Therapeutic Advances in Gastroenterology最新文献

Background: As an uncommon serological pattern, the effect of hepatitis B e antigen/anti-hepatitis B e (HBeAg/anti-HBe) coexistence on peginterferon-α (Peg-IFN-α) therapy in patients with chronic hepatitis B (CHB) remains unknown. Moreover, Peg-IFN-α is clinically limited due to several side effects. It is of significant value to early identify the favored population for Peg-IFN-α therapy in CHB patients.

Objectives: This study aimed to analyze the impact of HBeAg/anti-HBe coexistence on the effectiveness of Peg-IFN-α and to construct a nomogram for predicting the occurrence of HBeAg seroconversion in treatment-naïve CHB patients with Peg-IFN-α therapy.

Design: Retrospective, case-control study of treatment-naïve CHB patients with Peg-IFN-α at a tertiary care center.

Methods: Data from HBeAg-positive treatment-naïve CHB patients were retrospectively analyzed. Clinical characteristics of the HBeAg/anti-HBe coexistence group were compared with those of the anti-HBe-negative group. In addition, univariate and multivariate logistic regression analyses were performed to identify independent risk factors for HBeAg seroconversion. The nomogram for the prediction of HBeAg seroconversion was constructed and evaluated.

Results: A total of 140 HBeAg-positive CHB patients were enrolled. Patients with HBeAg/anti-HBe coexistence accounted for 11.4% of HBeAg-positive patients, and their hepatitis B surface antigen (HBsAg) and HBeAg levels were significantly lower than those of anti-HBe negative patients, but the HBeAg seroconversion rate was higher after Peg-IFN-α treatment. As revealed by multivariate logistic analysis, HBeAg/anti-HBe coexistence, baseline HBsAg, baseline HBeAg, and alanine aminotransferase ratio at baseline were independent correlates of HBeAg seroconversion. The nomogram model constructed based on these four independent correlates demonstrated good discrimination (area under the curve = 0.866), calibration, and clinical adaptability.

Conclusion: HBeAg/anti-HBe coexistence is associated with a higher HBeAg seroconversion rate, and the nomogram model constructed based on HBeAg/anti-HBe coexistence performs well in predicting HBeAg seroconversion in treatment-naïve CHB patients treated with Peg-IFN-α therapy.

Background: The comparable evaluation of computed tomography enterography (CTE), enteroscopy, and intestinal ultrasound in small bowel Crohn's disease (CD) is imprecise.

Objectives: The purpose of this study was to analyze the findings of enteroscopy, CTE, and intestinal ultrasound to determine the advantages and disadvantages of each method for the evaluation of small bowel CD.

Design: It was a single-center, observational, retrospective study.

Methods: The differences in localization of disease lesions, mucosal inflammation, and transmural inflammation between enteroscopy, CTE, and intestinal ultrasound for evaluation of small bowel CD were compared.

Results: A total of 198 patients with small bowel CD were included in the analysis. CTE and intestinal ultrasound had a lower detection rate of upper intestinal lesions compared with enteroscopy (p < 0.05). Enteroscopy was better than CTE and intestinal ultrasound in the detection of stenosis (p < 0.001), and the assessment of fistula by CTE was better than that by enteroscopy and intestinal ultrasound (p < 0.05). Enteroscopy, CTE, and intestinal ultrasound differed in the assessment of inflammatory activity, and the agreement of the three methods was poor (all intra-class correlation coefficient <0.75).

Conclusion: Enteroscopy is superior to CTE and intestinal ultrasound for the assessment of upper intestinal CD lesions. Enteroscopy, CTE, and intestinal ultrasound were not consistent in evaluating inflammatory activity, and the three methods may need to be combined for an accurate assessment.

Faecal microbiota transplantation (FMT) is increasingly used for diseases associated with a disrupted intestinal microbiome, mainly Clostridioides difficile infection. Encapsulated FMT is a patient-friendly application method that improves accessibility and convenience. Capsule processing may be standardised, but validation protocols are warranted. This review aimed to describe published validation methods for encapsulated FMT. Original studies reporting using encapsulated faecal formulations were included, regardless of indication. Studies were excluded if they did not address processing and validation or used non-donor-derived content. We conducted a comprehensive scoping review, implementing a systematic search strategy in PubMed, Embase and Web of Science. Processing data and validation methods were registered during full-text analysis and combined to create an overview of approaches for assessing quality in encapsulated FMT processing. The searches identified 324 unique studies, of which 44 were included for data extraction and analysis. We identified eight validation covariables: donor selection, pre-processing, preservation, oxygen-sparing processing, microbial count, viability, engraftment and clinical effect outcomes, from which we constructed a model for quality assessment of encapsulated FMT that exhaustively categorised processing details and validation measures. Our model comprised three domains: (1) Processing (donor selection and processing protocol), (2) Content analysis (microbiota measures and dose measures) and (3) Clinical effect (engraftment and clinical outcomes). No studies presented a reproducible capsule protocol; their validation strategies were sparse and divergent. The validation of FMT capsules is heterogeneous, and processing requires relevant standardisation protocols, mainly focusing on capsule content. Future studies should report validation covariables to enable accurate comparative assessments of clinical effects.

Background: Linaclotide, a guanylate cyclase-C agonist, is indicated for irritable bowel syndrome with constipation (IBS-C). However, real-world data on the safety and patient-reported outcomes (PROs) of linaclotide are scarce in Chinese patients with IBS-C.

Objectives: To assess the real-world safety and PROs of linaclotide in the Chinese IBS-C population.

Design: Multicenter, prospective observational study.

Methods: Adults with IBS-C who had taken or planned to take at least one dose of linaclotide 290 μg were enrolled and followed up for 3 months. Face-to-face visits were conducted at baseline (V1), Week 4 ± 7 days (V2), and Week 12 ± 7 days (V3). Primary endpoints included the incidences of adverse events (AEs), AEs by severity, adverse drug reactions (ADRs), serious AEs (SAEs), and AEs leading to treatment interruption, discontinuation, and death. Secondary endpoints included mean treatment satisfaction at V2 and V3, and mean overall Irritable Bowel Syndrome-Quality of Life (IBS-QoL) at V2.

Results: Out of 3000 enrolled patients, 2963 took at least one dose of linaclotide and were analyzed. Overall, 712 patients (24.0%) reported 1095 AEs, which were mostly mild (89.9%). Diarrhea, reported in 297 out of the 2963 patients analyzed (10.0%), was the most common AE. No severe diarrhea was reported. Totally, 319 patients (10.8%) reported ADRs. Forty-six patients (1.6%) reported 50 SAEs and two cases were considered related to linaclotide treatment. Fifty-one (1.7%) and 70 patients (2.4%) interrupted and discontinued treatment due to AEs, respectively. One patient died of hepatic cancer, which was considered unrelated to linaclotide treatment. During the follow-up, the mean (±SD) treatment satisfaction increased numerically and continuously (V1, 2.8 ± 1.3 (n = 1721); V2, 3.5 ± 1.1 (n = 1705); V3, 3.9 ± 1.0 (n = 833)). The mean (±SD) overall IBS-QoL increased numerically from 73.2 ± 16.6 (n = 1924) at V1 to 80.2 ± 15.5 (n = 1738) at V2.

Conclusion: In the Chinese real-world setting, linaclotide was safe and well tolerated in patients with IBS-C. Numerically, there are trends toward improvement in PROs with linaclotide treatment.

Background: Coeliac disease (CeD) is a chronic immune-mediated disease triggered by exposure to dietary gluten in genetically predisposed individuals. The burden of CeD on patients and the healthcare system remains poorly evaluated in Germany.

Objectives: To assess the healthcare resource utilisation (HCRU) and costs of diagnosed CeD patients in a German claims database.

Design: A retrospective CeD case-control study was conducted using German claims data between 2017 and 2021.

Methods: CeD diagnosis was defined by at least one inpatient or two outpatient diagnostic codes (International Statistical Classification of Diseases and Related Health Problems, 10th Revision, German Modification (ICD-10-GM) K90.0) within four quarters (irrespective of calendar year) for CeD during the study period. Controls (non-CeD patients) were matched in a ratio of 5:1 by age, Charlson Comorbidity Index, sex and region. HCRU (hospitalisations, outpatient visits, medication use, sick leaves) and healthcare costs (outpatient services, inpatient services, outpatient pharmaceuticals, sick leaves and aids and remedies) were compared between CeD patients and controls.

Results: From the 3,352,188 patients with continuous enrolment during the study period (2017-2021), 8258 (0.25%) patients were identified as having a CeD diagnosis. The mean number of hospitalisations and outpatient visits within 5 years was 1.8- and 1.5-fold higher among matched CeD patients (n = 8243) compared to their controls (n = 41,215), resulting in an excess healthcare cost of €5251. Inpatient expenses were the main cost driver and accounted for 31.5% of total incremental costs.

Conclusion: The current study showed that CeD patients have considerably higher HCRU and related costs compared to matched controls. Our findings suggest the need for improved treatment options for CeD patients in addition to a gluten-free diet.

Background: Endoscopic submucosal dissection (ESD) is the first-line treatment for gastric mucosal lesions. The artificial ulcers caused by ESD can lead to bleeding, perforation, and other adverse events.

Objectives: This study aimed to evaluate the efficacy of alternate mucosa-submucosa clip in preventing adverse events following ESD for gastric mucosal lesions.

Design: Multicenter retrospective observational study.

Methods: Data from 924 patients who underwent ESD for gastric mucosal lesions were retrospectively collected and categorized into completely closed and unclosed groups based on postoperative wound management. The incidence of adverse events and postoperative wound healing rate at 1 and 3 months were compared between the groups, and the factors related to delayed bleeding after ESD were analyzed.

Results: The rate of delayed hemorrhage was lower in the completely closed group than in the unclosed group (0.8% vs 7.6%; p < 0.001), and subgroup analysis showed that this effect was consistent across all subgroups. The postoperative abdominal pain score was lower in the completely closed group than in the unclosed group (0 vs 2, p < 0.001). One month postoperatively, the wound healing rate was higher in the completely closed group (77.6% vs 55.1%; p < 0.001). Multivariable analysis showed that the presence of ulcers or scars on the lesion surface, and lesions located in the lower one-third of the stomach were risk factors for postoperative bleeding.

Conclusion: Application of alternate mucosa-submucosa clip closing the wound of ESD reduced the risk of postoperative bleeding, alleviated postoperative abdominal pain, and promoted artificial wound healing.

Background: Refractory esophageal stricture is the common complication of extensive endoscopic submucosal dissection (ESD), without satisfactory endoscopic treatment strategies. We evaluated the efficacy, safety, and long-term patency of the modified endoscopic radial incision and selective cutting combined with short-term stenting (RISC-STS) for the treatment of refractory esophageal stenosis.

Methods: This was a retrospective study. Patients diagnosed with refractory esophageal stricture from June 2016 to June 2023 were enrolled. Efficacy, safety, and risk factors for dysphagia after RISC-STS operation were assessed.

Results: Compared with clinical symptoms before RISC-STS, there was no significant improvement in the times of stricture recurred (p = 0.75). However, the narrowest diameter of esophageal stenosis was significantly larger after RISC-STS treatment (p = 0.04). Corresponding dysphagia scores after RISC-STS were obviously lowered according to the Mellow-Pinkas grading scale (p = 0.002). More cases ((14 (60.87%) vs 5 (21.74%)) received valid symptom-relief periods after RISC-STS (p = 0.0004). The complications of RISC-STS include perforation (4.35%), fever (4.35%), and pain (30.43%). Univariate Cox analysis suggested that resection length >7 cm of scar tissue was a risk factor for refractory dysphagia after RISC-STS.

Conclusion: The present study revealed that RISC-STS is an effective and safe technique for refractory esophageal stricture with lower restenosis, higher valid symptom-relief rate, and fewer complications.

Colorectal cancer (CRC) is the third most prevalent cancer globally and poses a significant health threat, making early detection crucial. This review paper explored emerging detection methods for early screening of CRC, including gut microbiota, metabolites, genetic markers, and artificial intelligence (AI)-based technologies. Current screening methods have their respective advantages and limitations, particularly in detecting precursors. First, the importance of the gut microbiome in CRC progression is discussed, highlighting how specific microbial alterations can serve as biomarkers for early detection, potentially enhancing diagnostic accuracy when combined with traditional screening methods. Next, research on metabolic reprogramming illustrates the relationship between metabolic changes and CRC, with studies developing metabolite-based detection models that show good sensitivity for early diagnosis. In terms of genetic markers, methylated DNA markers like SEPTIN9 have demonstrated high sensitivity, although further validation across diverse populations is necessary. Lastly, AI technology has shown immense potential in improving adenoma detection rates, significantly enhancing the quality of colonoscopic examinations through image recognition techniques. This review aims to provide a comprehensive perspective on new strategies for CRC screening, emphasizing the potential of noninvasive detection technologies and the prospects of AI and genomics in clinical applications. Despite several challenges, this review advocates for future large-scale prospective studies to validate the effectiveness and cost-effectiveness of these new screening methods while promoting the implementation of screening protocols tailored to individual characteristics.

Background: Potassium-competitive acid blocker (P-CAB)-based therapies are emerging as promising alternatives for eradicating Helicobacter pylori infection. However, the comparative efficacy of P-CAB-based therapy versus proton-pump inhibitor (PPI)-based therapy in treating H. pylori infection remains uncertain.

Objectives: This meta-analysis evaluated the efficacy and safety of P-CAB-based therapies, including Vonoprazan (VPZ) and Tegoprazan (TPZ), compared to PPI-based therapies for H. pylori infection. Subgroup analysis assessed the influence of drug history, experimental drug, treatment duration, combination therapies, and geographic regions on treatment outcomes.

Design: Meta-analysis.

Data sources and methods: Comprehensive searches were conducted in major databases, including PubMed, Embase, the Cochrane Library, and Web of Science, up to January 1, 2024. The primary outcome was the eradication rate, analyzed by intention-to-treat (ITT). Secondary outcomes included adverse events. Heterogeneity among studies was assessed using the χ² test and the I ² test. I ² > 50% or p < 0.05 indicated significant heterogeneity.

Results: The analysis totally included 28 randomized controlled trials (RCTs) comprising 37 studies and 8818 patients diagnosed with H. pylori infection. Of these, 14 RCTs, including 20 studies and 4286 patients, compared P-CAB-based therapy with 14-day bismuth-based quadruple therapy (BQT). P-CAB-based therapy exhibited superior eradication rates compared to both 14-day BQT and PPI-based therapy (ITT analysis: 87.0% vs 79.8%, risk ratio (RR) = 1.08, 95% CI: 1.04-1.12, p < 0.0001; and 85.6% vs 77.8%, RR = 1.09, 95% CI: 1.05-1.12, p < 0.00001, respectively). This enhanced efficacy was particularly pronounced in patients with clarithromycin-resistant infections (73.7% vs 41.5%, RR = 1.53, 95% CI: 1.07-2.20, p = 0.02). Subgroup analysis demonstrated higher eradication rates with P-CAB-based therapy in treatment-naïve participants, VPZ recipients, and those receiving 7- or 14-day regimens (dual, triple, or quadruple therapy). However, no significant differences were observed in treatment-experienced subgroups, TPZ recipients, or those on 10-day regimens. In addition, P-CAB-based therapy showed a lower incidence of adverse events than PPI-based treatments (RR = 0.73, 95% CI: 0.63-0.86, p < 0.0001).

Conclusion: P-CAB-based therapies are more effective than traditional PPI-based treatments for eradicating H. pylori infection, with a reduced incidence of adverse events.

Prospero registration: CRD42024503665.

Last decades led to a revolution in the management of ulcerative colitis (UC), due to the development of novel advanced therapies and the identification of increasingly ambitious therapeutic goals. Nevertheless, a subset of patients, refractory to available therapies, still requires proctocolectomy with ileal pouch-anal anastomosis (IPAA). Pouchitis, an inflammatory condition of the ileal pouch, is the most common long-term complication of IPAA, affecting almost one-half of patients in the first 10 years after surgery. Symptoms of pouchitis include increased stool frequency, urgency, and abdominal discomfort, significantly affecting patients' quality of life. Traditionally the mainstay treatment of acute pouchitis involves the use of antibiotics, but one-fifth of patients develop chronic pouchitis (CP), which may be dependent or resistant to antibiotics, posing significant challenges in the management of this condition. Currently, there is still no consensus on the optimal management for CP, though recent progress in understanding the pathophysiology of pouchitis has paved the way for innovative therapeutic approaches, based on biological therapies and small molecules. This review aims to discuss the recent advanced therapies available for pouchitis and provide a comprehensive review on the topic to guide physicians in their clinical practice.