Current Opinion in Gastroenterology最新文献

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: 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, I 2 : 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: 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: 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: 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 highlights the management, maternal and fetal outcomes, and the critical role of prepregnancy counseling for women with portal hypertension (PHT), a topic of growing clinical relevance as pregnancies in women with PHT have increased over the last two decades.

Recent findings: Pregnancy exacerbates PHT due to physiological changes that increase blood flow and vascular resistance, raising the risk of life-threatening complications like variceal bleeding. The distinction between noncirrhotic (NCPH) and cirrhotic portal hypertension (CPH) is essential, as maternal risks vary significantly.

Summary: Optimal care for women with PHT requires preconception counseling to assess risks, adjust medications, and plan necessary investigations such as variceal and splenic artery aneurysm screening and, if necessary, plan additional interventions. A multidisciplinary team - including hepatologists, obstetricians, anesthetists, and radiologists - is crucial for personalized management, addressing both the mode of delivery and peripartum care. While PHT complicates pregnancy, favorable outcomes are achievable with proactive planning and close follow-up during pregnancy.

Purpose of review: Crohn's disease (CD), requires accurate diagnosis and regular monitoring to manage disease activity, prevent complications, and improve outcomes. Intestinal ultrasound (IUS) has emerged as a noninvasive, real-time imaging modality, offering a valuable alternative to traditional diagnostic techniques such as magnetic resonance enterography (MRE), endoscopy and capsule endoscopy (CE). This review examines recent advances in IUS for the diagnosis and monitoring of small bowel CD, with a focus on its applications, benefits, and limitations.

Recent findings: Recent studies have demonstrated that IUS provides high sensitivity and specificity in detecting key markers of disease activity, including bowel wall thickness (BWT), bowel wall flow (BWF), and bowel wall stratification (BWS). Advances in IUS techniques, such as elastography and contrast-enhanced ultrasound (CEUS), have expanded its diagnostic and prognostic capabilities, potentially enabling differentiation between inflammation and fibrosis. However, challenges remain, including operator dependency, variability in scoring systems, and reduced sensitivity for superficial mucosal abnormalities. Efforts to standardize parameters and improve training have shown promise in addressing these limitations.

Summary: IUS is a critical complementary tool for assessing disease activity, transmural healing, and postoperative recurrence in small bowel CD. Its noninvasiveness, cost-effectiveness, and real time assessment make it well suited for routine clinical use. Nonetheless, further multicentre studies are needed to validate scoring systems, optimize integration with other modalities, and improve consistency across clinical settings. IUS holds significant potential for advancing personalized care in small bowel CD, though ongoing research is required to refine its applications and maximize its clinical utility.

Purpose of review: The role of gluten and wheat in irritable bowel syndrome (IBS) is unclear, whereas it plays a key-role in the diagnosis and treatment of noncoeliac gluten or wheat sensitivity (NCGWS). This review aims to provide the most recent insights in pathophysiological mechanisms and to summarize the evidence for a gluten- or wheat-free diet in IBS and NCGWS.

Recent findings: The exact role of gluten and wheat in IBS and NCGWS pathophysiological mechanisms remains complex. However, recent findings suggest a role for antigliadin antibodies to identify those IBS patients who may benefit from a gluten-free diet and low levels of fecal calprotectin to differentiate IBS and NCGWS. The importance of gut-brain interactions in self-reported gluten sensitive individuals was shown by a strong nocebo effect, although a role of gluten could not be excluded. Evidence for a gluten-free diet remains debatable in both conditions, whereas a wheat-free diet may have more potential, especially in NCGWS.

Summary: IBS and NCGWS are two closely related conditions with a complex and largely unrevealed pathophysiology. The role of gluten may have been overestimated in the past, but it is likely that certain wheat components, along with gut-brain interactions, play a role in both conditions.

Purpose of review: Portal vein thromboses (PVT) is a common clotting disorder that can be seen in patients with and without cirrhosis. There are no current clinical guidelines on management of portal vein thromboses in these two distinct populations given most studies are retrospective and comprised of heterogenous cohorts.

Recent findings: When evaluating PVT, patients must first be stratified into those with cirrhosis and those without cirrhosis. In addition, a novel nomenclature can help categorize specific PVT types and determine the need and response to anticoagulation. The management of PVT in patients with cirrhosis varies and is primarily dependent on whether the PVT is recent or chronic. In contrast, patients without cirrhosis are almost always anticoagulated to avoid complications of PVT. Direct oral anticoagulants, low-molecular weight heparin, and vitamin-K antagonists have all been used in patients with and without cirrhosis, without clear guidance on optimal treatment duration and surveillance.

Summary: Direct oral anticoagulants are increasingly used for patients with PVT though there is limited data on the safety and efficacy of these medications. The risk/benefit profiles of various anticoagulants must be considered when choosing a therapeutic anticoagulant. There are ongoing studies evaluating outcome measures of different anticoagulants in patients with PVT. Large, multicenter, randomized controlled trials may help elucidate the efficacy of anticoagulants on various outcome measures in PVT, including recanalization, bleeding, and survival.