Gut and Liver最新文献

Background/aims: Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder influenced by stress, microbial dysbiosis, and immune activation. Microbiota-directed therapies, including fecal microbiota transplantation and probiotics, show promise, but their sex-specific effects remain unclear. We compared the therapeutic effects of lyophilized fecal microbiota (LFM) with Bifidobacterium longum BBH016 in male and female Wistar rats subjected to repeated water avoidance stress.

Methods: Fecal pellet output (FPO), colonic mast cell infiltration, and fecal short-chain fatty acids were measured. Gut microbial composition and function were analyzed by 16S rRNA sequencing and Kyoto Encyclopedia of Genes and Genomes pathway prediction.

Results: Both interventions significantly reduced FPO and mast cell infiltration in males but had less pronounced effects in females. Microbiota analyses revealed sex-dependent responses, with distinct microbial trajectories in each treatment group. Using linear discriminant analysis effect size, we identified seven key taxa with treatment- or sex-specific enrichment. Alistipes onderdonkii and Bacteroides uniformis consistently increased in both LFM- and B. longum-treated groups, regardless of sex. Bacteroides finegoldii and Barnesiella intestinihominis were specifically enriched in the LFM group. In males, Blautia faecis and Fusicatenibacter saccharivorans were enriched following the interventions, whereas Parabacteroides goldsteinii appeared exclusively in stressed males. Functional predictions revealed the enrichment of estrogen signaling and bile acid pathways in males and the attenuation of proinflammatory pathways in females following LFM. Correlations between microbial taxa and host outcomes were predominantly observed in male rats.

Conclusions: These findings highlight sex-specific microbial and host responses to microbiota-targeted therapies in a stress-induced IBS model, emphasizing sex as a biological variable in designing personalized microbiome-based treatments.

Background/aims: Postpolypectomy bleeding (PPB) is a major complication of pedunculated colonic polyps. Various prophylactic interventions, including clips, endoloops, and epinephrine injections, have been proposed to prevent PPB; however, their comparative effectiveness remains unclear. This study aimed to evaluate the efficacy of these interventions through a network meta-analysis.

Methods: We searched the MEDLINE, EMBASE, and Cochrane CENTRAL databases for randomized controlled trials that compared the effectiveness of clips, endoloops, and epinephrine injection in the prevention of PPB in pedunculated polyps with a head diameter ≥10 mm. Primary outcomes included immediate and delayed PPB. Data synthesis was performed with the netmeta package in R, which integrates direct and indirect evidence and yields odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Of 601 identified studies, 11 trials involving 2,096 patients were included. In the network meta-analysis, endoloops (OR, 0.23; 95% CI, 0.08 to 0.63), clips (OR, 0.25; 95% CI, 0.14 to 0.48), and epinephrine injection (OR, 0.33; 95% CI, 0.11 to 0.96) were significantly more effective than no treatment in the prevention of immediate bleeding. Combinations of endoloops or clips with epinephrine injection also demonstrated satisfactory efficacy. For delayed bleeding, no significant differences were observed among the interventions or between each intervention and no treatment, which may be due to the small number of events across studies. According to surface under the cumulative ranking curve rankings, endoloops plus epinephrine injection was the most effective method for preventing immediate PPB, followed by endoloops and clips alone.

Conclusions: This network meta-analysis supports the use of endoloops with epinephrine as the most effective strategy for preventing immediate bleeding after resection of pedunculated colonic polyps, while current measures remain insufficient for delayed bleeding.

Background/aims: Severe alcoholic hepatitis (SAH) is a life-threatening form of alcoholic liver disease resulting in high short-term mortality. Mesenchymal stem cells (MSCs) have potent immunomodulatory effects and have been evaluated in various clinical trials for the treatment of chronic liver diseases. However, clinical evidence in patients with alcoholic hepatitis remains scarce, and the underlying mechanisms of MSCs in this population are not yet fully understood.

Methods: An integrative meta-analysis identified conserved transcriptomic signatures of alcoholic hepatitis. These signatures were validated in an ethanol-induced murine model. A mouse model of SAH was induced via subacute ethanol exposure (5 g/kg) combined with thioacetamide injection. MSCs were administered at two concentrations (5×10⁵ or 1×10⁶ cells), depending on the treatment group.

Results: In the animal model, MSCs treatment visibly alleviated liver injury induced by thioacetamide and ethanol. Significant reductions in tumor necrosis factor-α (p<0.05) and α-smooth muscle actin (p<0.01) levels were observed, accompanied by notable changes in inducible nitric oxide synthase, interleukin-1β, and transforming growth factor-β1 levels. From the meta-analysis, seven upregulated and 17 downregulated genes were identified. Subsequent quantitative polymerase chain reaction and Western blot analyses consistently validated four upregulated genes that demonstrated overlapping expression patterns across both the meta-analysis and in vivo experiments.

Conclusions: MSCs therapy significantly attenuates liver injury, inflammation, and fibrosis in SAH model mice. The observed messenger RNA-protein expression mismatches highlight the complexity of molecular regulation in acute hepatitis and underscore the importance of multilevel analysis in evaluating stem cell therapy. These results provide valuable insights into the mechanisms of MSC-mediated liver repair and suggest key targets for MSC therapy and response assessment in SAH.

Background/aims: Given the limited data on the long-term outcomes of non-curative resection (non-CR) following endoscopic submucosal dissection (ESD) for patients with superficial esophageal squamous cell carcinoma (SESCC), we compared the clinical outcomes of patients who did and did not achieve curative resection (CR).

Methods: This retrospective, single-center study reviewed data of patients with SESCC who underwent ESD at a tertiary referral center in Korea between 2011 and 2021. Non-CR was defined as the presence of any of the following: lymphovascular invasion, submucosal invasion, or positive vertical resection margin on ESD. Clinical outcomes and tumor-related characteristics were assessed.

Results: Most patients (93.3%, 28/30) in the non-CR group underwent additional treatment, including 11 who underwent surgery and 17 who received radiotherapy, whereas no patients in the CR group required additional surgery or radiotherapy. During a median follow-up of 58 months, the cumulative rate of recurrence was 0.9% (1/108) in the CR group and 16.7% (5/30) in the non-CR group. The 5-year overall survival rate was higher in the CR group, although the between-group difference was not statistically significant (91.1% vs 82.3%, p=0.873). The 5-year recurrence-free survival rates were 98.7% and 83.2% for the CR and non-CR groups, respectively (p<0.001). The overall adverse event rates were similar between the two groups (16.7% vs 20.0%, p=0.878).

Conclusions: ESD followed by appropriate treatment can yield acceptable long-term outcomes, even when CR is not achieved. These findings suggest that ESD may be a viable first-line treatment strategy for SESCC, even in patients who are unlikely to achieve CR, particularly high-risk surgical patients.

Background/aims: Zastaprazan (JP-1366) is a novel potassium-competitive acid blocker with a fast onset and prolonged duration. This study aimed to assess the efficacy and safety of zastaprazan versus lansoprazole in patients with gastric ulcers.

Methods: A total of 329 subjects with confirmed gastric ulcers participated in a phase 3, multicenter, randomized, double-blind, active-controlled clinical study. Subjects were randomized to receive zastaprazan 20 mg or lansoprazole 30 mg once daily up to 8 weeks. The primary endpoint was the cumulative healing rate of gastric ulcers as confirmed by upper gastrointestinal endoscopy at 8 weeks in patients. Secondary endpoints included ulcer healing rate, symptom recovery, quality of life changes, and safety assessment results.

Results: In the per-protocol set, the cumulative healing rate at 8 weeks was 100.00% (146/146) for zastaprazan 20 mg and 97.06% (132/136) for lansoprazole 30 mg, while at week 4, the healing rates were 93.84% (137/146) and 91.91% (125/136), respectively. Zastaprazan was noninferior to lansoprazole in ulcer healing, while the incidence of adverse events was comparable between groups. Gastrin levels increased during the treatment and declined after the treatment in both groups.

Conclusions: An 8-week therapy involving zastaprazan 20 mg demonstrated noninferiority to lansoprazole 30 mg in the cumulative rate of healing of gastric ulcers at 8 weeks, and the two demonstrated similar safety profiles. (ClinicalTrials.gov identifier NCT05448001).

Background/aims: This study aimed to investigate the influence of metabolic dysfunction-associated steatotic liver disease (MASLD) and body mass index (BMI) on the incidence of Alzheimer disease (AD) in the general South Korean population.

Methods: The National Screening Program for Transitional Ages collected data from 66-year-old dementia-free Koreans in 2010 and 2011. MASLD was diagnosed based on the fatty liver index (≥30) and the presence of metabolic components, and overweight/obese status was defined as a BMI ≥23 kg/m². The primary outcome was the development of AD up to December 2021. Multivariable Cox analyses were performed to evaluate whether the presence of MASLD or overweight/obese status influenced the risk of developing AD.

Results: A total of 376,902 dementia-free individuals aged 66 years were included in this cohort. The participants were categorized into four groups: overweight/obese non-MASLD (30.4%, n=114,528), overweight/obese MASLD (37.0%, n=139,551), lean non-MASLD (29.9%, n=126,692), and lean MASLD (2.7%, n=10,131). During a mean follow-up period of 10.38±1.90 years, 23,874 individuals (6.3%) were newly diagnosed with AD. Compared to the overweight/obese non-MASLD group, the adjusted hazard ratios (95% confidence interval) for AD in the lean MASLD, lean non-MASLD, and overweight/obese MASLD groups were 1.34 (1.24 to 1.45), 1.08 (1.04 to 1.13), and 1.13 (1.09 to 1.17), respectively.

Conclusions: A normal/underweight BMI and the presence of MASLD synergistically increased the risk of AD. The lean MASLD group had a higher risk of developing AD than the overweight/obese MASLD group, suggesting that the clinical relevance of MASLD for incident AD differs based on the BMI.

Background/aims: Helicobacter pylori is a pathogen that causes chronic gastritis and peptic ulcer diseases and is a carcinogen responsible for the development of malignancies, including gastric cancer. In the current era of high antimicrobial resistance, rifabutin-based triple therapy is recommended as a salvage therapy. Bismuth has not only a strong bacteriostatic effect but also a synergic effect when combined with antibiotics. Our study aimed to compare and evaluate the eradication rates between rifabutin-based triple therapy and rifabutin with bismuth-containing quadruple therapy as salvage treatments.

Methods: In this single-center study, patients who received rifabutin-based triple therapy and rifabutin with bismuth-containing quadruple therapy after failure of conventional therapy, including first- and second-line treatment, between January 2016 and July 2024, were retrospectively investigated. A total of 53 patients who received rifabutin-based triple therapy and 50 who received bismuth-containing quadruple therapy were included.

Results: In the rifabutin-based triple therapy group, eradication was achieved in 32 out of 53 patients (60.4%; 95% confidence interval [CI], 46.8% to 74.0%). In the bismuth-containing quadruple therapy group, eradication was achieved in 40 out of 50 patients (80.0%; 95% CI, 68.5% to 91.5%), demonstrating significant therapeutic benefit (p=0.030). Adverse events, including nausea, epigastric discomfort, and lethargy, were significantly more frequent in the bismuth-containing quadruple therapy group (p=0.007), but they were mild and tolerable enough not to affect compliance (p=0.329).

Conclusions: Rifabutin with bismuth-containing quadruple regimen as a salvage treatment achieved significantly superior eradication efficacy over the rifabutin-based triple regimen. Further multicenter prospective studies are needed to provide additional supporting evidence.

The global burden of hepatocellular carcinoma (HCC) has shifted from viral to nonviral etiologies. However, successful antiviral therapy does not fully eliminate the risk of HCC, underscoring the demand for more effective surveillance strategies. Current screening methods, such as semiannual ultrasonography and the measurement of α-fetoprotein levels, offer suboptimal sensitivity for early detection. A cost-effective, reliable surveillance approach remains an unmet need. The Barcelona Clinic Liver Cancer staging system provides a framework to guide HCC therapy; yet, some gray zone exists, particularly for patients with intermediate-stage disease. Although tyrosine kinase inhibitors and immunotherapies have transformed the therapeutic landscape, their efficacies vary among patients, highlighting the necessity for personalized treatment strategies. In response to these challenges, artificial intelligence (AI) approaches have emerged as transformative tools in healthcare. By processing complex, nonlinear relationships and uncovering hidden patterns in clinical data, AI methods offer capabilities beyond those of traditional statistical methods. Furthermore, AI-driven multi-omics analysis holds promise for identifying novel biomarkers, thereby advancing precision medicine for HCC patients. This review introduces the potential of AI applications in enhancing the diagnosis, treatment, and prognosis of HCC.

Background/aims: Early detection and removal of colon polyps are critical for preventing colorectal cancer. Computer-aided detection (CADe) systems have been introduced to increase the polyp detection rate (PDR) during colonoscopy, potentially enhancing its effectiveness. This study aimed to evaluate the efficacy of a CADe system in colorectal neoplasm detection.

Methods: This prospective, randomized controlled trial was conducted at two tertiary centers (May 2023 to April 2025). Patients were randomly assigned to CADe or conventional colonoscopy and underwent screening, surveillance, or diagnostic colonoscopy. The primary endpoint was the adenoma detection rate (ADR), while the secondary endpoints were the PDR, relative risk (RR) of polyp detection, adenomas per colonoscopy (APC), and factors influencing adenoma detection.

Results: Of 1,004 enrolled patients, 998 were randomly allocated into CADe and conventional colonoscopy groups (497 CADe system and 501 conventional colonoscopy). The CADe group had greater polyp counts (2.2 per colonoscopy vs 1.4 per colonoscopy; p<0.001) and APC values (1.2 vs 0.8; p<0.001). The CADe group showed significantly higher PDRs (72.2% vs 54.5%; p<0.001; RR, 2.173; 95% confidence interval [CI], 1.669 to 2.828) and ADRs (52.3% vs 36.1%; p<0.001; RR, 1.940; 95% CI, 1.505 to 2.499). CADe also significantly increased the detection rate of hyperplastic polyps (p=0.007; RR, 1.474; 95% CI, 1.113 to 1.952) and increased the detection rates across all sizes and locations. In multivariable analysis, CADe use was the strongest independent predictor of adenoma detection (odds ratio, 1.914; 95% CI, 1.467 to 2.496), outweighing male sex, older age, diagnostic indication, and withdrawal time.

Conclusions: Real-time CADe-assisted colonoscopy significantly increased PDR and ADR and proved to be a strong independent predictor of adenoma detection (cris.nih.go.kr, KCT0009664).

Colonoscopy plays a pivotal role in colorectal cancer (CRC) screening and reduces CRC incidence and mortality. Its effectiveness depends on colonoscopist performance, which can vary. Missed lesions during colonoscopy can lead to post-colonoscopy CRC (PCCRC), making high-quality colonoscopy essential for maximizing the preventive benefit of CRC screening. This review highlights the significance of colonoscopy quality indicators and practices for improvement. Bowel preparation, cecal intubation, and withdrawal time are key process indicators for procedure quality and are closely associated with the adenoma detection rate (ADR) and PCCRC risk. Given the role of colonoscopy in preventing CRC through the removal of precancerous lesions, the ADR serves as the core quality metric and the most reliable predictor of PCCRC. Serrated polyps have gained attention in colonoscopy quality research, as 15% to 30% of CRCs arise from serrated lesions, with an increased detection rate inversely associated with PCCRC risk. This emphasizes the critical need for continuous efforts by colonoscopists to enhance performance quality. Systemic interventions, audits and feedback during endoscopist education, basic and enhanced withdrawal and inspection techniques, and technologies such as mucosal exposure devices and computer-aided detection have demonstrated efficacy in increasing the ADR. While artificial intelligence has shown promise in increasing the ADR, inconsistent outcomes in real-world studies underscore the continued importance of the fundamental aspects of high-quality colonoscopy techniques, including complete mucosal exposure. Understanding quality indicators and ensuring high-performance quality in daily practice will ultimately lead to better CRC prevention outcomes.