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Les néoplasies neuroendocrines sont des cancers dont la prévalence et l’incidence sont en constante augmentation. Ces tumeurs présentent entre elles des différences importantes, notamment d’un point de vue pronostique. Les facteurs pronostiques les plus importants sont de nature histomorphologiques, à savoir le grade de prolifération déterminé par le Ki67 et le degré de différenciation. La localisation, le stade TNM, l’âge et l’indice de performance du patient au diagnostic sont autant d’autres facteurs ayant un impact sur la survie. Les principaux biomarqueurs disponibles en pratique clinique présentent plusieurs limitations. L’imagerie fonctionnelle, par 68Ga-DOTA-NOC/TATE/TOC et PET-FDG, joue un rôle important dans la stratification du risque. Plusieurs biomarqueurs circulants et tissulaires sont à l’étude; à l’avenir, ils pourraient permettre une meilleure appréciation du risque et aider à la stratégie thérapeutique.

De prevalentie en de incidentie van neuro-endocriene tumoren stijgen gestaag. Er zijn grote verschillen tussen die tumoren onderling, o.a. wat de prognose betreft. De belangrijkste prognostische factoren zijn van pathologisch-anatomische aard, meer bepaald de mate van vermenigvuldiging gemeten met de Ki67-index en de mate van differentiatie. Andere factoren die invloed hebben op de overleving, zijn de ligging, het TNM-stadium, de leeftijd en de performance score van de patiënt op het ogenblik van de diagnose. We beschikken over meerdere biomarkers, maar die vertonen toch heel wat beperkingen. Functionele beeldvorming met 68Ga-DOTA-NOC/TATE/TOC en FDG-PET-scan is belangrijk bij het ramen van het risico. Er zijn meerdere biomarkers in het bloed en de weefsels in onderzoek. Mogelijk zullen die ons in de toekomst een beter idee van het risico geven en helpen bij de keuze van de behandeling.

Two years ago, many experts spoke out in favour of changing the nomenclature of the most common liver disease in the world, non-alcoholic fatty liver disease (NAFLD). This was the subject of an editorial in the Acta Gastroenterologica Belgica Journal. Even though many researchers still mention that its pathophysiology remains poorly understood or that the exact mechanisms remain to be elucidated, it would be dishonest not to recognise a common factor, namely the metabolic context (metabolic syndrome, insulin resistance and possibly type 2 diabetes, overweight or obesity) in the pathogenesis of this liver disease. The term “MAFLD” for “metabolic dysfunction-associated fatty liver disease” therefore makes sense. It is indeed more logical to call something by what it is than by what it is not. Here, we would like to draw attention to data from two recent interesting scientific articles, which, in our view, indirectly support the use of “MAFLD” nomenclature.

Introduction Metabolic dysfunction-associated fatty liver disease (MAFLD) relates to steatosis occurring in the setting of a metabolic risk condition such as type 2 diabetes mellitus (T2DM). T2DM is an important risk factor for MAFLD and vice-versa. Despite the high prevalence and serious clinical implications of MAFLD in patients with T2DM, it is often overlooked in clinical practice. Aim To assess the feasibility of outpatient systematic screening for MAFLD in T2DM patients. To do so, we determined the respective prevalence of steatosis and severe fibrosis using simple non-invasive tools, as per national guidelines (Francque S. Acta Gastroenterol Belg. 2018). We estimated patients’ adherence to more accurate fibrosis screening by vibration-controlled transient elastography (VCTE) if indicated by clinical-biological testing. Methods We conducted a 12-months monocentric prospective study involving ambulatory T2DM patients who attended on a regular basis the diabetes clinic at Cliniques universitaires Saint-Luc between June 2021 and May 2022. Based on national and international guidelines, in case of positive screening for liver steatosis – using fatty liver index (FLI) – or advanced fibrosis – using a combination of non-alcoholic fatty liver disease fibrosis score (NFS) and fibrosis-4 (FIB-4) –patients were invited to undergo abdominal Doppler-ultrasound and/or VCTE. In case of elevated transaminase level, patients were further assessed to at least exclude viral hepatitis B and C, alpha-1-antitrypsin deficiency and biological markers of autoimmune hepatitis (elevated immunoglobulin G). Results A total of 213 patients were included in the study. 67.1 % of patients were male, mean age was 62 years and mean body mass index 31.3 kg/m². Three patients reported an alcohol consumption of more than 30 (male) or 20 (female) g/day. FLI classified most of the patients in the high (76.7 %) or indeterminate (18.8 %) risk category for steatosis, while only 4.5 % were classified a

Alcohol use disorder (AUD) is a chronic relapsing disease associated with malnutrition, metabolic disturbances, and gut microbiota alterations that are correlated with the severity of psychological symptoms. This study aims at supplementing AUD patients with prebiotic fiber during alcohol withdrawal, in order to modulate the gut microbiota composition and to evaluate its effect on gastrointestinal tolerance, metabolism, and patient’s behavior. A randomized, double-blind, placebo-controlled study included 50 AUD patients assigned to inulin versus maltodextrin daily supplementation for 17 days. Biological measurements (fecal microbial 16S rDNA sequencing, serum biology), dietary intake, validated psychological questionnaires, and gastrointestinal tolerance assessment were performed before and after the intervention. Inulin significantly decreased the richness and evenness and induced changes of 8 genera (q < 0.1) including Bifidobacterium and Bacteroides. Prebiotic had minor effects on gastrointestinal symptoms and nutritional intakes compared to placebo. All patients showed an improvement in depression, anxiety, and craving scores during alcohol withdrawal regardless of the intervention group. Interestingly, only patients treated with inulin significantly improved the sociability score and had an increased serum level of brain-derived neurotrophic factor. This pilot study shows that inulin is well tolerated and modulates the gut microbiota and the social behavior in AUD patients, without further improving other psychological and biological parameters as compared to placebo. Gut2Brain study, clinicaltrial.gov: NCT03803709, https://clinicaltrials.gov/ct2/show/NCT03803709

La maladie stéatosique du foie liée à une dysfonction métabolique (MAFLD) touche un quart de la population mondiale, dont certains d’entre eux évolueront vers une forme plus sévère appelée stéatohépatite non-alcoolique (NASH). Le principal facteur menant à cette pathologie est une alimentation déséquilibrée. Aucun traitement médicamenteux n’est reconnu à ce jour. Seule la prise en charge hygiénodiététique permet une amélioration des lésions histologiques de la NASH grâce à une perte de poids. Néanmoins, l’efficacité des régimes standards, la compliance des patients et la capacité à maintenir la perte de poids à long terme sont des difficultés fréquemment rencontrées. Dans cet article, nous analysons les données scientifiques récentes de différents types d’alimentation (régime méditerranéen, jeûne intermittent, régime cétogène) permettant d’apporter des bénéfices hépatiques et parfois extrahépatiques. Les inconvénients ou limites possibles sont également discutés. Le bénéfice éventuel d’autres stratégies nutritionnelles (café, acides gras oméga-3, polyphénols…) est finalement présenté. Le changement de mode alimentaire peut, dès lors, être adapté aux attentes du patient et occasionner des bénéfices indépendamment de la perte de poids., Metabolic dysfunction-associated fatty liver disease (MAFLD) affects a quarter of the world’s population,some of whom will progress to a more severe form called non-alcoholic steatohepatitis (NASH). Themain factor leading to this condition is an unbalanced diet. No drug treatment is approved to date andonly dietary management can improve the histological lesions of NASH through weight loss. However,the efficacy of standard diets, patient compliance and the ability to maintain weight loss over the longterm are common difficulties. In this review, we analyze recent scientific data on different types of diet(Mediterranean diet, intermittent fasting, ketogenic diet), which can bring benefits on general and liverhealth. Drawbacks or limitations are also listed. The possible benefit of other nutritional strategies (coffeeconsumption, omega-3, polyphenols...) is discussed. The value of dietary change could be tailored to thepatient’s needs without necessarily imposing an intense weight loss.

Alcohol-related liver disease (ALD) ranges from never-decompensated ALD (ndALD) to the life-threatening decompensated phenotype, known as alcohol-related hepatitis (AH). A multidimensional study of the clinical, histological and molecular features of these subtypes is lacking. Two large cohorts of patients were recruited in an international, observational multicentre study: a retrospective cohort of patients with ndALD (n=110) and a prospective cohort of patients with AH (n=225). Clinical, analytical, immunohistochemistry and hepatic RNA microarray analysis of both disease phenotypes were performed. Age and mean alcohol intake were similar in both groups. AH patients had greater aspartate amino transferase/alanine amino transferase ratio and lower gamma-glutamyl transferase levels than in ndALD patients. Patients with AH demonstrated profound liver failure and increased mortality. One-year mortality was 10% in ndALD and 50% in AH. Histologically, steatosis grade, ballooning and pericellular fibrosis were similar in both groups, while advanced fibrosis, Mallory-Denk bodies, bilirubinostasis, severe neutrophil infiltration and ductular reaction were more frequent among AH patients. Transcriptome analysis revealed a profound gene dysregulation within both phenotypes when compare to controls. While ndALD was characterised by deregulated expression of genes involved in matrisome and immune response, the development of AH resulted in a marked deregulation of genes involved in hepatocyte reprogramming and bile acid metabolism. Despite comparable alcohol intake, AH patients presented with worse liver function compared with ndALD patients. Bilirubinostasis, severe fibrosis and ductular reaction were prominent features of AH. AH patients exhibited a more profound deregulation of gene expression compared with ndALD patients.

Adrenocortical carcinoma is a rare and aggressive tumour. The only curative treatment is surgery with negative margins. In most series, the average lesion size ranges from 5.5 to 15 cm. We report the case of a 27-year-old female with hyperandrogenism and Cushing syndrome due to a right adrenocortical carcinoma of 19.7 cm. The tumour abutting on liver and vena cava and the presence two nodules in liver required extensive surgery including a right posterior sectionectomy and an en bloc resection of the adrenal mass together with the right kidney and the gallbladder. The vena cava was also resected with a reconstruction using a pericardial patch since it was invaded on its border. Pathological examination confirmed an adrenocortical carcinoma, with tumour invasion of vessels, tumour capsule, vena cava and two metastases in the liver (pT4N0M1). All margins were negative. Three months after surgery, two lung nodules, cardio-phrenic and internal mammary adenomegalies were noticed on a PET/CT scan, justifying the initiation of chemotherapy, alongside with mitotane. After a 10-month follow-up, CT scan was stable excepted for a lung nodule growing from 4 to 7 mm. Targeted stereotaxic radiotherapy was then administered. Twenty-two months after surgery, the patient has improved considerably and all signs of hyperandrogenism and Cushing syndrome have resolved. This case of adrenocortical carcinoma illustrates one of the largest tumours among those reported. It demonstrates the feasibility and effectiveness of a multimodal approach in its treatment even if it is giant and at high risk.

Sleep disturbances are common in patients with functional dyspepsia. Our aim was to assess the relationship between subjective sleep and quality of life and to identify factors associated with impaired sleep in functional dyspepsia. One thousand two hundred and twenty patients referred for functional gastrointestinal disorders at a single tertiary care center between end 2017 and June 2019 were studied using a self-administered questionnaire. 355 patients with Rome IV-based functional dyspepsia were identified. Sleep was assessed using both the (PSQI) and the (ISI). The severity of dyspeptic symptoms was assessed using the (TSS). Quality of life was assessed by the (GIQLI). Anxiety and depression levels were evaluated using the (HAD) scale. Among the 355 patients with functional dyspepsia, 66 (18.6%) patients displayed normal sleep quality whereas 289 (81.4%) patients had altered sleep quality. Functional dyspepsia patients with sleep disturbances were older (48.1 ± 15.4 vs. 41.4 ± 16.0, = 0.0009), had decreased quality of life (GIQLI: 75.3 ± 18.5 vs. 92.1 ± 15.4, < 0.0001), greater severity of their symptoms (TSS: 18.9 ± 3.6 vs. 17.2 ± 3.9, = 0.0007), and higher anxiety and depression scores (HADS: 17.7 ± 7.2 vs. 11.9 ± 5.1, < 0.0001). A correlation was found between sleep quality and quality of life [ = -0.43 (95% CI: -0.51 to -0.34), < 0.0001]. Independent factors predicting poor sleep quality were age [OR 1.03 (95% CI = 1.01-1.05), = 0.006], depression level [OR 1.27 (95% CI = 1.16-1.39); < 0.0001], and the severity of dyspeptic symptoms [OR 1.13 (95% CI = 1.04-1.22); = 0.004]. A high prevalence of sleep disturbances was found in patients suffering from functional dyspepsia, with 81% of them having altered sleep quality and 61% having insomnia based on subjective assessment. Altered sleep quality and insomnia were associated with altered quality of life, higher severity of symptoms, and higher anxiety and depression scores in this disorder.

Itopride, a mixed D2 antagonist and cholinesterase inhibitor, has prokinetic effects on gastric motility. The Leuven Postprandial Distress Scale is a validated patient-reported outcome instrument for functional dyspepsia (FD) postprandial distress syndrome (PDS). We aimed to use the LPDS to assess treatment outcome in PDS and PDS/EPS (epigastric pain syndrome). Patients with PDS, with or without non-predominant EPS symptoms, were enrolled in an 8-week double-blind placebo-controlled multi-center trial with itopride (100 mg t.i.d.). Patients completed LPDS diaries and questionnaires to assess treatment response. Mann-Whitney test and mixed models were used. One hundred patients (79% females, 39.1 ± 1.5 yo) were included. No significant difference was observed between treatment arms (p = 0.6). Compared to baseline, itopride treatment significantly improved the LPDS score (p = 0.001) and all individual symptoms (p < 0.0001). In the placebo arm, this was only the case for belching and epigastric pain (p < 0.05). In an exploratory analysis, outcomes in "pure" PDS (n = 45) and overlapping PDS/EPS (n = 55) patients were assessed and showed that the latter subgroup has the largest benefit with itopride compared to placebo (p = 0.03). Using the LPDS score in a pilot controlled trial in FD, itopride shows no therapeutic benefit over placebo after 8 weeks of treatment. In an exploratory post hoc analysis, itopride but not placebo was associated with improvement of symptoms compared to baseline, and this was most prominent in patients with overlapping PDS/EPS. The efficacy of itopride in this subgroup needs to be evaluated in a large study using the same outcome measure. (clinialtrials.org ref.: NCT04647955).

BACKGROUND: Dietary interventions targeting the gut microbiota have been proposed as innovative strategies to improve obesity-associated metabolic disorders. Increasing physical activity (PA) is considered as a key behavioral change for improving health. We have tested the hypothesis that changing the PA status during a nutritional intervention based on prebiotic supplementation can alter or even change the metabolic response to the prebiotic. We confirm in obese subjects and in high-fat diet fed mice that performing PA in parallel to a prebiotic supplementation is necessary to observe metabolic improvements upon inulin. METHODS: A randomized, single-blinded, multicentric, placebo-controlled trial was conducted in obese participants who received 16 g/day native inulin versus maltodextrin, coupled to dietary advice to consume inulin-rich versus -poor vegetables for 3 months, respectively, in addition to dietary caloric restriction. Primary outcomes concern the changes on the gut microbiota composition, and secondary outcomes are related to the measures of anthropometric and metabolic parameters, as well as the evaluation of PA. Among the 106 patients who completed the study, 61 patients filled a questionnaire for PA before and after intervention (placebo: n = 31, prebiotic: n = 30). Except the dietitian (who provided dietary advices and recipes book), all participants and research staff were blinded to the treatments and no advices related to PA were given to participants in order to change their habits. In parallel, a preclinical study was designed combining both inulin supplementation and voluntary exercise in a model of diet-induced obesity in mice. RESULTS: Obese subjects who increased PA during a 3 months intervention with inulin-enriched diet exhibited several clinical improvements such as reduced BMI (- 1.6 kg/m2), decreased liver enzymes and plasma cholesterol, and improved glucose tolerance. Interestingly, the regulations of Bifidobacterium, Dialister, and C

Whether gastroparesis is associated with a shortened life expectancy remains uncertain as no systematic study has evaluated the impact of gastroparesis on mortality, based on gastric emptying (GE) tests. This study aimed to assess whether delayed GE was predictive of mortality. GE was measured using a 13C-octanoic acid breath test in 1563 consecutive patients. Delayed GE at baseline defined the gastroparesis group. Patients were followed up for a mean of 8.9 years, yielding 13 466 patients per year. Mortality was assessed using the French CepiDc database with data from local civil registries. The cause of death was determined from medical records. Mortality rates were assessed using the Kaplan-Meier method and hazard ratio (HR) was calculated using the Cox regression model. Age and symptoms severity were not different among patients with normal GE (n = 1179) and with delayed GE (n = 384) while diabetes mellitus was more frequent in the gastroparesis group. Kaplan-Meier analysis showed increased mortality in the gastroparesis group compared to patients with normal GE. Cox regression model identified delayed GE as independently associated with increased mortality (HR = 1.63[1.09-2.42]; P = 0.02). Other independent factors associated with increased mortality included age, male sex, and diabetes. No difference was observed between groups for the cause of death, with cancer and cardiovascular disease being the leading causes. This study has shown that gastroparesis, diagnosed on GE tests, was associated with increased mortality, independently of age, sex, BMI or diabetes status (NCT04918329).

Background and study aims: The role of malnutrition on the prognosis of hospitalized cirrhotic patients is incompletely studied. Our aim was to determine the prevalence of malnutrition, functional scores and their impact on prognosis of hospitalized cirrhotic patients. Patients and methods: This retrospective study included all patients with cirrhosis hospitalized in the gastroenterology unit at Saint-Luc university hospital, Brussels between April 2014 and September 2014. Nutritional status was evaluated according to minimum clinical summary diagnostic criteria. Cirrhosis-related complications or death occurrence were analysed in a one-year follow-up. Results: 95 cirrhotic patients were assessed for nutritional status and outcomes. Malnutrition affected 45.3% of patients and was more frequent with the severity of cirrhosis: 29% in Child-Pugh A, 48.8% in Child-Pugh B and 72.2% in Child-Pugh C patients. 58.9% of patients developed cirrhosis-related complications (60.7% in the malnutrition group vs. 39.3%, p<0.001, OR 5.06, IC95 1.90-14.58) and 33.7% of patients died (68.75% vs. 31.25%, p=0.002, OR 4.33, IC95 1.62-12.28). Adjusting for age, sodium, MELD, Charlson index, hepatocellular carcinoma, platelets, diabetes, prognostic nutritional index and Braden scale, malnutrition was significantly associated with higher mortality and morbidity rates with an OR of 3.56 (CI95 1.55-8.16) and 2.09 (CI95 1.16-3.77) respectively. Braden scale was significantly associated with higher mortality (p=0.027, OR 1.25, CI95 1.03-1.52) whereas prognostic nutritional index was associated with higher morbidity (p=0.001, OR 0.94, CI95 0.900.98). Conclusion: Malnutrition is highly prevalent in hospitalized cirrhotic patients. Malnutrition, low prognostic nutritional index and low Braden scale are associated with poor outcomes in cirrhosis. (Acta gastroenterol. belg., 2022, 85, 1-9).

L'intestin humain est colonisé par une variété de microbes qui influencent les réponses métaboliques, le système immunitaire et le système nerveux. Les habitudes alimentaires sont des facteurs importants qui façonnent la quantité de graisse intra-hépatique (stéatose) et la composition du microbiote intestinal. De nombreux modèles animaux d'exposition à l’alcool ou à des régimes riches en lipides et en glucides ont mis en évidence le rôle clé des altérations du microbiote intestinal, de la perméabilité intestinale et de la translocation des produits microbiens dans le développement de la maladie stéatosique, qu’elle soit alcoolique (ALD) ou métabolique (MAFLD). C’est pour cette capacité à pouvoir exercer un effet néfaste sur la santé que l’on parle de « dysbiose » intestinale. Cependant, chez l'être humain, il n'existe pas de signature claire définissant un microbiote de patient alcoolique ou métabolique. L'absence de consensus sur cette signature précise est probablement due à l'hétérogénéité de la maladie stéatosique, aux éventuels médicaments concomitants, comorbidités et aux différents critères de sélection ou d'évaluation. Cet axe intestin-foie doit également être analysé en tenant compte des autres tissus qui peuvent participer au contexte métabolique, à savoir le tissu adipeux et le muscle. Les changements les plus fréquemment retrouvés sont une augmentation de l'abondance relative de Proteobacteria, Enterobacteria, Escherichia et Candida albicans et une diminution de l'abondance de Coprococcus et Eubacterium. Les produits microbiens les mieux caractérisés sont les produits bactériens. Ils comprennent des fragments des bactéries elles-mêmes (comme les lipopolysaccharides, des composants de la membrane des bactéries Gram négatif) et également des métabolites bactériens. Parmi ceux-ci, certains peuvent jouer un rôle bénéfique (indole, acides gras à courte chaîne comme le butyrate, certains acides biliaires secondaires…) et d’autres un rôle péjoratif (éthanol end

Functional dyspepsia and bladder pain syndrome are well-known to overlap with irritable bowel syndrome. Whether functional dyspepsia overlaps with bladder pain syndrome remains unknown. Our aim was to evaluate the presence of bladder pain syndrome in functional dyspepsia patients and its impact. All consecutive patients with investigated dyspeptic symptoms in our tertiary care center between March 2015 and November 2018 were studied. Functional dyspepsia and irritable bowel syndrome were diagnosed according to Rome III and IV criteria while bladder pain syndrome was diagnosed using ESSIC criteria. Validated questionnaires were filled to assess quality of life (GIQLI), anxiety and depression (HADS), sleep (PSQI), and insomnia (ISI). Dyspeptic symptoms severity was assessed individually for eight dyspeptic complaints. Among 1453 patients with dyspeptic symptoms, 61.4% fulfilled Rome criteria for functional dyspepsia. Bladder pain syndrome was present in 16.0% of the patients not fulfilling diagnostic criteria for functional dyspepsia, 22.2% of patients with functional dyspepsia alone, and 36.4% of patients with overlapping functional dyspepsia and irritable bowel syndrome (p-values <0.0001). In patients with bladder pain syndrome overlapping with functional dyspepsia, dyspeptic symptoms severity, anxiety, depression, and insomnia levels were higher while quality of life and sleep quality were reduced (p-values <0.0001). These results were even more pronounced in case of overlap with irritable bowel syndrome (p-values <0.0001). Bladder pain syndrome is present in 26.9% of functional dyspepsia patients and is associated with higher gastrointestinal, psychological distresses, and sleep symptom burdens, and with reduced quality of life.

No abstract available

Data on procedural outcome and quality of endoscopic retrograde cholangiopancreatography (ERCP) in Belgian practice are scarce. The aim of this study is to assess current status of ERCP-performance in Belgium. National multi-institutional survey (online questionnaire) among members of the Belgian Society of Gastrointestinal Endoscopy (BSGIE), conducted in the period June-August 2018. The RIZIV/INAMI provided real-life data on the total number of ERCPs performed in Belgium. Forty-five responders completed the survey (for 43 centers performing ERCP), providing information for 8368 ERCPs performed in 45% (43/95) of institutions performing ERCP in Belgium. Fifty-eight percent of centers performed > 100 ERCPs/year and 7% of centers (n=3) performed < 50 ERCPs/year. According to the RIZIV/INAMI data, low case-volume centers are underrepresented in this survey. The most common ERCPindication was stone extraction (52%). 74% of endoscopists had more than 10 years of experience in performing ERCP. The majority of centers had their own written protocol (84%) for microbiological duodenoscope surveillance. Monitoring of cannulation rate and post-ERCP pancreatitis (PEP) was only performed in a minority of centers (30%). The majority of centers (76%) provided verbal informed consent relating to the ERCP-procedure ; a minority also requested a written informed consent (23%). 65% of centers systematically use NSAIDs for PEP prophylaxis. This is the first survey of ERCP performance in Belgium. There were wide variations in practice. Adherence to key performance measures and measurement and evaluation of ERCP performance in daily practice at center and endoscopist level are not uniformly widespread.

Surgical resection of colorectal liver metastases (CRLM) is the first choice of treatment when possible, aims to maximize patient survival and represents the only hope for a cure. In the last few years, the introduction of new molecules for neoadjuvant chemotherapy has made it possible to reduce tumour size to allow for a surgical resection, which may not otherwise have been feasible. Nonetheless, metastatic colorectal cancer continues to have a poor prognosis. In this thesis we undertook an in-depth analysis of the pathological characterization of CRLM to understand which parameters influence prognosis in a retrospective and in a prospective cohort of patients resected for CRLM. Then we explored the possible role of morphological heterogeneity of the pathological features regarding outcome. Our investigations demonstrated the clinical relevance of a complete pathological evaluation of all CRLM to stratify patient prognosis after surgery and attempted to provide another piece in the puzzle to understand tumoural heterogeneity and its possible influence on disease outcome., (MED - Sciences médicales) -- UCL, 2022

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the evidence of steatosis in the setting of a metabolic risk condition such as type 2 diabetes mellitus (T2DM). Indeed, T2DM and liver steatosis share common pathophysiological mechanisms, and one can lead to the other. MAFLD can progress from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis as well as hepatocellular carcinoma (HCC). Because of the lack / disparity of guidelines for MAFLD screening, which is asymptomatic in its early stages, it is not rare that diabetic patients are belatedly diagnosed with NASH cirrhosis or HCC. We therefore recommend systematic non-invasive tests (NITs) that calculate an estimate of the risk based on readily available anthropometric and biological parameters. These include the fatty liver index (FLI) for steatosis detection and at least one of the following for fibrosis: non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 index (FIB-4) or Hepamet fibrosis score (HFS). Indeed, NFS and FIB-4 are the best predictors of liver-related events, while FIB-4 and HFS correlate with overall mortality. Systematic literature review found only few retrospective or cross-sectional studies using NITs for systematic steatosis and fibrosis screening in T2DM patients, with a crucial need for prospective studies. This screening strategy will allow targeted patients to be referred for further liver investigation (e.g. ultrasound, elastometry) and care. Current treatment modalities of MAFLD in T2DM patients range from lifestyle and dietary interventions to specific glucose-lowering drugs that recently showed some benefits regarding MAFLD, such as pioglitazone, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. Other treatments are currently under investigation.

Carbohydrate antigen 19-9 (CA 19-9) is a biological marker used to diagnose and monitor the progression of various cancers. Elevated CA 19-9 has also been sporadically observed in Helicobacter pylori infected patients. Similar to H. pylori, animalhosted non-H. pylori Helicobacter (NHPH) species can induce gastroduodenal lesions in humans. We report the first case of CA 19-9 elevation related to H. suis gastritis and its normalisation after eradication. A CA 19-9 screening prescribed as part of a regular check up by the general practitioner was found elevated in a 68-year-old man presenting chronic dyspeptic symptoms. Medical investigations were negative for presence of neoplasia or biliary obstruction. Upper gastrointestinal endoscopy confirmed the presence of chronic gastritis and H. suis was identified in gastric biopsies. The standard treatment for H. pylori successfully eradicated H. suis with normalisation of CA 19-9 levels. In addition to H. pylori, infection with NHPH species should be considered as an additional cause of elevated CA19-9.

Irritable bowel syndrome (IBS) is characterised by recurrent abdominal pain related to defaecation or associated with altered stool frequency or consistency. Despite its prevalence, major uncertainties in the diagnostic and therapeutic management persist in clinical practice. A Delphi consensus was conducted by 20 experts from Belgium, and consisted of literature review and voting process on 78 statements. Grading of recommendations, assessment, development and evaluation criteria were applied to evaluate the quality of evidence. Consensus was defined as > 80 % agreement. Consensus was reached for 50 statements. The Belgian consensus agreed as to the multifactorial aetiology of IBS. According to the consensus abdominal discomfort also represents a cardinal symptom, while bloating and abdominal distension often coexist. IBS needs subtyping based on stool pattern. The importance of a positive diagnosis, relying on history and clinical examination is underlined, while additional testing should remain limited, except when alarm features are present. Explanation of IBS represents a crucial part of patient management. Lifestyle modification, spasmolytics and water-solube fibres are considered first-line agents. The low FODMAP diet, selected probiotics, cognitive behavioural therapy and specific treatments targeting diarrhoea and constipation are considered appropriate. There is a consensus to restrict faecal microbiota transplantation and gluten-free diet, while other treatments are strongly discouraged. A panel of Belgian gastroenterologists summarised the current evidence on the aetiology, symptoms, diagnosis and treatment of IBS with attention for the specificities of the Belgian healthcare system.

Appendiceal neuroendocrine neo-plasms (aNENs) are a diverse group of malignant neoplasms of varying biological behavior for which information about manage-ment and outcome is sparse, with the majority of available studies being retrospective, including only a limited number of patients, and therefore not necessarily reflecting the reality in the community. In the present study clinical, epidemiological and pathological data of appendiceal neuroendocrine neoplasms in Belgium is provided and compared with current literature. A population-based study was conducted by linking data of the Belgian Cancer Registry with medical procedures in the Belgian Health Insurance database for patients diagnosed with aNEN between 2010 and 2015. We found an aNEN incidence of 0.97/100.000 person years in Belgium. Neuroendocrine carcinoma of the appendix are rare. Most appendiceal neuroendocrine tumors (aNETs) are small G1 tumors. Positive lymph nodes are often found in tumors larger than 2cm, especially aNET G2. A rapid uptake of changing classifications was seen in the community. However, systematic reporting of risk factors for small aNEN can still be improved and should be stimulated. In 9% of cases, reclassifications had to be made, pointing out that in a retrospective analysis, original pathological reports should be checked for specific parameters, before reliable conclusions can be drawn.

No abstract available

Background and Aims: The prevalence of insulin resistance (IR) and type 2 diabetes mellitus (T2DM) is higher in patients with cirrhosis, compared to control patients without liver disease. The exact mechanism for this is unknown but could include liver inflammation. In this study, we investigate whether cirrhosis is the primum movens of IR or if impaired insulin sensitivity is already present in non-cirrhotic patients with chronic liver diseases. Method: Patients were recruited and divided into three groups: control (CTL), active chronic liver disease without cirrhosis (CLD) and cirrhosis (CIR). In patients not taking pharmacological treatment for T2DM, IR was quantified using the homeostasis model assessment of insulin resistance (HOMA-IR). The proportion of patients treated for T2DM was recorded in each group. Additionally, HOMA-IR levels among different disease etiologies were compared. The study was approved by the local ethics committee. Results: 422 patients were included in our study, 16 were controls, 278 had a CLD and 128 were cirrhotic (CIR). The causes of liver disease were as follows: metabolic-dysfunction associated fatty liver disease (MAFLD, n=206), alcoholic liver disease (ALD, n=117), active chronic hepatitis C (HCV, n=59), other cause (n=24). IR, represented by a HOMA-IR value exceeding 2.5, is already present in patients with non-cirrhotic CLD (median HOMA-IR 4.0). HOMA-IR levels lie between those seen in CTL (median HOMA-IR 1.3) and CIR patients (median HOMA-IR 5.7), with a statistically significant difference between the three groups (p-value <0.001). Median glycemia in the CLD and CIR groups is the same (98 mg/dL and 99 mg/dL respectively) but insulinemia is different (101.5 pmol/L and 132.3 pmol/L respectively) resulting in distinct HOMA-IR values in CLD and CIR patients (p=0.018). Compared to CLD patients, patients in the CIR group are also characterised by a higher age, higher AST levels and a lower platelet count consistent with portal hype

Chronic alcohol consumption is one of the leading causes of chronic liver disease and liver-related deaths worldwide. Only up to 20% of patients with an alcohol use disorder (AUD) progress to advanced stages of alcohol-associated liver disease (ALD) from the benign form of the disease, namely simple steatosis. This process is usually silent at early disease stages and the mechanisms underlying disease progression are yet incompletely understood. Recent reports have highlighted the role of the gut-liver axis in ALD. However, data in early human ALD were scarce. Therefore, this PhD work aimed at investigating dysfunctions of the intestinal barrier in AUD patients and their relationship with activation of immune responses contributing to ALD progression. We here revealed a specific diminution of effector immune cells in the duodenal mucosa and the presence of a tolerogenic immune status associated with changes in the gut microbiota and elevated translocation of microbial products in patients with progressive ALD. These microbial products activated circulating monocytes and liver inflammatory responses, thus contributing to systemic inflammation and ALD progression. The results of this PhD thesis support the contribution of gut barrier dysfunctions in human ALD pathogenesis., (BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2022

No abstract available

Vedolizumab (VDZ) is a gutselective integrin inhibitor used to treat Crohn's disease (CD) and ulcerative colitis (UC). This retrospective study assessed effectiveness and treatment persistence of VDZ in a Belgian reallife cohort of CD and UC patients. CD and UC patients from 15 Belgian centers, who started VDZ between 01/09/2015 and 31/06/2016 and attended ≥1 visit after the first VDZ infusion, were included. Data were collected before first infusion, at week (W)10, W14 (CD patients only), month (M)6 and last follow-up. Treatment response and remission rates (changes in disease activity scores) and treatment persistence (Kaplan-Meier analysis) were assessed. Of the 348 patients receiving at least one dose of VDZ, 325 (202 CD, 45 biologic-naïve; and 123 UC, 42 biologic-naïve) patients were included in data analyses. At M6, 87.6% (176/201) of CD and 86.1% (105/122) of UC patients were still on VDZ treatment, 75.6% (34/45) and 83.9% (26/31) achieved clinical response, and 66.7% (44/66) and 42.9% (15/35) were in remission. At M6 remission rates was significantly higher while response rates tended to be higher among biologic-naïve versus biologic-failure CD patients. VDZ offers an effective treatment option in real-life settings and treatment effectiveness appears higher in biologic-naïve versus biologic-failure CD patients. (Acta gastroenterol. belg., 2020, 83, 15-23).

The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. Not applicable. DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR. Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).

no abstract available

Endoscopic ultrasound-guided digestive anastomosis (EUS-A) is a new alternative under evaluation in patients presenting with afferent limb syndrome (ALS) after Whipple surgery. The aim of the present study is to analyze the safety and effectiveness of EUS-A in ALS. This is an observational multicenter study. All patients ≥18 years old with previous Whipple surgery presenting with ALS who underwent an EUS-A using a lumen-apposing metal stent (LAMS) between 2015 and 2021 were included. The primary outcome was clinical success, defined as resolution of the ALS or ALS-related cholangitis. Furthermore, technical success, adverse event rate, and mortality were evaluated. Forty-five patients (mean age: 65.5 ± 10.2 years; 44.4% male) were included. The most common underlying disease was pancreatic cancer (68.9%). EUS-A was performed at a median of 6 weeks after local tumor recurrence. The most common approach used was the direct/freehand technique (66.7%). Technical success was achieved in 95.6%, with no differences between large (≥15 mm) and small LAMS (97.4% vs. 100%, P = 0.664). Clinical success was retained in 91.1% of patients. A complementary treatment by dilation of the stent followed by endoscopic retrograde cholangiopancreatography through the LAMS was performed in three cases (6.7%). There were six recurrent episodes of cholangitis (14.6%) and two procedure-related adverse events (4.4%) after a median follow-up of 4 months. Twenty-six patients (57.8%) died during the follow-up due to disease progression. EUS-A is a safe and effective technique in the treatment of malignant ALS, achieving high clinical success with an acceptable recurrence rate.

Despite efforts from various endoscopy societies, reporting in the field of endoscopy remains extremely heterogeneous. Harmonisation of clinical practice in endoscopy has been highlighted by application of many clinical practice guidelines and standards pertaining to the endoscopic procedures and reporting are underlined. The aim of the proposed "standardised reporting" is to (1) facilitate recognition of gastrointestinal neuroendocrine neoplasms (NEN) on initial endoscopy, (2) to enable interdisciplinary decision making for treatment by a multidisciplinary team, (3) to provide a basis for a standardised endoscopic follow-up which allows detection of recurrence or progression reliably, (4) to make endoscopic reports on NEN comparable between different units, and (5) to allow research collaboration between NEN centres in terms of consistency of their endoscopic data. The ultimate goal is to improve disease management, patient outcome and reduce the diagnostic burden on the side of the patient by ensuring the highest possible diagnostic accuracy and validity of endoscopic exams and possibly interventions.

no abstract available

EUS has evolved into a therapeutic modality for gastrointestinal disorders. Simulators, ex vivo models, and phantoms are the current teaching methods for therapeutic EUS (TEUS). We create and evaluate a high-fidelity simulated live animal model (HiFi SAM) for teaching endoscopists TEUS. Designing a curriculum that uses HiFi SAM and enables trainees to perform realistic procedures with expert mentors. Twenty-seven trainees participated in a 3-day program with 6 h of theoretical and 14 h of hands using life HiFi SAM. Eighteen experts participated. Twenty-two (20-25) TEUS were defined for each HiFi SAM, and 616 were performed in all. Of 616/264 (43%) were evaluated with a mean of 88 per course (ranging between 80 and 95). Ninety-one percent (240/264) of the procedures were completed successfully. In 24, success was not achieved due to technical and/or model problems. Student rating of HiFi SAM was: 71% excellent rating (scale 8-10) and 95% excellent/good. The HiFi SAM procedure evaluation was (scale 1-5): fine-needle biopsy: 4.79, radiofrequency: 4.76, common bile duct and gallbladder drainage: 4.75, cystic drainages: 4.72, neurolysis: 4.55, microbiopsy: 4.50, and hepatogastric drainage: 4.04, with an overall satisfaction rate of 4.56 (91%). A short survey showed: 83% would recommend absolutely (17% most likely), 33% think that ITEC training was sufficient for their practice, and 66% would like additional training, especially more practice in specific techniques rather than more clinical case discussion. Regarding impact on their practice, 66% of the trainees started a new procedure and/or noted improvement in previous ones. HiFi SAM is a complex model; however, experts and trainees are satisfied with the training this new curriculum provided.

Acrometastasis is an uncommon metastatic location appearing in the small bones of hands and feet (1). Its low incidence, around 0,1% of all bone metastases, may be due to the subclinical presentation and the lack of attention to the extremities in routine examination (1- 5). However, it sometimes represents the first expression of an occult malignancy (1-4). The symptoms are aspecific and may mimic a local infection, an inflammatory disease (arthritis, tenosynovitis) or a dermatologic lesion (1-5). The correct diagnosis of this atypical entity is important to draw the attention of the clinicians to the metastatic dissemination of the disease, to initiate adequate treatment and reduce patient morbidity.

Selective internal radiation therapy (SIRT) is part of the treatment strategy for hepatocellular carcinoma (HCC). Strong clinical data demonstrated the effectiveness of this therapy in HCC with a significant improvement in patient outcomes. Recent studies demonstrated a strong correlation between the tumor response and the patient outcome when the tumor-absorbed dose was assessed by nuclear medicine imaging. Dosimetry plays a key role in predicting the clinical response and can be optimized using a personalized method of activity planning (multi-compartmental dosimetry). This paper reviews the main clinical results of SIRT in HCC and emphasizes the central role of dosimetry for improving it effectiveness. Moreover, some patient and tumor characteristics predict a worse outcome, and toxicity related to SIRT treatment of advanced HCC patient selection based on the performance status, liver function, tumor characteristics, and tumor targeting using technetium-99m macro-aggregated albumin scintigraphy can significantly improve the clinical performance of SIRT.

Pancreatic exocrine insufficiency (PEI) is a common condition in patients with pancreatic cancer (PC). PEI can be due to the tumor, which, if located in the head, causes obstruction of the pancreatic duct with subsequent atrophy of the pancreatic parenchyma, or it can be the consequence of pancreatic surgical resection. The standard treatment of PEI is pancreatic enzyme replacement therapy (PERT). Clinical data to support the use of PERT in PC are however limited. There are very few randomized clinical trials that evaluated PERT in PC. Most data come from observational studies. Despite this limited clinical evidence, PERT treatment for PEI is an essential part of supportive therapy to ensure optimal nutritional status in PC patients who will receive surgery, neoadjuvant/adjuvant or palliative treatment. The objective of this review is to increase the awareness about PEI in PC patients and to provide expert recommendations on the use of PERT in resected, borderline resectable and unresectable patients, based on clinical experience and literature review.

Different surveillance strategies for patients with low-risk branch-duct (BD) intraductal papillary neoplasm (IPMN) have been described. The aim of this study was to describe the natural history of low-risk BD-IPMN, and to identify risk factors for the development of worrisome features (WF)/high-risk stigmata (HRS) and of pancreatic malignancies. This was a multicentre retrospective study of patients with BD-IPMN who were under active surveillance between January 2006 and December 2015. Patients were eligible if they had a low-risk lesion and had a minimum follow-up of 24 months. Outcomes were development of WF/HRS or cytologically/histologically confirmed malignant IPMN. Of 837 patients included, 168 (20 per cent) developed WF/HRS. At the end of the observation time, 132 patients (79 per cent) with WF/HRS were still under surveillance without progression to pancreatic cancer. Factors associated with the development of WF or HRS in multivariable analysis included localized nodules (versus diffuse: hazard ratio (HR) 0.43, 95 per cent c.i. 0.26 to 0.68), cyst size 15-19 mm (versus less than 15 mm: HR 1.88, 1.23 to 2.87) or at least 20 mm (versus less than 15 mm: HR 3.25, 2.30 to 4.60), main pancreatic duct size over 3 mm (versus 3 mm or less: HR 2.17, 1.41 to 3.34), and symptoms at diagnosis (versus no symptoms: HR 2.29, 1.52 to 3.45). Surveillance in an endoscopy-oriented centre was also associated with increased detection of WF or HRS (versus radiology-oriented: HR 2.46, 1.74 to 3.47). Conservative management of patients with low-risk BD-IPMN is safe and feasible.

Endoscopic papillectomy is a minimally invasive treatment for benign tumors of the ampulla of Vater or early ampullary carcinoma. However, reported recurrence rates are significant and risk factors for recurrence are unclear. The aims of this study were to evaluate the efficacy and safety of endoscopic papillectomy and to identify risk factors for recurrence and adverse events. All patients who underwent endoscopic papillectomy at five tertiary referral centers between January 2008 and December 2018 were included. Recurrence was defined as the detection of residue on one of the follow-up endoscopies. Treatment success was defined as the absence of tumor residue on the last follow-up endoscopy. A total of 227 patients were included. The resections were in 64.8% of cases. The mean lesion size was 20 mm (range: 3-80) with lateral extension in 23.3% of cases. R0 resection was achieved in 45.3% of cases. The recurrence rate was 30.6%, and 60.7% of recurrences were successfully treated with additional endoscopic treatment. Finally, treatment success was achieved in 82.8% of patients with a median follow-up time of 22.3 months. R1 resection, intraductal invasion, and tumor size > 2 cm were associated with local recurrence. Adverse events occurred in 36.6% of patients and included pancreatitis (17.6%), post-procedural hemorrhage (11.0%), perforation (5.2%), and biliary stenosis (2.6%). The mortality rate was 0.9%. Endoscopic papillectomy is an effective and relatively well-tolerated treatment for localized ampullary tumors. In this series, R1 resection, intraductal invasion, and lesion size > 2 cm were associated with local recurrence.

Various prognostic factors are associated with overall survival (OS) after resection of distal cholangiocarcinoma (dCCA). The objective of this study was to develop and validate a prediction model for 3-year OS after pancreatoduodenectomy for dCCA. The derivation cohort consisted of all patients who underwent pancreatoduodenectomy for dCCA in the Netherlands (2009-2016). Clinically relevant variables were selected based on the Akaike information criterion using a multivariate Cox proportional hazards regression model, with model performance being assessed by concordance index (C-index) and calibration plots. External validation was performed using patients from the Belgium Cancer Registry (2008-2016), and patients from two university hospitals of Southampton (U.K.) and Verona (Italy). Independent prognostic factors for OS in the derivation cohort of 454 patients after pancreatoduodenectomy for dCCA were age (HR 1.02, 95% CI 1.01-1.03), pT (HR 1.43, 95% CI 1.07-1.90) and pN category (pN1: HR 1.78, 95% CI 1.37-2.32; pN2: HR 2.21, 95% CI 1.63-3.01), resection margin status (HR 1.79, 95% CI 1.39-2.29) and tumour differentiation (HR 2.02, 95% CI 1.62-2.53). The prediction model was based on these prognostic factors. The optimism-adjusted C-indices were similar in the derivation cohort (0.69), and in the Belgian (0.66) and Southampton-Verona (0.68) validation cohorts. Calibration was accurate in the Belgian validation cohort (slope = 0.93, intercept = 0.12), but slightly less optimal in the Southampton-Verona validation cohort (slope = 0.88, intercept = 0.32). Based on this model, three risk groups with different prognoses were identified (3-year OS of 65.4%, 33.2% and 11.8%). The prediction model for 3-year OS after resection of dCCA had reasonable performance in both the derivation and geographically external validation cohort. Calibration slightly differed between validation cohorts. The model is readily available via www. pancreascalculator.com to inform patients from

OBJECTIVES: Fluoropyrimidines such as 5-Fluorouracil (5-FU), capecitabine and tegafur are drugs that are often used in the treatment of maliginancies. The enzyme dihydropyrimidine dehydrogenase (DPD) is the first and rate limiting enzyme of 5-FU catabolism. Genetic variations within the DPYD gene (encoding for DPD protein) can lead to reduced or absent DPD activity. Treatment of DPD deficient patients with fluoropyrimidines can result in severe and, rarely, fatal toxicity. Screening for DPD deficiency should be implemented in practice. METHODS: The available methods in routine to screen for DPD deficiency were analyzed and discussed in several group meetings involving members of the oncological, genetic and toxicological societies in Belgium: targeted genotyping based on the detection of 4 DPYD variants and phenotyping, through the measurement of uracil and dihydrouracil/uracil ratio in plasma samples. RESULTS: The main advantage of targeted genotyping is the existence of prospectively validated genotype-based dosing guidelines. The main limitations of this approach are the relatively low sensitivity to detect total and partial DPD deficiency and the fact that this approach has only been validated in Caucasians so far. Phenotyping has a better sensitivity to detect total and partial DPD deficiency when performed in the correct analytical conditions and is not dependent on the ethnic origin of the patient. CONCLUSION: In Belgium, we recommend phenotype or targeted genotype testing for DPD deficiency before starting 5-FU, capecitabine or tegafur. We strongly suggest a stepwise approach using phenotype testing upfront because of the higher sensitivity and the lower cost to society.

In the last 5 years, the landscape of oncologic treatment has been deeply modified with the development and use of immune checkpoint inhibitors (ICIs) that exert their antitumoral effect by reverting the exhausted phenotype of tumor-infiltrating lymphocytes. This innovative therapeutic strategy has widely changed the prognosis of some advanced neoplastic diseases such as melanoma and lung cancer, providing durable remission for a significant number of patients. Unfortunately, immune-related adverse events (irAEs), especially ICI-induced hepatitis, may be very severe in some cases, impairing the prognosis of the patient. Guidelines available today on the diagnosis and management of ICI-induced hepatitis are mainly based on expert opinions and case series. This lack of large data is explained not only by the low incidence of hepatic adverse events but also by their clinical heterogeneity and variable severity. In this article, we will review the clinical, biological, and histological characteristics of ICI-induced liver injury. We will discuss the current knowledge on their pathological mechanisms and their therapeutic strategy based on immunosuppressive treatment for more severe cases. Regarding severity assessment, we will discuss the gap between the oncologist and the hepatologist's point of view, highlighting the need for multidisciplinary management. While initially developed for notably less frequent diseases than neoplastic ones, gene therapy is going to be a revolution for the treatment of diseases not responding to pharmacological therapy. Limited but growing data describe liver injury after the administration of such therapy whose exact physiopathology remains unknown. In this article, we will discuss the available data supporting the role of gene therapies in the onset of drug-induced liver injury and related mechanisms. We will describe the clinical context, the biological and histological features, and the management currently proposed.

Alcohol use is a leading cause of chronic liver disease worldwide, and changes in the microbiome associated with alcohol use contribute to patients' risk for liver disease progression. Less is known about the effects of alcohol use on the intestinal viral microbiome (virome) and interactions between bacteriophages and their target bacteria. We studied changes in the intestinal virome of 62 clinically well-characterized patients with alcohol use disorder (AUD) during active alcohol use and after 2 weeks of alcohol abstinence, by extracting virus-like particles and performing metagenomic sequencing. We observed decreased abundance of Propionibacterium, Lactobacillus, and Leuconostoc phages in patients with active AUD when compared with controls, whereas after 2 weeks of alcohol abstinence, patients with AUD demonstrated an increase in the abundance of Propionibacterium, Lactobacillus, and Leuconostoc phages. The intestinal virome signature was also significantly different in patients with AUD with progressive liver disease, with increased abundance of phages targeting Enterobacteria and Lactococcus species phages compared with patients with AUD with nonprogressive liver disease. By performing moderation analyses, we found that progressive liver disease is associated with changes in interactions between some bacteriophages and their respective target bacteria. In summary, active alcohol use and alcohol-associated progressive liver disease are associated with changes in the fecal virome, some of which are partially reversible after a short period of abstinence. Progression of alcohol-associated liver disease is associated with changes in bacteriophage-bacteria interactions.

Neuroendocrine neoplasms (NENs) are rare tumours with variable clinical behaviour. Their natural history is ideally best approached in large, multicentre and multinational registries with long-term patients' follow-up. The European Neuroendocrine Tumour Society registry aims to obtain information regarding NEN outcomes and prognostic factors in a European frame. We collected data from 7 national NEN registries (Belgium, Czech Republic, Germany, Greece, Poland, Spain, Switzerland), representing 10,102 patients. Anonymised/pseudonymised data were collected in a secured server. Descriptive statistical methods were applied, as well as Kaplan-Meier survival curves and multivariable analyses for prognostic factors of overall survival (OS). median age of the study population was 60 years (range: 18-102), 48% were female. Common primary tumour sites were pancreas (27%) and small intestine (21%). Stage 4 disease was found in 47% of patients, while 26/10/16% had stage 1/2/3 disease, respectively. Grading (n = 6952) was G1/2/3 in 48/37/15% of the patients, respectively. Surgery was the main treatment, provided to 71% of patients, followed by somatostatin analogues (32%), chemotherapy (20%), Peptide receptor Radionuclide Therapy (PRRT) (9%) and targeted therapies (8%). OS at 5 years was 74%, influenced by grade, stage and tissue of origin in multivariate analysis. A Ki67 cut-off value set at 55% within the G3 group allowed to separate 2 groups with a meaningful different OS. We report the first analysis of the European Neuroendocrine Tumour Society registry, comprising 10,102 patients with NEN from 7 European countries. This large cohort study describes prognostic factors for the survival of NENs throughout Europe, including primary tumour site, grade, stage and treatment.

Studies investigating the gut-liver axis have largely focused on bacteria, whereas little is known about commensal fungi. We characterized fecal fungi in patients with non-alcoholic fatty liver disease (NAFLD) and investigated their role in a fecal microbiome-humanized mouse model of Western diet-induced steatohepatitis. We performed fungal internal transcribed spacer 2 sequencing using fecal samples from 78 patients with NAFLD, 16 controls and 73 patients with alcohol use disorder. Anti-Candida albicans (C. albicans) IgG was measured in blood samples from 17 controls and 79 patients with NAFLD. Songbird, a novel multinominal regression tool, was used to investigate mycobiome changes. Germ-free mice were colonized with feces from patients with non-alcoholic steatohepatitis (NASH), fed a Western diet for 20 weeks and treated with the antifungal amphotericin B. The presence of non-obese NASH or F2-F4 fibrosis was associated with a distinct fecal mycobiome signature. Changes were characterized by an increased log-ratio for Mucor sp./Saccharomyces cerevisiae (S. cerevisiae) in patients with NASH and F2-F4 fibrosis. The C. albicans/S. cerevisiae log-ratio was significantly higher in non-obese patients with NASH when compared with non-obese patients with NAFL or controls. We observed a different fecal mycobiome composition in patients with NAFLD and advanced fibrosis compared to those with alcohol use disorder and advanced fibrosis. Plasma anti-C. albicans IgG was increased in patients with NAFLD and advanced fibrosis. Gnotobiotic mice, colonized with human NASH feces and treated with amphotericin B were protected from Western diet-induced steatohepatitis. Non-obese patients with NAFLD and more advanced disease have a different fecal mycobiome composition to those with mild disease. Antifungal treatment ameliorates diet-induced steatohepatitis in mice. Intestinal fungi could be an attractive target to attenuate NASH. Non-alcoholic fatty liver disease is one of the most co

Fetuin-A, a plasma multifunctional protein known to play a role in insulin resistance, is usually presented as a liver secreted protein. However, fetuin-A adipose tissue production has been also described. Here, we evaluated fetuin-A production by the liver and the adipose tissue during metabolic dysfunction-associated fatty liver disease (MAFLD)-non-alcoholic steatohepatitis (NASH) development. Fetuin-A was evaluated by enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), Western blot, and immunofluorescence in male foz mice fed a normal diet (ND) or a high fat diet (HFD) at various timepoints and in MAFLD-NASH patients. Foz mice fed a short-term HFD developed liver steatosis, insulin resistance, and increased circulating levels of fetuin-A compared to ND-fed mice. In mice and patients with NASH, fetuin-A was located not only in healthy or steatotic hepatocytes but also in some macrophages forming lipogranulomas. In both mice and humans, a significant amount of fetuin-A was present in the adipose tissue compared to the liver. However, messenger ribonucleic acid levels and cell culture experiments indicate that fetuin-A is produced by the liver but not by the adipose tissue. In conclusion, fetuin-A is produced by steatotic hepatocytes at early timepoints in MAFLD and correlates with insulin resistance both in mice and humans. In NASH, fetuin-A also co-localizes with activated liver macrophages and could be interpreted as a signal released by damaged hepatocytes.

Whereas chronic rejection, opportunistic infections, post-transplant lymphoproliferative disorder, hemophagocytic lymphohistiocytosis, biliary tract issues, and cardiovascular side effects of immunosuppressive drugs are frequently reported as late complications in liver transplanted patients, intrahepatic portal venous aneurysm following liver transplantation remains exceptional and unusual. We report the case of a 25-year-old man who underwent a liver transplantation in 1997 because he had glycogen storage disease type 4. The patient developed a late postoperative complication, an intrahepatic portal aneurysm, and 2 episodes of acute cholangitis. By reviewing and scoping the literature, we tried to spotlight the best therapeutic attitude concerning the management of this rare complication.