The sucrase-isomaltase (SI) gene encodes sucrase-isomaltase enzyme found on the intestinal brush-border that has a major function in the hydrolysis of sucrose, oligosaccharides, and starch. Mutations disrupting its function cause genetic sucrase-isomaltase deficiency (GSID). Variants leading to mild to moderate reductions in enzyme activity may mimic disorders of gut-brain interaction (DGBI), and differentiating the etiology is crucial for initiating appropriate treatment. In this study, we aim to determine the rate of GSID in individuals who underwent whole exome or clinical exome sequencing (WES/CES) for indications other than chronic gastrointestinal symptoms in a single-center cohort. We also focused on a second group, the pediatric DGBI patients, who underwent SI gene analysis, to evaluate the rate of GSID in pediatric DGBI patients and assess the clinical utility of SI gene testing in GSID diagnosis. We retrospectively reviewed 980 patients who underwent WES/CES between 2017-2022, and 148 pediatric patients with DGBI evaluated between May 2021 and August 2022 who received SI gene analysis. The frequency of symptomatic GSID was found to be 0.3% among patients who underwent WES/CES, whereas it was 10% among pediatric DGBI patients. In DGBI patients carrying SI gene mutations, clinical improvement with a sucrose- and starch-free diet in combination with a sacrosidase response proved effective for establishing a diagnosis in all cases. GSID has been frequently detected among pediatric DGBI patients. SI gene analysis combined with a sucrose-restricted diet and a sacrosidase challenge provides a reliable, non-invasive approach for definitive diagnosis.

Background Perihilar cholangiocarcinoma (pCCA) is a rare malignancy originating from the bile duct bifurcation which is often diagnosed in an advanced stage. At presentation, most patients present with jaundice requiring biliary drainage. Palliative chemotherapy (pCTx) has a positive impact on survival and quality of life. The primary aim of this study was to investigate the impact of biliary drainage on pCTx initiation in patients with non-resected pCCA. Methods Individual patient data from all Dutch patients diagnosed with non-resected pCCA between 2015 and 2020 were retrieved from the Netherlands Cancer Registry. Primary outcome were factors associated with initiation of pCTx, analysed by multivariable competing risk regression analysis. Results A total of 1265 patients were included, of whom 242 patients (19.1%) received pCTx after a median interval of 72 days [IQR 43–110 days] after initial presentation. Patients who underwent biliary drainage did not receive pCTx more often. If performed, drainage at a referral hospital (HR:0.65, 95%CI: 0.42–0.99), ≥3 drainage procedures performed (HR:0.53, 95%CI: 0.32–0.88), and drainage performed ≥14 days after presentation (HR:0.70, 95%CI: 0.49–0.99) were associated with no pCTx. Median overall survival for those who received pCTx and those who did not was 12.8 months [95%CI: 11.7–14.2] and 2.7 months [95%CI: 2.4–3.1]. Conclusion The need for biliary drainage did not affect the initiation of pCTx. When indicated, biliary drainage should be performed as quick as possible in an academic center to improve the rate of patients receiving pCTx.

Background Iron deficiency is common in patients with inflammatory bowel disease (IBD) and may lead to a variety of distressing symptoms negatively impacting quality of life. Aims This prospective observational cohort study aimed to assess quality of life, measured using the Short Form-36 (SF-36) questionnaire before and after treatment with high-dose intravenous iron in patients with IBD and iron deficiency. Materials and methods Over a 15-month period, 130 patients with a well-established diagnosis of IBD (either ulcerative colitis (UC) or Crohns disease (CD)) and confirmed iron deficiency were consecutively assessed for study eligibility at two university hospitals in South-Eastern Norway. Of these, 112 patients were included in the per protocol set. Demographic characteristics were recorded at study inclusion. Clinical, and biochemical variables, as well as SF-36 questionnaires were collected just before and 5–7 weeks after treatment with intravenous iron. Results An improvement was observed in six of the eight SF-36 domains six weeks after treatment with intravenous iron. Females had lower scores compared to males at both visits, but there were no differences between UC and CD patients. Both sexes and the two diagnoses had a significant increase in vitality scores. Haemoglobin level was a significant predictor for improvement of quality of life. Conclusions Treatment with high dose intravenous iron improves quality of life in IBD patients and iron deficiency and particularly in those with anaemia. The most significant improvements were observed in vitality and energy levels, suggesting a clinically meaningful change.

Background and aims Long-term outcomes for Crohn’s disease (CD) patients treated with infliximab (IFX) remain suboptimal. We developed and validated a clinical decision support tool (CDST) to predict sustained remission in CD patients treated with infliximab (IFX). Methods This multicenter observational study analyzed 746 CD patients across three cohorts. Sustained clinical remission (CREM) was defined as steroid-free Crohn’s Disease Activity Index (CDAI) <150 at week 104. Using logistic regression, predictors were weighted by inverse variance. The CDST was internally validated (Cohort I, n = 113) and externally validated (Cohort II, n = 367). Results Key predictors of CREM included: prior biologic exposure (−18 points), penetrating disease (B3 phenotype, −7 points), albumin (+0.5/gL), younger age (−0.3/year), and absence of antibody to infliximab formation (ATI, +17 points). The model demonstrated strong discrimination (AUC 0.791 [95% CI 0.708–0.875]) and calibration (Brier score: 0.191). External validation AUC was 0.611 (95% CI 0.546–0.675), indicating modest generalizability. Risk stratification via CDST categorized patients into low- (<6 points), intermediate- (6–25), and high-risk (>25) groups. A cutoff of 25 points predicted 2-year CREM with 60% (95%CI 53.2%–66.5%) sensitivity and 52% (95% CI 41.2%–1.8%) specificity. Conclusions We developed and validated a CDST to identify CD patients likely to achieve sustained remission on IFX therapy. By stratifying patients into distinct risk profiles, it guides personalized therapy initiation and monitoring.

Background Severe alcohol-associated hepatitis (AH) remains a major challenge in clinical practice due to its limited treatment options and high short-term mortality. Although corticosteroids have long been the mainstay of treatment, their use has been declining because of concerns about side effects and contraindications. Aim We aimed to summarize the current standards for corticosteroid use in severe AH, with a specific focus on differentiating absolute from relative contraindications. Methods This narrative review integrates evidence from randomized clinical trials, observational cohort studies, and contemporary guideline statements pertaining to corticosteroid therapy in severe alcohol‑associated hepatitis. Results The majority of individuals with severe AH present with concomitant complications such as infection, acute kidney injury, or gastrointestinal bleeding. Emerging data indicates that, with the developments in diagnostic methods, treatment strategies, and supportive care, that were previously considered absolute contraindications are now being recognized as relative. Corticosteroid treatment can be administered safely once certain concomitant conditions have been stabilized or resolved. On the other hand, such severe presentations, as identified by markedly elevated Maddrey’s discriminant function, MELD score, or acute-on-chronic liver failure (ACLF) grade, determine a poor response to corticosteroid treatment and high risk of complications Conclusions In the setting of severe AH, while certain conditions require a temporary corticosteroid treatment delay, others necessitate alternative approaches. Individuals with a low likelihood of responding, early liver transplantation, extracorporeal therapy, microbiota-based therapeutics, or palliative care should be considered in the earlier settings.

Aims To investigate predictive factors in patients with non-curable malignant hilar biliary obstruction (mHBO) and identify those with a life expectancy of 30 days or less, who would not benefit from palliative biliary drainage. Materials and methods A retrospective analysis of consecutive palliative patients undergoing percutaneous or endoscopic biliary drainage for mHBO at Groote Schuur and Tygerberg Hospitals, Cape Town, between 1 January 2015 and 1 January 2023. Demographic and baseline clinical parameters, laboratory test results, tumour characteristics and intervention type were compared in patients who survived ≤ 30 days to those who survived > 30 days after index intervention. Results A total of 294 patients were included in the study, of whom 135 survived ≤ 30 days and 159 > 30 days. Regression analysis using a Cox proportional hazard model showed that Eastern Cooperative Oncology Group performance status ≥ 2, strictures secondary to hepatocellular carcinoma, serum levels of albumin < 30 g/L and serum levels of total and conjugated bilirubin > 250 μmol/L predicted survival of ≤ 30 days. Conclusions These predictive factors should be considered by the multidisciplinary team regarding the decision to perform biliary drainage during end-of-life care or rather proceed to solely medical and symptomatic relief in patients with non-curable mHBO.

Background To evaluate the efficacy and safety of potassium-competitive acid blockers (P-CABs) versus proton pump inhibitors (PPIs) in the treatment of gastroesophageal reflux disease (GERD) through a meta-analysis, explores the preliminary pharmacoeconomic advantages. Methods Randomized controlled trials (RCTs) comparing P-CABs and PPIs for GERD treatment were identified from database, up to July 2025. After processing the studies and extracting the data. RevMan and Stata was used for data analysis. A preliminary pharmacoeconomic analysis was performed based on market survey data. Results A total of 10 RCTs (5133 participants) were included. P-CABs demonstrated better overall efficacy than PPIs [risk ratio (RR) = 0.72, P = 0.02]. Sensitivity analysis indicated higher applicability in Asian populations (RR = 0.69, P = 0.01). Subgroup analysis showed P-CABs had a significant advantage over lansoprazole (P < 0.001, RR = 0.50), but not over esomeprazole (P = 0.93). P-CABs were superior in the low-dose group, 2-week and 8-week treatment courses group. In the high-dose P-CABs group, 4-week treatment courses group, heartburn relief group and adverse event rates were comparable to PPIs. Pharmacoeconomic analysis revealed that CERP-CABs ≈ 0.1 CNY/day (d)/1%cure rate (1%CR); CERPPIs ≈ 0.01 CNY/d/1%CR; ICER = 3.125 CNY/d/1%CR. Conclusions P-CABs demonstrate relatively greater efficacy than PPIs, especially in Asian populations. However, in terms of symptom relief, mid-term efficacy and safety both classes show comparable effects. PPIs are more cost-effective in specific contexts. Due to the limited follow-up duration in the included studies, the conclusions are applicable only to short-term symptom control.

Objectives The real-world clinical course of hepatocellular carcinoma (HCC) remains poorly understood. We aimed to describe the prognosis of Danish patients with HCC treated with curative-intent resection or ablation strategies. Methods This was a population-based, historical cohort study of all patients with HCC within two Danish regions (population 2 million). Information was extracted from patients’ medical records. Patients diagnosed with HCC in 2013–2023 and treated first-line with resection/ablation with curative intent were included. We used multistate models, competing risk analyses, and cause-specific Cox models to describe the clinical course and examine risk factors for recurrence. Results The cohort comprised 296 patients [79% male; median age 69 years (IQR 62–76); 60% (n = 179) with cirrhosis (alcohol-related, n = 76; viral hepatitis-related, n = 57)] treated first-line with resection (40%; n = 117) or ablation (60%; n = 179). The risk of early recurrence (within 2 years) was 55% (95% CI 50–61) and similar for resection- and ablation-treated patients. Five years post resection/ablation, 10% of patients remained alive and recurrence-free. Alpha-fetoprotein was a strong predictor of recurrence, and a high Child-Pugh score and high comorbidity burden were predictors of death without recurrence. The 10-year probability of receiving systemic treatment was 24%. For the total cohort, the median survival time was 3.5 years (IQR 1.5–5.9) and the median recurrence-free survival time was 1.1 years (IQR 0.5–2.4). Conclusion This population-based real-world study demonstrated that current curative-intent treatment strategies for early HCC are insufficient for long-term disease control, and that we need more effective management and follow-up of patients with HCC.