Introduction

Gastroenterologists face dual demands from clinical practice and academic research, necessitating efficient literature processing. While large language models (LLMs) show promise as healthcare tools, their variable performance in literature interpretation remains understudied, particularly regarding content completeness and reliability. This study systematically evaluates four prominent LLMs (ChatGPT-4o, Claude-3.5sonnet, Doubao-pro, Deepseek-V3) in explaining five gastroenterology literature types (original articles, case reports, reviews, editorials, guidelines), providing evidence-based recommendations for practical applications.

Aims & Methods

We tasked four LLMs with interpreting 125 gastroenterology publications (25 per literature type, 5 interpretations per article) spanning artificial intelligence, endoscopy, gastrointestinal cancers, and inflammatory bowel disease. Five gastroenterologists assessed interpretations using five criteria:
1. Accuracy: Correct identification of study design.
2. Format compliance: Adherence to predefined structure.
3. Content completeness: Key concept coverage (quantified via standardized rating scales).
4. Conciseness: Absence of extraneous content.
5. Reliability: Absence of hallucinated content.
Domain experts developed literature-specific completeness scales. Statistical analysis employed Pearson's chi-square tests for categorical variables (accuracy, format compliance, conciseness, reliability) and Kruskal-Wallis tests with Dunn's post-hoc comparisons for completeness scores. We applied Bonferroni correction for multiple comparisons (R version 4.4.2), with α=0.05 defining statistical significance.

Results

The 625 evaluations revealed significant inter-model differences across all metrics (p<0.001). ChatGPT-4o and Deepseek-V3 demonstrated superior accuracy (99.2% vs 100.0%) and format compliance (97.6% vs 99.2%) compared to Claude-3.5sonnet and Doubao-pro. Claude-3.5sonnet produced the most concise outputs (99.4%), while Deepseek showed the lowest concision (92.8%). Doubao exhibited perfect reliability (100.0%) versus 93.6%-97.0% in other models. Median completeness scores ranked: ChatGPT-4o (84.5%) > Claude-3.5sonnet (80.0%) = Doubao-pro (80.0%) > Deepseek-V3 (79.3%), with ChatGPT-4o significantly worse than others (Dunn's test, p<0.05).

Conclusion

Gastroenterologists can select LLMs based on the application priority of literature processing: ChatGPT-4o and Deepseek-V3 excel in accuracy and format compliance; Claude-3.5sonnet offers superior conciseness; while Doubao-pro demonstrates optimal reliability.

Introduction

An important issue for unresectable advanced stage hepatocellular carcinoma (uHCC) patients with Child-Pugh class B liver cirrhosis (CP-B), is lack of safe treatment options that show therapeutic efficacy, thus it is considered to be an unmet need. Atezolizumab plus bevacizumab (At/Bv) and durvalumab plus tremelimumab (Dur/Tre) have each been used as first-line systemic immunotherapy for uHCC.

Aims & Methods

The present study aimed to elucidate clinical outcomes of uHCC patients with CP-B treated with those combination treatments. The records of 169 uHCC patients with CP-B in Japan, treated with At/Bv or Dur/Tre as first-line systemic therapy from 2020 to 2024 at participating institutions were examined (median age: 73 years, males: 143, Child-Pugh score 7:8:9 = 121:43:5, BCLC stage B:C = 65:104, At/Bv:Dur/Tre = 131:38). Each regimen was analyzed for therapeutic efficacy and safety, and the results compared, in a retrospective manner.

Results

Using RECIST, ver. 1.1, the objective response rate (ORR) was shown to be 25.9% in the At/Bv group, and 18.4% in the Dur/Tre group (p=0.08). Disease control rate (DCR) was significantly higher in the At/Bv group (64.9% vs. 39.5%, p=0.01). There were no significant differences between the groups for progression-free survival (PFS) [At/Bv vs. Dur/Tre=5.3 vs. 3.5 months (95% CI: 3.9–6.5 and 2.3–7.2, respectively), p=0.90], overall survival (OS) [10.5 vs. 12.5 months (95% CI: 9.1–13.3 and 7.9–NA, respectively), p=0.58], or post-progression survival (PPS) [4.9 vs. 7.5 months (95% CI: 3.7–7.5 and 2.2–NA, respectively), p=0.60]. The rate of incidence of immune-related adverse events (irAEs) of any grade was 11.5% in the At/Bv group and 23.7% in the Dur/Tre group (p=0.07), while irAEs of grade 3 or higher were noted in 3.1% and 15.8%, respectively (p=0.02) significantly greater in the Dur/Tre group).

Conclusion

The incidence rate of irAEs in each group was similar to that observed in clinical trials previously performed for these regimens. uHCC patients with CP-B, who received Dur/Tre had a greater rate of incidence of high-grade irAEs, while the At/Bv group had a better DCR, though there were no significant differences for PFS, OS, or PPS between the groups. Neither treatment was found to sufficiently improve the prognosis of uHCC patients with CP-B. Development of safe and effective treatment options for patients affected by uHCC, that can be administered even to those with CP-B remains necessary.

Disclosure

Atsushi Hiraoka: lecture fee Chugai, AstraZeneca, and Lilly.

Introduction

Primary sclerosing cholangitis (PSC) is a progressive autoimmune cholestatic liver disease often associated with inflammatory bowel disease (IBD), particularly ulcerative colitis [1]. In PSC, reduced expression and function of the bile acid receptor GPBAR1 (TGR5) in cholangiocytes is associated with a dysfunctional gut–liver immune axis and impaired resolution of inflammation [2,3]. Parallelly, the transcription factor RORγt in Th17 cells sustains IL-17 perpetuating IL-23-driven intestinal [4] and liver inflammation [5]. While GPBAR1 mediates anti-inflammatory responses to secondary bile acids, RORγt governs Th17 differentiation and cytokine secretion. Recent clinical studies have demonstrated that IL-23 inhibitors, such as risankizumab [6] and mirikizumab [7], are effective in treating IBD, highlighting the significance of the IL-23/IL-17 axis. GPBAR1/RORγt dual simultaneous modulation represents a novel strategy to counteract the fibrotic and inflammatory environment characteristic of PSC.

Aims & Methods

We evaluated the therapeutic efficacy of PBT002, a dual GPBAR1 agonist and RORγt inverse agonist, in modulating immune and fibrotic pathways in PSC. Transcriptomic distribution of target genes was assessed using publicly available single-cell RNA-sequencing datasets from healthy human livers [8]. Differential gene expression was validated in two independent cohorts of patients with PSC and PBC, and further confirmed in an external validation cohort (GSE159676). Functional studies were performed in vitro using primary human cholangiocytes (NHC), immortalized hepatic stellate cells (LX-2), primary monocyte-derived macrophages and CD4+ T lymphocytes. In vivo efficacy was assessed in Abcb4^⁻/⁻ mice treated with PBT002 (10 mg/kg/day) for 12 weeks.

Results

Single-cell transcriptomic analysis revealed that IL-17 and IL-23 cytokines are predominantly expressed by immune cells, whereas their receptors (IL23R, IL17RA, IL17RC, IL17RE) are enriched in epithelial cells, including hepatocytes and cholangiocytes. Deconvolution analysis of liver bulk transcriptomes from PSC and PBC cohorts showed features of immune exhaustion, with a mild upregulation of pro-inflammatory markers and IL-17 receptor subunits, along with prominent overexpression of PD-L1, a known pro-fibrotic mediator. In vitro, exposure of hepatic stellate cells, macrophages, and CD4+ T cells to supernatants from inflamed cholangiocytes induced strong activation, which was reversed by PBT002 treatment. In vivo, PBT002 significantly reduced hepatocellular damage, as shown by decreased serum ALT, AST, ALP, and bilirubin levels. Histological analyses revealed marked reductions in periductal inflammation and liver fibrosis. Gene expression profiling confirmed significant downregulation of M1 and Th17-associated genes (Rorc, Il17f, Il22, Il23a) in colon and liver. Bile acid profiling showed restoration of key GPBAR1 agonists and RORγt antagonists (DCA, 3-oxo-DCA, allo-LCA), while microbiota analysis demonstrated increased abundance of protective taxa (e.g., Blautia, Sutterellaceae), inversely associated with disease severity.

Conclusion

PBT002 exerts potent immunomodulatory effects in experimental PSC by rebalancing M1/M2 and Th17/Treg homeostasis through dual GPBAR1 activation and RORγt inhibition. These effects correlate with restoration of bile acid and microbiota profiles, confirming the key role of the microbiota–bile acid–immune axis in PSC and supporting PBT002’s clinical development for immune-mediated cholangiopathies, particularly in PSC-IBD overlap.

References

1. Fiorucci, S. et al. Bile Acids-Based Therapies for Primary Sclerosing Cholangitis: Current Landscape and Future Developments. Cells 13, (2024).
2. Di Giorgio, C. et al. Liver GPBAR1 Associates With Immune Dysfunction in Primary Sclerosing Cholangitis and Its Activation Attenuates Cholestasis in Abcb4-/- Mice. Liver Int. Off. J. Int. Assoc. Study Liver 45, e16235 (2025).
3. Reich, M. et al. Downregulation of TGR5 (GPBAR1) in biliary epithelial cells contributes to the pathogenesis of sclerosing cholangitis. J. Hepatol. 75, 634–646 (2021).
4. Biagioli, M. et al. Development of dual GPBAR1 agonist and RORγt inverse agonist for the treatment of inflammatory bowel diseases. Pharmacol. Res. 208, 107403 (2024).
5. Garcia Moreno, A. S. et al. IL-17 signaling in primary sclerosing cholangitis patient-derived organoids. Hepatol. Commun. 8, (2024).
6. Louis, E. et al. Risankizumab for Ulcerative Colitis: Two Randomized Clinical Trials. JAMA 332, 881–897 (2024).
7. D’Haens, G. et al. Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis. N. Engl. J. Med. 388, 2444–2455 (2023).
8. Andrews, T. S. et al. Single-Cell, Single-Nucleus, and Spatial RNA Sequencing of the Human Liver Identifies Cholangiocyte and Mesenchymal Heterogeneity. Hepatol. Commun. 6, 821–840 (2022).

Introduction

Current therapies for inflammatory bowel disease (IBD) suppress inflammation rather than inhibiting underlying microbial drivers. Treatment failures of frontline interventions, including corticosteroids, can lead to dose escalation and risk of adverse effects.^1,2 Bacteria with pro-inflammatory potential, like adherent-invasive Escherichia coli (AIEC), have been postulated as a possible microbial driver in Crohn’s disease (CD), however, targeting these bacteria with precision in IBD remains challenging.^3,4 Most antibiotics have broad-spectrum activity and disturb the background microbiome, which may exacerbate inflammation.⁵ Attention has shifted towards bacteriophages, yet their underlying mechanisms of treating IBD, and how they may work as an adjunctive therapy, remains elusive.

Aims & Methods

We aimed to assess whether and how phage therapy, specific for a CD-associated bacterium, reduces colitis severity using gnotobiotic mouse models.
In vitro kill curves and biofilm challenges were used to identify lytic phage candidates. Adult germ-free C57BL/6 mice were colonized with altered Schaedler-flora (ASF) and E. coli NRG857c (NRG), a CD-associated isolate. After 3 weeks, mice were treated with an NRG-specific lytic phage (1x10⁹ PFU/dose; daily or TIW) or vehicle (PBS) for 2 weeks (n=6/group) and then exposed to 1 cycle of dextran sulfate sodium (2%; DSS) in drinking water. PBS-treated mice (n=6) not exposed to DSS served as controls. Phage treatment was also tested in a spontaneous model of colitis using C57BL/6NTac-Il10^em8Tac (IL-10^-/-) mice, treated weekly. Mice were monitored daily for weight, stool consistency, and occult blood. Fecal contents were cultured to determine bacterial load, and the expression of NRG fimS was quantified using qPCR as an assessment of virulence. At endpoint, colon tissues were collected for histological and immunohistochemistry analysis to quantify colitis severity and NRG infiltration, respectively. Additional C57BL/6 mice were colonized and treated as previously described. During colitis induction, mice received a low-dose of budesonide (2μg/day)⁶ (n=5) or vehicle (n=5) until endpoint. Mice were monitored daily for disease activity and colon tissues were collected for histological analysis. HPLC was used to determine active budesonide levels.

Results

HER259 was identified as a lytic phage against CD-associated AIEC NRG. In ASF and NRG colonized mice, HER259 reduced clinical symptoms (p< 0.001, p< 0.001) and histological scores (p< 0.0001, p< 0.001) in chemical induced and spontaneous colitis, respectively. A 1-log reduction in NRG bacterial load was observed in HER259-treated mice (p< 0.001). Reisolated NRG exhibited a reduced FimS ON/OFF ratio (p-value < 0.01). Immunohistochemistry revealed reduced infiltration of NRG into the lamina propria following HER259 treatment, with greater accumulation in the epithelium. HER259 treatment increased the efficacy of a sub-therapeutic dosing regimen of budesonide (p< 0.001), which was independent of microbial-based drug metabolism as determined by HPLC.

Conclusion

Our results demonstrate that lytic phage targeting a CD-associated bacterium attenuates colitis in two gnotobiotic mouse models. The intervention did not lead to complete eradication of the disease-driving agent, but instead modulated bacterial virulence mechanisms and enhanced responses to corticosteroid therapy. The data suggests that alternative mechanisms should be considered when translating phage therapy to treat IBD in clinical trials.

References

1. Yan, Y. et al. Commensal bacteria promote azathioprine therapy failure in inflammatory bowel disease via decreasing 6-mercaptopurine bioavailability. Cell Rep Med 4, 101153 (2023).
2. Nagayama, M., Gogokhia, L. & Longman, R. S. Precision microbiota therapy for IBD: premise and promise. Gut Microbes 17, 2489067 (2025).
3. Darfeuille-Michaud, A. et al. High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn’s disease. Gastroenterology 127, 412–421 (2004).
4. A, D.-M. et al. Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn’s disease. Gastroenterology 115, 1405–1413 (1998).
5. Nelson, R. L., Suda, K. J. & Evans, C. T. Antibiotic treatment for Clostridium difficile-associated diarrhoea in adults. Cochrane Database Syst Rev 3, (2017).
6. Bercik, P. et al. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice. Gastroenterology 139, (2010).

Introduction

The integration of artificial intelligence (AI) into nursing practice offers a significant opportunity to enhance patient care and support clinical decision-making. This study examines the deployment of a customized generative language model (GPT) as a clinical assistant in outpatient digestive care. The tool aims to streamline access to evidence-based information and promote structured patient follow-up. While its implementation holds considerable potential for improving efficiency and fostering clinical learning, it also presents challenges related to validation, user adoption, and building trust among nursing professionals.

Results & Findings

A digital tool named Digestive Nursing Follow-Up was developed and piloted in the Gastroenterology Departments of two university hospitals in Spain during Q1 2025. The tool was integrated into four clinical domains: inflammatory bowel disease, gastroesophageal reflux disease, irritable bowel syndrome, and advanced endoscopy. The AI assistant was designed to: Collect and organize structured clinical data; Provide evidence-based clinical suggestions aligned with institutional protocols; Facilitate learning and care continuity. Prior to implementation, participating nurses underwent a one-hour training session. The tool was then incorporated into routine consultations, and nurses were surveyed pre- and post-intervention using a 5-point Likert Scale. Open-ended feedback was also collected.

Summary & Discussion

80% of nurses rated the tool as easy to use following training, and 75% reported high satisfaction, citing improved time management and a reduction in repetitive tasks. Positive perceptions centered on enhanced consultation efficiency and clinical safety. However, concerns were expressed regarding the balance between technology and patient-centered care, as well as the need for ongoing training and more personalized outputs.

Conclusion

Among the strengths identified were improved time management, support for clinical decision-making, and enhancement of standardized nursing practice. The main weaknesses were resistance to change and the initial learning curve, which required additional support. Opportunities include the potential of AI to strengthen professional training, enhance professional autonomy, and contribute to the standardization of clinical procedures. The tool reinforces clinical safety by being based on established protocols, and its use can accelerate their implementation and promote continuous learning, helping to consolidate a more efficient care model. The observed technological dependence was more associated with increased consultation efficiency, highlighting the importance of progressive and balanced integration with clinical practice.

References

1. Exploring the deep learning of artificial intelligence in nursing: a concept analysis with Walker and Avant’s approach. BMC Nurs. 2024;23:170. doi:10.1186/s12912-024-02170-x.
2. Examining the Role of AI in Changing the Role of Nurses in Patient Care: Systematic Review. JMIR Nurs. 2025;1:e63335. doi:10.2196/63335.
3. Artificial intelligence in healthcare: a scoping review of perceived threats to patient rights and safety. Arch Public Health. 2024;82:1414. doi:10.1186/s13690-024-01414-1.
4. Revolutionizing healthcare: the role of artificial intelligence in clinical practice. BMC Med Educ. 2023;23:4698. doi:10.1186/s12909-023-04698-z.
5. Utilization of Generative Artificial Intelligence in Nursing Education: A Topic Modeling Analysis. Educ Sci. 2023;14:1234. doi:10.3390/educsci14111234.
6. Human-centered design and evaluation of AI-empowered clinical decision support systems: a systematic review. Front Comput Sci. 2023;5:1187299. doi:10.3389/fcomp.2023.1187299.
7. Generative AI in healthcare: an implementation science informed translational path on application, integration and governance. Implement Sci. 2024;13:357. doi:10.1186/s13012-024-01357-9.
8. Telehealth and Remote Patient Monitoring Innovations in Nursing Practice: State of the Science. OJIN: The Online Journal of Issues in Nursing. 2022;27(2):1-15.
9. Artificial Intelligence and Digital Innovations in Nursing Care. Nurs Rep. 2023;13(1):45-60.