Gut and Liver最新文献

Background/aims: Despite medical advances in recent decades, the mortality rate of advanced liver cirrhosis remains high. Although liver transplantation remains the most effective treatment, candidate selection is limited by donor availability and alcohol abstinence requirements. Bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has shown promise for the treatment of advanced cirrhosis. However, trials tend to involve small patient samples, and long-term follow-up studies are lacking. In this study, BM-MSC transplantation outcomes were assessed using real-world evidence (RWE) along with dynamic matching to reduce bias.

Methods: A control group was selected using exposure density sampling to reduce immortal time bias. Mortality rates were compared using Kaplan-Meier survival analysis and Cox proportional-hazard regression models, with adjustments for baseline characteristics.

Results: The cumulative incidences of 5-year mortality were 0%, 5.0%, and 11.3% at 1, 3, and 5 years in the BM-MSC group, compared with 7.0%, 10.9%, and 42.1% in the control group, respectively. Kaplan-Meier analysis revealed no significant difference in 1-year mortality between the BM-MSC and control groups (p=0.140). However, 3- and 5-year mortalities were significantly lower in the BM-MSC group (p<0.001). The adjusted hazard ratios for 5-year mortality in the BM-MSC group were 0.18 (95% confidence interval [CI], 0.04 to 0.87) and 0.14 (95% CI, 0.02 to 0.82) under the two models, indicating a lower mortality risk than in controls.

Conclusions: This study highlights the potential of BM-MSC transplantation in reducing long-term mortality in patients with alcoholic cirrhosis. The use of RWE provides a valuable framework for evaluating treatment efficacy and overcoming randomized controlled trial limitations, setting a precedent for future clinical research.

Background/aims: Early-onset inflammatory bowel disease (EO-IBD) poses a global health challenge with its distinct clinical manifestations and complex progression.

Methods: In this study, IBD cases occurring before age 20 were defined as EO-IBD. Data were extracted from the Global Burden of Disease 2021 database. Temporal trends were assessed using Joinpoint regression analysis, and future epidemiological trends were projected using the Bayesian age-period-cohort (BAPC) model. Health disparities across various sociodemographic index (SDI) regions were quantified using the slope index of inequality and concentration index.

Results: From 1990 to 2021, the global number of EO-IBD cases increased, while the incidence rates showed minimal change. Mortality and disability-adjusted life years (DALYs) rates briefly increased before a rapid decline after 1992. In 2021, males had higher mortality and DALYs rates due to EO-IBD than females. The highest mortality and DALYs rates were observed in the <5 years and 15 to 19 years age groups. Geographically, high SDI regions had the highest incidence, prevalence, and DALYs rates, while low SDI regions had the highest mortality rates. BAPC projections indicate that by 2036, the age-standardized incidence rate and prevalence rate will increase, whereas the age-standardized mortality rate and DALYs rates will continue to decline.

Conclusions: The incidence of EO-IBD is projected to exhibit an increasing trend in the future. Although the global mortality and DALYs rates of EO-IBD have decreased, significant disparities persist across age groups and regions. Targeted prevention and control strategies are needed to address the needs of high-risk populations and regions.

Background/aims: Patient-derived organoids (PDOs) are promising preclinical models that replicate critical tumor features. However, intratumoral heterogeneity challenges the clinical utility of PDOs, especially in capturing diverse tumor cell subpopulations.

Methods: Single-cell transcriptomics was used to analyze PDOs from distinct sites within a single gastric cancer tumor, aiming to assess their ability to reflect intratumoral heterogeneity.

Results: The PDOs displayed similarities in gene expression but also exhibited distinct profiles. Single-cell analysis of PDOs revealed upregulation of markers for neuroendocrine tumors, which was validated via immunohistochemistry staining of neuron-specific enolase in the primary tumor. Notably, heat shock proteins showed significant variability among the PDOs, impacting immune responses. Tumors with abundant heat shock proteins are reported to have increased cytotoxic T cell activity.

Conclusions: Intratumoral heterogeneity poses challenges for PDO-based models, highlighting the need for comprehensive assessment. Despite their limitations, PDOs offer valuable insights into precision medicine for patients with gastric cancer, aiding in the development of therapeutic strategies.

Background/aims: Despite the global burden of functional abdominal pain disorder (FAPD) and its four subtypes (irritable bowel syndrome [IBS], functional dyspepsia [FD], abdominal migraine [AM], and functional abdominal pain not otherwise specified [FAP-NOS]), studies involving an estimation of FAPD prevalence based on the Rome III or IV criteria are limited. Therefore, we aimed to estimate the prevalence of FAPD and its four subtypes.

Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Embase, Google Scholar, and the Cochrane Library. Studies that were performed with the general population and applied Rome III or IV diagnostic criteria were included. Data were extracted to estimate the prevalence of FAPD using a random-effects model with 95% confidence intervals (CIs). Heterogeneity was assessed using the I² statistic. The study protocol was preregistered with PROSPERO (CRD420251004116).

Results: The overall prevalence of FAPD was 10.89% (95% CI, 9.51% to 12.48%), with pooled prevalence rates of 11.84% (10.29% to 13.61%) with the Rome III criteria and 8.42% (6.10% to 11.62%) with the Rome IV criteria. With the Rome III criteria, IBS had the highest prevalence, while FD had the lowest. In contrast, with the Rome IV criteria, the prevalence of IBS, AM, and FAP-NOS decreased, whereas FD became the most prevalent, affecting approximately one in 23 individuals, compared to one in 51 individuals affected by IBS, one in 68 individuals affected by AM, and one in 115 individuals affected by FAP-NOS. Additionally, females exhibited higher prevalence rates of FAPD and all its subtypes than males.

Conclusions: The diagnostic criteria of Rome IV are stricter than those of Rome III, which likely affects the estimated prevalence of FAPD and its subtypes.

Background/aims: The relationship between Helicobacter pylori (HP) eradication and osteoporosis development remains inadequately elucidated. This study aimed to ascertain whether HP eradication therapy confers protective effects against osteoporosis progression.

Methods: Subjects without osteoporosis who underwent esophagogastroduodenoscopy with concurrent HP testing were prospectively recruited between May 2003 and February 2023 at Seoul National University Bundang Hospital. Participants were stratified into two cohorts: those with successful HP eradication and those without. Osteoporosis was diagnosed using dual-energy X-ray absorptiometry, and the risk of osteoporosis was assessed using Cox proportional hazards regression analysis.

Results: The successfully eradicated cohort comprised 730 individuals (mean age, 56.4 years; 67.5% female), compared with 116 individuals (mean age, 56.2 years; 74.1% female) in the non-eradicated cohort. Osteoporosis occurred in 179 subjects (24.5%) in the eradicated group and in 40 subjects (34.5%) in the non-eradicated group. Significant risk factors for osteoporosis included female sex (hazard ratio [HR], 3.12; 95% confidence interval [CI], 1.93 to 5.05; p<0.001), advanced age (HR, 1.08; 95% CI, 1.06 to 1.10 per year; p<0.001), and persistent HP infection (HR, 1.60; 95% CI, 1.13 to 2.28; p=0.009). In subgroup analyses according to sex and age, HP eradication demonstrated a significant reduction in osteoporosis risk in females (p=0.005) than in males, especially among females aged ≥50 years (p=0.003). However, this change was not pronounced in males.

Conclusions: HP eradication may serve as a preventive intervention against osteoporosis development, particularly among female subjects (ClinicalTrials.gov: NCT06818591).

Background/aims: Studies have demonstrated that gastroesophageal reflux disease has an unfavorable effect on sleep. However, it is largely unknown whether erosive esophagitis (EE) is associated with sleep issues.

Methods: Study participants were 335,883 Korean adults who underwent upper endoscopy and completed the Pittsburgh Sleep Quality Index (PSQI) as part of a health check-up. Study participants were divided into an EE group and a non-EE group. Multivariable adjusted logistic regression analysis was used in calculating the odds ratio (OR) and 95% confidence interval (CI) (adjusted OR [95% CI]) for poor sleep quality, long sleep induction time, interrupted sleep, sleep pill use, and short sleep duration in the two groups. Subgroup analysis was conducted after stratifying the EE group patients on the basis of the extent of EE (Los Angeles classification [LA]-A, LA-B/C/D).

Results: While the prevalence of EE was higher in men (11.1%) than women (1.8%), the mean PSQI score was higher in women (5.3±2.7) than in men (4.9±2.3). In men, EE was associated with poor sleep quality (adjusted OR, 1.04; 95% CI, 1.01 to 1.08), long sleep induction time (adjusted OR, 1.10; 95% CI, 1.03 to 1.18), and interrupted sleep (adjusted OR, 1.11; 95% CI, 1.04 to 1.19). Subgroup analysis showed that LA-A was significantly associated with poor sleep quality (adjusted OR, 1.04; 95% CI, 1.01 to 1.08), long sleep induction time (adjusted OR, 1.11; 95% CI, 1.03 to 1.19), and interrupted sleep (adjusted OR, 1.12; 95% CI, 1.04 to 1.20) in men. In contrast, women failed to show a significant association between EE and sleep issues.

Conclusions: EE was associated with a modest increase in the likelihood of poor sleep quality, long sleep induction time, and interrupted sleep among men.

Background/aims: The efficacy of proton pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) in the treatment of eosinophilic esophagitis (EoE) has been well established. This study aimed to clarify the impact of PPIs/P-CABs on esophageal wall thickness and clinical symptoms in EoE patients.

Methods: Patients who were consecutively diagnosed with asymptomatic esophageal eosinophilia and EoE and treated with PPIs/P-CABs were assessed in this study. Esophageal wall thickness before and after treatment was evaluated using endoscopic ultrasonography.

Results: Thirteen patients were asymptomatic, while 20 presented with gastrointestinal symptoms at baseline. Treatment led to significant decreases in symptom scores, the EoE Endoscopic Reference Scores, and the EoE Histologic System Scores compared with those at baseline. Following treatment, significant reductions were observed in the total esophageal wall thickness (TWT) and thickness from the surface to the muscular layer (TSM) across the upper, middle, and lower esophagus compared with baseline values (median TWT, 2.0 mm vs 1.7 mm, p=0.005; 2.3 mm vs 1.9 mm, p=0.004; 2.9 mm vs 2.3 mm, p<0.001; median TSM, 1.1 mm vs 0.9 mm, p=0.001; 1.3 mm vs 1.1 mm, p<0.001; 1.8 mm vs 1.4 mm, p<0.001, respectively). Similar trends were observed in the lower esophagus of patients with asymptomatic esophageal eosinophilia, with the TWT and TSM values significantly lower after treatment (median TWT, 2.7 mm vs 2.5 mm, p=0.045; median TSM, 1.7 mm vs 1.5 mm, p=0.008, respectively). These findings were consistent in patients treated with either PPIs (p=0.027 and p=0.018, respectively) or P-CABs (p<0.001 and p<0.001, respectively).

Conclusions: PPIs/P-CABs reduce esophageal wall thickening, particularly in the mucosal and submucosal layers.

Background/aims: Silymarin has been reported to be hepatoprotective and to improve liver function; however, its clinical effectiveness in specific liver diseases remains unclear. This study aimed to evaluate the impact of Legalon, which contains silymarin as its active ingredient, on changes in liver function test values and to assess its potential use as a practical treatment option for liver diseases.

Methods: This multicenter retrospective cohort study used the Common Data Model. Data were collected from adult patients with liver disease who were first prescribed Legalon between January 1, 2013, and December 31, 2022, across 10 medical institutions in South Korea. Changes in liver function test values at follow-up time points were compared with baseline values.

Results: Patients who were prescribed Legalon for at least 6 months showed a statistically significant decrease in liver function test values (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) compared with baseline values. At 3 and 6 months, aspartate aminotransferase decreased by approximately 23.18% and 24.54%, alanine aminotransferase decreased by 20.24% and 25.12%, and alkaline phosphatase decreased by 3.02% and 5.90%, respectively. All three parameters showed a sustained decline.

Conclusions: Our findings indicate that silymarin (Legalon) induces a significant reduction in liver function test values, thus suggesting that this drug exerts medium to long-term hepatoprotective benefits. Moreover, the synergistic effects of silymarin with standard treatments highlight its potential as a complementary therapy for liver diseases.

Background/aims: Pancreatic ductal adenocarcinoma (PDAC) is a challenging cancer to treat and has a poor prognosis and limited treatment options. In this study, the anticancer effects of disulfiram combined with copper (DSF/Cu) on PDAC cells, including those resistant to 5-fluorouracil, was assessed.

Methods: Human pancreatic cancer cells (BxPC-3 and CFPAC-1) and their 5-fluorouracil-resistant (5FUR) counterparts were treated with DSF/Cu to assess cytotoxicity. Expression levels of nuclear factor E2-related factor-2 (NRF-2) and heme oxygenase-1 (HO-1) were analyzed by reverse transcription quantitative polymerase chain reaction and Western blotting, while intracellular reactive oxygen species (ROS) levels were evaluated using H2DCFDA staining and flow cytometry. The effects of DSF/Cu on protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways were evaluated by Western blot analysis. In vivo efficacy was investigated using a xenograft mouse model, in which mice were orally administered DSF (75 mg/kg) and Cu (2 mg/kg) twice weekly for 5 weeks.

Results: We demonstrated that DSF/Cu effectively induced cytotoxicity in both pancreatic cancer cells and their 5FUR counterparts by modulating ROS levels, NRF-2 levels, and associated survival pathways. DSF/Cu treatment significantly decreased NRF-2 expression and reduced ROS levels, specifically in 5FUR cells. DSF/Cu facilitated NRF-2-independent HO-1 expression and differentially modulated Akt and MAPK signaling pathways in pancreatic cancer cells and their 5FUR counterparts. In vivo studies using a xenograft mouse model confirmed the antitumor efficacy of DSF/Cu, as evidenced by reduced tumor volumes and NRF-2 expression.

Conclusions: These findings highlight the potential of DSF/Cu as a novel and effective therapeutic strategy for PDAC, specifically for overcoming resistance to standard therapies.

Background/aims: To construct a new model based on folate receptor-positive circulating tumor cells (FR⁺-CTC) for the preoperative prediction of peritoneal metastasis in gastrointestinal malignancies and to apply this model in clinical practice.

Methods: Patients with gastrointestinal malignancies who had undergone preoperative FR⁺-CTC counts were retrospectively collected. Risk factors for peritoneal metastasis in patients with gastrointestinal malignancies were identified using a logistic regression model. The "pROC" package in R software was employed to plot the receiver operating characteristic curve for predicting peritoneal metastasis in these patients based on identified risk factors. Spearman correlation analysis was performed to assess the relationship between FR⁺-CTC counts and risk factors.

Results: A total of 396 patients meeting the inclusion criteria were finally included in the study. The number of FR⁺-CTC, albumin level, total protein level, and cancer antigen 125 (CA-125) level were identified as risk factors affecting peritoneal metastasis in gastrointestinal malignancies. The number of FR⁺-CTC was significantly negatively correlated with albumin (R=-0.21, p<0.001), and total protein levels (R=-0.10, p=0.047), and a positively correlated with CA-125 level (R=0.15, p=0.004). The number of FR⁺-CTCs was significantly higher in patients with peritoneal metastasis, lymph node metastasis, vascular invasion, neural invasion, and in those with stage T3-4 and III-IV gastrointestinal malignancies (p<0.05 for all). The model demonstrated stable predictive capacity, as validated through 10-fold cross-validation.

Conclusions: FR⁺-CTCs can serve as a novel biomarker for gastrointestinal malignancies. A new model based on FR⁺-CTCs demonstrated strong predictive capabilities for the preoperative assessment of peritoneal metastasis in gastrointestinal cancers.