Mette Munk Lauridsen

Background: Hospitalisations represent major clinical events in cirrhosis, yet prediction based on clinical variables alone remains limited. Objective: Given the role of the gut microbiome in disease progression, we evaluated whether gut metagenomic profiles are associated with 90-day hospitalisation and provide additional prognostic information beyond clinical features in a multinational outpatient cirrhosis cohort. Design: We enrolled 679 outpatients with cirrhosis from seven countries and performed stool metagenomic profiling, including taxonomic, functional pathway and antibiotic resistance gene (ARG) analyses, with 90-day follow-up. Machine learning models were developed using clinical and microbiome features for predicting non-elective hospitalisations. Results: 25% of patients required hospitalisation within 90 days. Hospitalised patients had more advanced cirrhosis, lower microbial diversity which was consistent across countries despite marked variation in microbial composition. Diet had a modest influence on microbiome structure. After adjustment for country, disease severity, cirrhosis aetiology and treatment, 19 bacterial species remained independently associated with hospitalisation, including enrichment of Enterococcus faecium and Veillonella rogosae and depletion of multiple commensal taxa. Functional profiling demonstrated coordinated taxonomic-functional alterations focusing on complex carbohydrate degradation pathways, glycan biosynthesis, lipid and nucleotide salvage pathways and association with antimicrobial resistance mechanisms. The combined clinical–microbiome model significantly outperformed both the clinical-only (area under the curve (AUC) 0.79) and microbiome-only (AUC 0.74) models, achieving an AUC of 0.84. Conclusion: Gut microbiome composition and function are associated with short-term hospitalisation risk and provide additional prognostic information beyond clinical variables in a multicountry cohort. Hospitalisation, regardless of country, is characterised by loss of short-chain fatty acid-producing taxa, functional shifts, ARG and pathway changes.

Background/objectives: Liver cirrhosis is a life-limiting, non-malignant condition with a high symptom burden, psychosocial challenges, and unpredictable disease trajectory. As such, patients with cirrhosis and their caregivers might benefit from palliative care (PC) interventions. However, in most clinical settings, PC is not yet an integral part of basic hepatology care. This scoping review aimed to map how patients with cirrhosis are identified for palliative care, which interventions are delivered, and which factors influence implementation. Methods: The review was conducted in accordance with Joanna Briggs Institute methodology and reported following the PRISMA-ScR guidelines. PubMed, CINAHL, and Scopus were searched. The initial search was conducted in November 2024 and updated in December 2025, June and August 2026. Quantitative, qualitative, and mixed-method studies involving adults (≥18 years) with liver cirrhosis, informal caregivers, and healthcare professionals were included. Data were charted descriptively and organized according to identification approaches, interventions, barriers, and facilitators. Results: In total, 39 studies were included. Patients were identified using identification tools, screening tools, clinical criteria, and prognostic scores. Interventions across inpatient, outpatient, and home-based settings included symptom management, prognostic communication, advance care planning, goals-of-care discussions, psychosocial support, and multidisciplinary collaboration. Overall, studies reported improvements in symptom management, communication, healthcare utilization, and informal caregiver outcomes. However, palliative care integration remained inconsistent and often occurred late. Key barriers included prognostic uncertainty, fragmented care pathways, limited training, and misconceptions about palliative care. Facilitators included education, structured assessment tools, and integration of palliative care into hepatology services. Conclusions: This review identified diverse approaches to patient identification and palliative care delivery, alongside key barriers and facilitators to implementation. Earlier integration of palliative care based on care needs, supported by communication, education, and interdisciplinary collaboration, may improve care for patients with cirrhosis.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disease globally, closely associated with obesity and metabolic syndrome. Despite its clinical significance, patients frequently experience stigmatization from society, healthcare professionals, and family, which may exacerbate psychological distress and hinder effective care. This study aims to explore how patients living with MASLD experience and interpret different dimensions of stigma. By examining stigma across healthcare, social, and personal contexts, the study offers insights into the hidden psychosocial burden of MASLD and may inform approaches to reduce stigmatization and promote more patient-centered and equitable care. Methods: Between 19 November 2024 and 6 February 2025, 23 adults diagnosed with MASLD (21 women, aged 35–70+ years) completed an anonymous online questionnaire comprising 4 demographic questions and 11 open-ended questions regarding their experiences of stigma, its emotional and social impact, and strategies for managing these experiences. Responses were analyzed thematically using Braun and Clarke’s six-phase framework to identify key domains. Results: Three overarching themes emerged: (1) Diagnosis, Symptoms, and Medical Experiences; (2) Emotional and Social Impact; and (3) Coping Strategies and Advocacy. Most participants reported incidental diagnosis, limited or conflicting medical guidance, and feeling blamed for lifestyle choices. Several participants described anxiety and depressive symptoms, while many reported social withdrawal and self-blame, illustrating the interplay of structural, public, and self-stigma. Coping strategies included peer support, self-education, and advocacy, yet participants emphasized that lifestyle changes remained challenging without professional guidance. Many expressed a need for holistic care addressing both medical and psychosocial needs. Conclusions: Stigma profoundly affects patients with MASLD, influencing healthcare experiences, emotional well-being, and social interactions. Interventions should target multiple levels of stigma, incorporating education for healthcare professionals, holistic care models, and accessible support systems. Further research is needed to identify effective strategies for reducing stigmatization and improving equity of care.

Human white adipose tissue undergoes major remodelling during sustained weight gain that may compromise tissue function and drive cardiometabolic comorbidities. Although weight loss reverses many of these complications, the cellular and molecular adaptations of adipose tissue to different weight loss interventions are poorly understood. Here we show how abdominal subcutaneous adipose tissue (SAT) in men and women with severe obesity adapts to modest lifestyle-induced (8–10%) weight loss followed by substantial bariatric surgery-induced (20–45%) weight loss, using single-nucleus RNA sequencing (snRNA-seq) combined with bulk RNA-seq, and three-dimensional light-sheet fluorescence microscopy. To enable interactive exploration, all snRNA-seq data are available in a browsable format on the Single Cell Portal (SCP2849). Lifestyle-induced weight loss activated proadipogenic gene programmes in progenitor cells, indicating early beneficial effects on SAT. Subsequent surgery-induced weight loss drove profound compositional and transcriptional remodelling of SAT, including increased vascularization and marked reduction of myeloid cell populations. Collectively, our study indicates that following major and sustained weight loss, SAT from individuals with severe obesity has the capacity to return to a state comparable to that observed in lean individuals.

INTRODUCTION: Liver transplantation (LT) recipients are at high risk of developing de novo metabolic syndrome (MetS), which contributes to cardiovascular and cerebrovascular morbidity. This study investigated serum and urinary metabolic changes after LT to identify microbial and metabolic markers associated with MetS development. METHODS: We conducted a prospective, 2-center longitudinal study with biospecimen collection pre-LT and at 6 months, 1 year, and 2–9 years post-LT. Nuclear magnetic resonance spectroscopy was used to characterize serum and urine metabolomic profiles from 73 to 44 patients, respectively. MetS was defined as body mass index >30 kg/m ² plus at least 1 additional metabolic abnormality. RESULTS: MetS prevalence increased from 11% pre-LT to 36% post-LT. Post-LT, serum metabolite profiles showed increased phosphocholines and lipid-CH ₃ (low density lipoprotein), whereas urine profiles demonstrated higher levels of trimethylamine- N -oxide (TMAO) and phenylacetylglutamine. Patients who developed or had persistent MetS exhibited smaller increases in serum phosphocholines and lipid-CH ₃ but greater elevations in urinary TMAO levels compared with patients who remained MetS-free. DISCUSSION: LT is followed by distinct metabolic shifts reflecting changes in both hepatic lipid metabolism and gut–liver microbial cometabolism. Elevated urinary TMAO, together with reduced serum phosphocholine and lipid-CH ₃ responses, characterize patients who develop post-LT MetS and may serve as early biomarkers of cardiometabolic risk in LT recipients.

Hepatic encephalopathy (HE) presents a significant challenge in liver transplantation (LT). On the one hand, LT can provide a curative treatment for HE by addressing its underlying cause, suggesting HE should be a strong indication for LT. Conversely, the severity of HE may reflect advanced liver disease and significant neurocognitive impairment, potentially complicating post-transplant outcomes and raising concerns about its suitability as an indication. This review will provide helpful insight to the hepatologist deciding whether HE should be considered an indication or a contraindication to liver transplantation in their patient. It gives an overview of the burden of HE pretransplant, HE’s current status in the transplant listing process, and pre- and post-transplant cognitive issues to be mindful of. The main take-away messages are that pre-transplant HE should be managed aggressively, that neurodegenerative disorders and other differential diagnoses to HE should be thoroughly excluded, and that immunosuppressants can cause new onset cognitive issues post-transplant and should be monitored closely. In the future, objective measures of HE severity should be included in the MELD score to enhance the fairness and efficacy of transplant listings, ensuring those with cirrhosis complicated by HE receive timely and appropriate treatment.

Background Metabolic dysfunction-associated steatotic liver disease (MASLD) affects roughly 1 in 3 adults and is a leading cause of liver transplants and liver related mortality. A deeper understanding of disease pathogenesis is essential to assist in developing blood-based biomarkers. Methods Here, we use data-independent acquisition mass spectrometry to assess disease-state associated protein profiles in human liver, blood plasma, and white adipose tissue (WAT). Results In liver, we find that MASLD is associated with an increased abundance of proteins involved in immune response and extracellular matrix (ECM) and a decrease in proteins involved in metabolism. Cell type deconvolution of the proteome indicates liver endothelial and hepatic stellate cells are the main source of ECM rearrangements, and hepatocytes are the major contributor to the changes in liver metabolism. In the blood, profiles of several MASLD-associated proteins correlate with expression in WAT rather than liver and so could serve as suitable liver disease predictors in a multi-protein panel marker. Moreover, our proteomics-based logistic regression models perform better than existing methods for predicting MASLD and liver fibrosis from human blood samples. Conclusions Our comprehensive proteomic analysis deepens the understanding of liver function and MASLD pathology by elucidating key cellular mechanisms and multi-organ interactions, and demonstrates the robustness of a proteomics-based biomarker panel to enhance diagnosis of MASLD and significant fibrosis.