Therapeutic Advances in Gastroenterology最新文献

Background: Managing patients with primary biliary cholangitis (PBC) who demonstrate an inadequate response to ursodeoxycholic acid or experience intolerable side effects remains a significant clinical challenge.

Objectives: This study aims to investigate the efficacy and safety of peroxisome proliferator-activated receptor (PPAR) agonists in the treatment of PBC.

Design: Meta-analysis and systematic review.

Methods: A systematic search of publications in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials was performed. Randomized controlled trials published in English that involved the treatment of PPAR agonists and reported on the levels of alkaline phosphatase (ALP), biochemical response rates, pruritus score, or severe and serious adverse events (AEs) were selected. The primary outcomes assessed were the effects of PPAR agonists on ALP levels and biochemical response rates. Secondary outcomes included the rates of severe or serious AEs and relief of pruritus.

Results: Fourteen studies with 1137 patients were included. Compared to the control group, PPAR agonists significantly reduced ALP levels by a mean difference of -155.87 U/L (95% confidence interval (CI): -208.30 to -103.44; random-effects). Patients who received PPAR agonists showed a significantly higher biochemical response rate (risk ratio (RR), 4.42; 95% CI: 2.37-8.26; random-effects). Furthermore, there was no significant difference in the rate of severe (RR, 1.05; 95% CI, 0.49-2.28) or serious AEs (RR, 1.02; 95% CI, 0.65-1.60) between the PPAR agonists and placebo groups.

Conclusion: PPAR agonists are effective and safe to treat patients with PBC.

Prospero trial registration: CRD42024545743.

Endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (EDGE) and endoscopic ultrasound-directed transenteric endoscopic retrograde cholangiopancreatography (EDEE) are innovative endoscopic techniques developed to overcome the challenges of biliary access in patients with surgically altered gastrointestinal anatomy. EDGE facilitates the creation of a gastro-gastric anastomosis, enabling endoscopic access to the excluded stomach and subsequent duodenum for endoscopic retrograde cholangiopancreatography (ERCP) procedures. Similarly, EDEE involves creating a gastro-jejunal anastomosis, allowing endoscopic access to the jejunum and hepaticojejunostomy for ERCP. These procedures are primarily indicated for patients with Roux-en-Y gastric bypass or other complex gastrointestinal surgeries that render traditional ERCP unfeasible. The major advantages of EDGE and EDEE include minimally invasive access to the biliary system, reduced procedural morbidity, and the ability to perform complex biliary interventions without additional surgeries. Using lumen-apposing metal stents in these procedures has further improved their safety and efficacy. This comprehensive review delves into EDGE and EDEE's technical nuances, clinical outcomes, and safety profiles. Our extensive literature searches reveal high procedural success rates and low complication incidences, establishing these methods as viable alternatives to traditional surgical and percutaneous approaches. We also discuss recent technological advancements, including developing enhanced stents and endoscopic ultrasound-guided instruments, which have refined these techniques and expanded their applications. Moreover, the review examines the integration of EDGE and EDEE with other therapeutic modalities, such as cholangioscopy and intraductal lithotripsy, to optimize treatment outcomes. Future directions emphasize the need for larger, multicenter trials to validate these findings further and create standardized protocols to ensure consistent procedural efficacy and safety. This review highlights the transformative potential of EDGE and EDEE in therapeutic endoscopy, advocating for their broader adoption in clinical practice and ongoing innovation in this rapidly evolving field.

Background: Endoscopic papillary balloon dilation (EPBD) has been recommended as a potential alternative to endoscopic sphincterotomy for common bile duct stones (CBDS), due to protecting the sphincter function.

Objectives: This retrospective study aims to evaluate the safety and efficacy of endoscopic nasobiliary drainage (ENBD) versus endoscopic retrograde biliary drainage (ERBD) after EPBD for CBDS.

Design: This study is a retrospective analysis of patients with CBDS who underwent EPBD followed by either ENBD or ERBD. It enrolled 283 patients, who underwent slow dilation and long-duration EPBD for CBDS with ENBD (eNbd group, n = 154) or ERBD (eRbd group, n = 129) from January 2022 to September 2023.

Methods: Propensity score matching (PSM) was used to balance preoperative baselines and intraoperative specifics, resulting in 220 matched patients (110 patients per group). The incidence rate of post-ERCP pancreatitis (PEP) was compared between the two groups, and risk factors for PEP were analyzed.

Results: After PSM, there were no significant differences in the baseline between the eNbd group and the eRbd group. The eNbd group exhibited significantly greater reduction in serum bilirubin levels compared to the eRbd group. Before PSM, the incidence rate of PEP was 2.6% (4/154) in the eNbd group and 8.5% (11/129) in the eRbd group (p = 0.027). After PSM, the incidence rate of PEP was 2.7% (3/110) in the eNbd group and 9.1% (10/110) in the eRbd group (p = 0.045). In addition, subgroup analysis revealed that patients with multiple stones may have a higher likelihood of developing PEP.

Conclusion: ENBD may be an optimal choice for patients with CBDS undergoing EPBD, and the presence of multiple stones may be particularly relevant when considering the risk of PEP.

Background: Crohn's disease (CD) is a chronic, relapsing and remitting inflammatory bowel disease that can be associated with significant bowel damage and disability. The Lémann Index (LI) is a validated tool for measuring cumulative bowel damage in CD patients through a comprehensive assessment of stricturing, penetrating and surgical lesions. However, prospective studies evaluating bowel damage progression in recently diagnosed CD patients remain limited.

Objectives: To characterise the absolute and longitudinal variations in bowel damage progression, as measured by the LI, in a cohort of recently diagnosed CD patients, and to assess its association with relevant disease features, including disease phenotype, treatment strategies, biomarkers and disability.

Design: Study protocol for the Crohn's Disease Cohort Study (CROCO Study), a multicentre, European, prospective cohort study.

Methods and analysis: Patients with recently diagnosed CD (within the previous 12 months) will be enrolled and followed up for 5 years. Patients will receive standard-of-care treatment determined by the practising gastroenterologist. Morphological assessments to measure the LI and to evaluate bowel damage progression will be performed at years 1, 3 and 5 after the diagnosis. Disability will be assessed annually using the Inflammatory Bowel Disease - Disability Index (IBD-DI). The primary outcome will be the absolute LI at year 3 following diagnosis. Predictors of bowel damage progression and the association between bowel damage and disability will be analysed.

Discussion: The CROCO study represents a unique multicentre cohort of recently diagnosed CD patients, designed to advance the understanding of CD's natural history and evolution. It will facilitate the development of composite scores for predicting bowel damage progression and provide valuable tools for designing future disease-modification trials.

Trial registration: NCT05420233.

Background: The efficacy of tofacitinib (TOFA) in various rheumatic diseases has generated interest in its potential benefits for treating spondyloarthritis (SpA) associated with ulcerative colitis (UC).

Objectives: RETUCAS (Real-world Effectiveness of Tofacitinib on Ulcerative Colitis-Associated Spondyloarthropathy) is the first study designed to evaluate the effectiveness of TOFA in UC-associated SpA.

Design: This was a prospective, multicentre, single-arm, observational study promoted by the Italian Group for the Study of Inflammatory Bowel Disease. Effectiveness was assessed using standardized rheumatologic scores.

Methods: Patients with UC and a confirmed diagnosis of active axial or peripheral SpA at baseline were enrolled. The primary endpoint was steroid-free joint response (SFJR) at weeks 8 and 52, defined as a decrease of ⩾1.1 units in Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (CRP) for axial SpA, or a decrease of >0.6 units in Disease Activity Score 28-CRP for peripheral SpA, without the use of corticosteroids.

Results: A total of 44 patients were enrolled: axial SpA: 9.1%; peripheral SpA: 70.4%; mixed axial and peripheral SpA: 20.5% All but two patients had previous exposure to biologic therapies, with more than half having failed two or more biologics. At week 8, SFJR was achieved in 52.3% of patients, with a significant difference between those with peripheral SpA and those with axial or mixed forms (67.7% vs 15.4%; p = 0.001). At week 52, SFJR was maintained in 59.1% of patients overall, again with better outcomes in peripheral SpA compared to axial/mixed SpA (71.0% vs 30.8%; p = 0.01).

Conclusion: This is the first prospective study specifically designed to assess Inflammatory Bowel Diseases-associated SpA. In patients with UC and refractory SpA-many of whom had previously failed multiple biologic therapies-TOFA demonstrated effectiveness, particularly in those with peripheral SpA.

Background: The impact of multiple substance use on the risk of pancreatitis remains underexplored.

Objective: To systematically review peer-reviewed observational studies assessing the association of multiple substance use with the risk of acute pancreatitis (AP) or chronic pancreatitis (CP) in adults.

Design: We conducted a systematic review informed by the Preferred Reporting Items for Systematic Review and Meta-Analyses guideline.

Data sources and methods: EMBASE, MEDLINE, and PsycINFO were searched up to March 2024. Reference lists of included studies were reviewed. From 5205 records identified, 181 relevant records were evaluated in full text. Studies evaluating the association of ⩾2 substances, including tobacco, alcohol, cannabis, and illicit substances, with AP or CP were included. Data were extracted by one reviewer, with quality control by a second reviewer. Quality assessments were independently conducted by two reviewers, with differences resolved by a third.

Results: Of 11 included studies, 6 investigated AP as the outcome and 5 examined CP. Among AP studies, 5 comparing smoking and alcohol to alcohol-only use showed high heterogeneity (I ² = 90.9%), with relative risks (RRs) from 1.40 to 11.40. One study examining cannabis and alcohol versus alcohol found a lower risk of AP in cannabis users. Among CP studies, four comparing smoking and alcohol to alcohol-only use were heterogeneous (I ² = 81%) with odds ratios 1.21-31.50. Where examined, smoking increases the risk of AP and CP in a dose-dependent fashion. Heavy alcohol users demonstrated a significant increase in CP risk across all smoking categories in one study.

Conclusion: Combined alcohol and tobacco use increases pancreatitis risk compared to single substance use, despite heterogeneity in RRs and exposure definitions. Evidence suggests a dose-dependent impact of smoking on pancreatitis risk when added to alcohol. Studies on the impact of a combination of other substance use on pancreatitis risk are needed.

Trial registration prospero: CRD42024503677.

Background: While several small sample size randomized controlled trials suggested the superiority of faecal microbiota transplantation (FMT) over placebo in ulcerative colitis (UC), the most effective modality to perform FMT remains unknown.

Objectives: To compare the efficacy of different modalities of FMT to induce clinical remission in patients with UC.

Data sources and methods: We performed a systematic review and network analysis (sources: MEDLINE, Embase, Cochrane CENTRAL; random effects model) of randomized controlled trials including at least one arm of FMT in adult patients with active UC. The primary endpoint, that is, clinical remission (total Mayo score ⩽2 with Mayo endoscopic score ⩽1), was assessed between weeks 6 and 12. Results are expressed as relative risks with 95% confidence intervals, adjusted for bowel cleansing and pre-FMT antibiotics. Ranking of FMT modalities was calculated as their surface under the cumulative ranking (SUCRA).

Results: Among the 12 selected studies, patients were exclusively bio-naïve in 4 studies (4/12), while between 9% and 32% had prior biologics exposure in the other trials. The risk of bias was low across all domains in seven studies. Contrary to upper gastrointestinal tract (GI) FMT (Relative risk (RR) = 1.1 (0.2-7.7)), oral capsule (RR = 7.1 (1.8-33.3)), lower GI FMT (RR = 4.5 (1.7-12.5) and combination of both (RR = 12.5 (2.1-100)) are more effective than placebo to induce clinical remission. The combination of lower GI FMT and oral capsule was significantly more effective than upper GI FMT to induce clinical remission (RR = 10.7 (1.1-104.2)). Combination of lower GI FMT and oral capsule ranked the highest for the induction of clinical remission (SUCRA = 0.93). Multidonor FMT did not perform better than single donor FMT. Autologous FMT ranked lower than placebo (SUCRA = 0.12 vs 0.22).

Conclusion: The combination of lower GI and oral capsule FMT seems to be the best modality of FMT for patients with UC. In clinical trials, autologous FMT should be avoided due to a potential detrimental effect.

Trial registration: PROSPERO registration number: CRD42023385511.

Many clinical studies arbitrarily define follow-up durations as short-term, mid-term, or long-term, without standardized criteria. To examine existing research on the use of infliximab in Crohn's disease to understand how these terms are defined and applied, a literature survey was conducted. Relevant studies were identified by querying Web of Science and Scopus with predefined keywords, focusing on articles that mentioned "short-term," "mid-term," or "long-term" in their title, abstract, or author keywords. The majority of the papers were published in gastroenterology and hepatology journals (75.6%), since 2010 (77.3%), and primarily involved retrospective data (64.8%). Most studies measured follow-up duration from the first infliximab infusion (65.3%). The mean follow-up durations were 4.06 months for short-term (based on 46 papers), 9.47 months for mid-term (based on 3 papers), and 37.58 months for long-term studies (based on 155 papers). Retrospective studies tended to have significantly longer mean durations for long-term follow-up than prospective studies. Notably, the ranges for short-term and long-term follow-ups overlapped, indicating inconsistent definitions across studies. Currently, there is no consensus on the durations associated with these terms. Standardized reporting with explicit timeframes in months or years is essential to improve comparability and clarity in future research.

Background: Increasing antibiotic resistance compromises therapeutic options for Helicobacter pylori (H. pylori) infection, especially in penicillin-allergic individuals.

Objectives: This trial aimed to assess the efficacy and safety of 14-day vonoprazan-minocycline (VM) dual therapy against bismuth-containing quadruple therapy (B-quadruple therapy), as initial treatment for H. pylori infection.

Design: This study was a single-center, open-label, and non-inferiority randomized controlled trial.

Methods: In this study, 240 individuals with H. pylori infection who have not received therapy were randomly assigned 1:1 to either the VM dual therapy group (vonoprazan 20 mg plus minocycline 100 mg, administered twice daily) or the B-quadruple therapy group (rabeprazole 10 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg, all administered twice daily). The primary outcome was to evaluate the non-inferiority of eradication rates between the two groups. Secondary outcomes included assessments of AEs and compliance.

Results: The eradication rates of VM dual group and B-quadruple therapy group were 87.5% and 88.3%, respectively, by intention-to-treat (ITT) analysis; 92.1% and 94.6% by modified ITT (mITT) analysis; and 92.0% and 95.5% by per-protocol (PP) analysis. The eradication rates of the VM group were non-inferior to those of the B-quadruple therapy group in ITT, mITT, and PP analyses (one-sided p-values were 0.02, 0.01, and 0.02). The incidence of AEs was higher in the B-quadruple therapy group (28.3%) than in the VM group (16.7%, p = 0.03). Good compliance was achieved in both groups (p = 0.60).

Conclusion: The VM dual therapy was not inferior to the B-quadruple therapy in the initial treatment of H. pylori infection, and the incidence of AEs was lower compared to B-quadruple therapy.

Trial registration: This trial was registered on the Chinese Clinical Trial Registry with the registration number ChiCTR2400081461.