Chronic intestinal and colonic pseudo-obstruction (CIPO) represent a severe and heterogeneous group of gastrointestinal motility disorders with symptoms of bowel obstruction in the absence of a mechanical cause. Neurological and neuromuscular diseases are among the most important etiological factors, caused by dysfunction of the enteric nervous system, extrinsic autonomic pathways and intestinal smooth muscle. However, intestinal dysmotility in these conditions remains frequently under-recognized leading to delayed diagnosis and substantial morbidity. In this review, we detailed the CIPO-related spectrum of clinical presentations and highlighted features that may suggest an underlying neurogenic or neuromuscular substrate. A structured diagnostic approach is outlined, integrating imaging, physiological testing and targeted investigations to detect enteric neuro-muscular impairment. Also, we examined the main pathophysiological mechanisms linking neurological diseases to intestinal dysmotility, including enteric neuropathies, extrinsic autonomic dysfunction, mitochondrial disorders, visceral myopathies and mixed phenotypes. Particular emphasis was placed on immune-mediated enteric neuropathies, which are of special clinical relevance because they may be affected and potentially reversed via immunomodulatory therapy. Management requires a multidisciplinary approach combining nutritional support, pharmacological/interventional strategies and treatment of complications. Identification of gastrointestinal involvement in neurology-related CIPO is critical to better understand underlying mechanisms and improve management of this challenging condition.

Despite two decades of therapeutic clinical trials in metabolic dysfunction-associated steatotic liver disease (MASLD), only two drugs have been approved so far for those with metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis but not cirrhosis. Treatment responses are variable and difficult to predict, reflecting the complexity of disease pathophysiology as well as the current inability to capture disease heterogeneity, all precluding making informed individualized choices that potentially might improve treatment results. Liver biopsy for diagnosis and efficacy assessment is to date a prerequisite in late-stage trials, which limits large-scale trials and translation to routine clinical practice, and also fails to capture that heterogeneity. Several non-invasive tests (NITs) have been developed as a diagnostic surrogate to reflect disease severity, mostly addressing fibrosis, which is the strongest predictor of liver-related outcomes. This article highlights the dissonance between drug development for 'at-risk' MASH that targets both active disease and fibrosis relying on strict histological criteria, and current NITs that have been proposed for patient selection for pharmacotherapy and monitoring in clinical practice but largely reflect fibrosis. Although increasing evidence suggests their usefulness in diagnosis and follow-up, their ability to capture disease heterogeneity and select the right patients for the right treatments seems limited. Emerging NITs are derived from disease pathophysiological mechanisms and integrate lipidomic and proteomic analysis with existing biomarkers, as well as with other parameters such as the genetic background, the liver microenvironment, or the gut microbiome. Utilizing novel NITs therefore has the potential to identify appropriate candidates for therapy and also monitor responses, allowing in the future for true personalized medicine. Furthermore, understanding the complex pathophysiological mechanisms can potentially unravel not only novel diagnostics but also innovative therapeutic targets. This could lead to (personalized) choices of drugs and drug combinations that engage multiple pathways to improve efficacy, not only in terms of liver disease, but also in relation to the cardiometabolic risk profile. Moving towards precision medicine in MASLD, information provided non-invasively via circulating biomarkers (liquid liver biopsy) may hence guide risk stratification and therapeutic decisions in the near future.

Steatotic liver disease (SLD) is a spectrum of highly prevalent liver diseases encountered at many different healthcare levels. Awareness about metabolic dysfunction-associated SLD (MASLD), MetALD (MASLD and increased alcohol intake) and ALD (alcohol-related liver disease) is increasing beyond hepatology, as reflected by the various SLD guidelines issued by scientific societies from different disciplines, including endocrinology. The guidance presented here aims to improve cross-disciplinary knowledge and know-how by providing guidance to healthcare professionals from a global, holistic, multi-society and multi-stakeholder perspective. The patient trajectory was used as an overarching anchor point to ensure uniform guidance at all points along the SLD spectrum, with the ultimate goal of improving patient identification and optimising care. This consensus guidance covers patient identification and risk stratification, relevant cross-disciplinary primary and secondary care approaches, referral to and from tertiary care and strategies for disease management and monitoring.

There is a need for robust evaluations of noninvasive biomarkers for metabolic dysfunction-associated steatotic liver disease. This prospective multicenter study assessed the diagnostic accuracy of imaging (including liver stiffness measurement (LSM) using magnetic resonance elastography (MRE) and FibroScan (vibration-controlled transient elastography (VCTE)), serum biomarkers (including NIS2+) and composite scores (including Agile 3+ and Agile 4) for centrally read steatohepatitis and fibrosis. For cirrhosis, several biomarkers exceeded the minimum acceptable performance criterion (MAC), including MRE (area under the receiver operating curve (AUC) 0.91; P < 0.01), VCTE-LSM (AUC 0.87; P < 0.01), Agile 3+ (AUC 0.89; P < 0.01) and Agile 4 (AUC 0.88; P < 0.01). Among 357 participants, fibrosis stages F0-F4 were present in 12%, 16%, 25%, 32% and 15%, respectively. NIS2+ had the highest diagnostic accuracy among serum biomarkers for metabolic dysfunction-associated steatohepatitis (MASH; AUC 0.83) and at-risk MASH (MASH with at least stage 2 fibrosis; AUC 0.82), although neither significantly exceeded the MAC (P = 0.15 and P = 0.19). Among imaging biomarkers, MRE showed the highest performance for MASH (AUC 0.71) and at-risk MASH (AUC 0.75), but these remained below the MAC. For fibrosis staging, performance was stronger: MRE met the MAC for advanced fibrosis (AUC 0.91; P < 0.01), as did Agile 3+ (AUC 0.84; P = 0.03). For cirrhosis, several biomarkers exceeded the MAC, including MRE (AUC 0.91; P < 0.01), VCTE-LSM (AUC 0.87; P < 0.01), Agile 3+ (AUC 0.89; P < 0.01) and Agile 4 (AUC 0.88; P < 0.01). Serum biomarkers tended to outperform imaging for identifying at-risk MASH, whereas elastography and composite scores showed excellent accuracy for staging advanced fibrosis and cirrhosis.

Eosinophilic gastrointestinal diseases (EGID) are characterized by abnormal and prominent eosinophilic inflammation of the gastrointestinal mucosa, associated with symptoms related to the segment involved, in the absence of secondary causes of eosinophilia. EGID may affect different parts of the gastrointestinal tract, causing eosinophilic oesophagitis (EoE), eosinophilic gastritis, eosinophilic enteritis and eosinophilic colitis either individually or in combination. Secondary causes of eosinophilic infiltration of the gastrointestinal tract include parasitic infections, the use of certain medications, vasculitis, allergic syndromes, haematological conditions and other inflammatory diseases. The incidence of EGID is increasing globally. EoE is the most reported form, with a prevalence of ~1 in 700 individuals. Several pathogenetic mechanisms are being investigated, in particular, the crosstalk between aeroallergens and mucosal inflammatory cell activation, which leads to a T helper 2 cell inflammatory response and disruption of epithelial barrier integrity. EGID is frequently associated with other T helper 2 cell-driven disorders, such as atopic dermatitis, allergic rhinitis and asthma. EGID is diagnosed through histological assessment, with biopsy samples of affected areas typically showing increased eosinophils, after excluding secondary causes of eosinophilia. For EoE, new treatments, including biologic therapies, are now available, whereas therapeutic options for non-EoE EGID remain limited. Patients' quality of life may be impaired owing to social and functional limitations from symptoms, such as dysphagia and food impaction in EoE, or diarrhoea and abdominal pain in eosinophilic colitis.