BACKGROUND & AIMS:Microscopic colitis (MC) is a leading cause of chronic diarrhea, particularly in older adults. Although many patients respond to budesonide, refractory and dependent cases pose major therapeutic challenges. Although the off-label use of advanced inflammatory bowel disease therapies is expanding, robust real-world data remain scarce. METHODS:Through the ECCO CONFER network, we conducted a multinational, retrospective study in patients with MC treated with biologics or small molecules following budesonide failure or intolerance. We systematically analyzed clinical outcomes, treatment durability, and predictors of therapeutic success. RESULTS:Among 229 treatment cycles in 142 patients, anti-tumor necrosis factor (TNF) agents were most frequently initiated (55.9%), followed by vedolizumab (28.8%) and Janus kinase (JAK) inhibitors (9.2%). Short-term clinical response and remission rates were highest with JAK inhibitors (95.2% and 81.0%, respectively), significantly outperforming anti-TNFs, vedolizumab, and ustekinumab (P < .01). Long-term drug persistence mirrored these findings: JAK inhibitors demonstrated a markedly lower discontinuation rate (23.8%) compared with other agents (56.3%; odds ratio, 5.07; 95% confidence interval, 1.52-16.9; P = .008). Multivariate analysis confirmed drug class as the only independent predictor of therapy continuation. Despite advanced therapies, 4.2% of patients ultimately required surgical intervention. CONCLUSIONS:This real-world study demonstrates the promising short- and long-term effectiveness of advanced therapies-particularly JAK inhibitors-in budesonide-refractory and budesonide-dependent MC. These findings pave the way for dedicated prospective trials and highlight evolving therapeutic strategies in MC.

Prognostic factors for the long-term evolution of chronic hepatitis B e antigen (HBeAg)-negative hepatitis B virus (HBV) infection may vary depending on local epidemiology. We aimed to identify these factors in France, where the epidemiology is influenced by diverse immigration. Hepatitis B surface antigen (HBsAg)-positive, HBeAg-negative adults with normal transaminase levels and viral loads < 20,000 IU/mL for 1 year, without viral co-infection or advanced liver disease, were enrolled for a 5-year follow-up. A total of 564 patients were recruited from 23 centres (54.4% women, mean age 42.3 ± 12 years, 47.7% from sub-Saharan Africa). HBV DNA was detectable but < 2000 IU/mL for most (71.3%). Genotypes E (27.8%) and A (20.0%) were predominant. The mean HBsAg titre was 3.8 ± 3.4 log IU/mL, > 1000 IU/mL in 60% of cases, and higher in genotype E (p < 0.0001). During follow-up, 18 patients received antiviral treatment, 9 for viral reactivation (0.3% per year) and 9 preemptively. HBsAg loss occurred in 39 patients (1.4% per year). These patients were older (p < 0.0001), more frequently treated for dyslipidemia, hypertension or diabetes (p < 0.05), and had lower baseline HBV DNA (p = 0.0112) and HBsAg (p < 0.0001), but similar levels of HBcrAg compared to those who did not clear HBsAg. Baseline HBsAg was the only independent predictor of HBsAg loss (p = 0.009). In this cohort, HBsAg < 153 IU/mL predicted clearance with 87% sensitivity and specificity. In conclusion, baseline HBsAg accurately predicted seroclearance at 5 years in patients with chronic HBeAg-negative infection, regardless of genotype, sex, or geographical origin, indicating that this marker is widely applicable for reducing the frequency of patient monitoring.

We report the first case of collagenous colitis attributed to perindopril use, in a 90-year-old woman. The patient developed diarrhea with hypokalemia, 3 weeks after perindopril was introduced in her medications for uncontrolled hypertension. Significant thickening of the basal epithelial membrane (up to 80μm) was found on random colon biopsies. Diarrhea resolved within 3 days after perindopril withdrawal. Four months later, left colon biopsies revealed a normalization of the basal membrane thickness. The intrinsic imputability of perindopril as the causative agent of microscopic colitis is considered to be reasonable by the French accountability technique. There was no rechallenge test conducted.

Abstract Background Microscopic colitis (MC) is a chronic inflammatory condition of the colon, resulting in an impaired quality of life due to debilitating watery diarrhea. First-line therapy consists of budesonide, though a subset of patients is refractory or becomes budesonide- dependent. Evidence for the efficacy of biologicals or small molecules in MC is sparse and limited to small case series. Hence, we aimed to generate more real-life efficacy data. Methods This retrospective series was collected as part of the CONFER project by ECCO and supported by the European Microscopic Colitis Group (EMCG). Cases of MC patients treated with advanced therapies were included through a standardised collection form. Clinical response was defined as a 50% reduction in stool frequency (SF); clinical remission was defined according to the Hjortswang criteria as < 3 stools/day or < 1 watery stool/day. Results Ninety-nine patients were identified (Table 1), of whom all but one were previously treated with budesonide. Reasons for budesonide discontinuation included primary non-response (PNR, 16.3%), refractory disease (34.7%), budesonide dependency (38.8%), or adverse events (AE, 10.2%). In total, 165 treatment cycles with advanced therapy (47 IFX, 40 ADA, 47 VDZ, 10 UST, 14 JAK inhibitors, 7 other) were reported. First-line advanced therapies included mainly anti-TNF (76.8%) and VDZ (20.2%) (Figure 1A). Patients were exposed to anti-TNF therapy for a median of 1.4 [0.5-3.1] years, with a significant drop in SF after induction (p<0.001), resulting in 50.0% clinical remission (Figure 1B). However, 63.0% ultimately discontinued anti-TNF therapy, mainly due to PNR (37.9%), loss-of-response (LOR, 36.2%) or AE (20.7%). VDZ induced 46.8% clinical remission, reflected in a significant drop in SF (p<0.001). Though, a 59.6% discontinuation rate was observed after a median 0.6 [0.3-1.3] years, mainly due to PNR (63.0%) and LOR (22.2%). Similarly, for UST a 40.0% clinical remission rate was accompanied by 60.0% therapy withdrawal, primarily due to PNR (83.3%). In contrast, JAK inhibition resulted in 78.6% clinical remission, with a substantial drop in SF (p=0.002) and 21.4% discontinuation rate after a median exposure of 0.6 [0.3-1.6] years. Conclusion Almost all advanced therapies are used in budesonide refractory or dependent MC, with anti-TNF agents the most often used first-line options. However, anti-TNF discontinuation is frequent due to lack/loss of efficacy. VDZ and UST could be alternatives, but also have a substantial discontinuation rate. In this retrospective series, the small number (n=14) of JAK inhibitor treated patients had the highest remission rate, suggesting further research on the role of JAK inhibitors in MC.

Background Data on the management of Hepatitis B-Delta (HB-D) by hepatogastroenterologists (HGs) practicing in nonacademic hospitals or private practices are unknown in France. Objective We aimed to evaluate the knowledge and practices of HGs practicing in nonacademic settings regarding HB-D. Methods A Google form document was sent to those HGs from May to September 2021. Results A total of 130 HGs (mean age, 45 years) have participated in this survey. Among HBsAg-positive patients, Delta infection was sought in only 89% of cases. Liver fibrosis was assessed using FibroScan in 77% of the cases and by liver biopsy in 81% of the cases. A treatment was proposed for patients with >F2 liver fibrosis in 49% of the cases regardless of transaminase levels and for all the patients by 39% of HGs. Responding HGs proposed a treatment using pegylated interferon in 50% of cases, bulevirtide in 45% of cases and a combination of pegylated interferon and bulevirtide in 40.5% of cases. Among the criteria to evaluate the treatment efficacy, a decrease or a normalization of transaminases was retained by 89% of responding HGs, a reduction of liver fibrosis score for 70% of them, an undetectable delta RNA and HBsAg for 55% of them and a 2 log 10 decline in delta viremia for 62% of the cases. Conclusion Hepatitis Delta screening was not systematically performed in HBsAg-positive patients despite the probable awareness and knowledge of the few responders who were able to prescribe treatments of hepatitis delta.

Appropriate prescription of Proton pump inhibitors (PPIs) remains an important concern amid the rising overuse. A gap exists in the literature regarding the benefit of PPI prophylaxis and the consequences of underprescription in patients at risk for upper gastrointestinal bleeding (UGIB). This study aims to describe the characteristics of hemorrhage in relation to PPI use in patients experiencing UGIB, with a focus on high-risk individuals requiring gastroprotection. Data from a French multicentric cohort of patients experiencing UGIB were analyzed. Patients using PPI were compared to those without PPI considering bleeding etiologies and outcomes of peptic ulcer disease (PUD)-related hemorrhage. The rate of PPI use and its effect on bleeding characteristics in high-risk populations, defined based on international guidelines, were also assessed. Among 2497 included patients, 31.1

Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract where early diagnosis and timely, appropriate management are essential to prevent severe complications and reduce the need for surgery. This review sought to investigate factors contributing to diagnostic delays in CD, which typically ranged from 5 to 16 months. Delays were often due to nonspecific symptoms that could be mistaken for irritable bowel syndrome (IBS) and were influenced by various factors including age, education level, smoking, NSAID use, and disease characteristics like isolated ileal involvement. Healthcare system disparities also played a significant role, with delays varying by access to care. The review highlighted that delayed diagnosis was linked to worse disease outcomes, such as increased severity and complications, and underscored the importance of early intervention combined with timely management. Strategies to mitigate delays included implementing red flag tools, using inflammatory biomarkers like fecal calprotectin, and enhancing public and healthcare provider awareness. Addressing these factors and improving referral pathways and healthcare system efficiencies were crucial for enhancing early diagnosis and patient outcomes.

BACKGROUND:The impact of inflammatory bowel disease (IBD) on caregivers has rarely been investigated. Our work aims to explore the burden of IBD on the different aspects of caregivers' lives. METHODS:We conducted an online survey via the social network of the French IBD patient organization addressed to patients' caregivers who were asked to fill in a questionnaire covering the impact of the disease on different aspects of their lives. Impacts were measured by a visual analog scale (VAS). A VAS score ≥5 of 10 was considered significantly high. We then performed uni- and multivariate analyses of predictors of higher impact on parents and partners, separately. RESULTS:A total of 853 caregivers participated, predominantly women (77%). The mean age was 48.5 years. Their relationship with the patient was mainly parents in 57.1% and partners in 30.6%. The type of IBD was Crohn's disease in 63% and ulcerative colitis in 35%. The psychological burden was the highest among parents and was mainly correlated with a lack of knowledge about IBD and professional compromise (P < .05). The impact on leisure was the highest among partners and was affected by psychological, sexual, and professional burdens (P < .05). About 50% of partners experienced an absent sexual relationship for weeks/months and decreased libido regardless of IBD type. Professional impact was greater in parents compared with partners, and 36% of caregivers needed work arrangements. CONCLUSIONS:IBD has a high impact on different aspects of life of patients' caregivers. Therefore, interventions to reduce the disease burden in this population are needed.

BACKGROUND:Medical treatment of inflammatory bowel disease (IBD) has evolved significantly, and treatment with immunomodulators is recommended. These medications may alter the patient's immune response and increase the risk of opportunistic infections. Our aim was to evaluate the prevalence and the incidence of acute or chronic HEV infection in IBD patients under immunomodulatory treatment.PATIENTS AND METHODS:We conducted a retrospective, multicenter, observational study between 2017 and 2018. IBD outpatients hospitalized for the infusion of immunomodulators were included in 16 French centers. During their daily hospitalization, blood samples were drawn for HEV serology (IgM and IgG) and HEV RNA detection.RESULTS:A total of 488 patients were included, of which 327 (67%) patients had Crohn's disease and 161 (33%) ulcerative colitis. HEV IgM was detected in 3 patients, but HEV RNA was undetectable in all patients. The HEV IgG seroprevalence rate was 14.2%. IgG-positive patients were older at sampling (p = 0.01) and IBD diagnosis (p = 0.03), had higher seafood consumption (p = 0.01) and higher doses of azathioprine (p = 0.03). Ileal and upper digestive tract involvement was more frequent in IgG-positive patients (p = 0.009), and ileocolic involvement was more frequent in IgG-negative patients (p = 0.01). Under multivariate analysis, age > 50 years [OR: 2.21 (1.26, to 3.85), p = 0.004] was associated with previous HEV infection.CONCLUSION:Systematic screening for HEV infection is not needed among IBD patients on immunomodulatory medications. However, in the event of abnormal liver test findings, HEV should be part of the classic diagnostic assessment.

INTRODUCTION:Microscopic colitis is a chronic inflammatory bowel disease characterised by normal or almost normal endoscopic appearance of the colon, chronic watery, nonbloody diarrhoea and distinct histological abnormalities, which identify three histological subtypes, the collagenous colitis, the lymphocytic colitis and the incomplete microscopic colitis. With ongoing uncertainties and new developments in the clinical management of microscopic colitis, there is a need for evidence-based guidelines to improve the medical care of patients suffering from this disorder.METHODS:Guidelines were developed by members from the European Microscopic Colitis Group and United European Gastroenterology in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists, pathologists and basic scientists, and voted upon using the Delphi method.RESULTS:These guidelines provide information on epidemiology and risk factors of microscopic colitis, as well as evidence-based statements and recommendations on diagnostic criteria and treatment options, including oral budesonide, bile acid binders, immunomodulators and biologics. Recommendations on the clinical management of microscopic colitis are provided based on evidence, expert opinion and best clinical practice.CONCLUSION:These guidelines may support clinicians worldwide to improve the clinical management of patients with microscopic colitis.

BACKGROUND AND AIMS:The disease course of microscopic colitis [MC] is considered chronic but benign. However, this assumption is based on mainly retrospective studies, reporting on incomplete follow-up of selective cohorts. Systematic, prospective and unbiased data to inform patients and healthcare professionals on the expected course of the disease and real-life response to therapy are warranted.METHODS:A prospective, pan-European, multi-centre, web-based registry was established. Incident cases of MC were included. Data on patient characteristics, symptoms, treatment and quality of life were systematically registered at baseline and during real-time follow-up. Four disease course phenotypes were discriminated and described.RESULTS:Among 381 cases with complete 1-year follow-up, 49% had a chronic active or relapsing disease course, 40% achieved sustained remission after treatment and 11% had a quiescent course. In general, symptoms and quality of life improved after 3 months of follow-up. A relapsing or chronic active disease course was associated with significantly more symptoms and impaired quality of life after 1 year.CONCLUSIONS:A minority of MC patients follow a quiescent disease course with spontaneous clinical improvement, whereas the majority suffer a chronic active or relapsing disease course during the first year after diagnosis, with persisting symptoms accompanied by a significantly impaired quality of life.

The MDMA (3,4-methylenedioxy-methamphetamine) is a synthetic psychotropic molecule of the amphetamine class. It is a stimulant of the central nervous system which possesses particular psychotropic characteristics, of a powerful serotoninergic which provides it in high doses or in case of regular use a neurotoxic power [1]. The MDMA is a consumable drug in the form of crystals or pills, more commonly known under the name of ecstasy.

Background and aims > According to clinical trials, the treatment of patients with chronic hepatitis C (CHC) with second-generation direct acting antiviral agents (DAAs) is highly efficient and well tolerated. The goal of this study was to investigate the effectiveness and safety of various combinations of these drugs during their first 2 years of use in the real-world practice of French general hospitals. Methods > Data from patients treated with all-oral DAAs in 24 French non-academic hospital centers from March 1, 2014 to January 1, 2016, were prospectively recorded. The sustained virological response 12-24 weeks after treatment (SVR 12-24) was estimated and severe adverse events (SAE) were evaluated and their predictive factors were determined using logistic regression. Results > Data from 1123 patients were analyzed. The population was 69% genotype (G) 1, 13% G3, 11.5% G4, 5% G2, 49% with cirrhosis and 55% treatment-experienced. The treatment regimens were sofosbuvir/ledipasvir (38%), sofosbuvir/daclatasvir (32%), sofosbuvir/simeprevir (17%), ombitasvir + paritaprevir + ritonavir (5%) (with dasabuvir 3.5%), and sofosbuvir/ribavirin (8%). Ribavirin was given to 24% of patients. The SVR 12-24 was 91.0% (95% CI: 89.2-92.5%). Sofosbuvir-ribavirin was less effective than other regimens. The independent predictors of SVR 12-24 by logistic regression were body weight, albumin, previous hepatocellular carcinoma and treatment regimen (sofosbuvir/ribavirin vs. others). Sixty-four severe adverse events (SAE) were observed in 59 [5.6%] patients, and were independently predicted by cirrhosis and baseline hemoglobin. Serum creatinine increased during treatment (mean 8.5%, [P < 10(-5)]), satisfying criteria for acute kidney injury in 62 patients (7.3%). Patient-reported overall tolerance was excellent, and patient-reported fatigue decreased during and after treatment. Conclusions > Second generation DAAs combinations are as effective and well tolerated in a "real-world" population as in clinical trials. Further studies are needed on renal tolerance.