Therapeutic Advances in Gastroenterology最新文献

Background: Pruritus is a symptom of several cholestatic liver diseases (CLDs) that can impair health-related quality of life (HRQoL). Despite evidence-based guideline therapy, managing cholestatic pruritus (CP) remains challenging, thus making the need for newer, more effective therapeutic agents more evident.

Objective: Our study evaluated the efficacy of existing CP therapies.

Design: Systematic review.

Data sources: From inception until March 2023, we conducted a comprehensive search of MEDLINE, Cochrane, EMBASE, Scopus, ClinicalTrial.gov, and other sources, including pharmaceutical webpages and conference proceedings published in English that reported on CP interventions.

Methods: Two reviewers independently conducted screening and full-text review of articles with extraction conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The methodological quality of studies included in our qualitative synthesis was assessed by using the Cochrane ROBINS-I and ROBINS-II tools for interventional studies and the National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The primary outcome assessed in our systematic review was the severity of CP after therapy.

Results: Of 3293 screened articles, 92 studies were eligible for inclusion in the qualitative synthesis. Some patients' HRQoL improved with evidence-based standard therapy. Others, particularly those with severe and refractory CP, often required conversion to or addition of experimental noninvasive (e.g., ondansetron) or extracorporeal liver support to alleviate CP. In addition, studies investigating a newer class drug, the ileal bile acid transporter inhibitor (IBATi), demonstrate its effectiveness in reducing serum bile acid and alleviating CP with sustained improvement noted in patients with the inherited childhood cholestatic disorders - progressive familial intrahepatic cholestasis and Alagille syndrome.

Conclusion: Our findings consolidate data on the efficacy of guideline-based approaches and newer therapies for CP. While the initial findings are promising, additional clinical trials will be needed to determine the full extent of IBATi's efficacy and potential use in treating other common CLDs. These results provide a foundation for future research and highlight the need for continued investigation into the management and treatment of CLDs.

Background: With the increase in antibiotic resistance, the success rate of Helicobacter pylori (H. pylori) eradication therapy has declined in recent years. Vonoprazan-amoxicillin (VA) dual therapy has been reported to be a promising regimen.

Objectives: To compare the efficacy and safety of VA dual therapy and bismuth quadruple therapy containing amoxicillin and clarithromycin for H. pylori first-line eradication, and to further analyze the effects of clarithromycin resistance on eradication rate.

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

Methods: Treatment-naïve H. pylori-infected patients were randomly allocated 1:1 to the VA group (vonoprazan 20 mg twice daily and amoxicillin 750 mg four times daily, for 14 days) or the RBAC group (rabeprazole 10 mg, bismuth potassium citrate 220 mg, amoxicillin 1000 mg and clarithromycin 500 mg twice daily, for 14 days). H. pylori clarithromycin resistance and CYP2C19 gene polymorphisms were detected with real-time polymerase chain reaction (PCR) technique. The eradication rates and adverse events were analyzed.

Results: A total of 151 patients were enrolled. The intention-to-treat (ITT), modified intention-to-treat (mITT), and per-protocol (PP) eradication rates and their 95% confidence intervals (95% CIs) were 94.6% (86.0-98.3%), 98.6% (91.3-99.9%), and 98.5% (90.9-99.9%) for VA group and 87.0% (77.0-93.3%), 91.8% (82.3-96.6%), and 93% (83.7-97.4%) for RBAC group. The eradication rate of the VA group was noninferior to the RBAC group in ITT, mITT, and PP analyses (p < 0.0001). In patients infected with strains of clarithromycin resistance point mutation, the eradication rate of the RBAC group decreased to lower than 90%, but the difference from the VA group did not achieve statistical significance (ITT eradication rate: 81.5% in the RBAC group and 96.2% in the VA group, p = 0.192). The incidence of adverse events in the VA group was 39.2%, which was significantly lower than that in the RBAC group (79.2%, p = 0.000).

Conclusion: The efficacy of VA dual therapy is noninferior to RBAC in H. pylori first-line eradication, with fewer adverse reactions.

Registration: This study was registered at the Chinese Clinical Trial Registry (ChiCTR2100052550) on 30 October 2021.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disease that involves host genetics, the microbiome, and inflammatory responses. The current consensus is that the disruption of the intestinal mucosal barrier is the core pathogenesis of IBD, including intestinal microbial factors, abnormal immune responses, and impaired intestinal mucosal barrier. Cumulative data show that nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are dominant mediators in maintaining the homeostasis of the intestinal mucosal barrier, which play critical roles in sensing the commensal microbiota, maintaining homeostasis, and regulating intestinal inflammation. Blocking NLRs inflammasome activation by botanicals may be a promising way to prevent IBD progression. In this review, we systematically introduce the multiple roles of NLRs in regulating intestinal mucosal barrier homeostasis and focus on summarizing the activities and potential mechanisms of natural products against IBD. Aiming to propose new directions on the pathogenesis and precise treatment of IBD.

Background: It remains unclear whether visceral adipose tissue (VAT) can predict the response of patients with Crohn's disease (CD) to anti-tumour necrosis factor-α (anti-TNF-α) therapy.

Objectives: This study aimed to investigate whether VAT predicts the efficacy of infliximab (IFX) for different sites of CD and its relationship with serum TNF-α levels and IFX serum trough concentration.

Design: This is a multicentre retrospective study.

Methods: Patients with CD treated with IFX from January 2014 to January 2021 were included. The perimeter of the visceral adipose area was obtained by a Computed Tomography (CT) scan. Participants were classified according to the lesion site (L₁, L₂, and L₃) and visceral fat area. The participants were divided into colon-uninvolved non-visceral obesity (L₁-VAT_L), colon-uninvolved visceral obesity (L₁-VAT_H), colon-involved non-visceral obesity (L₂ + L₃-VAT_L), and colon involved visceral obesity (L₂ + L₃-VAT_H) groups. The end points of this study were set as disease remission status at 6 and 12 months.

Results: The final cohort included 140 patients. Regarding efficacy at 6 and 12 months, there was a significant difference between L₁-VAT_L (73.8% versus 36.8%, p = 0.006) and L₁-VAT_H (81.0% versus 47.4%, p = 0.008) groups. In the analysis of serum TNF-α levels and IFX serum trough concentrations, there was a significant difference between L₁-VAT_L and L₁-VAT_H (59.5 pg/mL versus 236.0 pg/mL, p_TNF-α = 0.006), (10.0 μg/mL versus 0.4 μg/mL, p_IFX = 0.000), and L₁-VAT_H and L₂ + L₃-VAT_H (78.7 pg/mL versus 118.6 pg/mL, p_TNF-α = 0.031), (0.4 μg/mL versus 6.40 μg/mL, p_IFX = 0.017).

Conclusion: In L₁ patients, the VAT level predicted the efficacy of IFX, with high VAT values indicating poor efficacy. The VAT level may be a useful radiological marker to predict the efficacy of IFX in patients with various types of CD.

During the past 3 years, the coronavirus disease 2019 (COVID-19) pandemic has had a great impact on people all over the world. However, it has become evident that disease manifestations and severity differ across age groups. Most children have a milder disease course than adults but possibly more pronounced gastrointestinal (GI) symptoms. Given the child's developing immune system, the impact of COVID-19 on disease development may differ compared to adults. This study reviews the potential bi-directional relationship between COVID-19 and GI diseases in children, focusing on common pediatric conditions such as functional GI disorders (FGID), celiac disease (CeD), and inflammatory bowel disease (IBD). Children with GI diseases, in general, and CeD and IBD, in particular, do not seem to have an increased risk of severe COVID-19, including risks of hospitalization, critical care need, and death. While infections are considered candidate environmental factors in both CeD and IBD pathogenesis, and specific infectious agents are known triggers for FGID, there is still not sufficient evidence to implicate COVID-19 in the development of either of these diseases. However, given the scarcity of data and the possible latency period between environmental triggers and disease development, future investigations in this field are warranted.

Background: Videocapsule endoscopy (VCE) and double-balloon enteroscopy (DBE) are part of the diagnostic and therapeutic work-up of indications other than suspected small bowel bleeding (OSBB). The literature is currently lacking studies describing these procedures in this particular setting.

Objectives: We assessed the clinical impact of VCE and DBE in a large monocentric cohort of OSBB patients, as compared to a control group of suspected small bowel bleeding (SSBB) patients who underwent enteroscopy over the same period.

Design: Monocentric, retrospective, cohort study.

Methods: We collected the data of consecutive patients with OSBB undergoing VCE and/or DBE from March 2001 to July 2020. The demographic and clinical parameters of the patients, technical characteristics, and adverse events for each procedure were collected. The impact of VCE and DBE was defined in terms of diagnostic yield (DY). The patients were subdivided according to the main indication into four groups: celiac disease, Crohn's disease (CD), neoplasia, and persistent gastrointestinal symptoms.

Results: A total of 611 VCEs and 387 DBEs were performed for OSBB. The main indications were complicated celiac disease and CD. The DYs of VCE and DBE overall were 53 and 61.7%, respectively, with some variance among the four groups. We report no statistical differences in the DY of VCE and DBE in SSBB vs OSBB (57.7% vs 53%, p = 0.0859 and 68.8% vs 61.7%, p = 0.0582, respectively). OSBB patients were significantly younger than those with SSBB. However, similarly to SSBB (k = 0.059), poor agreement between the enteroscopic techniques was found in the OSBB population (k = 0.109). The safety of both procedures in OSBB was comparable to that in SSBB patients.

Conclusion: VCE and DBE are effective and safe in suspected OSBB, where their role is similar to that in SSBB, their main indication.

Background: The endoscopic submucosal dissection (ESD) is a technically demanding and time-consuming procedure, with an increased risk of adverse events compared to standard endoscopic resection techniques. The main difficulties are related to the instability of the operating field and to the loss of traction. We aimed to evaluate in a pilot trial a new endoscopic platform [tissue retractor system (TRS); ORISE, Boston scientific Co., Marlborough, MA, USA], designed to stabilize the intraluminal space, and to provide tissue retraction and counter traction.

Method: We prospectively enrolled all consecutive patients who underwent an ESD for sigmoid/rectal lesions. The primary outcome was the rate of technical feasibility. Further technical aspects such as en-bloc and R0 resection rate, number of graspers used, circumferential incision time, TRS assemblage time, submucosal dissection time, and submucosal dissection speed were provided. Clinical outcomes (recurrence rate and adverse events) were recorded as well.

Results: In all, 10 patients (M/F 4/6, age: 70.4 ± 11.0 years old) were enrolled. Eight out of 10 lesions were located in the rectum. Average lesion size was 31.2 ± 2.7 mm, and mean lesion area was 1628.88 ± 205.3 mm². The two sigmoid lesions were removed through standard ESD, because the platform assemblage failed after several attempts. All rectal lesions were removed in an en-bloc fashion. R0 resection was achieved in 7/8 (87.5%) patients in an average procedure time of 60.5 ± 23.3 min. None of the patients developed neither intraprocedural nor postprocedural adverse events.

Conclusion: TRS-assisted ESD is a feasible option when used in the rectum, with promising result in terms of efficacy and safety outcomes. Nevertheless, our pilot study underlines few technical limitations of the present platform that need to be overcome before the system could be widely and routinely used.

Background: Acid sensitivity can be altered in patients with gastroesophageal reflux disease (GERD). Secondary peristalsis helps clear gastro-esophageal refluxate and residual ingested food bolus.

Objectives: The aim of this study was to investigate the associations among acid sensitivity, esophageal mucosal integrity, chemical clearance, and secondary peristalsis before and after esophageal acid infusion.

Design: This was an investigator-initiated, prospective, cross-sectional study.

Methods: Adult reflux patients underwent high resolution manometry and 24 h impedance-pH monitoring off acid suppression to identify GERD phenotypes, including non-erosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH). Secondary peristalsis was assessed using five rapid 20 mL air injections into the esophagus before and after infusion of hydrochloric acid (0.1 N) into the mid-esophagus. Conventional acid infusion parameters recorded included lag time, intensity rating, and sensitivity score. Chemical clearance was evaluated using the post-reflux swallow-induced peristaltic wave (PSPW), and mucosal integrity was assessed by the mean nocturnal baseline impedance (MNBI) derived from impedance-pH monitoring.

Results: A total of 88 patients (age 21-64 years, 62.5% women) completed the study including 12 patients with NERD, 45 with RH, and 31 with FH. There was no significant difference in acid infusion parameters between patients with NERD, RH, and FH. Upon acid infusion, patients who exhibited successful secondary peristalsis had longer lag time, higher MNBI, and shorter bolus contact time than those without secondary peristalsis. Meanwhile, patients with intact PSPW demonstrated significantly higher intensity ratings in response to acid perfusion and higher MNBI than those with impaired PSPW. The lag time correlated positively with MNBI (r = 0.285; p = 0.007).

Conclusion: In conclusion, the protective effect of esophageal secondary peristalsis and chemical clearance on esophageal mucosal integrity was demonstrated. Concerning acid sensitivity, longer lag time in patients with intact secondary peristalsis may be attributed to better esophageal mucosal integrity, while stronger intensity ratings may have a greater tendency to induce PSPW and protect esophageal mucosal integrity.

Background: Helicobacter pylori (H. pylori) is a group 1 carcinogen and the etiological agent of gastric diseases such as gastritis, ulcers, and gastric cancer. It infects approximately half of the world's population. Risk factors associated with H. pylori infection include socioeconomic status, lifestyle, and diet.

Objectives: This study aimed to evaluate the association between eating habits and H. pylori infection in patients from a reference hospital in Central Brazil.

Design: This cross-sectional study included 156 patients from 2019 to 2022.

Methods: Data were collected using a structured questionnaire on sociodemographic and lifestyle characteristics and a validated food frequency questionnaire. The H. pylori infection status (positive versus negative) was determined using the histopathological method. After grams/day, foods were stratified into tertiles of consumption (low, medium, and high). Simple and multiple binary logistic regression models were used in the analysis of odds ratios (ORs) and their respective 95% confidence intervals (CIs), with a 5% significance level.

Results: The prevalence of H. pylori infection was 44.2% (69/156 patients). Infected individuals had a mean age of 49.6 ± 14.6 years; 40.6% were men, 34.8% were aged 60 years or older, 42.0% were unmarried, 7.2% had higher education, 72.5% were non-white, and 30.4% were obese. In the H. pylori-positive group, 55.1% were alcohol drinkers and 42.0% were smokers. The results of multiple analyses showed that the chance of H. pylori infection was higher among male participants (OR = 2.25; CI = 1.09-4.68) and individuals with obesity (OR = 2.68; CI = 1.10-6.51). Participants with moderate consumption of refined grains (bread, cookies, cakes, breakfast cereal) (OR = 2.41; CI = 1.04-5.62) and fruits (OR = 2.53; CI = 1.08-5.94) were more likely to be infected.

Conclusion: In this study, male sex, obesity, and the consumption of refined grains and fruits were positively associated with H. pylori infection. Further research is needed to investigate this association and elucidate the underlying mechanisms.

Since the discovery of Helicobacter pylori (H. pylori) as the causative organism for gastric and duodenal ulcers four decades ago and subsequent recognition as class 1 gastric carcinogen, countless numbers of studies have been conducted and papers published, on the efficacy of various management strategies to eradicate the infection. In adults, a global consensus by the experts in the field concluded that H. pylori gastritis is an infectious disease and requires treatment irrespective of the presence or absence of symptoms due to the potential for serious complication like peptic ulcer disease and gastric neoplasia. However, although more than half the world's population harbors H. pylori, these serious complications occur only in a small minority of the infected population, even less so in childhood. More importantly, there is accumulating evidence for beneficial role of H. pylori against many chronic health conditions, from several epidemiological and laboratory studies. No doubt, eradication therapy is indicated in children with H. pylori-related peptic ulcer disease. Even though the pediatric guidelines from various learned societies recommend against a "test and treat" strategy, this is not always adhered to. With the accumulating evidence of the possible beneficial role of H. pylori, it is time to pause and think, are we causing more harm than good by eradicating H. pylori in every child who has this bug?