Journal of Gastroenterology and Hepatology最新文献

Background and aim: Ulcerative colitis (UC) is a chronic inflammatory disease driven by immune dysregulation. PANoptosis, a novel form of programmed cell death, has been implicated in inflammatory diseases, but its specific role in UC remains unclear. This study aimed to identify PANoptosis-related genes (PRGs) that may contribute to immune dysregulation in UC.

Methods: Using bioinformatics analysis of the GEO databases, we identified seven hub PRGs. Based on these genes, we developed a predictive model to differentiate UC patients from healthy controls, and evaluated its diagnostic performance using ROC curve analysis. We further conducted functional enrichment, GSVA, and immune infiltration analyses. Immunohistochemistry (IHC) was used to validate the expression of hub genes in UC patients.

Results: The prediction model, based on the seven hub genes, exhibited diagnostic ability in discriminating UC patients from controls. Furthermore, these hub PRGs were found to be associated with immune cells, including dendritic cells, NK cells, macrophages, regulatory T cells (Tregs), and CD8+ T cells. They were also linked to key signaling pathways implicated in UC pathogenesis, such as IFNγ, TNFα, IL6-and JAK-STAT3, as well as hypoxia and apoptosis. Immunohistochemistry analysis validated the expression levels of hub PRGs in UC patients using paraffin sections of intestinal biopsy specimens.

Conclusions: This study identified PANoptosis-related genes with potential diagnostic value for UC and suggest that PANoptosis may contribute to the pathogenesis of UC by regulating specific immune cells and interacting with key signaling pathways. This highlights the potential importance of PANoptosis-related genes as therapeutic targets in UC management.

Background/aims: Endoscopic sphincterotomy (EST) is a standard treatment for common bile duct (CBD) stones. Endoscopic sphincterotomy combined with endoscopic papillary large balloon dilation (EST-EPLBD) is an effective treatment for difficult CBD stones. This study aims to evaluate and compare the effectiveness and adverse effects of EST-EPLBD and EST in treating large CBD stones.

Methods: We retrospectively analyzed the data of 85 patients with large CBD stones who underwent either EST or EST-EPLBD, resulting in successful CBD stone extraction from January 2018 to June 2022. Propensity score inverse weighting was performed to reduce the possible bias in baseline characteristics between the two treatment groups. The success rate of complete stone removal in the first session, mechanical lithotripsy use, and adverse events were analyzed by multivariable risk regression analysis.

Results: The rate of complete stone removal in one session of the EST-EPLBD group was higher than that of the EST group at 28.78% (95% confidence interval [CI] 4.43, 50.1; p = 0.003). Mechanical lithotripsy use was decreased in the EST-EPLBD group by 25.81% (95% CI 42.33,9.28; p = 0.002). However, the incidence of adverse events is comparable.

Conclusion: EST-EPLBD may be utilized in the treatment of CBD stones that exceed a diameter of 10 mm. The EST-EPLBD increased the rate of complete stone removal in a single session and reduced the need for mechanical lithotripsy. Conversely, the incidence rate of adverse events is similar.

Background: Bowel colonization with antimicrobial-resistant bacteria has been associated with worse clinical outcomes in patients with cirrhosis; however, it has not been studied in patients with acute-on-chronic liver failure (ACLF). We evaluated whether fecal isolation of carbapenem-resistant gram-negative bacteria (CR-GNB) among patients with ACLF affects short-term outcomes.

Methods: Patients of APASL-ACLF (n = 339) were screened between June 2020 and December 2021, and 150 were included. Stool cultures were carried out at baseline and every 5 days thereafter until discharge or death. All surviving patients were followed until 60 days after discharge.

Results: Mean age was 44.8 (8.8) years, with 86% males and alcohol as etiology in 66%. CR-GNB organisms were isolated from stool in 42% of hospitalized ACLF patients, with E. coli and Klebsiella pneumoniae as the most common species. Patients with CR-GNB fecal carriage were associated with higher CTP, MELD, and DF scores but not with recent antibiotics, proton pump inhibitors, or lactulose use. Extraintestinal infections developed in 59.3% overall, most commonly UTI, pneumonia, and SBP. Infectious complications developed in 57.3% and 19.7% with and without CR-GNB in the stool (RR: 5.5; p < 0.001). Peripheral cultures were positive in 60.7% with infections, with species concordant with the fecal isolates found in 90.7%. Isolation of CR-GNB from stool and high bilirubin were independently associated with both in-hospital mortality and 60-day mortality (p = 0.05).

Conclusions: Hospitalized ACLF patients with CR-GNB in the stool have a significantly higher risk of extraintestinal infections, in-hospital mortality, and short-term mortality up to 60 days.

Trial number: [NCT04383106].

Background and aim: No prospective studies have verified the incidence of cholecystitis in patients using the covered self-expandable metallic stent. In this study, we aimed to investigate the incidence of cholecystitis and its risk factors after low axial force covered self-expandable metallic stent placement for malignant distal biliary obstruction.

Methods: This multicenter prospective study included patients diagnosed with unresectable distal biliary obstruction between November 2019 and October 2022 who underwent low axial force covered self-expandable metallic stent placement.

Results: The technical success in the 93 analyzed patients was 100% and clinical success was 98.9%. The 70-mm covered self-expandable metallic stent was the most used in 53 patients (57.0%), followed by the 80-mm type in 27 patients (29.0%), 60-mm type in 12 patients (12.9%), and 50-mm type in 1 patient (1.1%). Cholecystitis after covered self-expandable metallic stent placement occurred in six patients (6.5%). The median time to onset was 46 days (range, 16-315 days), with 1 case in the early stage and five cases in the late stage. There was one mild case, one moderate case, and four severe cases. The presence of tumor involvement at the orifice of the cystic duct was identified as an independent risk factor (odds ratio, 17.0; 95% confidence interval, 1.5-195.1; p = 0.023).

Conclusions: The presence of tumor involvement at the orifice of the cystic duct was an independent risk factor for the development of cholecystitis after low axial covered self-expandable metallic stent placement.

Trial registration: University Hospital Medical Information Network (UMIN) (http://www.umin.ac.jp, registration number: UMIN 000038209).

Background and aim: Individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) who are at an increased risk of cardiovascular disease (CVD) are critical to identify and manage. We aimed to assess whether the risk of CVD in patients with MASLD differed according to the type or number of cardiometabolic risk factors.

Methods: This longitudinal cohort study involved 5674 adults who underwent at least two health checkups between 2004 and 2021. Steatotic liver disease (SLD) was assessed using ultrasonography and participants with SLD were classified as having either non-MASLD or MASLD. CVD risk was evaluated using coronary artery calcium (CAC) progression as measured using multidetector computed tomography scans.

Results: Over an average 5.8-year follow-up period, patients with MASLD exhibited faster CAC progression than those with non-MASLD (18% vs 11%, P < 0.01). MASLD with any cardiometabolic risk factor exacerbated CAC progression; however, the degree of CAC progression was similar among the different risk components. The adjusted ratios (95% CI) of CAC progression rates comparing non-MASLD with MASLD with one, two, three, four, and five cardiometabolic risk factors were 1.02 (0.99, 1.06), 1.04 (1.01, 1.08), 1.07 (1.03, 1.10), 1.08 (1.05, 1.11), and 1.11 (1.07, 1.15), respectively.

Conclusions: In individuals with MASLD, all cardiometabolic risk factors contributed to the deterioration of coronary atherosclerosis, with no specific factor exerting a dominant influence. Coronary atherosclerosis progression is directly associated with the cumulative number of cardiometabolic risk factors. Therefore, identifying and managing an increasing number of these factors is imperative in clinical practice, even when MASLD is diagnosed based on only one risk factor.

Background and aim: Hepatic ischemia-reperfusion (I/R) injury is the primary cause of liver dysfunction and liver failure, commonly occurring in liver transplantation, hepatectomy, and hemorrhagic shock. Polo-like kinase 2 (PLK2), a pivotal regulator of centriole duplication, plays a crucial role in cell proliferation and injury repair. However, the function of PLK2 in hepatic I/R remains unclear.

Methods: The effect of PLK2 was investigated in the mouse hepatic I/R model and the hepatocyte hypoxia-reoxygenation (H/R) model. Liver injury was assessed by serum transaminase and hematoxylin and eosin staining. Cell apoptosis was analyzed using TUNEL analysis and immunoblotting. Inflammatory factors were evaluated by reverse transcription-quantitative polymerase chain reaction. Mice or cultured cells during the I/R or H/R were treated by overexpressing PLK2. ROS fluorescence staining was used to assess oxidative stress injury.

Results: PLK2 was upregulated after hepatic I/R injury. Overexpressed PLK2 significantly improved liver enzyme levels and alleviated liver histological injury. Moreover, PLK2 decreased hepatocyte apoptosis and inhibited the expression of inflammatory factors in liver. Mechanistically, PLK2 increased the phosphorylation of GSK3β and enhanced expression of the antioxidant enzyme HO-1, leading to less ROS production. Inhibition of the HO-1 aggravated ROS generation and abolished the protective effect of PLK2.

Conclusion: Overall, these findings revealed that PLK2 enhanced HO-1 expression and reduced oxidative stress damage in hepatic I/R injury, and this protective effect related to GSK3β activity.

Background and aim: Non-responsive celiac disease (NRCD) is defined as ongoing symptoms despite 6-12 months of gluten-free diet (GFD), the only known treatment for celiac disease (CeD). There is inconsistency in studies describing the proportion of patients having NRCD and its various causes among patients with CeD. We therefore conducted a systematic review and meta-analysis to determine the prevalence and causes of NRCD.

Methods: The PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases were searched for original studies reporting the proportion of patients with persistent symptoms after ≥ 6 months of GFD. Studies reporting the etiologies of NRCD were also identified. The systematic review was conducted as per the Meta-analysis of Observational Studies in Epidemiology guidelines. Statistical analysis was performed in STATA.

Results: Of 2965 search results, nine studies met the inclusion and exclusion criteria. Five studies (n = 4414) reported data on prevalence, and seven studies (n = 790) reported the causes of NRCD. The pooled prevalence of NRCD was 22% (95% confidence interval, 11-35%). Among patients with NRCD, inadvertent exposure to gluten was the most common cause (33%), followed by functional gastrointestinal disorders including irritable bowel syndrome in 16%. Refractory CeD type II along with its premalignant and malignant sequelae was observed in 7% of patients with NRCD.

Conclusion: One in five patients with CeD may not respond to GFD and would likely be classified as NRCD. Inadvertent gluten exposure was the cause of ongoing symptoms in one-third of patients with NRCD. Improving adherence to GFD along with developing novel therapeutics to mitigate symptoms due to ongoing gluten exposure is critical.

Background and aim: Tegoprazan, a potassium-competitive acid blocker, can be used as a substitute for proton pump inhibitors in Helicobacter pylori eradication therapy; some studies have reported improved efficacy. In Korea, where clarithromycin resistance rates are high, we aimed to compare the efficacies of tegoprazan-based concomitant and bismuth quadruple therapies.

Methods: We retrospectively analyzed data from patients with H. pylori infection who received either 10-day tegoprazan-based concomitant therapy or 14-day tegoprazan-based bismuth quadruple therapy as first-line treatment. The primary outcome was H. pylori eradication rate, with secondary outcomes including adverse events and insufficient medication rates.

Results: Among the 1082 patients included in the study, 620 and 462 were treated with tegoprazan-based concomitant and bismuth quadruple therapies, respectively. Intention-to-treat analysis demonstrated no difference in eradication rates between the tegoprazan-based concomitant and bismuth quadruple therapy groups (74.7% [95% confidence interval-CI, 71.1-78.0%] vs 74.7% [95% CI, 70.6-78.5%], P = 0.999). Per-protocol analysis also showed similar eradication rates between the two groups (88.0% [95% CI, 85.0-90.6%] vs 89.7% [95% CI, 86.3-92.5%], P = 0.424). The overall adverse event rates (49.6% vs 39.2%, P = 0.001) and insufficient medication rates (4.8% vs 2.4%, P = 0.036) were higher in the bismuth quadruple therapy group than in the concomitant therapy group.

Conclusions: The eradication rates of tegoprazan-based 10-day concomitant therapy and 14-day bismuth quadruple therapy were comparable. However, because of its shorter treatment duration, better medical adherence, and lower incidence of adverse events, tegoprazan-based concomitant therapy may be preferable in regions with high rates of clarithromycin and metronidazole resistance.

Background and aim: Early predictors of morbidity after pancreaticoduodenectomy (PD) can guide tailored postoperative management. Preoperative inflammatory data in patients who underwent PD remained poorly studied in investigating the clinical significance of predicting postpancreatectomy acute pancreatitis (PPAP) and PPAP-associated postoperative pancreatic fistula (POPF).

Methods: The clinical data of 467 patients receiving PD between January 2020 and December 2022 were retrospectively reviewed. Preoperative inflammatory data were stratified according to PPAP, and independent risk factors were analyzed. Multivariate logistic regression and subgroup analyses were conducted to compare risk factors of PPAP-associated POPF and non-PPAP-associated POPF.

Results: PPAP occurred in 17.6% of patients. The incidence of other complications increased following PPAP. Among the preoperative inflammatory factors, only interleukin-6 (IL-6) increased (P < 0.001), leading to a higher incidence of PPAP and POPF (P < 0.001; P = 0.002). The area under the curve of IL-6 in predicting PPAP was 0.71 (0.65-0.77; P < 0.001). Abnormal preoperative IL-6 levels (odds ratio [OR]: 5.01; P < 0.001), soft pancreatic texture (OR: 2.15; P = 0.007), and pathology (OR: 2.03; P = 0.012) were independent risk factors for PPAP. The subgroup analysis showed that increased IL-6 (OR: 1.01; P = 0.006) and soft pancreatic texture (OR: 2.05; P = 0.033) resulted in a higher risk of PPAP-associated POPF, while increased IL-8 (OR: 1.01; P = 0.007), older age (OR: 1.05; P = 0.008), and higher body mass index (OR: 1.12; P = 0.021) correlated with non-PPAP-associated POPF.

Conclusion: PPAP is common after PD; a high preoperative IL-6 level can predict its occurrence, in addition to associated POPF, which could be due to a preoperative proinflammatory status.