The determinants of the response to checkpoint immunotherapy in hepatocellular carcinoma (HCC) remain poorly understood. The organisation of the immune response in the tumour microenvironment (TME) is expected to govern immunotherapy outcomes but spatial immunotypes remain poorly defined.

The understanding that changes in microbiome composition can influence chronic human diseases and the efficiency of therapies has driven efforts to develop microbiota-centred therapies such as first and next generation probiotics, prebiotics and postbiotics, microbiota editing and faecal microbiota transplantation. Central to microbiome research is understanding how disease impacts microbiome composition and vice versa, yet there is a problematic issue with the term 'dysbiosis', which broadly links microbial imbalances to various chronic illnesses without precision or definition. Another significant issue in microbiome discussions is defining 'healthy individuals' to ascertain what characterises a healthy microbiome. This involves questioning who represents the healthiest segment of our population-whether it is those free from illnesses, athletes at peak performance, individuals living healthily through regular exercise and good nutrition or even elderly adults or centenarians who have been tested by time and achieved remarkable healthy longevity.This review advocates for delineating 'what defines a healthy microbiome?' by considering a broader range of factors related to human health and environmental influences on the microbiota. A healthy microbiome is undoubtedly linked to gut health. Nevertheless, it is very difficult to pinpoint a universally accepted definition of 'gut health' due to the complexities of measuring gut functionality besides the microbiota composition. We must take into account individual variabilities, the influence of diet, lifestyle, host and environmental factors. Moreover, the challenge in distinguishing causation from correlation between gut microbiome and overall health is presented.The review also highlights the resource-heavy nature of comprehensive gut health assessments, which hinders their practicality and broad application. Finally, we call for continued research and a nuanced approach to better understand the intricate and evolving concept of gut health, emphasising the need for more precise and inclusive definitions and methodologies in studying the microbiome.

Oncogenic 'hotspot' mutations of KRAS and GNAS are two major driver alterations in intraductal papillary mucinous neoplasms (IPMNs), which are bona fide precursors to pancreatic ductal adenocarcinoma. We previously reported that pancreas-specific KrasG12D and GnasR201C co-expression in p48Cre; KrasLSL-G12D; Rosa26LSL-rtTA; Tg (TetO-GnasR201C) mice ('Kras;Gnas' mice) caused development of cystic lesions recapitulating IPMNs.

TNF-like cytokine 1A (TL1A) and its functional receptor, death-domain receptor 3 (DR3), are members of the TNF and TNFR superfamilies, respectively, with recognised roles in regulating innate and adaptive immune responses; additional existence of a decoy receptor, DcR3, indicates a tightly regulated cytokine system. The significance of TL1A:DR3 signalling in the pathogenesis of inflammatory bowel disease (IBD) is supported by several converging lines of evidence. Herein, we aim to provide a comprehensive understanding of what is currently known regarding the TL1A/DR3 system in the context of IBD. TL1A and DR3 are expressed by cellular subsets with important roles for the initiation and maintenance of intestinal inflammation, serving as potent universal costimulators of effector immune responses, indicating their participation in the pathogenesis of IBD. Recent evidence also supports a homoeostatic role for TL1A:DR3 via regulation of Tregs and innate lymphoid cells. TL1A and DR3 are also expressed by stromal cells and may contribute to inflammation-induced or inflammation-independent intestinal fibrogenesis. Finally, discovery of genetic polymorphisms with functional consequences may allow for patient stratification, including differential responses to TL1A-targeted therapeutics. In conclusion, TL1A:DR3 signalling plays a central and multifaceted role in the immunological pathways that underlie intestinal inflammation, such as that observed in IBD. Such evidence provides the foundation for developing pharmaceutical approaches targeting this ligand-receptor pair in IBD.

Cholangiocarcinoma (CCA) is a very difficult-to-treat cancer. Chemotherapies are little effective and response to immune checkpoint inhibitors is limited. Therefore, new therapeutic strategies need to be identified.

Tumourigenesis in right-sided and left-sided colons demonstrated distinct features.

Sphincter of Oddi disorders (SOD) are contentious conditions in patients whose abdominal pain, idiopathic acute pancreatitis (iAP) might arise from pressurisation at the sphincter of Oddi. The present study aimed to measure the benefit of sphincterotomy for suspected SOD.

To examine the hepatic effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) through a head-to-head comparison with glucagon-like peptide-1 receptor agonists (GLP-1RA) or thiazolidinediones (TZD) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

The absolute number of annual cases of gastric cancer in Europe is rising. The Council of the European Union has recommended implementation of gastric cancer screening for countries or regions with a high gastric cancer incidence and death rates. However, as of 2024 no organised gastric cancer screening programme has been launched in Europe.There are several ways to decrease gastric cancer burden, but the screen and treat strategy for Helicobacter pylori (H. pylori) seems to be the most appropriate for Europe. It has to be noted that increased use of antibiotics would be associated with this strategy.Only organised population-based cancer screening is recommended in the European Union, therefore gastric cancer screening also is expected to fulfil the criteria of an organised screening programme. In this respect, several aspects of screening organisation need to be considered before full implementation of gastric cancer prevention in Europe; the age range of the target group, test types, H. pylori eradication regimens and surveillance strategies are among them. Currently, ongoing projects (GISTAR, EUROHELICAN, TOGAS and EUCanScreen) are expected to provide the missing evidence. Feedback from the decision-makers and the potential target groups, including vulnerable populations, will be important to planning the programme.This paper provides an overview of the recent decisions of the European authorities, the progress towards gastric cancer implementation in Europe and expected challenges. Finally, a potential algorithm for gastric cancer screening in Europe is proposed.

Epidemiological and translational data increasingly implicate environmental pollutants in inflammatory bowel disease (IBD). Indeed, the global incidence of IBD has been rising, particularly in developing countries, in parallel with the increased use of chemicals and synthetic materials in daily life and escalating pollution levels. Recent nationwide and ecological studies have reported associations between agricultural pesticides and IBD, particularly Crohn's disease. Exposure to other chemical categories has also been linked with an increased risk of IBD. To synthesise available data and identify knowledge gaps, we conducted a systematic review of human studies that reported on the impact of environmental pollutants on IBD risk and outcomes. Furthermore, we summarised in vitro data and animal studies investigating mechanisms underlying these associations. The 32 included human studies corroborate that heavy and transition metals, except zinc, air pollutants, per- and polyfluorinated substances, and pesticides are associated with an increased risk of IBD, with exposure to air pollutants being associated with disease-related adverse outcomes as well. The narrative review of preclinical studies suggests several overlapping mechanisms underlying these associations, including increased intestinal permeability, systemic inflammation and dysbiosis. A consolidated understanding of the impact of environmental exposures on IBD risk and outcomes is key to the identification of potentially modifiable risk factors and to inform strategies towards prediction, prevention and mitigation of IBD.

Advancements in omics technologies and artificial intelligence (AI) methodologies are fuelling our progress towards personalised diagnosis, prognosis and treatment strategies in hepatology. This review provides a comprehensive overview of the current landscape of AI methods used for analysis of omics data in liver diseases. We present an overview of the prevalence of different omics levels across various liver diseases, as well as categorise the AI methodology used across the studies. Specifically, we highlight the predominance of transcriptomic and genomic profiling and the relatively sparse exploration of other levels such as the proteome and methylome, which represent untapped potential for novel insights. Publicly available database initiatives such as The Cancer Genome Atlas and The International Cancer Genome Consortium have paved the way for advancements in the diagnosis and treatment of hepatocellular carcinoma. However, the same availability of large omics datasets remains limited for other liver diseases. Furthermore, the application of sophisticated AI methods to handle the complexities of multiomics datasets requires substantial data to train and validate the models and faces challenges in achieving bias-free results with clinical utility. Strategies to address the paucity of data and capitalise on opportunities are discussed. Given the substantial global burden of chronic liver diseases, it is imperative that multicentre collaborations be established to generate large-scale omics data for early disease recognition and intervention. Exploring advanced AI methods is also necessary to maximise the potential of these datasets and improve early detection and personalised treatment strategies.

Potential coeliac disease (PCD) is characterised by positive serological and genetic markers of coeliac disease with architecturally preserved duodenal mucosa. The clinical outcomes and rates of progression to overt coeliac disease in patients with PCD remain uncertain. In this systematic review and meta-analysis, we aimed to evaluate the clinical outcomes of patients with PCD.

In patients with Crohn's disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse (>6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn's Disease Patients in Sustained Steroid-free Remission on Combination Therapy).