Current Opinion in Gastroenterology最新文献

Purpose of review: Celiac disease (CeD) is a chronic autoimmune disorder of the small intestine triggered by gluten ingestion in genetically predisposed individuals. The cornerstone of CeD management remains a strict adherence to a lifelong gluten-free diet (GFD), although such a dietary restriction can lead to an altered quality of life and may not be easy to follow for many patients. These challenges highlighted the need for alternative therapies. This review aims to explore the latest advancements in these therapeutic avenues, emphasizing mechanisms of action, clinical efficacy, and safety profiles of drugs currently in advanced stages of clinical testing.

Recent findings: Recent advances in the understanding of CeD pathophysiology have catalyzed the development of new therapeutic approaches, which include strategies to modify gluten processing in the gut, block gluten-triggered immune responses, or restore immune tolerance to gluten.

Summary: While these therapies are not poised to take the place of GFD, they represent promising treatment alternatives that could enhance the quality of life and minimize long-term consequences in CeD patients. Further research, as well as phase III clinical trials of those already conducted, are needed to establish the feasibility of integrating these novel drugs in the clinical management of CeD.

Purpose of review: Patient-reported outcome (PRO) measures validated in primary sclerosing cholangitis (PSC) are needed for clinical trials. This review describes the recent US Food & Drug Administration (FDA) Patient-Focused Drug Development (PFDD) guidelines, existing PRO measures used in PSC studies, and the design of PSC-specific symptom measures adherent with the guidelines.

Recent findings: FDA released updated guidance reflecting best practices for the design and evaluation of clinical outcome assessments (including PROs) and the design of trial endpoints. Two recent systematic reviews (2018, 2020) identified multiple PRO measures used in PSC studies, with two additional measures published since. Of these, four were developed in samples inclusive of PSC patients and six have been psychometrically evaluated in PSC. Published evidence to sufficiently support alignment with the recent guidance is sparse. We review the design of three symptom measures for PSC to illustrate alignment with FDA guidance, including qualitative and quantitative studies to provide evidence for their validity for use in adult PSC trials.

Summary: Investigators planning to use PRO measures as study endpoints for PSC need to be adherent with the recent FDA guidelines and build the evidence base to support the measure as fit-for-purpose as an endpoint for clinical trials.

Purpose of review: Low phospholipid-associated cholelithiasis (LPAC) syndrome is a rare genetic form of intrahepatic cholesterol lithiasis, affecting mainly young adults. This review describes the recent advances in genetic and clinical characterization, diagnosis and management of LPAC syndrome.

Recent findings: Recent publications report data from several retrospective cohorts. These cohorts describe the main clinical features, the most frequent radiological lesions, complications, the results of biliary endoscopic procedures and the prognosis associated with LPAC syndrome.

Summary: LPAC syndrome has been linked to a partial defect in the ATP binding cassette subfamily B member 4 (ABCB4) gene encoding the canalicular phospholipid transporter multidrug resistance protein 3, but this mechanism would explain only half the cases, or even fewer. This syndrome is characterized by the appearance of cholelithiasis at an abnormally early age (before 40) and by the persistence of biliary symptoms after cholecystectomy. The diagnosis is usually confirmed by an ultrasound scan of the liver, which reveals the presence of intrahepatic microlithiasis, as evidenced by comet-tail images or microspots along the intrahepatic bile ducts. Ursodeoxycholic acid, at a daily dose of 5-15 mg/kg, is the reference treatment. If not performed prior to diagnosis, cholecystectomy should be avoided wherever possible. In complicated or refractory forms, endoscopic biliary intervention may be necessary.

Purpose of review: This review explores the emerging concept of "deep response" in primary biliary cholangitis (PBC), defined by the normalization of biochemical markers, particularly alkaline phosphatase and bilirubin. It examines its potential as a new standard for disease management and its implications for long-term patient outcomes, health policies, and clinical decision-making.

Recent findings: Recent studies suggest that achieving a deep response significantly improves long-term outcomes in some patients with PBC. In particular, a significant complication-free survival gain was observed among patients who at baseline were at high risk for disease progression. However, limitations in data and the variability in patient populations pose challenges for universal adoption of this standard.

Summary: Deep biochemical response represents a promising new standard for optimizing PBC management, offering measurable goals for clinicians and potentially improved long-term outcomes for patients. However, further research is necessary to better define the appropriate biochemical thresholds, understand the risks of overprescribing, and identify patient subgroups that are most likely to benefit from this strategy. A balanced, patient-centered approach incorporating deep response into comprehensive management could improve care for high-risk PBC patients.

Purpose of review: Whether low birth weight (LBW) and preterm delivery (PD) are associated with the risk of developing celiac disease (CD) in children remains unclear. This systematic review and meta-analysis aimed to evaluate the association between LBW and PD with CD development in children.

Recent findings: We searched PubMed, Embase, Scopus, Web of Science, and Google Scholar databases based on the Mesh terms to find observational studies that investigated the association of LBW and PD with CD development in children up to July 18, 2024. This systematic review was based on the PRISMA 2020 checklist. Heterogeneity between studies was assessed with Cochran's Q and I2 tests. Meta-regression was used to control heterogeneity. Publication bias was evaluated using Egger's test. Finally, ten studies involving 3 434 290 participants were included. Based on 10 studies, the pooled prevalence of LBW was 6.4 per 1000 children with CD. A pooled estimate of ten studies did not show a significant relationship between LBW and the risk of developing CD in children [odds ratio (OR): 0.96, 95% confidence interval (CI): 0.76, 1.16, I2: 67.9%, P: 0.001). Also, the pooled estimate of six studies did not show a significant relationship between PD and the risk of developing CD in children (OR: 0.98, 95% CI: 0.81, 1.16, I2: 67.5%, P: 0.001).

Summary: We found no evidence of an association between LBW and PD with the risk of developing CD in children.

Purpose of review: Metabolic dysfunction-associated steatotic liver disease (MASLD) is present in 25-35% of individuals in the United States. The purpose of this review is to provide the contextual framework for hepatic ketogenesis in MASLD and to spotlight recent advances that have improved our understanding of the mechanisms that drive its development and progression.

Recent findings: Traditionally, hepatic ketogenesis has only been considered metabolically during prolonged fasting/starvation or with carbohydrate deplete ketogenic diets where ketones provide important alternative energy sources. Over the past 2 years, it has become increasingly clear from preclinical rodent and human clinical studies that hepatic ketogenic insufficiency is a key contributor to the initiation and progression of MASLD.

Summary: A more thorough understanding of the metabolic dysregulation that occurs between the liver and extrahepatic tissues has significant potential in the development of innovative nutritional and pharmacological approaches to the treatment of MASLD.

Purpose of review: This review aims to highlight the transformative impact of artificial intelligence in the field of gastrointestinal endoscopy, particularly in the detection and characterization of colorectal polyps.

Recent findings: Over the past decade, artificial intelligence has significantly advanced the medical industry, including gastrointestinal endoscopy. Computer aided diagnosis - detection (CADe) systems have shown notable success in increasing ADR. Recent meta-analyses of RCTs have demonstrated that patients undergoing colonoscopy with CADe assistance had a higher ADR compared with conventional methods. Similarly, computer aided diagnosis - characterization (CADx) systems have proven effective in distinguishing between adenomatous and nonadenomatous polyps, enhancing diagnostic confidence and supporting cost-saving measures like the resect-and-discard strategy. Despite the high performance of these systems, the variability in real-world adoption highlights the importance of integrating artificial intelligence as an assistive tool rather than a replacement for human expertise.

Summary: Artificial intelligence integration in colonoscopy, through CADe and CADx systems, marks a significant advancement in gastroenterology. These systems enhance lesion detection and characterization, leading to improved diagnostic accuracy, training outcomes, and clinical workflow efficiency. While artificial intelligence offers substantial benefits, the optimal approach involves using artificial intelligence to augment the expertise of endoscopists, ensuring that clinical decisions remain under human oversight.

Purpose of review: Multiple endoscopic ultrasound (EUS) guided therapeutic interventions have been developed for the management of benign and malignant pancreaticobiliary and gastrointestinal luminal pathology. Recent high-quality evidence is increasingly validating these interventions and positioning them within evidence-based therapeutic algorithms.

Recent findings: Here we review therapeutic EUS-guided interventions including pancreatic fluid collection drainage, gastroenterostomy, biliary drainage, pancreatic duct drainage and gallbladder drainage. The most up-to-date high-quality evidence supporting these interventions is presented including comparative data with other conventional treatment options. Newer emerging interventions such as tumor ablation are also reviewed. Current controversies and future avenues for research are discussed. The key role of EUS-guided interventions in managing pancreaticobiliary pathology in patients with a surgically altered anatomy is highlighted.

Summary: Multiple EUS therapeutic interventions have evolved from experimental or rescue options to now well established first- and second-line interventions over other endoscopic, percutaneous and surgical alternatives with the support of high-quality data. Further research is needed to better optimize patient selection and guide long term postintervention follow-up.