Journal of Gastroenterology and Hepatology最新文献

Background and aim: The triglyceride-glucose (TyG) index and alanine aminotransferase (ALT) are emerging biomarkers linked to metabolic disturbances and liver health. Nonetheless, the combined impact of these markers on predicting new-onset steatotic liver disease (SLD) and its metabolic and alcohol-associated subtypes remains unclear. This study aimed to investigate the association of TyG and ALT, individually and combined, in incident SLD in the Korean Genome and Epidemiology Study (KoGES) and UK Biobank cohorts.

Methods: This study utilized data from two large population-based cohorts: KoGES (adults aged 40-69 years from South Korea [2001-2002]) and UK Biobank (participants aged 37-73 years from the United Kingdom [2006-2010]). Participants without baseline SLD were classified into four groups based on TyG index and ALT levels, and the incidence of SLD was compared among these groups to assess risk.

Results: Elevated baseline TyG index and ALT levels were significantly associated with a higher risk of new-onset SLD and its subtypes in both cohorts. The highest HRs and ORs were observed in individuals with both markers elevated (2.39 in KoGES; 3.89 in UK Biobank). Survival analyses confirmed significantly lower survival probabilities in high-risk groups (p < 0.001). Predictive accuracy was highest with the combined TyG index + ALT model, outperforming either marker alone (p < 0.001).

Conclusions: Elevated combined baseline TyG index and ALT levels were significantly associated with increased risk of SLD and its subtypes. Combined use of these markers may be valuable for early identification and risk stratification of individuals at risk for SLD.

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 aims: Cellular senescence is a hallmark of several liver diseases, including primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). Senescent cholangiocytes exhibit a senescence-associated secretory phenotype (SASP), characterized by profibroinflammatory mediator release. Current cost-effective biomarkers predicting disease progression, particularly for PSC, are limited and often lack mechanistic relevance. We sought to define a plasma biomarker signature for PSC and PBC.

Methods: Plasma from early- and late-stage PSC and PBC, alcoholic liver disease (ALD), inflammatory bowel disease (IBD) patients, and healthy controls was analyzed. Seventy-one analytes were quantified using Luminex Multiplex Immunoassay or enzyme-linked immunosorbent assay (ELISA). Principal component analysis (PCA) identified key patterns. Findings from the PSC cohort were then applied to additional cohorts.

Results: Second principal component (PC2) (17 analytes, 17.1% variability) best separated PSC from controls. ANOVA showed significant differences in PC2 between early PSC vs. controls (p = 0.0001), late PSC vs. controls (p < 0.0001), and early vs. late PSC (p < 0.0001). PC2 analytes also distinguished early PBC vs. controls (p < 0.0332), late PBC (p < 0.0001), and ALD (p < 0.0001), and early vs. late PBC (p < 0.0001), but not IBD vs. controls (p = 0.119). Logistic regression using PC2 demonstrated strong discrimination of early- and late-stage PSC (AUC = 0.86) and control vs. early-stage PSC (AUC = 0.83).

Conclusion: This is the first study to define a plasma SASP biomarker signature associated with cholestatic liver disease. These analytes track disease stage and represent both mechanistic indicators and potential clinical trial endpoints.

Background: Fontan-associated liver disease (FALD) is a long-term complication after Fontan surgery, and the development of hepatocellular carcinoma (HCC) in relatively young patients has become a major clinical concern. This study aimed to clarify the diagnostic triggers, clinicopathological characteristics, treatment strategies, and outcomes of FALD-HCC.

Methods: We retrospectively reviewed 297 patients with FALD who visited our department between 2003 and 2025. Among them, 28 patients (9.4%) developed HCC. Diagnostic triggers, tumor characteristics, initial treatment modalities, and clinical courses were analyzed.

Results: HCC developed at a median age of 32.6 years, with an interval of 26.1 years after Fontan surgery. Diagnosis was triggered by tumor marker elevation, including alpha-fetoprotein and/or des-gamma-carboxy prothrombin, in 46.4% of patients, routine surveillance imaging in 35.7%, and symptom-driven imaging in 17.9%. Most patients had a single tumor, frequently located in the peripheral liver. At diagnosis, 71.5% were classified as stage I or II disease. Histological evaluation, available in selected cases, revealed variable tumor differentiation and advanced fibrosis in noncancerous liver tissue. Initial treatments included hepatic resection, transcatheter arterial chemoembolization, stereotactic body radiotherapy, proton beam therapy, systemic therapy, or palliative care alone in patients with advanced liver failure. Three-year survival rates were favorable, reaching 100% in patients treated with hepatic resection or stereotactic body radiotherapy.

Conclusions: When FALD-HCC was detected at an early stage through surveillance, a broad range of treatment options, including locoregional therapies, could be applied and were associated with favorable clinical outcomes. Although selection bias limits direct comparison, treatment of FALD-HCC should be considered.

Background and aim: We examined post hoc the effect of budesonide oral suspension (BOS/Eohilia) 2.0 mg twice daily (b.i.d.) on dysphagia symptom outcomes in patients with eosinophilic esophagitis (EoE).

Methods: Patients aged 11-55 years who received BOS 2.0 mg b.i.d. or placebo during phase 2 or phase 3, 12-week, double-blind, placebo-controlled clinical trials (MPI 101-06 and SHP621-301) were included. The Kaplan-Meier method captured time to first dysphagia symptom response (≥ 30% reduction in the Dysphagia Symptom Questionnaire [DSQ] score from baseline). Efficacy outcomes using the DSQ at weeks 4, 8, and 12 of therapy were: the proportion of patients with complete dysphagia symptom resolution; change from baseline in the number of dysphagia-free days; and the proportion of patients with dysphagia symptoms, but without adaptive behaviors or pain. Each outcome was measured based on daily DSQ records in the 2 weeks before each study visit.

Results: Overall, 411 patients from MPI 101-06 (BOS, n = 51; placebo, n = 42) and SHP621-301 (BOS, n = 213; placebo, n = 105) were included. Median time to first dysphagia symptom response was significantly shorter for BOS- than placebo-treated patients (MPI 101-06, p = 0.0239; SHP621-301, p = 0.0156), with separation between groups at week 2, the earliest time point measured. At all time points, higher proportions of BOS- than placebo-treated patients had complete dysphagia symptom resolution or had dysphagia symptoms but no adaptive behaviors or pain. BOS- versus placebo-treated patients also had greater improvements from baseline in the number of dysphagia-free days.

Conclusions: BOS is efficacious in managing dysphagia in EoE across several symptom metrics.

Clinicaltrials: gov: NCT01642212; NCT02605837.

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive cancers, typically diagnosed at an advanced stage due to its subtle and often absent early symptoms. Despite representing only 3% of new cancer cases, it is projected to become the second leading cause of cancer-related deaths by 2030. Currently, early diagnosis remains a significant challenge, and survival rates remain poor due to the lack of effective screening tools.

Methods: We conducted a comprehensive literature review to explore the most recent advances in PDAC detection, focusing on novel biomarkers, liquid biopsies, artificial intelligence (AI)-enhanced imaging, and non-invasive surveillance strategies. We examined the role of circulating tumor DNA (ctDNA), microRNAs, and volatile organic compounds (VOCs) as diagnostic tools, alongside the integration of advanced imaging modalities like MRI, EUS, and MRCP in high-risk individuals, including those with hereditary cancer syndromes.

Results: Emerging technologies, such as AI-driven imaging and liquid biopsy, have shown promising improvements in detecting PDAC at earlier, potentially resectable stages. Surveillance strategies for high-risk populations, including BRCA1/2 mutation carriers and individuals with Lynch syndrome, have demonstrated increased detection of Stage I PDAC, offering a significant opportunity for curative intervention. AI and machine learning techniques are also enhancing the sensitivity and specificity of imaging, providing a new frontier in early-stage diagnosis.

Conclusion: The integration of molecular diagnostics, advanced imaging technologies, and AI may enable a paradigm shift in PDAC detection, transitioning from late to early-stage diagnosis and potentially improving survival rates. However, further clinical validation and standardization of these technologies are essential to ensure their widespread clinical adoption. The future of PDAC detection lies in a multimodal, personalized approach, optimizing diagnostic accuracy and early intervention for high-risk individuals.

Objectives: Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is effective and safe for poor surgical candidates; however, it remains technically challenging with potential serious adverse events. This study evaluated the learning curve for EUS-GBD for safe and effective procedures.

Methods: From January 2016 to January 2024, 146 patients underwent EUS-GBD performed by three endosonographers. We analyzed the baseline characteristics, procedural outcomes, and learning curves using cumulative sum (CUSUM) analysis.

Results: No significant differences were found among the three operators regarding technical success (96.4% vs. 94% vs. 95.1%; p = 0.85), clinical success (96.4% vs. 92% vs. 95.1%; p = 0.61), mean procedure time (8.0 ± 5.7 vs. 9.9 ± 7.9 vs. 9.9 ± 5.1 min; p = 0.24), or procedural adverse events (12.7% vs. 20% vs. 9.8%; p = 0.35). CUSUM analysis revealed that proficiency in procedure time was achieved after performing 27 procedures. Comparing procedure time before and after achieving technical proficiency, technical success (90.6% vs. 98.8%, p = 0.04), clinical success (89.1% vs. 98.8%, p = 0.02), and procedure time (14.45 ± 6.13 min vs. 5.09 ± 2.23 min, p < 0.01) were improved. Adverse event proficiency was reached in 23 procedures, with notable improvements post-proficiency; technical success (87.5% vs. 99%, p = 0.02), clinical success (85.4% vs. 99%, p = 0.01), and procedure time were also improved (15.04 ± 6.43 min vs. 6.33 ± 3.99 min, p < 0.01).

Conclusions: Based on CUSUM analysis, approximately 23 procedures may be required to achieve technical proficiency in EUS-GBD with regard to minimizing adverse events, while 27 procedures are necessary to reach proficiency in terms of procedure time.