Fecal calprotectin measurement as a biomarker of severe disease phenotype in celiac disease and non-celiac enteropathies.

BACKGROUND: Fecal calprotectin (FC) is a non-invasive biomarker of gut inflammation, but its role in celiac disease (CD) and non-celiac enteropathies (NCEs) is undefined. AIMS: To retrospectively evaluate FC in patients with CD and NCEs as a tool for assessing disease activity and predicting long-term outcomes. METHODS: Patients with uncomplicated and complicated CD, and NCEs with data on FC, evaluated at our center between June-2008 and December-2023, were enrolled. The relationship between elevated FC (>50 mg/kg) and disease activity was statistically analysed and Cox regression adjusted for age and sex was used to compare development of complications and mortality in patients with elevated and normal FC. RESULTS: 177 patients (109F, mean age at diagnosis 39±20 years, 132 CD, 17 complicated CD, 28 NCEs) were enrolled. 55 patients had elevated FC, which was associated with lack of clinical and histological response to therapy (both p < 0.001). During a median follow-up of 103 months (IQR 54-176), 22 patients developed complications (15.4 %) and 21 died (11.9 %). Elevated FC was significantly more common in complicated CD (70.6 %) and NCEs (67.9 %) than in uncomplicated CD (18.2 %), p < 0.001. Elevated FC was independently predictive of developing complications (HR 4.8,95 %CI 1.4-17.7, p = 0.01) and mortality (HR 4.8,95 %CI 1.6-14.3, p < 0.01). CONCLUSION: FC is a promising non-invasive biomarker for assessing disease severity and long-term outcomes in CD and NCEs.

A Case of Ischemic Pituitary Apoplexy Secondary to ACTH-Secreting Macroadenoma.

Background: Pituitary apoplexy (PA) represents a rare but extremely serious complication of pituitary adenoma. It is characterized by the rapid onset of headache, nausea and vomiting, changes in vision, paralysis of the oculomotor nerves and alteration of the sensory. Due to the rarity of this complication and the non-specificity of symptoms, the patient's clinical presentation may not be interpreted correctly, leading to a diagnostic delay and a worsening of prognosis. Case Description: This case report relates to a 73-year-old man with ACTH-secreting macroadenoma infiltrating the cavernous sinuses bilaterally and causing the rapid onset of headache, bilateral eyelid ptosis, complete bilaterally ophthalmoplegia and bitemporal hemianopia. The patient underwent urgent surgery to remove the lesion by transsphenoidal route and subsequent monitoring of pituitary function by endocrinologist specialist obtaining a near-total recovery from illness. Conclusions: PA is often characterized by the appearance of unilateral ocular or neurological deficits, while a clinical presentation given by ophthalmoplegia and bilateral ptosis is a very rare condition, difficult to find in the literature. Therefore, similar symptoms should not be underestimated and should raise the diagnostic suspicion of PA. In this case, in fact, a prompt treatment and multidisciplinary management of the patient allowed to markedly improve the prognosis. Furthermore, the instrumental findings supported a picture of ischemic pituitary apoplexy without signs of haemorrhage, a condition reported only sporadically in the literature.

UnTWISTing intestinal fibrosis: single-cell transcriptomics deciphers fibroblast heterogeneity, uncovers molecular pathways, and identifies therapeutic targets.

Intestinal fibrosis is a severe complication of Crohn's disease, often requiring surgical intervention. Despite extensive research efforts, an effective treatment to prevent or reverse intestinal fibrosis remains elusive. In this issue of the JCI, Zhang, Wang, and colleagues employed single-cell RNA sequencing to uncover mechanisms of the fibrotic process. They identified a key fibroblast subset of TWIST1+FAP+ cells that interacts with CXCL9+ macrophages. TWIST1 emerged as a central regulator of the fibrotic microenvironment, representing a promising therapeutic target for effectively treating intestinal fibrosis.

Medullary carcinomas of the nonampullary small intestine: association with coeliac disease, mismatch repair deficiency, PD-L1 expression, and favourable prognosis.

AIM: Gastrointestinal medullary carcinoma is a rare histologic subtype of adenocarcinoma. As nonampullary small bowel medullary carcinomas (SB-MCs) are poorly characterized, we aimed to analyse their clinicopathologic and immunohistochemical features and to compare them with nonmedullary small bowel adenocarcinomas (NM-SBAs). METHODS AND RESULTS: Surgically resected SBAs collected through the Small Bowel Cancer Italian Consortium were classified as SB-MCs (carcinomas with ≥50% of tumour fulfilling the typical histologic criteria of MC) or NM-SBAs. Immunohistochemistry for cytokeratin (CK)7, CK20, CDX2, programmed death-ligand 1 (PD-L1) and mismatch repair proteins was performed in both SB-MCs and NM-SBAs. SB-MCs were also tested for CK8/18, synaptophysin, SMARCB1, SMARCA2, SMARCA4, and ARID1A and for Epstein-Barr virus (EBV)-encoded RNAs by in-situ hybridization. MLH1 promoter methylation status was evaluated in MLH1-deficient cases. Eleven SB-MCs and 149 NM-SBAs were identified. One (9%) SB-MC was EBV-positive, while 10 (91%) harboured mismatch repair deficiency (dMMR). MLH1 promoter hypermethylation was found in all eight dMMR SB-MCs tested. Switch/sucrose nonfermentable deficiency was seen in two (18%) SB-MCs, both with isolated loss of ARID1A. Compared with NM-SBAs, SB-MCs exhibited an association with coeliac disease (P < 0.001), higher rates of dMMR (P < 0.001), and PD-L1 positivity by both tumour proportion score and combined positive score (P < 0.001 for both), and a lower rate of CK20 expression (P = 0.024). Survival analysis revealed a better prognosis of SB-MC patients compared to NM-SBA cases (P = 0.02). CONCLUSION: SB-MCs represent a distinct histologic subtype, with peculiar features compared to NM-SBAs, including association with coeliac disease, dMMR, PD-L1 expression, and better prognosis.

Pro- and anti-inflammatory cytokines: the hidden keys to autoimmune gastritis therapy.

Autoimmune gastritis (AIG) is an autoimmune disorder characterized by the destruction of gastric parietal cells and atrophy of the oxyntic mucosa which induces intrinsic factor deficiency and hypo-achlorhydria. AIG predominantly affects the antral mucosa with AIG patients experiencing increased inflammation and a predisposition toward the development of gastric adenocarcinoma and type I neuroendocrine tumors. The exact pathogenesis of this autoimmune disorder is incompletely understood although dysregulated immunological mechanisms appear to major contributors. This review of autoimmune gastritis, an unmet medical need, summarizes current knowledge on pro- and anti-inflammatory cytokines and strategies for the discovery of novel biomarkers and potential pharmacological targets.

Occurrence and characteristics of endoscopic gastric polyps in patients with autoimmune gastritis (AGAPE study): A multicentric cross-sectional study.

BACKGROUND: Autoimmune gastritis (AIG) leads to increased gastrin (G) levels due to hypo-achlorhydria, providing proliferative stimuli on the gastric mucosa. AIMS: To evaluate the incidence and characteristics of gastric polyps in AIG patients across six tertiary centers in Italy. METHODS: A multicentric, cross-sectional study enrolled patients with AIG diagnosed from January 2000 to June 2023, who underwent at least one endoscopy. Data on demographics, clinical history, biochemical profiles, and endoscopic and histopathological findings were systematically collected. RESULTS: Among 612 AIG patients followed for a median of 4 years, 222 (36.3 %) developed at least one gastric polyp. Of these, 214 were non-endocrine lesions detected in 162 patients, including 151 inflammatory (70.5 %), 29 adenomatous (13.6 %), 18 fundic gland polyps (8.4 %), 13 adenocarcinomas (6.1 %), and one MALT lymphoma. Additionally, 108 patients had gastric neuroendocrine neoplasms (gNENs), with 48 also having non-endocrine polyps. Older age and higher gastrin and chromogranin A levels were associated with polyp occurrence. No differences in OLGA/OLGIM stages or Helicobacter pylori status were noted among patients with and without lesions. CONCLUSION: This large multicentric study underscores the substantial occurrence of gastric polyps in AIG patients, including notable rates of gNENs and adenocarcinomas, emphasizing the importance of proactive endoscopic surveillance and histopathological examination for effective management.

Vitamin B12 status in hospitalised cancer patients: Prevalence and clinical implications of depletion and hypervitaminosis.

BACKGROUND & AIMS: The prevalence and clinical significance of vitamin B12 alterations in patients with cancer are poorly understood. We aimed to assess the prevalence and risk factors of vitamin B12 depletion or hypervitaminosis in patients with cancer. METHODS: We retrospectively included hospitalised patients with cancer in 2017-2022. Plasma B12 levels were stratified as very low (VL, <200 pg/ml), low (L, 200-299 pg/ml), normal (N, 300-812 pg/ml), or high (H, ≥813 pg/ml). We collected demographic and several clinical data (e.g., comorbidities, nutritional status, ECOG-PS, cancer site and stage). Univariate and multivariate analyses for factors associated to the vitamin B12 status were fitted. RESULTS: 788 patients (F/M ratio 1.05, median age 72 years, [25th, 75th percentiles 62, 78 years]) were included. Vitamin B12 was VL in 14.1%, L in 19.4%, N in 49.4%, and H in 17.1% cases. Vitamin B12 distribution increased significantly as function of ECOG-PS levels. Patients with breast cancer were characterized by the highest median B12 value, while colorectal cancer patients by the lowest. Vitamin B12 was also significantly higher in advanced compared to early-stage patients as well as in those who had liver failure. Multivariate analysis showed that the probability of H vs. VL B12 levels was significantly increased in patients with hypoproteinemia, hypo-prealbuminemia, and ECOG-PS≥2, and decreased in those with colorectal and gastric cancer. CONCLUSION: Vitamin B12 impairment is common in cancer patients. Increased vitamin B12 is associated with an impaired clinical status, while vitamin B12 depletion is more common in early-stage cancer and in elderly patients.

Molecular Mechanisms Underlying Loss of Vascular and Epithelial Integrity in Irritable Bowel Syndrome.

BACKGROUND & AIMS: The pathophysiology of irritable bowel syndrome (IBS) is multifactorial and includes epithelial barrier dysfunction, a key element at the interface between the gut lumen and the deeper intestinal layers. Beneath the epithelial barrier there is the vascular one representing the last barrier to avoid luminal antigen dissemination The aims of this study were to correlate morpho-functional aspects of epithelial and vascular barriers with symptom perception in IBS. METHODS: Seventy-eight healthy subjects (controls) and 223 patients with IBS were enrolled in the study and phenotyped according to validated questionnaires. Sugar test was used to evaluate in vivo permeability. Immunohistochemistry, western blot, and electron microscopy were used to characterize the vascular barrier. Vascular permeability was evaluated by assessing the mucosal expression of plasmalemma vesicle-associated protein-1 and vascular endothelial cadherin. Caco-2 or human umbilical vein endothelial cell monolayers were incubated with soluble mediators released by mucosal biopsies to highlight the mechanisms involved in permeability alteration. Correlation analyses have been performed among experimental and clinical data. RESULTS: The intestinal epithelial barrier was compromised in patients with IBS throughout the gastrointestinal tract. IBS-soluble mediators increased Caco-2 permeability via a downregulation of tight junction gene expression. Blood vessel density and vascular permeability were increased in the IBS colonic mucosa. IBS mucosal mediators increased permeability in human umbilical vein endothelial cell monolayers through the activation of protease-activated receptor-2 and histone deacetylase 11, resulting in vascular endothelial cadherin downregulation. Permeability changes correlated with intestinal and behavioral symptoms and health-related quality of life of patients with IBS. CONCLUSIONS: Epithelial and vascular barriers are compromised in patients with IBS and contribute to clinical manifestations.

Distinguishing Features of Autoimmune Gastritis Depending on Previous Helicobacter pylori Infection or Positivity to Anti-Parietal Cell Antibodies: Results From the Autoimmune gastRitis Italian netwOrk Study grOup (ARIOSO).

INTRODUCTION: To describe the clinical features and the risk of developing gastric tumors in patients with autoimmune gastritis (AIG). METHODS: This was a retrospective, longitudinal, multicenter study conducted at 8 Italian tertiary referral centers. We retrieved clinical data from all histologically proven patients with AIG. Differences between Helicobacter pylori -exposed vs H. pylori -naive and anti-parietal cell antibody (PCA)-positive vs PCA-negative patients were investigated. The rate of gastric adenocarcinoma and type 1 gastric neuroendocrine neoplasm (gNEN) was assessed. A multivariable model for factors associated with gNEN was fitted. RESULTS: A total of 1,598 patients with AIG (median age 58 years, interquartile range 46-68; F:M ratio 2.7:1) were included. H. pylori -naive patients were more likely to have a first-degree family history of AIG (14.7% vs 8.9%; P = 0.012), type 1 diabetes mellitus (4.9% vs 2.3%; P = 0.025), and pernicious anemia (30.9% vs 21.1%; P = 0.003). PCA-positive patients had significantly more associated autoimmune diseases (59.0% vs 42.9%; P < 0.001) and were more likely to have been diagnosed by a case-finding strategy (15.3% vs 2.6%; P < 0.001). Overall, 15 cases (0.9%) of gastric adenocarcinoma and 153 cases (9.6%) of gNEN occurred, with a global rate of 0.12 (95% confidence interval [CI] 0.07-0.20) and 1.22 (95% CI 1.03-1.42) per 100 person/year, respectively. Having a vitamin B12/iron deficiency manifestation at AIG diagnosis was associated with a 16.44 (95% CI 9.94-27.20 P < 0.001) hazard ratio of gNEN. DISCUSSION: The "pure" AIG pattern has typical features of an autoimmune disease and seems to be unrelated to H. pylori . In a tertiary referral setting, the risk of developing overt gastric adenocarcinoma is low, while patients with vitamin B12 deficiency complications at onset may benefit from a more intense endoscopic follow-up for early gNEN detection.

Opening the doors of precision medicine: novel tools to assess intestinal barrier in inflammatory bowel disease and colitis-associated neoplasia.

Mounting evidence underscores the pivotal role of the intestinal barrier and its convoluted network with diet and intestinal microbiome in the pathogenesis of inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CRC). Moreover, the bidirectional association of the intestinal barrier with the liver and brain, known as the gut-brain axis, plays a crucial role in developing complications, including extraintestinal manifestations of IBD and CRC metastasis. Consequently, barrier healing represents a crucial therapeutic target in these inflammatory-dependent disorders, with barrier assessment predicting disease outcomes, response to therapy and extraintestinal manifestations.New advanced technologies are revolutionising our understanding of the barrier paradigm, enabling the accurate assessment of the intestinal barrier and aiding in unravelling the complexity of the gut-brain axis. Cutting-edge endoscopic imaging techniques, such as ultra-high magnification endocytoscopy and probe-based confocal laser endomicroscopy, are new technologies allowing real-time exploration of the 'cellular' intestinal barrier. Additionally, novel advanced spatial imaging technology platforms, including multispectral imaging, upconversion nanoparticles, digital spatial profiling, optical spectroscopy and mass cytometry, enable a deep and comprehensive assessment of the 'molecular' and 'ultrastructural' barrier. In this promising landscape, artificial intelligence plays a pivotal role in standardising and integrating these novel tools, thereby contributing to barrier assessment and prediction of outcomes.Looking ahead, this integrated and comprehensive approach holds the promise of uncovering new therapeutic targets, breaking the therapeutic ceiling in IBD. Novel molecules, dietary interventions and microbiome modulation strategies aim to restore, reinforce, or modulate the gut-brain axis. These advancements have the potential for transformative and personalised approaches to managing IBD.

Infections and gender: clues for diagnosis of adrenal insufficiency-a case report and a review of the literature.

The clinical presentation of adrenal insufficiency, a condition causing adrenal hormone deficiency, is characterised by non-specific symptoms and signs: consequently, an important diagnostic delay is often evident which correlates with an increased mortality. This case report shows how the clustering of some symptoms and signs may hamper the diagnostic suspicion for this condition: serum electrolyte alterations and weight loss, when associated to recurrent infections and, in female patients, an empty sella may further guide the clinician towards a diagnosis of adrenal insufficiency. Accordingly, a clinical approach taking into account gender medicine could improve the diagnostic workup.

Eosinophilic esophagitis in the era of biologics.

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic inflammatory, disabling disorder characterized by prominent eosinophilic inflammation of the esophagus, leading to troublesome symptoms including dysphagia and food impaction. The natural history of EoE is poorly known, but it may lead to esophageal strictures. The therapeutic armamentarium is expected to grow in the near future, especially due to the availability of novel biological therapies targeting crucial inflammatory pathways of EoE. AREAS COVERED: In this review, we discuss the main clinical features and natural history of EoE, focusing on the current therapeutic strategies, as well as past and current trials investigating biologics for its treatment. EXPERT OPINION: Dupilumab has been the first approved biologic drug for the treatment of EoE; long-term studies assessing how it could change the natural history of EoE are awaited. Novel biological drugs or other molecules are currently under study and could change the current treatment algorithms in the near future. Proper drug positioning and long term 'exit strategies' are yet to be defined.

Practical approach to acute pancreatitis: from diagnosis to the management of complications.

The purpose of this review is to provide a practical guide for the clinical care of patients with acute pancreatitis (AP) from the management of the early phases of disease to the treatment of local complications. AP is one of the most frequent causes of gastroenterological admission in emergency departments. It is characterized by a dynamic and unpredictable course and in its most severe forms, is associated with organ dysfunction and/or local complications, requiring intensive care with significant morbidity and mortality. Initial therapy includes adequate fluid resuscitation, nutrition, analgesia, and when necessary critical care support. In recent years, the development of minimally invasive tailored treatments for local complications, such as endoscopic drainage, has improved patients' acceptance and outcomes. Despite this, the management of AP remains a challenge for clinicians. The present review was conducted by the authors, who formulated specific questions addressing the most critical and current aspects of the clinical course of AP with the aim of providing key messages.

Prebiotics, probiotics, synbiotics and postbiotics to adolescents in metabolic syndrome.

The prevalence of childhood and adolescent obesity has globally reached alarming dimensions and many adolescents affected by obesity already present one or more obesity-related comorbidities. In recent years, emerging evidence supporting the role of gut microbiota in the pathophysiology of metabolic diseases has been reported and the use of prebiotics, probiotics, synbiotics and postbiotics as a strategy to manipulate gut microbiota has become popular. The aim of this review is to explore the relationship between gut microbiota and metabolic syndrome in adolescents and to discuss the potential use of prebiotics, probiotics, synbiotics and postbiotics for the prevention and treatment of this clinical picture in adolescence. According to the most recent literature, prebiotics, probiotics and synbiotics have no clear effect on MetS, but a possible modulation of anthropometric parameters has been observed after synbiotic supplementation. Only one study has examined the role of postbiotics in alleviating metabolic complications in children with obesity but not in adolescents. More extensive research is needed to support the conclusions drawn so far and to develop effective microbiome-based interventions that may help improving the quality of life of children and adolescents exposed to the increasing prevalence of MetS.

Eosinophilic esophagitis in adults and adolescents: epidemiology, diagnostic challenges, and management strategies for a type 2 inflammatory disease.

Background: Eosinophilic esophagitis (EoE) is recognized as a chronic type 2 inflammatory disease characterized by the eosinophilic infiltration of the esophageal tissue, posing a significant disease burden and highlighting the necessity for novel management strategies to address unmet clinical needs. Objectives: To critically evaluate the existing literature on the epidemiology and management of EoE, identify evidence gaps, and assess the efficacy of current and emerging treatment modalities. Design: An extensive literature review was conducted, focusing on the epidemiological trends, diagnostic challenges, and therapeutic interventions for EoE. This was complemented by a survey among physicians and consultations with a scientific expert panel, including a patient's association (ESEO Italia), to enrich the study findings. Data sources and methods: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, scrutinizing epidemiological studies and management research to compile comprehensive insights into the disease's landscape. The physician survey and expert panel discussions aimed to bridge identified evidence gaps. Results: The review included 59 epidemiological and 51 management studies, uncovering variable incidence and prevalence rates of EoE globally, with an estimated diagnosed prevalence of 41 per 100,000 in Italy. Diagnostic challenges were identified, including nonspecific symptoms and the lack of definitive biomarkers, which complicate the use of endoscopy. Treatment options such as elimination diets, proton-pump inhibitors, and swallowed corticosteroids were found to have varying success rates, while Dupilumab, an emerging therapy targeting interleukin (IL)-4 and IL-13, shows promise. Conclusion: Despite advancements in understanding and managing EoE, significant unmet clinical needs remain, particularly in biomarker identification, therapy personalization, and cost-effectiveness evaluation. A comprehensive, multidimensional approach to patient management is required, emphasizing the importance of early symptom recognition, accurate diagnosis, and tailored treatment strategies. Dupilumab offers potential as a novel treatment, underscoring the need for future research to explore the economic and social dimensions of EoE care pathways.

Understanding and improving care for eosinophilic esophagitis: bridging gaps in diagnosis and treatment Eosinophilic esophagitis (EoE) is a chronic inflammatory condition affecting the esophagus. We reviewed studies on how common EoE is and how it's managed. In Italy, about 41 out of 100,000 people may have it. Diagnosis can be tricky due to vague symptoms, and current treatments vary in effectiveness. We found a need for better ways to diagnose and treat EoE, including exploring new therapies. A promising development is a biologic called Dupilumab. Future research should also consider the costs and social aspects of caring for people with EoE.

Artificial intelligence and endo-histo-omics: new dimensions of precision endoscopy and histology in inflammatory bowel disease.

Integrating artificial intelligence into inflammatory bowel disease (IBD) has the potential to revolutionise clinical practice and research. Artificial intelligence harnesses advanced algorithms to deliver accurate assessments of IBD endoscopy and histology, offering precise evaluations of disease activity, standardised scoring, and outcome prediction. Furthermore, artificial intelligence offers the potential for a holistic endo-histo-omics approach by interlacing and harmonising endoscopy, histology, and omics data towards precision medicine. The emerging applications of artificial intelligence could pave the way for personalised medicine in IBD, offering patient stratification for the most beneficial therapy with minimal risk. Although artificial intelligence holds promise, challenges remain, including data quality, standardisation, reproducibility, scarcity of randomised controlled trials, clinical implementation, ethical concerns, legal liability, and regulatory issues. The development of standardised guidelines and interdisciplinary collaboration, including policy makers and regulatory agencies, is crucial for addressing these challenges and advancing artificial intelligence in IBD clinical practice and trials.

Superior bowel preparation quality for colonoscopy with 1L-PEG compared to 2L-PEG and picosulphate: Data from a large real-world retrospective outpatient cohort.

BACKGROUND: Several randomized clinical trials comparing different bowel preparations (BP) have shown similar efficacy; however, there is a lack of real-world studies on this topic. AIMS: This study aims to identify the most effective BP regimen in a real-world setting and any predictors of inadequate BP. METHODS: A retrospective single-center study was conducted over 14 months at an academic hospital including outpatient colonoscopies in which adult patients did not teach on how to perform BP before colonoscopy. Colonoscopies with 1L-PEG, 2L-PEG and picosulphate mixtures were considered. A multivariable analysis for factors associated to poor BP was fitted. RESULTS: Overall, 1779 patients (51 %F, 60±14) years were included. The 1L-PEG regimen provided a higher rate of BP adequacy at multivariate analysis (adjusted OR 2.30, 95 %CI 1.67-3.16,p < 0.001) and was associated with higher median Boston Bowel Preparation Scale score (p < 0.001), higher rate of right-colon cleansing (p < 0.001) and exam completion (p = 0.04). Furthermore, we identified male sex, history of constipation, active smoking, previous pelvic surgery, concomitant psychiatric/neurological or chronic kidney diseases as predictors of inadequate BP. CONCLUSIONS: This is the largest real-world study comparing 1L-PEG to other BP regimens. Our results suggest 1L-PEG provides better BP in a non-controlled setting, improving clinical practice quality and minimizing the need for repeated colonoscopies and saving healthcare resources.

Comorbidity and multimorbidity in patients with cirrhosis, hospitalised in an internal medicine ward: a monocentric, cross-sectional study.

OBJECTIVES: There are no data regarding the prevalence of comorbidity (ie, additional conditions in reference to an index disease) and multimorbidity (ie, co-occurrence of multiple diseases in which no one holds priority) in patients with liver cirrhosis. We sought to determine the rate and differences between comorbidity and multimorbidity depending on the aetiology of cirrhosis. DESIGN: This is a subanalysis of the San MAtteo Complexity (SMAC) study. We have analysed demographic, clinical characteristics and rate of comorbidity/multimorbidity of patients with liver cirrhosis depending on the aetiology-alcoholic, infectious and non-alcoholic fatty liver disease (NAFLD). A multivariable analysis for factors associated with multimorbidity was fitted. SETTING: Single-centre, cross-sectional study conducted in a tertiary referral, academic, internal medicine ward in northern Italy (November 2017-November 2019). PARTICIPANTS: Data from 1433 patients previously enrolled in the SMAC study were assessed; only those with liver cirrhosis were eventually included. RESULTS: Of the 1433 patients, 172 (median age 79 years, IQR 67-84; 83 females) had liver cirrhosis. Patients with cirrhosis displayed higher median Cumulative Illness Rating Scale (CIRS) comorbidity (4, IQR 3-5; p=0.01) and severity (1.85, IQR 16.-2.0; p<0.001) indexes and lower educational level (103, 59.9%; p=0.003). Patients with alcohol cirrhosis were significantly younger (median 65 years, IQR 56-79) than patients with cirrhosis of other aetiologies (p<0.001) and more commonly males (25, 75.8%). Comorbidity was more prevalent in patients with alcohol cirrhosis (13, 39.4%) and multimorbidity was more prevalent in viral (64, 81.0%) and NAFLD (52, 86.7%) cirrhosis (p=0.015). In a multivariable model for factors associated with multimorbidity, a CIRS comorbidity index >3 (OR 2.81, 95% CI 1.14 to 6.93, p=0.024) and admission related to cirrhosis (OR 0.19, 95% CI 0.07 to 0.54, p=0.002) were the only significant associations. CONCLUSIONS: Comorbidity is more common in alcohol cirrhosis compared with other aetiologies in a hospital, internal medicine setting.