Journal of Gastroenterology and Hepatology最新文献

Hepatocellular carcinoma (HCC) remains one of the most prevalent and lethal malignancies worldwide, characterized by late diagnosis, limited therapeutic options, and poor prognosis. Conventional systemic therapies such as sorafenib and its successors provide only modest survival benefits and are frequently complicated by toxicity and drug resistance. In recent years, immunotherapy has emerged as a promising avenue, yet its efficacy is often restricted by the profoundly immunosuppressive tumor microenvironment (TME). Within this landscape, exosomes-nanoscale extracellular vesicles secreted by tumor, stromal, and immune cells-have gained increasing attention for their central role in intercellular communication. They influence immune modulation, metabolic reprogramming, and therapeutic resistance, while also serving as potential biomarkers, nanocarriers, and vaccine platforms. Tumor-derived exosomes (TEXs) contribute to immune evasion by suppressing CD8⁺ T cells, polarizing macrophages toward protumoral phenotypes, and enhancing immune checkpoint resistance. Conversely, engineered exosomes demonstrate significant therapeutic potential by reprogramming TAMs, improving drug delivery, and acting as cancer vaccines. Despite these advances, challenges remain in exosome biogenesis, heterogeneity, large-scale production, and off-target effects, which hinder clinical translation. Furthermore, interactions between exosomes and gut microbiota in modulating hepatic immunity represent an emerging frontier with unexplored therapeutic implications. Continued advances in bioengineering, nanotechnology, and systems biology are expected to refine exosome-based therapies, offering novel, personalized strategies to improve outcomes for HCC patients.

Background and aim: Endoscopic ultrasound (EUS)-guided drainage is widely used for postoperative pancreatic fluid collections (PO-PFCs). However, concerns regarding adverse events persist. We aimed to assess clinical outcomes and identify risk factors for adverse events following endoscopic ultrasound-guided drainage of postoperative pancreatic fluid collections after distal pancreatectomy.

Methods: We retrospectively analyzed 124 patients who underwent EUS-guided drainage for PO-PFCs following distal pancreatectomy. The clinical and procedural data were also evaluated. Risk factors for adverse events and post-procedural bleeding were identified using univariate and multivariate logistic regression analyses. Subgroup analyses were performed before and after the introduction of the electrocautery-enhanced lumen-apposing metal stent (EC-LAMS).

Results: Technical and clinical success rates were 100% and 92.7%, respectively. Adverse events occurred in 25.8% (32/124) of patients. Moderate-to-severe bleeding occurred in 11 patients, of whom 10 required embolization or emergency surgery. Paracolic gutter extension was an independent risk factor for adverse events. Factors associated with post-procedural bleeding included paracolic extension, longer procedure time, antiplatelet or anticoagulant use, and the combined use of electrocautery and mechanical dilators. In the subgroup analysis before and after EC-LAMS introduction, adverse events were less frequent (31.9% vs. 18.2%), but the difference was not statistically significant (p = 0.10).

Conclusions: EUS-guided drainage of PO-PFCs is effective but carries the risk of adverse events. Ongoing refinements in the technique and device design appear to have improved safety over time. Careful case selection and early recognition of adverse events are essential for optimizing patient outcomes.

Background and aims: Gastric varices (GV) are a major complication of portal hypertension, with a high risk of severe bleeding. Conventional endoscopic glue injection or endoscopic ultrasound (EUS) directed therapies have been used for treatment. However, each has its limitations. EUS-guided combination of coil and glue injection has emerged as a potential strategy to improve outcomes. This meta-analysis compares the efficacy and safety of EUS-coil and glue to other endoscopic modalities in GV management.

Methods: Five databases were systematically searched until October 2024. Data were pooled using risk ratios (RRs) with 95% confidence intervals (CIs) via a random-effect model. Heterogeneity was assessed using the I² statistic, and subgroup and sensitivity analyses were performed. The risk of bias in studies and the certainty of the evidence were evaluated.

Results: Nine studies with 579 patients met the inclusion criteria. Compared with other modalities, EUS-coil and glue had a lower risk of reintervention (RR = 0.32, 95% CIs = 0.21-0.50) and a higher rate of GV obliteration (RR = 1.18, 95% CIs = 1.03-1.37). There was no significant difference in mortality risk (RR = 0.87, 95% CIs = 0.54-1.40). The overall risk of adverse events (RR = 0.55, 95% CIs = 0.34-0.90) was lower, particularly rebleeding (RR = 0.36, 95% CIs = 0.22-0.59). The certainty of evidence ranged from very low to moderate due to bias and study heterogeneity.

Conclusions: EUS-coil and glue injection offers superior efficacy and a favorable safety profile compared with other endoscopic treatments for GV. However, the quality of the evidence warrants further well-designed studies to assess long-term outcomes.

Background and aim: The consumption of meat, particularly processed and red meat, is believed to increase the risk of colorectal cancer (CRC). This study aims to conduct a meta-analysis to clarify the association between the consumption of red meat, processed meat, and white meat with the risk of CRC, thereby providing a scientific foundation for CRC prevention.

Methods: As of March 2024, we comprehensively searched the Cochrane Library, PubMed, and EMBASE databases for relevant studies. A random-effects model was utilized to calculate the relative risk (RR) and 95% confidence interval (CI), while the I² statistic was used to evaluate the heterogeneity among the studies. Funnel plots and Egger's test were used to assess publication bias, and stratified analyses were conducted based on tumor site, gender, geographic region, and the MD scoring system.

Results: This study includes a total of 31 studies, comprising 12 cohort studies and 19 case-control studies. In cohort studies, the associations observed were as follows: red meat: OR = 1.11 (95% CI: 1.02-1.20), processed meat: OR = 1.17 (95% CI: 1.09-1.25), and white meat: OR = 0.95 (95% CI: 0.72-1.19). In case-control studies, the associations were as follows: red meat: OR = 1.12 (95% CI: 1.03-1.20), processed meat: OR = 1.12 (95% CI: 1.00-1.23), and white meat: OR = 0.95 (95% CI: 0.85-1.24).

Conclusion: The consumption of red and processed meat demonstrated a statistically significant positive correlation with an elevated risk of CRC; however, the consumption of white meat did not exhibit such an association.

Background: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a group of chronic intestinal diseases possibly linked to genetic, environmental, and dietary factors. Recently, studies on caffeine intake and IBD risk have increased, but results remain controversial.

Objective: To explore the relationship between caffeine intake and IBD risk through a systematic review and meta-analysis.

Methods: This study searched multiple databases for prospective, cross-sectional and case-control studies examining caffeine intake and IBD risk, including CNKI, VIP, Wanfang, PubMed, Embase, JBI, and WOS, from database inception to May 21, 2024. Two researchers independently extracted literature data and evaluated quality using Stata 16.0 software for meta-analysis.

Results: A total of 21 studies with 13 209 participants were included. The meta-analysis showed no significant association between caffeine intake and IBD (RR = 0.84, 95% CI = 0.68-1.04). In Americans, caffeine increased UC risk by 68% (RR = 1.68, 95% CI = 1.17-2.42). Age analysis showed caffeine increased IBD risk by 4.52 times in those ≤18 (RR = 4.52, 95% CI = 1.59-12.88) but decreased risk by 7% in those >18 (RR = 0.93, 95% CI = 0.73-1.18). Coffee reduced UC risk by 57% (RR = 0.43, 95% CI = 0.29-0.65), tea by 46% (RR = 0.54, 95% CI = 0.31-0.92). Caffeine increased CD risk by 80% in smokers (RR = 1.80, 95% CI = 1.25-2.60).

Conclusion: The relationship between caffeine intake and IBD risk varies by region, age, caffeine source, smoking, and education level. In Asia and Europe, coffee and tea reduce UC risk, whereas in America and among adolescents, caffeine may increase UC risk. Smoking and education level also significantly influence this relationship, suggesting various factors must be considered to assess caffeine's impact on IBD risk accurately.

Nonalcoholic fatty liver disease (NAFLD) is commonly associated with overweight and obesity. But an increasing number of cases involve lean individuals, who tend to experience worse liver outcomes. In this study, we established mouse models of both obese and lean NAFLD by feeding mice a Western diet (WD) ad libitum and a WD with 30% caloric restriction (CR), respectively, to investigate the effects of piperine. After 12 weeks, hepatocyte lipid deposition and liver injury were similar in lean and obese NAFLD mice. Piperine treatment significantly reduced serum ALT levels and hepatic triglyceride (TG) content, alleviating hepatic steatosis in both groups. The mechanism of action involved the downregulation of fatty acid uptake, as evidenced by reduced expression of PPARγ and CD36, as well as the promotion of lipolysis through upregulation of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL). Additionally, piperine enhanced hepatic mitochondrial β-oxidation in the obese NAFLD model by upregulating carnitine palmitoyltransferase 1A (CPT1A). In conclusion, feeding a WD with 30% CR successfully induced lean NAFLD in mice, and piperine effectively alleviated NAFLD in both lean and obese mice.

Objective: The immune checkpoint Tim-3 has been implicated in the pathogenesis of primary biliary cholangitis (PBC), but its precise role in modulating macrophage polarization and immune dysregulation remains unclear. This study aimed to define the expression patterns of Tim-3 in PBC patients and elucidate its functional impact on macrophage behavior and disease progression.

Methods: Bulk RNA sequencing was performed using peripheral blood mononuclear cells (PBMCs) derived from PBC patients. The expression of Tim-3 and Toll-like receptor (TLR) 2 was assessed using flow cytometry. A murine model of autoimmune cholangitis was established using syngeneic bile duct protein. The Tim-3/Galectin-9 pathway was blocked using α-lactose both in vivo and in vitro. Short hairpin RNA (shRNA)-mediated silencing of ATF3 expression was conducted in THP-1 cells to explore its role in macrophage regulation.

Results: Our results revealed a significant pro-inflammatory innate immune response in the periphery of PBC patients. Advanced PBC patients exhibited reduced M2-like Kupffer cells and decreased expression of Tim-3 and ATF3, whereas Galectin-9 expression was upregulated. TLR2 activation downregulated Tim-3 and ATF3 expression in macrophages. Blockade of the Tim-3/Galectin-9 pathway with α-lactose exacerbated experimental autoimmune cholangitis, reduced M2 Kupffer cells and ATF3 expression, and increased CXCL10 levels in the liver. Furthermore, silencing ATF3 impaired the suppressive effects of the Tim-3/Galectin-9 pathway on TLR2-activated macrophages and primary murine Kupffer cells.

Conclusion: These findings highlight the prominent pro-inflammatory innate immune response in PBC patients and demonstrate that ATF3 partially mediates the immunomodulatory effects of the Tim-3/Galectin-9 pathway on macrophages.

Gastric intestinal metaplasia (GIM), a precancerous gastric lesion, represents a critical transitional stage in the Correa cascade that progresses from chronic inflammation to gastric adenocarcinoma (GAC). Emerging evidence implicates neutrophils as key orchestrators of GIM pathogenesis through multifaceted interactions within the tumor microenvironment. Therapeutic strategies targeting neutrophil activation, migration, and effector functions, including autophagy modulation and phenotypic reprogramming to an anti-inflammatory N2 state, hold promise in reversing GIM progression. This review synthesizes the current knowledge on neutrophil-mediated mechanisms and explores clinically actionable pathways for GIM reversibility.