the safety profile of these medications in clinical practice.

Background/Objectives: The attenuation coefficient (AC) is a quantitative ultrasound parameter that describes the frequency-dependent reduction of acoustic energy as ultrasound waves propagate through biological tissues. Recently, AC has gained increasing relevance in abdominal ultrasound as an objective and reproducible biomarker for tissue characterization, particularly in the assessment of diffuse parenchymal diseases. Unlike conventional qualitative B-mode imaging, AC provides standardized numerical measurements that improve interobserver reproducibility and facilitate longitudinal monitoring. Methods: This review provides a comprehensive and critical overview of the current clinical applications of AC measurements in abdominal ultrasound, mainly focusing on liver steatosis quantification. Emphasis is placed on the comparative evaluation of commercially available AC-based technologies, highlighting their methodological differences, validation evidence, and diagnostic performance to support future efforts toward harmonization and standardization across ultrasound platforms. Results: Several studies have demonstrated a strong correlation between AC values and established reference standards, including magnetic resonance imaging–proton density fat fraction (MRI-PDFF) and histopathological grading, supporting its role in the noninvasive evaluation of liver steatosis. The growing clinical adoption of AC has been accompanied by the development of multiple vendor-specific software implementations integrated into modern ultrasound systems. Although these platforms share a common physical basis, they differ substantially in algorithmic design, signal processing strategies and region-of-interest selection. These differences may influence absolute AC values and diagnostic cutoff thresholds, therefore limiting direct comparability across systems. Another factor that further contributes to the heterogeneity of reported cutoff values is the variability in validation approaches, with some technologies validated against liver biopsy and others against MRI-PDFF. Conclusions: AC is a promising quantitative ultrasound biomarker for noninvasive liver steatosis assessment, showing strong correlation with histology and MRI-PDFF. However, inter-vendor variability currently limits cross-platform comparability. Standardized acquisition protocols, unified quality-control criteria, phantom-based cross-calibration, and consistent vendor-specific reporting are essential to ensure reliable longitudinal monitoring and broader clinical implementation.

Background/Objectives: Crohn’s disease (CD) is one of the most frequent causes of short bowel syndrome (SBS), a severe clinical condition with huge morbidity and social costs. SBS occurs when, following intestinal resections, the remaining small bowel in continuity is less than 200 cm in length. Intestinal failure (IF) can complicate SBS when intravenous nutritional or electrolyte supplementation is required to maintain dietary needs. The primary aim of this study was to identify clinical predictive factors of SBS in a cohort of outpatients with CD. Methods: We conducted a prospective, single-center, cohort study enrolling consecutive CD outpatients at a tertiary-level inflammatory bowel disease center. Detailed demographic and clinical features were collected. Significant factors associated with the onset of SBS in the univariate analysis were input into a multivariate logistic regression model to identify independent predictors of SBS. Results: In total, 232 CD patients (52.6% male, median age 49 years [IQR 37–60]) were included: 24.6% of them were smokers; extraintestinal manifestations (EIMs) were present in 21.6% of patients; and 67.7% of patients had at least one intestinal resection (27% of them with more than one surgical intervention). At enrollment, 96.1% of patients were on advanced therapies, and considering the course of the disease, 24.6% of patients were exposed to ≥3 different advanced therapies. A total of 18 patients had SBS and 9 had IF. In univariate analysis, the following variables were statistically associated with the risk of developing SBS: disease duration (p < 0.001), upper gastrointestinal disease localization (L4) (p < 0.001), penetrating behavior (p = 0.023), perianal disease (p = 0.036), length of first intestinal resection (p < 0.001), shorter time elapsing from CD diagnosis to start the first advanced therapy (p < 0.001), and treatment with advanced therapy after first intestinal resection (p < 0.001). In multivariate analysis, disease duration (OR 1.083, 95% C.I. 1.025–1.145, p = 0.005) and L4 (OR 20.079, 95% C.I. 2.473–163.06, p = 0.005) were independently associated with the development of SBS. Conversely, the number of different advanced therapies before the onset of SBS was independently associated with a reduced risk of developing SBS (OR 0.247, 95% C.I. 0.107–0.58, p = 0.001). Conclusions: Our data identifies several clinical features that could possibly predict the development of SBS in CD. Further studies with a larger sample size are needed to confirm our findings.