Journal of Gastroenterology and Hepatology最新文献

Background and aim: Krüppel-like factors15 (KLF15) is a cancer suppressor in many cancers. However, its precise function in the development of hepatocellular carcinoma (HCC) remains unclear. Lipogenesis is necessary for the development of HCC. This research aims to investigate the role of KLF15 in the regulation of hepatic lipid production and HCC progression.

Methods: The binding relationships among genes were confirmed by ChIP, dual luciferase assays, and Co-IP. Lipogenesis was examined by oil red O staining. Triglyceride and cholesterol levels were measured through commercial kits. The effect of treatment on HCC cell viability, proliferation, migration, and invasion were assessed using CCK-8, clone formation, or transwell assays. A subcutaneous tumorigenic model was utilized to explore the effects of PDLIM2 in HCC in vivo.

Results: KLF15 were downregulated in human HCC tissues. KLF15 overexpression reduced lipid droplet production, suppressed the expression of genes associated with lipogenesis, and promoted cell proliferation, migration, and invasion. KLF15 suppressed the NF-κB pathway through transcriptional activation of PDLIM2. PDLIM2 knockdown attenuated the effect of KLF15 overexpression on HCC. WSB2 degraded KLF15 through ubiquitination to promote HCC lipogenesis and development.

Conclusion: The ubiquitination degradation of KLF15 was mediated by WSB2, which led to transcriptional repression of PDLIM2 and further activation of the NF-κB pathway, ultimately promoting HCC lipogenesis and development.

Background and aim: The impact of different anti-thrombotic agents on patients with suspected small bowel bleeding (SSBB) who underwent balloon-assisted enteroscopy (DAE) is unclear. We aimed to examine the clinical effects and predictive factors of DAE based on the thromboembolic agents used.

Methods: We enrolled 399 patients with SSBB from a web-based DAE registry across 30 medical centers in South Korea. Among them, 291 patients did not receive anti-thrombotic agents, whereas 80, 22, and 6 patients received anti-platelet agents, direct oral anti-coagulants (DOACs), and warfarin, respectively.

Results: Diagnostic yields were similar across groups; however, therapeutic yields differed: 25.4%, 37.5%, 63.6%, and 83.3% in patients treated with no anti-thrombotic agents, anti-platelets, DOACs, and warfarin, respectively (p < 0.001). The multivariable logistic regression revealed that patients treated with DOACs and warfarin experienced significantly higher therapeutic yields (odds ratio [OR]: 2.803 and 9.526, respectively; 95% confidence interval [CI]: 1.048-7.500 and 1.061-85.481, respectively; p = 0.040 and 0.044, respectively) than those treated with no anti-thrombotic agents. The re-bleeding rates in patients treated with no anti-thrombotic agents, anti-platelets, DOACs, and warfarin were 9.6%, 6.3%, 13.6%, and 50.0%, respectively (p = 0.069). In the multivariable logistic regression analysis, patients treated with warfarin exhibited higher re-bleeding rates than those not treated with anti-thrombotic agents (OR: 9.393, 95% CI: 1.809-48.764, p = 0.008).

Conclusions: The diagnostic yield of DAE did not differ based on the anti-thrombotic agent type, whereas the therapeutic yield of DAE in DOAC and warfarin users was high. Careful monitoring for re-bleeding is advised in DOAC as well as warfarin users.

Background: Eosinophilic gastrointestinal disorders (EGIDs) are primary immune-mediated disorders, with significant morbidity and long-term sequelae. Temporal trends in incidence and prevalence are on the rise, but studies outside Europe and North America are sparse.

Methods: Based on retrospective Electronic Medical Records (EMR) data, we studied a large population cohort during the years 2014-2021 of all patients diagnosed with EGIDs. Incidence rate and prevalence were calculated for each year during the study cohort stratified by disease location, age, and sex.

Results: Between 2014 and 2021, among a population of 2.4 million persons, the incidence rate of EGIDs tripled from 2.51 (95% CI: 1.78-3.23) to 7.88 (95% CI: 6.75-9.01) per 100 000 person-years. Most (85.1%) were patients with eosinophilic esophagitis (EoE). The increased temporal trend was almost identical among all subgroups, including patients with EoE, patients with non-EoE EGIDs, and patients with EGIDs with esophageal involvement. The prevalence of EGIDs increased from 14.53 (95% CI: 12.80-16.26) to 51.43 (95% CI: 48.60-54.26) per 100 000 persons. In 2021, at the end of the study, the prevalence of EoE was 39.54 (95% CI: 37.05-42.02) per 100 000 persons, and the prevalence of non-EoE EGID was 11.89 (95% CI: 10.53-13.26) per 100 000 persons.

Conclusions: The incidence and prevalence of EGIDs in Israel have risen steeply during the last decade. The main contribution came from the increased incidence rate of patients with EoE. By the end of the surveillance period, the increased temporal trends did not reach a plateau.

Background: Studies have reported the benefits of tranexamic acid (TXA) in controlling bleeding across various conditions. However, the effect of TXA in upper gastrointestinal bleeding (UGIB) remains controversial, and its therapeutic impact when combined with acid suppression, particularly proton pump inhibitors (PPIs), which are considered first-line therapy for bleeding peptic ulcers, has not been reported.

Methods: We systematically searched PubMed, Embase, and Google Scholar from January 1987 to June 2024 using predefined keywords to identify RCTs meeting our inclusion criteria, including details of TXA dosage, route of administration, and choice of acid suppressants. Data from selected trials were extracted, and a meta-analysis was performed using random-effects modeling.

Results: Six trials with 709 participants were included. Baseline patient characteristics in the selected trials were balanced. The rebleeding rate, mortality, need for blood transfusion, units of blood transfused, and need for salvage therapy were compared. The TXA with acid suppression group significantly reduced the risk of rebleeding (RR: 0.63, 95% CI: 0.41-0.96), units of blood transfused (mean difference: -1.08, 95% CI: -1.44 to -0.71), and the need for salvage therapy (RR: 0.28, 95% CI: 0.12-0.64). No significant difference was observed in mortality rate (RR: 0.74) and need for blood transfusion (RR: 1.01) between the two groups, but outcomes favored the TXA and acid suppression group.

Conclusions: We suggest combining TXA with acid suppression as a first-line therapy for UGIB patients. Further trials should be conducted to determine the optimal dose and route of TXA administration for better care.

Background: Many patients with colorectal polyposis demonstrate negative results in germline mutation test. This study aimed to uncover genetic variants associated with nonhereditary colorectal polyposis using a genome-wide association study (GWAS).

Methods: At a single referral university hospital, between January 2012 and September 2021, 638 patients with ≥ 10 biopsy-proven cumulative polyps on colonoscopy without germline mutations related to hereditary colorectal cancer or polyposis were included. The control group comprised 1863 individuals from the Korea Medical Institute, each having undergone at least two colonoscopies, all of which were normal. This study utilized GWAS to identify susceptibility loci for nonhereditary colorectal polyposis. Genetic differences between patients with and without ≥ 10 polyp recurrences were analyzed using Cox proportional hazards models.

Results: GWAS revealed 71 novel risk single-nucleotide polymorphisms (SNPs) not seen in previous colorectal cancer and polyp GWAS. Five genes (UPF3A, BICRA, CBWD6, PDE4DIP, and ABCC4) overlapping seven SNPs (rs566295755, rs2770288, rs1012003, rs201270202, rs71264659, rs1699813, and rs149368557), previously linked to colorectal cancer, were identified as significant risk factors for nonhereditary colorectal polyposis. Two novel genes (CNTN4 and CNTNAP3B), not previously associated with colorectal diseases, were identified. Three SNPs (rs149368557, rs12438834, and rs9707935) were significantly associated with higher risk of recurrence of polyposis. The gene overlapping with rs149368557 was ABCC4, which was also significantly associated with an increased risk of nonhereditary colorectal polyposis.

Conclusion: This study identified 71 novel risk variants for nonhereditary colorectal polyposis, with three SNPs (rs149368557, rs12438834, and rs9707935) indicating significant associations with increased risk of polyposis recurrence.

Background: Fecal incontinence (FI) is a debilitating condition defined as recurrent uncontrolled passage of fecal material according to Rome IV. Although FI greatly impacts patients' health-related quality of life (HRQOL), there have been few studies about the prevalence of FI in the Japanese general population. The aim of this study was to investigate the epidemiology of FI using Rome IV criteria in Japan.

Methods: This was a cross-sectional internet survey for Japanese individuals aged 18 to 79 years using a questionnaire about demographics, comorbidities, lifestyle, abdominal symptoms, bowel habits, HRQOL, and disorders of gut-brain interaction according to Rome IV diagnostic criteria. Multivariate linear regression analysis identified factors associated with FI fulfilling Rome IV criteria (Rome IV FI).

Results: Overall, 9995 subjects were analyzed. Of which, 9.5% of the participants had at least one episode of FI in the last 3 months, and the prevalence of Rome IV FI was 1.2%. HRQOL was significantly impaired in patients with Rome IV FI compared to continent individuals. Major functional bowel disorders overlapped with 39.5% of Rome IV FI where functional diarrhea (25.8%) was the most predominant. The overlap further impaired HRQOL in Rome IV FI patients. Alcohol consumption (odds ratio 1.82, 95% CI 1.24-2.66, p = 0.002) was independently related to Rome IV FI apart from gastroesophageal reflux disease, irritable bowel syndrome, functional abdominal bloating/distension, and functional diarrhea.

Conclusions: The prevalence of Rome IV FI was 1.2% in Japan. Further study is warranted to investigate the effect of lifestyle modification on the management of FI.

Background and aim: The T cell receptor (TCR) can recognize a vast number of antigens and is closely associated with the pathogenesis of various diseases including autoimmune diseases and malignancies. However, the clinical significance of the TCR repertoire and its post-treatment changes remain unclear in liver diseases.

Methods: We performed next-generation sequencing (NGS)-based TCR analysis using DNA obtained from peripheral blood mononuclear cells (PBMCs) of healthy donors (HD, n = 5), primary biliary cholangitis (PBC, n = 5), autoimmune hepatitis (AIH, n = 5), and hepatocellular carcinoma (HCC, n = 5) and evaluated the changes after treatment.

Results: Baseline TCR repertoire analysis demonstrated that TCR clonotype usage is restricted and diversity is low in all three disease groups (PBC, AIH, and HCC), particularly in PBC and AIH compared to HD (p < 0.05). Following treatment, clonotype usage and diversity did not change significantly, except in AIH, where diversity decreased further (p < 0.05 for clone Shannon diversity and clone evenness). Disease-specific usage of TCR beta genes and specific changes after therapy were observed in all groups. Analysis of clonotypes shared with other individuals (public clonotypes) revealed that nine public clonotypes in PBC, eight in AIH, and eight in HCC disappeared after treatment. Motif analysis identified one characteristic motif (NQPQH) in PBC.

Conclusions: The diversity of the TCR repertoire, TCR beta chain usage, clonotypes, and motifs and their post-treatment changes are disease-specific in each liver disease, indicating that further TCR repertoire studies are needed to accelerate the understanding of liver disease pathogenesis from an immunological perspective.