Introduction

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, predominantly diagnosed in patients with chronic liver diseases. The absence of specific biomarkers and the typically asymptomatic progression of the disease lead to delayed diagnosis. Patients with liver disease, including HCC, exhibit alterations in the gut microbiome and increased bacterial permeability, factors that may influence disease progression and patient outcomes. In recent years, there has been a growing interest in exploring circulating microbiome signatures as potential indicators of liver disease stutus, providing a new avenue for understanding HCC.

Aims & Methods

Aims: To identify the signatures of the circulating blood microbiome associated with hepatocellular carcinoma, response to treatment and disease prognosis.
Methods: This study conducted a post-hoc analysis of the SORAMIC clinical trial utilizing peripheral blood plasma samples. For this analysis, blood plasma samples from a cohort of 71 patients with HCC were examined (25 treated with Sorafenib and 46 with SIRT/Sorafenib). Peripheral blood samples were collected at two time points: baseline (prior to the initiation of anti-tumor therapy) with all 71 patients included, and post-therapy (7 to 9 weeks after treatment) with 39 patients included. Additionally, peripheral blood samples were obtained from 52 control subjects, who were endoscopically diagnosed with colonic diverticulosis, to compare against the patient group. The composition of the circulating blood microbiome was assessed through 16S rRNA gene sequencing, targeting the V1-V2 hypervariable regions. Subsequent analyses focused on identifying associations with potential novel biomarkers for diagnosis, prognosis, and response to treatment.

Results

Patients with HCC had significantly diminished α-diversity of the circulating blood microbiome as compared to controls. Significant differences were also observed in between microbial communities of these two cohorts based on Bray-Curtis dissimilarity index. Patients with HCC had significantly higher levels of Proteobacteria and Bacteroidetes and lower levels of Firmicutes and Campylobacterota. Differential abundance analysis revealed that families of Gordoniaceae, Cryomorphaceae, Burkholderiaceae, Comamonadaceae, Enterobacteriaceae were significantly enriched in patients with HCC. At the genus level, patients with HCC had higher levels of Gordonia, Fluviicola, Burholderia, Limnohabitans and Escherichia/Shigella and lower levels of Corynebacterium. HCC patients, who responded to treatment with SIRT/Sorafenib showed an increase in blood bacterial diversity, enrichment of families Burkholderiales incertae sedis, Arcobacteraceae, Peptostreptococcaceae, Moraxellaceae, genera Sphaerotilus, Aliacrobacter, Rhodoluna, Giesbergeria, Microbacterium, Romboutsia, Arcicella, Pseudorhodoferax and depletion in families Gordoniaceae, Cryomorphaceae and genera Cloacibacterium, Gordonia, Limnohabitans, Fluviicola after the treatment. Levels of Acinetobacter, Enhydrobacter and Micrococcus in the blood before the HCC treatment were associated with patient prognosis.

Conclusion

Patients with HCC exhibit a unique circulating blood microbiome profile characterized by reduced bacterial diversity. Response to treatment is linked to an increase in α-diversity and changes in the circulating microbiome profile. Specific members of the circulating microbiome show potential prognostic capabilities, suggesting their utility as biomarkers for predicting disease progression and treatment outcomes in HCC.

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is a widespread chronic liver condition closely associated with obesity, insulin resistance, and dyslipidemia. Recent evidence points to gut microbiota dysbiosis as a key player in MASLD pathogenesis, affecting intestinal barrier function and systemic inflammation.

Aims & Methods

The aim was to investigate gut microbiota composition in patients with MASLD and assess its association with disease progression and gut barrier dysfunction. A total of 152 MASLD patients and 150 matched controls without liver pathology were examined. Diagnosis was confirmed by ultrasound and steatometry, alongside assessment of cardiometabolic risk factors. Gut microbiota composition was analyzed using real-time PCR, focusing on Bacteroidetes, Firmicutes, and Actinobacteria. Hydrogen breath testing was used to diagnose small intestinal bacterial overgrowth (SIBO), and the presence of Akkermansia muciniphila was evaluated as a marker of gut barrier integrity.

Results

MASLD patients demonstrated a significant increase in Firmicutes (50.3%) and Actinobacteria (15.3%) proportions compared to controls, with a higher Firmicutes/Bacteroidetes (F/B) ratio. SIBO was detected in 52% of MASLD patients versus 40.5% in controls (p<0.05). The presence of Akkermansia muciniphila was notably lower in MASLD patients (33%) compared to controls (63%), suggesting impaired gut barrier function. Strong positive correlations were observed between Actinobacteria abundance and the F/B index (r=0.75, p<0.05), while Akkermansia muciniphila presence negatively correlated with MASLD development (r=–0.69, p<0.05).

Conclusion

Gut microbiota dysbiosis, characterized by elevated Firmicutes and Actinobacteria and reduced Akkermansia muciniphila, is closely associated with MASLD pathogenesis. The findings highlight the potential of microbiota-targeted interventions for improving gut barrier function and modifying disease progression in MASLD patients.

Introduction

Eosinophilic esophagitis (EoE) is a chronic, condition linked to a type 2 inflammatory response and frequently associated to other atopic conditions. EoE may presents either sporadically, or with aggregation of cases within a same family. Limited information has been provided on the differences in clinical characteristics and disease features between sporadic and familiar EoE, largely due to the lack of large patient cohorts.

Aims & Methods

To find differences in sporadic and familiar cases of EoE which may support distinct clinical management, a cross-sectional analysis of the multicenter EoE CONNECT registry was performed. Demographic and clinical from patients recruited at 42 hospitals in 4 European countries were extracted on March 28th, 2025. Information extracted included 1) age at diagnosis and diagnostic delay; 2) symptoms leading to diagnosis; 3) disease endoscopic and histologic features at diagnosis; and 4) atopic concomitances.

Results

	S-EoE	F-EoE
Age at diagnosis (n= 3,179) <18 years old	18.5%	30.6%
Inflammatory Score (n= 2,723)	1.62 ± 1.3	1.93 ± 1.32
Fibrosis Score (n=2,723)	1.04 ± 1.04	0.97 ± 1.08
Fibrosis (n=1,701)	58.6 %	62.8 %
EoE-Phenotype (n=3,017)
Inflammatory	75.9 %	79.6 %
Mixed	12.6 %	8.6 %
Stricturing	11.5 %	11.8 %

Overall, 4,053 patients (75.4 % males, mean age 33.3 ±15.2 years) were analyzed, including 3028 (74.7 %) sporadic (S-EoE), 714 (17.6%) without familiar data and 311 (7.7 %) familiar (F-EoE) cases including 89 families. Among the family forms, n= 76 families showed 2 affected members, n= 11 presented 3 members, and n= 2 with 4 members. In 85/89 families we identified the index case consisting in sons (13), parents (23), siblings (38), or other distant kinships.
The F-EoE forms were diagnosed at younger mean ± SD ages than S-EoE (29.8±15.6 vs. 33.7±15.1; p<0.001) and included a higher proportion of pediatric patients (considered as those below 18 at diagnosis; 30.6% vs. 18.5%; p<0.001)
Symptoms leading to EoE diagnosis were similar across study groups, with slightly higher presences of abdominal pain (as they included more pediatric cases; 7.7% vs. 4.5%; p=0.01) and chocking episodes (7.7% vs. 4.5%; p=0.01) among F-EoE.
Endoscopy presented more severe features according to EREFS among F-EoE (mean ± SD being 2.86 ± 1.66 vs. 2.64 ± 1.68; p=0.054) at the expense of both fibrotic and inflammatory features, despite only the later reach statistical significance (1.93 ± 1.32 vs. 1.62 ± 1.3; p<0.001). Esophageal biopsies exhibited higher mean ± SD peak eosinophil counts in F-EoE cases (57.11 ± 40.7 vs. 52.87 ± 37.97; p=0.04).
F-EoE were more allergic patients, as they presented a higher mean ± SD number of concomitant atopies (1.44 ± 1.25 vs. 1.25 ± 1.22; p=0.009) and all were more common among them, with conjunctivitis and hives reaching statistical significance (p=0.01 and p=0.002 respectively). Overall, a higher proportion of F-EoE had at least one atopy compared to S-EoE (69.4 % vs. 63.8%).

Conclusion

F-EoE seems to present more severely, with earlier onset, more inflammatory load in endoscopy and biopsies and higher concomitant allergic manifestations.

Introduction

Intestinal point-of-care ultrasound, as standardized by the International Bowel Ultrasound Group (IBUS), has emerged as a valuable tool for diagnosing, monitoring, and managing patients with Inflammatory Bowel Disease (IBD). While IBUS emphasizes a structured intestinal assessment, some European centers adopt a more comprehensive approach, combining intestinal ultrasound with a complete abdominal examination.
The Karolinska Centre for Digestive Health, a tertiary referral institution providing specialized care to approximately 4,500 patients with IBD, established a dedicated Gastrointestinal Ultrasound Unit in October 2023. This unit offers advanced diagnostic services to both hospitalized patients and those treated on an outpatient basis.

Aims & Methods

This retrospective study aimed to assess the prevalence of secondary extraintestinal findings in IBD patients undergoing comprehensive abdominal ultrasound between October 4, 2023, and March 4, 2025. All patients underwent ultrasound assessments that included both intestinal and abdominal imaging. Patients referred for indications unrelated to intestinal ultrasound (IUS), as well as those undergoing repeat examinations, were excluded from the analysis to ensure data consistency.
All examinations were performed by a single gastroenterologist with 25 years of ultrasound experience. In cases where secondary extraintestinal findings were identified, patients’ electronic medical records were reviewed to determine whether these findings represented new diagnoses or previously known conditions.

Results

The study included 348 patients with IBD, 201 (58%) females and 147 (42%) males, with a mean age of 42.4 years. Among these, 260 (75%) were referred internally by our IBD Outpatient Clinic, 47 (13%) by the Gastroenterology Ward, 33 (10%) by private outpatient clinics, and the remainder from other healthcare sites. IUS revealed evidence of intestinal inflammation in 144 patients (42%), while findings were normal in 204 patients (58%).
Furthermore, 150 patients presented with a total of 195 secondary extraintestinal findings, of which 113 (58%) represented newly identified pathologies. Among all secondary findings, the majority, 104 (53%), were related to the hepatobiliary system, including 33 newly diagnosed cases of hepatic steatosis and 17 new cases of cholecystolithiasis. One patient demonstrated ultrasound features suggestive of primary sclerosing cholangitis (PSC) and is currently undergoing further evaluation. Additional findings involved the reproductive system (29/15%), urinary system (15/7%), spleen (32/16%), and pancreas (5/2%). Various other intra-abdominal findings were also identified (37/18%). Notably, one patient presented with a suspicious mass in the right iliac fossa, and another demonstrated ultrasound findings suggestive of a prostatic tumor; both cases were referred for further oncologic evaluation. Additionally, three patients were newly diagnosed with intraductal papillary mucinous neoplasm (IPMN), which was subsequently confirmed via magnetic resonance imaging, and all were enrolled in the national IPMN surveillance protocol.

Conclusion

A considerable proportion of patients with IBD were found to have previously unknown extraintestinal abdominal pathologies, underscoring the essential role of comprehensive ultrasound examination that combines both intestinal and abdominal assessment. Fortunately, only a minority of these findings resulted in changes to patient management.

Disclosure

Francesca Bresso has acted as national and/or local principal investigator for clinical trials for Janssen, Ferring, and AbbVie. Charlotte Hedin served as a speaker and/or advisory board member for AstraZeneca, AbbVie, Dr. Falk Pharma and the Falk Foundation, Galapagos, Janssen, Pfizer, Ferring, Takeda, and Tillotts Pharma and received grant support from Tillotts Pharma and Takeda. Stephan L. Haas has served as a speaker for Takeda, Santax Medico, Tillotts Pharma, Johnson & Johnson, and Mediahuset. The rest of the authors have nothing to declare.

Introduction

Fructans or fructooligosaccharides are included in the spectrum of FODMAP (fermented) sugars, which are relevant in the induction of symptoms in patients with disorders of gut-brain interaction (DGBI) and in non-coeliac gluten sensitivity (1). Fructans have been shown to induce visceral hypersensitivity, an increase in mucosal mast cells, and changes in the colonic mucosal barrier in mice, and hypersensitivity associated with an altered gut microbiome in humans (2-5). Breath tests are used in the assessment of intolerances to several FODMAPs, but the test is poorly standardised for fructans (6).

Aims & Methods

A standardised breath test with fructans (10g Orafti^®HSI) was performed afer a 24-hour low-FODMAP diet and >8-hour fast. Exhaled hydrogen and methane concentrations were measured every 30 minutes until 5h, and synchronised symptom assessments performed for 24h (composite symptom index score, SI, 7) in 600 successive male (33%) and female patients of average age 41 years referred to our gastroenterology practice with DGBI (irritable bowel syndrome and/or functional dyspepsia, Rome 4 criteria). Breath gas concentration thresholds of >20ppm and >8ppm above baseline were used for hydrogen and methane, respectively.

Results

The SI was positive in 61.2% (n=367) of patients within 24 hours of fructan ingestion. The SI peaked in the first 3 hours in 17.5% (n=105) and in the first 5 hours in 42.5% (n=255) of patients. Suprathreshold increases in hydrogen and methane concentrations within 5 hours were seen in 62.7% and 14.9% of patients, respectively. Discordant SI and breath gas results were obtained in 35.1% (hydrogen) and 57.8% (methane) of patients. A negative SI with a suprathreshold hydrogen or methane result occurred in 18.2% and 5.2%, respectively. A positive SI with a subthreshold hydrogen or methane result occurred in 16.9% and 52.6%, respectively. Suprathreshold concentrations in methane and not in hydrogen were apparent in 4.5%. Main symptoms during tests were excessive flatulence (58.8%), bloating (50.3%), abdominal fullness (49.3%), abdominal cramps (29.0%), nausea (26.7%), GORD (26.7%), diarrhoea (9%) and extra-GI symptoms (16.2%).

Conclusion

Standardised oral provocation with fructans resulted in familiar clinical symptoms in a majority of patients with DGBI, suggesting a high prevalence of fructan intolerance. Due to the slow fermentation of intestinal fructans and the associated delayed symptoms, prolonged data collection over at least 12, preferably 24 hours is recommended. The test duration of 3 hours currently commonly used in test centres is inadequate. Symptom and breath gas concentration results are often divergent, as is known from other FODMAP breath tests, and validation against clinical outcome results is required. Fructans are of interest in DGBI as the current literature suggests they have both protective as well as detrimental effects on intestinal physiology, which may be dependent on the resident microbiota.

References

1. Gry I et al. Gastroenterology 2018;154:529–539
2. Kamphuis JBJ et al. Gastroenterology 2020;158:652-663
3. Chen BR et al. World J Gastroenterol 2017;23:8321-8333
4. Kamphuis JBJ et al. FASEB J. 2022;36:e22297
5. Chumpitazi BP et al. Aliment Pharmacol Ther 2021;53:499-509
6. Fedewa A et al. Curr Gastroenterol Rep 2014;16:370
7. Wilder-Smith CH et al. Aliment Pharmacol Ther 2013;37:1074-83

Introduction

Tofacitinib, filgotinib, and upadacitinib, are Janus kinase inhibitors (iJAKs) approved for inflammatory bowel disease (IBD) treatment. Although no direct comparative studies exist, potential differences in efficacy and safety are attributed to in vitro-demonstrated affinity of each molecule for different JAK isoforms. JAK1 plays a crucial role in modulating cytokine-mediated immune responses, such as IL-6 and interferon, which are involved in inflammation and skin homeostasis. Its inhibition can promote conditions that may trigger acne.
Acne may be increased in iJAK-treated patients, meaning a clinical challenge for gastroenterologists.

Aims & Methods

A retrospective study was conducted at ten referral centers in Spain, including all IBD patients who had received iJAK therapy and had at least 3 months of follow-up. Demographic data, disease-related variables, and acne characteristics when appropriate, were collected. Univariate and multivariate logistic regressions were used to identify risk factors for acne; model discrimination was assessed by AUC.

Results

A total of 549 patients included: 258 (47%) were women; 354 (64%) had ulcerative colitis, 191 (35%) had Crohn’s disease and 1% had indeterminate colitis. Mean age was 41 years (IQR 30-52). 219 patients (40%) were treated with tofacitinib, 281 (51%) with upadacitinib, and 49 (9%) with filgotinib.
Ninety patients (16%) developed acne during iJAK treatment: 69% were mild, with only 4 severe cases (4%). Acne occurred early (median onset 42 days, IQR 7-122), predominantly on the face (56%), trunk (13%) or both (31%). Acne morphology included comedones (60%), papules (59%), pustules (39%), nodular-cystic (12%), scarring (9%); 48% showed more than one morphology.
Thirty-six patients received specific acne treatment: 89% topical (antiseptics, benzoyl peroxide, retinoids), 69% systemic (antibiotics, retinoids, antiandrogens), and 44% combined treatment. 83% of those patients responded to acne specific treatment, and only 8 patients (9% of those with acne; 1.5% overall) had to discontinue iJAK treatment, with acne resolving in all cases.
Acne developed in 26%, 6% and 6% of upadacitinib, tofacitinib and filgotinib treated patients respectively (p=0.001). Multivariate analysis showed that acne development was associated with upadacitinib (OR 10.28;IC95%=4,7–22,6; p<0,001) and history of acne (OR 3.52; IC95%=1,5–8,3; p=0,004), while older age (>35 years, OR 0.31; IC95% 0,11–0,83; p=0,02) and Crohn’s disease (OR 0.47; IC95% 0,25–0,90; p=0,02) showed to be protective. This model was reliable in predicting acne development (AUC 0.79). Additionally, univariate analysis showed high dose of iJAK was also associated with acne development, which could not be confirmed in multivariate analysis.

Conclusion

Acne occurred in a relevant proportion of iJAK-treated patients, was generally mild and manageable with dermatological care, and rarely required treatment discontinuation. Risk factors for iJAK-associated acne included use of upadacitinib (probably reflecting a greater affinity for JAK1) and history of acne, while older age and Crohn’s disease were protective.
Gastroenterologists should be aware of both likelihood and management of this specific adverse event when considering iJAK therapy.

Disclosure

Y G-L, MC, GB, ER, IB, DC, M B-dA, LM, I M-J, DG, IV have provided scientific advisory / participated in educational activities / received unrestricted research grants / received payments for lecturing from Johnson & Johnson, ​Takeda, Pfizer, Amgen, AbbVie, Lilly, AlfaSigma, Ferring, Gilead.

Introduction

Capsule endoscopy is the first-line examination for digestive bleeding with likely origin in the small bowel, in hemodynamically stable patients. In the 2022 update, ESGE guidelines recommend that, in the context of overt bleeding, capsule enteroscopy should be performed as soon as possible, ideally within the first 48 hours. In the previous guidelines, published in 2015, the recommended window was 14 days.

Aims & Methods

This study aimed to evaluate the improvement in yield offered by the new recommendations regarding the timing of urgent capsule enteroscopy. Patients with suspected overt middle gastrointestinal bleeding between January 2005 and November 2022 were retrospectively analyzed. Diagnostic and therapeutic yield, rebleeding rate, and mortality were compared when capsule enteroscopy was performed within the first 48 hours, within the first 14 days, or between the 3rd and 14th day after admission.

Results

A total of 138 patients were included (58.7% men, median age 66 years), 87 of whom (63.0%) underwent capsule enteroscopy within the first 48 hours after hospital admission. The median follow-up was 55 months (5-180). The diagnostic yield (presence of blood or lesions with bleeding potential) was slightly higher when capsule enteroscopy was performed within the first 48 hours (81.6% versus 76.5%, p=0.349). On the other hand, capsule enteroscopy within the first 48 hours was significantly associated with higher therapeutic yield (endoscopic, radiologic, or surgical treatment) - 54.0% versus 39.2%, p=0.02. The rebleeding rate was significantly lower in patients undergoing enteroscopy within 48 hours after admission (19.5% versus 29.4%, p=0.04). On the other hand, overall mortality at 36 months did not differ between strategies (21.8% and 25.5%, p=0.401).

Conclusion

Performing capsule endoscopy within the first 48 hours, as recommended by recently published guidelines, is associated with favourable short- and long-term clinical outcomes.