Therapeutic Advances in Gastroenterology最新文献

Background: Endoscopic radiofrequency ablation (RFA) is used for the treatment of unresectable malignant biliary obstruction (MBO). The postoperative adverse events associated with RFA treatment have gained importance.

Objective: To investigate the early adverse events and their risk factors associated with RFA for the treatment of MBO.

Design: Observational retrospective study.

Methods: We collected data from patients diagnosed with MBO and treated with endoscopic RFA at our hospital between January 2010 and June 2022. Based on the collected data, the patients were divided into two groups: the adverse event group and the nonadverse event group. Early postoperative adverse events were recorded, and risk factors were assessed.

Results: One hundred and twenty patients with MBO underwent endoscopic RFA, with 20 developing adverse events (16.6%; 20/120). Among these, 13 patients (10.8%) developed biliary infection after RFA treatment, while 7 (5.8%) developed acute pancreatitis, and no bleeding or perforation occurred. Type 2 diabetes mellitus, bile duct stricture length >2.5 cm, segmental RFA, and the proportion of patients receiving single stent drainage were all significantly greater in the adverse event group compared to the nonadverse event group (p < 0.05). The results of the logistic regression analysis showed that type 2 diabetes, segmental RFA, and single stent drainage were the three independent risk factors for getting a biliary infection after RFA therapy.

Conclusion: Unresectable MBO combined with type 2 diabetes mellitus, segmental RFA, and postoperative single stent drainage can be the risk factors for adverse events after RFA. More attention should be paid to patients with multiple risk factors and preventive measures should be taken.

Background: Three liters of polyethylene glycol administered in a split dose is a commonly recommended regimen for bowel preparation before colonoscopy.

Objectives: The aim of this study was to compare the quality and tolerability of low-dose (2 L) polyethylene glycol combined with linaclotide (2 L+L) versus the 3 L polyethylene glycol (PEG) bowel preparation regimen.

Design: A noninferiority, prospective, multicenter, randomized controlled trial.

Methods: In this noninferiority, prospective, multicenter, randomized controlled study, patients scheduled for colonoscopy were enrolled and randomized to receive a 3 L PEG or 2L PEG+L regimen. The quality of bowel preparation and patients' discomfort was assessed.

Results: Over 12 months, 458 patients were randomized into 3 L PEG and 2 L+L groups. The primary endpoints showed that the 2 L+L regimen was superior to the 3L PEG regimen in overall bowel cleansing scores (Ottawa Bowel Preparation Scale: 3.3 ± 2.1 vs 3.7 ± 2.1, p = 0.021), but no significant difference in adequate bowel preparation rate between the two groups according to the OBPS score (97% vs 97.4%, p = 0.791). Before colonoscopy, patients in the 2 L +L regimen group had lower bloating scores (0.5 (0, 2) vs 1 (0, 3), p = 0.013), discomfort scores (1 (0, 2) vs 1 (0, 3), p = 0.006), and intolerability scores (1 (0, 3) vs 2 (0, 4), p = 0.016) than did those in the 3L PEG group.

Conclusion: Two liters of polyethylene glycol combined with linaclotide may be an alternative regimen to 3 L of PEG taken in split doses for bowel preparation before colonoscopy.

Trial registration: ChiCTR2100041992.

Background: Inflammatory bowel disease (IBD) presents unique challenges in elderly patients due to comorbidities and treatment-related risks.

Objectives: This study evaluates ustekinumab (UST) and vedolizumab (VDZ) efficacy and safety in elderly Crohn's disease (CD) patients.

Design: A retrospective cohort study at a tertiary medical center.

Methods: CD patients aged ⩾60 years (elderly) treated with UST, compared to non-elderly (<60 years) patients treated with UST and elderly patients treated with VDZ. Clinical response was evaluated using the Harvey-Bradshaw index (HBI) and clinical biomarkers, alongside monitoring steroid use, hospitalization rates, treatment persistence, and surgical interventions.

Results: The study included 166 CD patients: 32 elderly and 65 non-elderly patients treated with UST, and 69 elderly patients treated with VDZ. The mean duration of follow-up was 10.8 ± 2.8 months in the non-elderly group, 9.97 ± 3.28 months in the elderly UST group, and 10.0 ± 3.29 months in the VDZ group. Elderly UST patients were more likely to receive corticosteroids at initiation than non-elderly UST patients (44% vs 14%, p = 0.001). At 12 months, clinical response rates did not significantly differ between elderly and non-elderly UST groups, respectively (48% vs 40%, p = 0.5). However, elderly UST patients exhibited higher hospitalization rates over time compared to non-elderly UST patients (6-month: 19% vs 6.2%, p = 0.077; 12-month: 19% vs 4.6%, p = 0.055; log-rank p = 0.004). No significant differences were observed in clinical response and remission rates between elderly UST and elderly VDZ patients at 6 and 12 months. At 6 months, a higher hospitalization rate was observed in the UST group (19% vs 4.3% p = 0.027), but this difference did not persist over time.

Conclusion: UST and VDZ are effective and safe treatments for elderly CD patients, despite higher hospitalization rates compared to non-elderly patients, likely due to age-related complications.

Background: Esophageal-gastric variceal bleeding (EGVB) is a serious complication in patients with liver cirrhosis, characterized by high mortality and rebleeding rates. The effect of sequential endoscopic therapy on patient mortality and rebleeding rates remains unclear.

Objectives: This study aimed to evaluate the effects of sequential endoscopic therapy on mortality and rebleeding rates in patients with EGVB.

Design: In this single-center retrospective study, 373 hospitalized cases of EGVB caused by liver cirrhosis, collected between November 2019 and November 2023, were divided into four groups according to different treatment methods: a sequential endoscopy group, emergency endoscopy group, emergency endoscopy plus transjugular intrahepatic portosystemic shunt (TIPS) group and control group.

Methods: Mortality and rebleeding rates were compared among the four groups using statistical analyses.

Results: The mortality and rebleeding rates of the sequential endoscopy group (3.7% and 19%, respectively) were significantly lower than those of the emergency endoscopy (22% and 36%, respectively), emergency endoscopy plus TIPS (33% and 28%, respectively), and control groups (33% and 51%, respectively) (p = 0.013 and p = 0.013, respectively).

Conclusion: Sequential endoscopic therapy may significantly reduce the mortality and rebleeding rates of patients with EGVB compared to other conventional treatment strategies. The findings of the study could help develop approaches benefiting EGVB treatment.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern worldwide. Liver biopsy is the gold standard for diagnosing and staging MASLD, but it is invasive and carries associated risks. In recent years, there has been significant progress in developing noninvasive techniques for evaluation. This review article discusses briefly current available noninvasive assessments and the various liver biopsy techniques available for MASLD, including invasive techniques such as transjugular and transcutaneous needle biopsy, intraoperative/laparoscopic biopsy, and the evolving role of endoscopic ultrasound-guided biopsy. In addition to discussing the various biopsy techniques, we review the current state of knowledge on the histopathologic evaluation of MASLD, including the various scoring systems used to grade and stage the disease. We also explore current and alternative modalities for histopathologic evaluation, such as whole slide imaging and the utility of immunohistochemistry. Overall, this review article provides a comprehensive overview of the progress in liver biopsy techniques for MASLD and compares invasive and noninvasive modalities. However, beyond clinical trials, the practical application of liver biopsy may be limited, as ongoing advancements in noninvasive fibrosis assessments are expected to more effectively identify candidates for MASLD treatment in real-world settings.

Background: Endoscopy is important for the diagnosis and treatment of acute upper gastrointestinal bleeding (AUGIB), especially acute variceal bleeding (AVB), in liver cirrhosis. However, the optimal timing of endoscopy remains controversial, primarily because the currently available evidence is of poor quality, and the definition of early endoscopy is also very heterogeneous among studies. Herein, a multicenter randomized controlled trial (RCT) is performed to explore the impact of the timing of endoscopy on the outcomes of cirrhotic patients with AVB.

Methods: A total of 368 cirrhotic patients presenting with AUGIB who are highly suspected to be from AVB will be enrolled. They will be stratified according to the severity of liver function and clinical presentation at admission and then randomly assigned at a 1:1 ratio into early (within 12 h after admission) and delayed (within 12-24 h after admission) endoscopy groups within each stratum. The primary outcomes include the rates of 5-day failure to control bleeding after admission and 6-week rebleeding. The secondary outcomes include 6-week mortality and incidence of adverse events.

Conclusion: Considering existing evidence originates from non-randomized studies, this RCT will provide high-quality evidence to uncover whether cirrhotic patients with AVB should undergo early endoscopy to control bleeding and improve survival.

Trial registration: ClinicalTrials.gov identifier: NCT06031402.

Background: Many women of childbearing age with inflammatory bowel disease (IBD) require advanced therapies. While biologics are largely low risk during pregnancy, the novel small molecules tofacitinib, filgotinib, upadacitinib and ozanimod (TFUO) have shown concerning teratogenic effects, and decreased fertility in animal studies. Therefore, their use in women of childbearing age needs careful consideration.

Design: RAND/University of California Los Angeles (UCLA) Appropriateness Method (RAM).

Objective: To evaluate the appropriateness of TFUO in women of childbearing age.

Methods: We convened a panel of six gastroenterologists, two IBD nurses, one IBD pharmacist and three expert patients. Following a literature review, 13 statements were drafted and voted upon in 2 rounds.

Results: All 13 statements were deemed appropriate. The panel concluded that women with IBD of childbearing age who wish to commence therapy with TFUO, need to use effective contraception and be counselled regarding the risk in unplanned pregnancies. For women using contraception while on Janus kinase inhibitor (JAKi) therapy, we suggest the preferred use of progesterone-only or non-hormonal long-acting contraception. TFUO are contraindicated during pregnancy and breast feeding. We recommend that women receiving TFUO cease therapy in time to establish clinical remission for at least 3 months prior to conception. Therapies other than TFUO should be considered as first-line therapy in women with IBD of childbearing age, except in select individual circumstances. TFUO may be appropriate for women of childbearing age after failure of, intolerance or contraindications to one biological agent.

Conclusion: TFUO should be avoided during pregnancy and breastfeeding, and alternative therapies should be considered as first-line treatments.

Summary: We provide clinical practice recommendations regarding the use of TFUO for IBD in women of childbearing age.

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) characterised by endoscopic inflammation, progressive bowel damage and gastrointestinal lesions. Although treatment strategies for CD have traditionally focused on a stepwise pharmacological approach to achieve clinical remission or symptom resolution, these treatment goals correlate poorly with disease activity. Thus, achieving full clinical remission and full endoscopic healing alone may be insufficient, as patients may remain at risk of inflammatory complications. Individualised 'treat-to-target' (T2T) pharmacological and treatment approaches represent a promising strategy for improving endoscopic remission and symptom resolution among patients with CD. The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) and STRIDE-II guidelines, launched in 2013 and later renewed, identified individualised targets for a T2T therapeutic approach for patients with IBD. These guidelines facilitate the individualisation of target treatment goals through evidence-based, long-term (health-related quality of life, absence of disability, endoscopic healing) and intermediate/short-term (abdominal pain, stool frequency, normalisation of biomarker levels) treatment targets, allowing patients and clinicians to consider the risk-to-benefit balance of goals and selected therapeutic strategies. This article aims to summarise the STRIDE-II guidelines and provide intellectual guidance for healthcare professionals to apply the STRIDE-II principles to current clinical practice in the United Kingdom (UK). Management recommendations for primary and secondary first-line non-responders are provided, along with suggestions for utilising the endoscopic outcomes scoring system in UK clinical practice.

Background: Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). It is known that non-serious treatment-emergent adverse events (TEAEs) may not lead to UC drug discontinuation but can affect treatment tolerability.

Objectives: This post hoc analysis evaluated the incidence of specific, common, non-serious TEAEs reported in the etrasimod UC clinical programme and the characteristics of affected patients.

Design: Data included patients from the Placebo-controlled UC cohort (phase II OASIS, and phase III ELEVATE UC 52 and ELEVATE UC 12 trials) receiving QD etrasimod (2 or 1 mg) or placebo.

Methods: Proportions and incidence rates (IRs; the number of patients with a TEAE divided by the total exposure in patient-years (PYs), per 100 PY) of Headache, Pyrexia, Nausea and Dizziness TEAEs were reported. Changes in heart rate among patients with Dizziness TEAEs were also evaluated.

Results: Among 943 patients (etrasimod 2 mg, N = 577 (276.7 PY); etrasimod 1 mg, N = 52 (11.4 PY); placebo, N = 314 (115.1 PY)), 48, 34, 27 and 21 patients experienced events of Headache, Pyrexia, Nausea and Dizziness, respectively. All events were non-serious; one patient treated with etrasimod was discontinued due to a Pyrexia TEAE. Numerically, IRs of Headache and Dizziness TEAEs were higher, and Nausea slightly higher, with etrasimod versus placebo (13.45 vs 8.63 per 100 PY, 6.52 vs 1.69 and 7.18 vs 5.13 per 100 PY, respectively); IRs were similar for Pyrexia. The duration of most TEAEs was 1-10 days.

Conclusion: In the etrasimod UC clinical programme, all Headache, Pyrexia, Nausea and Dizziness events were non-serious. Headache and Dizziness were more frequent, and Nausea slightly more frequent, among patients receiving etrasimod versus placebo. The post hoc nature of this analysis is a limitation. These results reiterate the favourable safety profile and tolerability of etrasimod.

Trial registration: ClinicalTrials.gov: NCT02447302; NCT03945188; NCT03996369.

Background: The efficacy of ustekinumab (UST) and infliximab (IFX) in Crohn's disease (CD) patients with intestinal stenosis remains uncertain.

Objective: This study aims to compare the efficacy of UST and IFX in the treatment of CD patients with intestinal stenosis.

Design: This was a retrospective and multicenter cohort study.

Methods: In this retrospective study, we included CD patients treated with IFX or UST at five centers. We assessed the clinical response rate at weeks 12 and 24, steroid-free clinical remission rate at weeks 24 and 52 for overall patients and those with stenosis, and objective examination (intestinal ultrasound and/or endoscopy) response rate at week 52 for stenosis patients.

Results: A total of 211 CD patients (106 IFX and 105 UST) were included, with 119 (56 IFX and 63 UST) having intestinal stenosis. In the overall patient population, there were no significant differences in clinical response rate and steroid-free clinical remission rate at weeks 12, 24, and 52 between the IFX and UST groups. In patients with stenosis, the steroid-free clinical remission rate at week 52 was significantly lower in the IFX group compared to the UST group (51.79% IFX vs 69.84% UST, p = 0.044). The objective examination response rate did not significantly differ between the IFX and UST groups at week 52 (66.67% IFX vs 76.19% UST, p = 0.690). In the UST group, steroid-free clinical remission rate was higher in bio-naïve patients than bio-experienced patients at week 24 (75.00% bio-naïve vs 55.38% bio-experienced, p = 0.043).

Conclusion: UST may be considered a more advantageous treatment option for those CD patients with intestinal stenosis, as it has better steroid-free clinical remission rates compared to IFX.