[Population screening for hepatic fibrosis : who to screen, why and how ?] / Dépistage de la fibrose hépatique dans la population.

The development of liver fibrosis is the consequence of histological remodeling of the liver parenchyma, reflecting chronic inflammatory liver disease or hepatocyte necrosis. These tissue modifications result in structural changes to the extracellular matrix, predisposing to progression to cirrhosis and hepatocellular carcinoma, whatever the underlying etiology. Recent data demonstrate the potential benefits of screening for hepatic fibrosis, in particular in order to detect and treat the cause of the underlying liver disease as early as possible, which could ultimately lead to the many known complications in cirrhotic patients. Early identification of the population at risk of hepatic fibrosis should precede screening, which may be initiated in the primary care physician's office and continued at a later stage by the specialist.

L'apparition d'une fibrose hépatique est souvent la conséquence d'une atteinte inflammatoire chronique du foie ou d'une ­nécrose hépatocytaire. Ces modifications tissulaires ont pour conséquence un changement structurel de la matrice extracellulaire, prédisposant à la progression vers une cirrhose ainsi qu'un carcinome hépatocellulaire, quelle que soit l'étiologie sous-jacente. Des données récentes démontrent le bénéfice ­potentiel du dépistage de la fibrose hépatique, afin de détecter et traiter au plus tôt la cause de la maladie ­hépatique sous-jacente qui pourrait, à terme, conduire aux nombreuses complications connues chez le patient cirrhotique. Une identification précoce de la population à risque de fibrose hépatique peut être initié au cabinet du médecin de premier recours et se poursuivre ultérieurement chez le ­spécialiste.

[An update on gastroparesis in 2024]. / Le point sur la gastroparésie en 2024.

Gastroparesis is a pathology associating upper digestive symptoms, such as nausea and vomiting, with impaired gastric emptying in the absence of mechanical gastric or duodenal obstruction. It has a major impact on patients' quality of life, can lead to undernutrition, and -increases overall mortality. Several schools of thought converge on the hypothesis of a clinico--pathological spectrum of gastric neuro-muscular dysfunction encompassing gastroparesis and functional dyspepsia, in particular the subtype known as "postprandial distress syndrome". Its management includes non--pharmacological interventions, such as hygienic--dietary measures, pharmacological interventions using prokinetic, antiemetic or neuromodulatory treatments, and endoscopic interventions.

La gastroparésie est une pathologie associant des symptômes ­digestifs hauts, tels que des nausées et des vomissements, à un défaut de la vidange gastrique en l'absence d'une obstruction ­mécanique gastrique ou duodénale. Elle a un fort retentissement sur la qualité de vie des patients, peut amener à la dénutrition et augmente globalement la mortalité. Plusieurs courants de pensée convergent vers l'hypothèse d'un spectre clinicopathologique de dysfonction neuromusculaire gastrique englobant la gastroparésie et la dyspepsie fonctionnelle, notamment du sous-­type appelé « syndrome de détresse postprandiale ¼. Sa prise en charge ­comprend des interventions non pharmacologiques, telles que des mesures hygiénodiététiques, des interventions pharmacologiques à l'aide de traitements procinétiques, anti­émétiques ou encore neuromodulateurs, et des interventions ­endoscopiques.

[Acute diarrhea: updates for primary care medicine in 2023]. / Diarrhées aiguës : nouveautés 2023 pour la médecine de premier recours.

Acute diarrheal disease is a frequent primary care reason for consultation, leading to direct and indirect health costs in high-income countries. Most patients presenting with acute diarrhea will have a favorable clinical course with just a symptomatic treatment. The challenge for the general practitioner is to identify the patients who need paraclinical exams and/or antibiotics. Molecular identification of pathogens in stool samples has developed over the past years and presents both advantages and limitations. Because of increasing microbial resistance to quinolones in Campylobacter and Shigella strains, azithromycin is now the first choice for an empiric antimicrobial therapy. This article will discuss these latest developments in the management of acute diarrhea in the primary care setting.

Les diarrhées aiguës sont un motif de consultation fréquent en médecine générale et engendrent des coûts directs et indirects importants dans les pays industrialisés. Les cas sont majoritairement bénins et évoluent de manière favorable avec un traitement symptomatique. Le défi pour le médecin généraliste est d'identifier les patient-e-s nécessitant des examens complémentaires et/ou un traitement antibiotique. Ces dernières années, les examens microbiologiques moléculaires des selles se sont développés ; ils ont des avantages, mais également des limitations. Sur le plan thérapeutique, l'azithromycine est désormais à privilégier comme antibiothérapie empirique en raison de l'accroissement du nombre de souches de Campylobacter et Shigella résistantes aux quinolones. Cet article discute ces nouveautés dans la prise en charge des diarrhées aiguës du point de vue du généraliste.

[Screening for preneoplastic lesions of the upper gastrointestinal tract]. / Dépistage des lésions prénéoplasiques du tube digestif haut.

Preneoplastic lesions of the esophagus and stomach are cellular abnormalities that have the potential to develop into cancer over time. They are detected during endoscopy and can be classified according to their specific cellular characteristics. Their treatment depends on the severity of the lesion and the individual factors of each patient. Treatment options may include regular endoscopic monitoring, treatment to reduce the risk of progression to cancer (anti-reflux therapy, antibiotics for H. pylori eradication), or endoscopic removal of the lesion. It is important to discuss any concerns about these lesions with a gastroenterologist and to follow recommendations for proper screening and treatment.

Les lésions prénéoplasiques de l'œsophage et de l'estomac sont des anomalies cellulaires ayant le potentiel de se développer en cancer au fil du temps. Elles sont détectées lors d'une endoscopie et peuvent être classées en fonction de leurs caractéristiques cellulaires spécifiques. Leur traitement dépend de la gravité de la lésion et des facteurs individuels de chaque patient. Les options de traitement peuvent inclure la surveillance endoscopique régulière, la prise de traitement permettant de réduire le risque de progression vers le cancer (traitement antireflux, antibiotique pour l'éradication de H. pylori) ou l'ablation endoscopique de la lésion afin de prévenir sa progression vers un cancer. Il est important de discuter avec un gastroentérologue de toute préoccupation concernant ces lésions et de suivre les recommandations de dépistage et de traitement appropriées.

Outcome of endoscopic vacuum therapy for duodenal perforation.

BACKGROUND: Duodenal defects are complex clinical situations, and their management is challenging and associated with high mortality. Besides surgery, endoscopic treatment options exist, but the size and location of the perforation can limit their application. We present a retrospective study, demonstrating a successful application of endoscopic vacuum therapy (EVT) for duodenal leaks. METHODS: We performed a retrospective study of all patients who underwent EVT for duodenal perforations between 2016 and 2021 at two tertiary centers. We analyzed demographic and clinical patient characteristics, surgical outcomes, leak characteristics, sponge-related complications, and success rate. RESULTS: Indications for treatment with EVT in the duodenum consisted of leak after duodenal suture of a perforated ulcer (n = 4), iatrogenic perforation after endoscopic resection (n = 2), iatrogenic perforation during surgery (n = 2), and anastomotic leak after upper gastrointestinal surgery (n = 2). EVT was used as a first-line treatment in seven patients and as a second-line treatment in three patients. EVT was successfully applied in all interventions (n = 10, 100%). Overall, EVT lead to definitive closure of the defects in eight out of ten patients (80%). No severe EVT-related adverse events occurred. CONCLUSION: EVT is safe and technically feasible, so it emerges as a promising endoscopic treatment option for duodenal leaks. However, multidisciplinary collaboration and management are important to reduce the occurrence of postoperative complications, and to improve recovery rates.

Evaluation of 30-day mortality in patients undergoing gastrointestinal endoscopy in a tertiary hospital: a 3-year retrospective survey.

OBJECTIVE: Despite international guidelines recommendations to use mortality as a quality criterion for gastrointestinal (GI) procedures, recent studies reporting these data are lacking. Our objective was to report death causes and rate following GI endoscopies in a tertiary university hospital. DESIGN: We retrospectively reviewed all GI procedures made between January 2017 and December 2019 in our tertiary hospital in Switzerland. Data from patients who died within 30 days of the procedure were recorded. RESULTS: Of 18 233 procedures, 251 patients died within 30 days following 345 (1.89%) procedures (244/9180 gastroscopies, 53/5826 colonoscopies, 23/2119 endoscopic ultrasound, 19/911 endoscopic retrograde cholangiopancreatography, 6/197 percutaneous endoscopic gastrostomies). Median age was 70 years (IQR 61-79) and 173/251 (68.92%) were male. Median Charlson Comorbidity Index was 5 (IQR 3-7), and 305/345 procedures (88.4%) were undertaken on patients with an ASA score ≥3. Most frequent indications were suspected GI bleeding (162/345; 46.96%) and suspected cancer or tumourous staging (50/345; 14.49%). Major causes of death were oncological progression (72/251; 28.68%), cardiopulmonary failure or cardiac arrest of unkown origin (62/251; 24,7%) and liver failure (20/251; 7.96%). No deaths were caused by complications such as perforation or bleeding. CONCLUSIONS: Progression of malignancies unrelated to the procedure was the leading cause of short-term death following a GI procedure. After improvements in periprocedural care in the last decades, we should focus on patient selection in this era of new oncological and intensive care therapies. Death rate as a quality criterion is subject to caution as it depends on indication, setting and risk benefit ratio.

[Endoscopic submucosal dissection: advances and perspectives]. / Dissection sous-muqueuse endoscopique : avancées et perspectives.

Endoscopic submucosal dissection (ESD) is a mini-invasive technique allowing to resect superficial lesions of the digestive tract and maintaining organ function. High technical expertise is required as well as a network approach with referring physicians, pathologists, radiologists, surgeons and oncologists. Rigorous selection of cases as well as endoscopic management of potential complications (hemorrhage, perforation) is mandatory. Therefore, ESD should preferably be performed in expert centers with high volumes of cases, in order to maintain competency and offer optimal patient's management. Most frequent indications in the Western world are early cancers of the esophagus, stomach and colon as well as non-non-lifting polyps and gastrointestinal stromal tumors (GIST).

La dissection sous-muqueuse (DSM) est une technique permettant la résection des lésions superficielles du tube digestif, de façon mini-invasive, afin de conserver la fonction de l'organe atteint. L'expertise technique aboutissant à ce geste doit s'accompagner d'un travail en réseau associant médecins référents, pathologistes, radiologues, chirurgiens et oncologues. Elle nécessite une sélection rigoureuse des indications, ainsi que la maîtrise des complications éventuelles (hémorragie, perforation) et doit préférablement être réalisée en centre expert, avec un volume suffisant de cas afin de maintenir la compétence. Les indications les plus fréquentes en Occident concernent les cancers super­ficiels de l'œsophage, de l'estomac et du côlon ainsi que les polypes ne se soulevant pas lors de l'injection sous-muqueuse et les tumeurs stromales gastro-intestinales (GIST).

[Management of a cystic lesion of the pancreas discovered incidentally]. / Prise en charge d'une lésion kystique du pancréas de découverte fortuite.

Pancreatic cysts (PC) are common and often discovered incidentally. The distinction between PC is essential, because of the potential malignancy of some lesions requiring surgical resection. The clinical orientation will depend on the clinical history and the radiological characteristics. Indeed, in front of all PCs, it is essential to characterize them using cross-sectional imaging (MRI) in order to highlight the worrisome features requiring further examinations by endoscopic ultrasonography and fine needle aspiration of the cysts to guide the diagnosis. Referral to an expert center will allow to propose to each patient an adequate approach: surgical resection, surveillance according to the recommendations or therapeutic abstention.

Les lésions kystiques du pancréas (LKP) sont fréquentes et souvent découvertes de manière fortuite. La distinction entre les différentes LKP est primordiale, en raison du potentiel dégénératif de certaines lésions. L'orientation clinique dépendra des antécédents personnels, du profil clinique et des caractéristiques radiologiques. Devant tout kyste du pancréas, il est primordial de caractériser les LKP à l'aide d'une imagerie en coupe (IRM) afin de mettre en évidence les signes péjoratifs nécessitant un complément d'examen par écho-endoscopie digestive (EED) avec ponction du liquide intrakystique afin de guider le diagnostic. L'orientation vers un centre expert permettra de proposer une attitude adaptée à la lésion et au patient : résection chirurgicale, surveillance selon les recommandations ou abstention thérapeutique.

Study protocol of a phase II study to evaluate safety and efficacy of neo-adjuvant pembrolizumab and radiotherapy in localized rectal cancer.

BACKGROUND: Reshaping the tumor microenvironment by novel immunotherapies represents a key strategy to improve cancer treatment. Nevertheless, responsiveness to these treatments is often correlated with the extent of T cell infiltration at the tumor site. Remarkably, microsatellite stable rectal cancer is characterized by poor T cell infiltration and, therefore, does not respond to immune checkpoint blockade. To date, the only available curative option for these patients relies on extensive surgery. With the aim to broaden the application of promising immunotherapies, it is necessary to develop alternative approaches to promote T cell infiltration into the tumor microenvironment of these tumors. In this regard, recent evidence shows that radiotherapy has profound immunostimulatory effects, hinting at the possibility of combining it with immunotherapy. The combination of long-course chemoradiotherapy and immune checkpoint inhibition was recently shown to be safe and yielded promising results in rectal cancer, however short-course radiotherapy and immune checkpoint inhibition have never been tested in these tumors. METHODS: Our clinical trial investigates the clinical and biological impact of combining pembrolizumab with short-course radiotherapy in the neo-adjuvant treatment of localized rectal cancer. This phase II non-randomized study will recruit 25 patients who will receive short-course preoperative radiotherapy (5 Gy × 5 days) and four injections of pembrolizumab starting on the same day and on weeks 4, 7 and 10. Radical surgery will be performed three weeks after the last pembrolizumab injection. Our clinical trial includes an extensive translational research program involving the transcriptomic and proteomic analysis of tumor and blood samples throughout the course of the treatment. DISCUSSION: Our study is the first clinical trial to combine short-course radiotherapy and immune checkpoint inhibition in rectal cancer, which could potentially result in a major breakthrough in the treatment of this cancer. Additionally, the translational research program will offer insights into immunological changes within the tumor and blood and their correlation with patient outcome. Taken together, our work will help optimizing future treatment combinations and, possibly, better selecting patients. TRIAL REGISTRATION: This study was registered with www. CLINICALTRIAL: gov : NCT04109755 . Registration date: June, 2020.

Mapping of etiologies of computed tomography-proven acute colitis: a prospective cohort study.

Our objective was to describe the etiologies of acute colitis and to identify patients who require diagnostic endoscopy. Patients with symptoms of gastrointestinal infection and colonic inflammation on CT were prospectively included. Those immunosuppressed, with history of colorectal cancer or inflammatory bowel disease (IBD), were excluded. Microbiological analysis of the feces was performed using PCR assays BD-Max and FilmArray (GI panel,) and fecal cultures. Fecal calprotectin was determined. Patients with negative BD-Max underwent colonoscopy. One hundred and seventy-nine patients were included. BD-Max was positive in 93 patients (52%) and FilmArray in 108 patients (60.3%). Patients with infectious colitis (n = 103, 57.5%) were positive for Campylobacter spp. (n = 57, 55.3%), Escherichia coli spp. (n = 8, 7.8%), Clostridioides difficile (n = 23, 22.3%), Salmonella spp. (n = 9, 8.7%), viruses (n = 7, 6.8%), Shigella spp. (n = 6, 5.8%), Entamoeba histolytica (n = 2, 1.9%) and others (n = 4, 3.9%). Eighty-six patients underwent colonoscopy, which was compatible with ischemic colitis in 18 patients (10.1%) and IBD in 4 patients (2.2%). Fecal calprotectin was elevated in all patients, with a mean concentration of 1922.1 ± 2895.6 µg/g, and was the highest in patients with IBD (8511 ± 9438 µg/g, p < 0.001). After exclusion of patients with infectious etiology, a fecal calprotectin > 625 µg/g allowed identifying patients with IBD with an area under ROC curve of 85.1%. To conclude, computed tomography-proven colitis was of infectious etiology in 57.5% of patients. The main pathogens identified were Campylobacter spp. (55.3%), Clostridioides difficile (22.3%) and Salmonella spp. (8.7%). Ischemic colitis (10.1%) and IBD (2.2%) were seldom represented. No colorectal cancer was found.

[Advances in gastroenterology and hepatology 2021]. / Gastroentérologie et hépatologie.

Among the recent advances in gastroenterology, colonoscopy with artificial intelligence is associated with a better quality of screening. In refractory UC, Ozanimod seems to be an interesting salvage treatment, which still needs to be validated by Swissmedic. Among the direct-acting anticoagulants, Rivaroxaban is more frequently associated with GI bleeding. The classification of oesophageal motor disorders has been recently revised, the Chicago v4.0 classification should be applied in diagnostic management. The use of Semaglutide seems to show very promising results in the management of metabolic steatosis. SARS-CoV-2 infection can be complicated by biliary tract disease, which can progress to hepatocellular failure.

Parmi les récentes avancées en gastroentérologie, la coloscopie couplée à une intelligence artificielle est associée à un dépistage de meilleure qualité. Lors de rectocolite hémorragique réfractaire, l'ozanimod semble être un traitement de sauvetage intéressant, qui doit encore être validé par Swissmedic. Parmi les anticoagulants à action directe, le rivaroxaban est plus fréquemment associé aux hémorragies digestives. La classification des troubles moteurs de l'œsophage a fait l'objet d'une révision récente, la classification de Chicago v4.0 doit être appliquée dans la prise en charge diagnostique. L'utilisation du sémaglutide semble montrer des résultats très prometteurs dans la prise en charge de la stéatose métabolique. L'infection par le virus à SARS-CoV-2 peut se compliquer d'une atteinte des voies biliaires, pouvant évoluer jusqu'à l'insuffisance hépatocellulaire.

Recent advances in the management of autoimmune pancreatitis in the era of artificial intelligence.

Autoimmune pancreatitis (AIP) is a type of immune-mediated pancreatitis subdivided into two subtypes, type 1 and type 2 AIP. Furthermore, type 1 AIP is considered to be the pancreatic manifestation of the immunoglobulin G4 (IgG4)-related disease. Nowadays, AIP is increasingly researched and recognized, although its diagnosis represents a challenge for several reasons: False positive ultrasound-guided cytological samples for a neoplastic process, difficult to interpret levels of IgG4, the absence of biological markers to diagnose type 2 AIP, and the challenging clinical identification of atypical forms. Furthermore, 60% and 78% of type 1 and type 2 AIP, respectively, are retrospectively diagnosed on surgical specimens of resected pancreas for suspected cancer. As distinguishing AIP from pancreatic ductal adenocarcinoma can be challenging, obtaining a definitive diagnosis can therefore prove difficult, since endoscopic ultrasound fine-needle aspiration or biopsy of the pancreas are suboptimal. This paper focuses on recent innovations in the management of AIP with regard to the use of artificial intelligence, new serum markers, and new therapeutic approaches, while it also outlines the current management recommendations. A better knowledge of AIP can reduce the recourse to surgery and avoid its overuse, although such an approach requires close collaboration between gastroenterologists, surgeons and radiologists. Better knowledge on AIP and IgG4-related disease remains necessary to diagnose and manage patients.

[The video capsule endoscopy]. / Vidéocapsule endoscopique.

The video capsule endoscopy allows the exploration or the unreachable part of the small intestine by a standard bidirectional endoscopy. It requires a specific device and a bowel preparation but it's an outpatient examination with an acceptable tolerance of the patients. There are several indications including an obscure gastrointestinal bleeding, an iron deficit anemia, Crohn's disease extension and phenotype, hereditary polyposis and coeliac disease. It doesn't include therapeutic options itself requiring an assisted enteroscopy if any lesion is detected. The use of a dissolvable Patency Capsule lowers the risk of a mechanical intestinal occlusion if a stenosis is suspected. The colon capsule endoscopy is very promising for the colorectal cancer screening and follow-up of inflammatory bowel diseases but it's not currently validated nor recommended.

La vidéocapsule endoscopique permet l'examen de l'intestin grêle, inaccessible par un bilan endoscopique bidirectionnel. C'est un examen ambulatoire peu contraignant nécessitant toutefois un dispositif spécifique et certaines consignes d'utilisation. Plusieurs indications sont reconnues, comme le saignement gastro-intestinal obscur, l'anémie ferriprive, la recherche de tumeur de l'intestin grêle et les maladies de Crohn ou cœliaque. Elle ne permet pas de geste thérapeutique et peut être complétée par une entéroscopie en cas de lésion décelée. Le risque d'occlusion intestinale par rétention de la capsule est restreint par l'essai d'une Patency Capsule soluble. La capsule colique semble prometteuse dans le dépistage du cancer colorectal ou le suivi de maladie inflammatoire chronique mais l'évidence est insuffisante pour la recommander.

Recent advances in gastrointestinal cancers.

Gastrointestinal cancers occur in a total of eight different locations, each of them with a different standard of care. This article is not an exhaustive review of what has been published in 2020. We have concentrated on the thirteen phase III randomized studies that are practice-changing. All these studies are oral presentations which have been given in one of the four major oncology congresses, namely American Society of Clinical Oncology (ASCO), ASCO gastrointestinal (GI), European Society of Medical Oncology (ESMO) and ESMO-GI. We provide a concise view of these major trials and their main outcomes, and put these results into context.

Management of Acute Wilsonian Hepatitis with Severe Hemolysis: A Successful Combination of Chelation and MARS Dialysis.

Wilson's disease is a rare hereditary disorder of copper metabolism leading to progressive accumulation of copper in several organs including the brain and the liver. Acute liver failure is a relatively rare hepatic manifestation of WD which may require urgent liver transplantation if medical treatment fails. We report here the case of a young woman who presented with classic acute Wilsonian hepatitis complicated by liver and renal failure and a severe hemolysis related to massive nonceruloplasmin bound copper accumulation requiring repeated blood transfusions. The early initiation of a combined treatment including conventional chelation therapy and repeated MARS dialysis sessions allowed a rapid control of hemolysis, a progressive decrease of free copper overload, and clinical recompensation without liver transplantation.

Clinical Presentation and Gene Expression of Acute Alcohol-Induced Microvesicular Steatosis Mimicking Alcoholic Hepatitis.

Acute alcoholic microvesicular steatosis (MIC) may complicate heavy alcohol intake and present as alcoholic hepatitis (AH) syndrome. However, detailed clinical, biological, and histologic data associated with MIC are scarce. We compared the clinical presentation, histologic features, and hepatic transcriptomic of patients presenting with AH due to either MIC or severe alcoholic steatohepatitis (ASH). In this case-control study, patients who drank heavily (>100 g/day) with the AH syndrome were included either in the MIC group (>50% severe microvesicular steatosis, no inflammation) or in the severe ASH group (polynuclear neutrophil infiltration, macrosteatosis, ballooned hepatocytes). All patients received standard supportive care plus steroids for those with severe ASH and were followed up for 3 months. Whole-liver transcriptome profiling was performed on liver snap-frozen biopsies. Compared to ASH (n = 24, mean age 49.3 years), patients in the MIC group (n = 12, mean age 49.1 years) had a higher reported alcohol intake (P < 0.01), lower Model for End-Stage Liver Disease score (P < 0.05), lower hepatic venous pressure gradient (P < 0.01), higher alanine aminotransferase (P < 0.02) and gamma-glutamyltransferase (P < 0.001), higher triglycerides (P < 0.001) and total cholesterol (P < 0.002), but similar bilirubin levels (P = 0.54). At histology, patients with MIC had a lower fibrotic stage compared to those with ASH (P < 0.001). A higher density of megamitochondria was seen in MIC compared to ASH (P < 0.05). During follow-up, death or transplantation occurred in 4/12 (33%) patients with MIC and 7/24 (29%) patients with severe ASH. Differential hepatic gene expression in MIC compared to ASH included down-regulation of genes related to inflammation and fibrosis and up-regulation of genes involved in lipid metabolism and mitochondrial function. Conclusion: MIC is an acute, noninflammatory, potentially severe alcoholic liver injury mimicking ASH, is associated with a lower fibrosis stage, and has a distinct gene expression profile.

NAFLD and MAFLD as emerging causes of HCC: A populational study.

BACKGROUND & AIMS: There are conflicting data regarding the epidemiology of hepatocellular carcinoma (HCC) arising in the context of non-alcoholic and metabolic-associated fatty liver disease (NAFLD and MAFLD). We aimed to examine the changing contribution of NAFLD and MAFLD, stratified by sex, in a well-defined geographical area and highly characterised HCC population between 1990 and 2014. METHODS: We identified all patients with HCC resident in the canton of Geneva, Switzerland, diagnosed between 1990 and 2014 from the prospective Geneva Cancer Registry and assessed aetiology-specific age-standardised incidence. NAFLD-HCC was diagnosed when other causes of liver disease were excluded in cases with type 2 diabetes, metabolic syndrome, or obesity. Criteria for MAFLD included one or more of the following criteria: overweight/obesity, presence of type 2 diabetes mellitus, or evidence of metabolic dysregulation. RESULTS: A total of 76/920 (8.3%) of patients were diagnosed with NAFLD-HCC in the canton of Geneva between 1990 and 2014. Between the time periods 1990-1994 and 2010-2014, there was a significant increase in HCC incidence in women (standardised incidence ratio [SIR] 1.83, 95% CI 1.08-3.13, p = 0.026) but not in men (SIR 1.10, 95% CI 0.85-1.43, p = 0.468). In the same timeframe, the proportion of NAFLD-HCC increased more in women (0-29%, p = 0.037) than in men (2-12%, p = 0.010) while the proportion of MAFLD increased from 21% to 68% in both sexes and from 7% to 67% in women (p <0.001). From 2000-2004 to 2010-2014, the SIR of NAFLD-HCC increased to 1.92 (95% CI 0.77-5.08) for men and 12.7 (95% CI 1.63-545) in women, whereas it decreased or remained stable for other major aetiologies of HCC. CONCLUSIONS: In a populational cohort spanning 25 years, the burden of NAFLD and MAFLD associated HCCs increased significantly, driving an increase in HCC incidence, particularly in women. LAY SUMMARY: Hepatocellular carcinoma (HCC) is the most common type of liver cancer, increasingly arising in patients with liver disease caused by metabolic syndrome, termed non-alcoholic fatty liver disease (NAFLD) or metabolic-associated fatty liver disease (MAFLD). We assessed all patients with HCC between 1990 and 2014 in the canton of Geneva (western Switzerland) and found an increase in all HCC cases in this timeframe, particularly in women. In addition, we found that HCC caused by NAFLD or MAFLD significantly increased over the years, particularly in women, possibly driving the increase in overall HCC cases.