Introduction

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis of the intra- and extrahepatic bile ducts. It is frequently associated with inflammatory bowel disease (IBD), particularly ulcerative colitis (UC). The coexistence of PSC and IBD poses clinical challenges due to the complex management of both intestinal and hepatic manifestations. While biological therapies have improved IBD outcomes, treatment options for PSC remain limited. Assessing the impact of IBD-targeted biological therapies on clinical outcomes in patients with concomitant PSC and IBD is therefore essential.

Aims & Methods

This observational multicenter retrospective study included 81 adult patients diagnosed with both PSC and IBD at three Italian tertiary referral centers between January 2004 and November 2024. Data collected included demographic and clinical characteristics, endoscopic findings, administered treatments, and clinical outcomes. Patients were grouped based on the treatment received: biological therapies (anti-TNF, anti-integrins, anti-ILs, JAK inhibitors) or conventional therapies (5-ASA, UDCA, corticosteroids, azathioprine). Time-to-event outcomes—including episodes of cholangitis, IBD-related surgery, colorectal cancer, cholangiocarcinoma, and liver transplantation—were analyzed using Kaplan-Meier estimates and compared by log-rank tests. Cox proportional hazards models were used to identify independent risk factors. Statistical significance was defined as p < 0.05.

Results

The cohort was predominantly male (70.4%), with median ages at PSC and IBD diagnoses of 35.0 ± 14.9 and 25.0 ± 13.7 years, respectively. UC was more prevalent than Crohn’s disease (72.8% vs. 27.2%), with pancolitis being the predominant UC phenotype (79.7%).IBD exhibited a generally indolent phenotype across the cohort, with rare complications in Crohn’s disease and frequent mucosal healing in UC (Mayo 0–1 in 64.8%).Biological therapies were administered to 49.4% of patients. Patients receiving biologics were younger at PSC diagnosis compared to those on conventional therapies (32.5 ± 14.85 vs. 39.6 ± 15.74 years; p = 0.05). Patients with Crohn’s disease had a significantly higher risk of intestinal surgery compared to those with UC (HR 4.2; 95% CI 1.2–14.2; p = 0.037).No significant difference in intestinal surgery incidence was observed between patients treated with biological versus conventional therapies. Kaplan-Meier analysis revealed no significant difference in the incidence of cholangitis between patients receiving biological and conventional therapies (log-rank p = 0.36). Likewise, there were no significant differences between the two groups regarding colorectal cancer, cholangiocarcinoma, or liver transplantation.

Conclusion

Biological therapies appear effective in controlling intestinal inflammation in PSC-associated IBD, with a favorable safety profile regarding malignancy and transplantation risk. However, they do not significantly impact the incidence of cholangitis. These findings provide a foundation for future studies and may help guide evidence-based therapeutic strategies in this complex patient population.

References

1. Van Munster, K. N., Bergquist, A. & Ponsioen, C. Y. Inflammatory bowel disease and primary sclerosing cholangitis: One disease or two? J. Hepatol. 80, 155–168 (2024).
2. Shah, A. et al. Efficacy and safety of biologics in primary sclerosing cholangitis with inflammatory bowel disease: A systematic review and meta-analysis. Hepatol. Commun. 8, (2024).
3. Kulkarni, C. et al. Association of Anti-TNF Therapy With Increased Risk of Acute Cholangitis in Patients With Primary Sclerosing Cholangitis. Inflamm. Bowel Dis. 27, 1602–1609 (2021).
4. Lynch, K. D., Keshav, S. & Chapman, R. W. The Use of Biologics in Patients with Inflammatory Bowel Disease and Primary Sclerosing Cholangitis. Curr. Hepatol. Rep. 18, 115–126 (2019).
5. Huynh, D., Rubtsov, D. & Khaing, M. M. Efficacy of Biologics in the Treatment of Primary Sclerosing Cholangitis Associated With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. Cureus (2024) doi:10.7759/cureus.56182.
6. Hedin, C. R. H. et al. Effects of Tumor Necrosis Factor Antagonists in Patients With Primary Sclerosing Cholangitis. Clin. Gastroenterol. Hepatol. 18, 2295-2304.e2 (2020).

Disclosure

Nothing to declare

Introduction

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive bile duct damage and cholestasis. While ursodeoxycholic acid (UDCA) is the first-line therapy, about 40% of patients have incomplete responses, necessitating alternative treatments.

Aims & Methods

This meta-analysis evaluates the efficacy and safety of novel oral anti-cholestatic agents for PBC, focusing on key biochemical and symptomatic outcomes. A systematic literature search was conducted across electronic databases. Eligible studies included randomized controlled, retrospective, and open-label trials investigating novel oral anti-cholestatic agents in PBC patients. Data on efficacy (e.g., alkaline phosphatase [ALP] reduction) and safety outcomes were extracted and analyzed using meta-analytic techniques.

Results

Ten studies involving 878 patients were analyzed. Investigated therapies included seladelpar, fenofibrate, saroglitazar, bezafibrate, elafibranor, and budesonide. Novel anti-cholestatic agents significantly lowered ALP levels compared to controls (SMD -2.80; 95% CI [-3.56, -2.03]; p<0.00001), with saroglitazar showing the largest effect size (SMD -4.62; 95% CI [-5.54, -3.70]). Subgroup analysis revealed that fibrates (fenofibrate, bezafibrate, and saroglitazar) demonstrated the most consistent ALP reduction across studies (SMD -3.15; 95% CI [-3.89, -2.41]; p<0.00001).
In addition to ALP reduction, several agents showed improvements in other liver function tests. Bilirubin levels decreased significantly with novel therapies (MD -0.22 mg/dL; 95% CI [-0.35, -0.09]; p=0.001). Gamma-glutamyl transferase (GGT) also showed substantial reduction (SMD -1.98; 95% CI [-2.56, -1.40]; p<0.00001).
Symptomatic improvements were observed, particularly for pruritus. Bezafibrate and seladelpar demonstrated the most promising results, with mean reductions in visual analog scale scores for pruritus of 30% and 35%, respectively. Fatigue scores also improved, though to a lesser extent (SMD -0.42; 95% CI [-0.68, -0.16]; p=0.002).
Safety profiles were comparable to controls, with no significant increase in serious adverse events (OR 1.21; 95% CI [0.81, 1.83]; p=0.35). The most common adverse events were mild gastrointestinal symptoms (10-15% of patients) and transient elevations in creatinine (5-8% of patients). No significant hepatotoxicity was observed across the studies.

Conclusion

Novel oral anti-cholestatic agents show promise in managing PBC patients with suboptimal UDCA responses, demonstrating significant improvements in biochemical markers and some symptomatic relief. However, study heterogeneity, small sample sizes, and limited follow-up durations restrict direct comparisons and generalizability. Further research is needed to confirm long-term efficacy and safety.

References

1 Trivella J, John BV, Levy C. Primary biliary cholangitis: Epidemiology, prognosis, and treatment. Hepatol Commun 2023; 7: e0179. [PMID: 37267215 DOI: 10.1097/HC9.0000000000000179]
2 Purohit T, Cappell MS. Primary biliary cirrhosis: Pathophysiology, clinical presentation and therapy. World J Hepatol 2015; 7: 926-941. [PMID: 25954476 DOI: 10.4254/wjh.v7.i7.926]
3 Tanaka A, Takikawa H, Mochida S, Koike K, Miwa H, Shimosegawa T. Changing nomenclature for PBC from ‘primary biliary cirrhosis’ to ‘primary biliary cholangitis’. J Gastroenterol 2016; 51: 748-749. [PMID: 27230619 DOI: 10.1007/s00535-016-1223-z]

Introduction

Type 1 gastric neuroendocrine tumors (T1-gNETs) are well-differentiated, typically indolent neoplasms associated with chronic atrophic gastritis (CAG) and hypergastrinemia, with nearly 100% long-term survival. However, they have a high recurrence rate of 30-60% within the first year after resection. Tumor size is the most critical prognostic factor, while the role of grading is less definitive compared to other digestive NETs. International guidelines recommend conservative management for tumors <1 cm, advocating for approaches such as endoscopic resection or surveillance, which have shown excellent outcomes. However, the management strategies and outcomes for tumors > 1 cm remain less clearly defined due to the lack of scientific data in this specific patient population.

Aims & Methods

This study aimed to investigate management strategies and clinical outcomes in a homogeneous population of patients with T1-gNETs > 1 cm. The findings are expected to provide valuable insights and guide the development of more effective management strategies.
The present study was designed as an international multicentric retrospective analysis, conducted in 7 Western centers. It included consecutive patients diagnosed with T1-gNETs >1 cm in diameter, collected between 2004 and 2023, with at least 12 months of follow-up. The primary endpoints were disease progression (DP) (tumor recurrence or metastasis development) and the Progression-Free Survival. The Cox regression method was used to identify factors associated with progression.

Results

The study included 104 patients (61 females, 43 males) with a median age of 61 years and a median tumor size of 15 mm (range 11–60 mm). 61.5% of tumors were classified as G1, 37.5% as G2, and 1% as G3. 75 patients (72.1 %) underwent endoscopic resection (27 EMR, 5 m-EMR, 14 ESD, 7 snare polypectomy, and 22 unspecified techniques). Surgical procedures were performed in 33 patients (31.7%), 13 of whom had previously undergone endoscopic resection. One patient (1%) received treatment with somatostatin analogues, while 8 patients (7.7%) received no treatment.
The R0 resection rate was 51.9%. During follow-up, 26 patients (25%) experienced recurrence, 7 (6.7%) developed metastases, and 12 (11.5%) died, with 2 deaths (1.9%) due to tumor-related causes. The median overall survival and progression-free survival were 59.5 months (range 13–215) and 51.5 months (range 4–215), respectively.
Univariate analysis showed that R0 resection (HR 0.32, p=0.02) and advanced endoscopic techniques (m-EMR/ESD) (HR 0.09, p=0.02) were associated with better outcomes. In contrast, other resection methods (standard EMR, snare polypectomy, or unspecified techniques) and tumor size were associated with a higher risk of disease progression (HR 10.13, p=0.02; HR 1.03, p=0.003, respectively).

Conclusion

T1-gNETs >1 cm often recur and can progress, exhibiting potentially aggressive behavior, especially in larger lesions. Endoscopic resection should employ advanced techniques to prevent incomplete removal, which is associated with poor outcomes.

Introduction

Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are chronic conditions with alternating phases of flare-ups and remission. Due to the persistent and often severe course of these diseases, effective treatment significantly improves patients' daily activities and overall functioning. [1] Given the uncertain prognosis and the frequent disease progression despite pharmacotherapy, it is important to explore additional interventions that could support traditional treatments. While physical activity may provide both anti-inflammatory and functional benefits in IBD, data on its efficacy and safety during disease exacerbation remain scarce. [2] This pilot study is the first real-world investigation into the effects of a supervised physical exercise training in patients hospitalized due to IBD flare.

Aims & Methods

This study aimed to evaluate the effects of an individualized, moderate-intensity, supervised physical exercise training on exercise tolerance, inflammation, and fatigue resistance in patients hospitalized due to IBD flare, and to explore baseline factors associated with greater benefit from the intervention. Patients were randomly assigned to an intervention group, receiving individual cycloergometer training during hospitalization, or to a control group without exercise. Both groups were well balanced at baseline, with no significant differences in demographic, clinical, or laboratory parameters. At both admission and discharge, all patients underwent standardized graded exercise tests to establish their exercise tolerance based on the lactate threshold and heart rate/power output response. Furthermore laboratory assessments, and the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) questionnaire were conducted.

Results

A total of 22 patients were included in the study, with 13 patients in the intervention group and 9 patients in the control group. Although FACIT-F scores improved in both groups, the intervention group demonstrated a significantly greater improvement (median change –39 points; IQR –49 to –11; p = 0.014) compared to the control group (median change –25 points; IQR –52 to –6; p = 0.30). Baseline FACIT-F scores were significantly correlated with changes in heart rate response response during exercise: patients with greater baseline fatigue and poorer functional status experienced greater improvement in exercise tolerance (r = –0.62, p = 0.028). Platelet counts remained more stable in the intervention group (median change +10 ×10³/µl; IQR –65 to +45) compared to a significant increase in the control group (median +74 ×10³/µl; IQR +44.5 to +101.75; p = 0.046). In the intervention group, greater reductions in calprotectin were strongly correlated with more favorable heart rate responses during a graded exercise test (r = –0.92, p = 0.009).

Conclusion

Supervised training program during hospitalization for IBD flare was associated with improved fatigue resistance and more favorable inflammatory responses. Patients with worse baseline functioning obtained greater benefit in exercise tolerance. These findings support the feasibility and potential therapeutic role of individualized physical activity in acute IBD care and highlight the need for further investigation in real-world settings.

References

1. Farrell D, Artom M, Czuber-Dochan W, Jelsness-Jørgensen LP, Norton C, Savage E. Interventions for fatigue in inflammatory bowel disease. Cochrane Database Syst Rev. 2020 Apr 16;4(4):CD012005. doi: 10.1002/14651858.CD012005.pub2.
2. Achtenberg M, Cibor D, Zwolińska-Wcisło M. Structured exercise in patients with inflammatory bowel disease: a literature review. Gastroenterology Review/Przegląd Gastroenterologiczny. 2025;20(1):36-40. doi:10.5114/pg.2025.148473.

Disclosure

Magdalena Achtenberg has received lecture fees and/or travel grants from Ferring and Eli Lilly, unrelated to the present work. Tomasz Dziubyna has received travel grants from Fresenius, unrelated to the present work. Małgorzata Zwolińska-Wcisło, Dorota Cibor, Karolina Gazda, Magdalena Wyrzykowska, Piotr Kosieniak, Maria Wiśniewska, Jerzy A. Żołądź, Marcin Grandys and Joanna Majerczak declare no conflict of interest.

Introduction

Sex-based differences in clinical outcomes are increasingly being recognised in acute care, yet few studies have examined whether upper gastrointestinal bleeding (UGIB) risk scores perform differently in male versus female patients. This study evaluated the discriminatory performance of five established UGIB risk scores in predicting inpatient mortality by sex.

Aims & Methods

This retrospective study included 1,003 patients who underwent inpatient oesophagogastroduodenoscopy (OGD) for UGIB between January 2025 and August 2023 at a UK tertiary care centre. Glasgow-Blatchford Score (GBS), CHAMPS, ABC, Japanese score, and MAP(ASH), were calculated for each patient. Binary Logistic regression examined sex as an independent factor for 30-day inpatient mortality, with UGIB aetiology also accounted for (variceal vs non-variceal). Receiver operating characteristic (ROC) curves were used to assess each score's performance in predicting inpatient mortality separately for male and female subgroups.

Results

Out of the 1,003 admissions, 59.2% and 40.8% were males and females, respectively, with crude analysis demonstrating female mortality being slightly higher (10.5%) compared to male (8.6%). However, this was found not to be significant (p: 0.304, OR 1.251, CI: 0.816-1.917). These findings were consistent regardless of UGIB aetiology (variceal vs non-variceal).
For the 30-day inpatient mortality outcome, the ABC score demonstrated strong discriminative performance in both males (AUC: 0.804) and females (AUC: 0.835). CHAMPS and MAP(ASH) also performed consistently, with CHAMPS yielding AUCs of 0.788 in males and 0.793 in females, and MAP(ASH) showing 0.767 and 0.781 in males and females respectively. GBS performed slightly better in females (AUC: 0.743) compared to males (AUC: 0.691). The Japanese score showed poor discrimination in both sexes, particularly in females (AUC: 0.577). Overall, ABC, CHAMPS, and MAP(ASH) performed reliably across sexes.

Conclusion

Whilst crude mortality rates were higher in females than males, gender did not show to be an independent predictor of inpatient mortality, which could, however, necessitate a larger cohort size to ascertain validity. Risk scores, particularly the ABC score, maintained high and consistent predictive accuracy for inpatient mortality in both male and female patients with UGIB. These findings support the use of these tools across genders and suggest minimal gender-related performance bias in risk stratification.

Clinical Case Summary

A 46-year-old man from Bolivia consulted for abdominal pain with watery diarrhoea and occasional rectorrhagia for the last 2 months, associated with asthenia and weight loss. Laboratory tests showed microcytic anaemia, elevated C-reactive protein, positive faecal occult blood and negative stool culture. Colonoscopy (Images 1, 2) revealed deep ulcers in the ileum and colon with discontinuous areas of respected mucosa. Treatment was started with oral methylprednisolone at a dose of 1 mg/kg, with a decrease in the stool rhythm. He returned to the emergency department due to worsening abdominal pain, and was admitted for follow-up care. Histology (Image 3) showed epithelioid granulomas of probable infectious origin, due to the intramacrophagic inclusions, so the corticosteroid treatment was suspended. The quick test for HIV was positive, with a viral load of 79,000 copies/ml and a CD4 count of 88 CD4/ml. Mantoux and IGRA were negative. PCR amplification for Histoplasma spp in ileal biopsy was positive. Amphotericin B was prescribed with prophylaxis of opportunistic infections with trimethoprim-sulfamethoxazole. After 2 weeks, antiretroviral treatment was started. The patient improved, the abdominal pain disappeared and his intestinal rhythm normalised, and he was discharged from hospital. On outpatient follow-up, he was asymptomatic, with resolution of the ulcers in the control colonoscopy and no evidence of fungal structures in the histological examination.
The infection by Histoplasma capsulatum is the most frequent endemic mycosis in the American continent. Intestinal involvement is rare, with a preference for the ileocecal region in the form of deep ulcers that can simulate an outbreak of Crohn disease, as in our case. The use of immunosuppressants, especially anti-TNF-alpha, may worsen its course, highlighting the importance of a broad differential diagnosis, taking into account the patient's epidemiological characteristics.

References

Image 1. Colonoscopy. Terminal ileum with large ulcer with fibrin background, oedema and perilesional erythema.
Image 2. Colonoscopy. Transverse colon with two large deep ulcers with fibrin background and raised edges.
Image 3. Biopsy of ileum. Non-caseating epithelioid granulomas with intramacrophagic inclusions in ileal tissue. HE 40x.

Introduction

Sessile serrated lesions (SSLs), alongside adenomas, play a significant role in the development of colorectal cancer (CRC). Recent studies suggest that the adenoma detection rate (ADR) alone may not be sufficient for predicting post-colonoscopy CRC. Consequently, the ASGE/ACG Quality Task Force has recently recommended the sessile serrated lesion detection rate (SSLDR) as a new priority indicator for colonoscopy quality. Reviewing the variability of SSLDR in the control groups of previous randomized controlled trials (RCTs) may help identify factors that influence study outcomes.

Aims & Methods

A systematic review was conducted using PubMed, Embase, and the Cochrane Library databases to collect data from control groups of RCTs that assessed methods for increasing polyp detection with high-definition white-light colonoscopy (up to March 14, 2025). Random-effects meta-analysis pooled SSLDRs and their 95% confidence intervals (CIs). Heterogeneity was assessed with the I² statistic. Univariable and multivariable meta-regressions were performed to examine associations between SSLDR and study settings (publication year, sample size, number of centers, study design, and geographic origin), demographics (mean age, male proportion), and technical parameters (type of intervention, proportion of screening colonoscopy, ADR, and withdrawal time). This study was registered in PROSPERO (ID: CRD420251012475).

Results

A total of 23,461 patients from 48 studies were included in the analysis. SSLDR in the control arms ranged from 0.3% to 21.5%, with a pooled value of 4.4% (95% CI: 3.3%-5.8%; I² = 93%). Univariable meta-regression analysis identified patient age (OR 1.112; 95% CI: 1.043-1.186) and gender (OR 1.038; 95% CI: 1.003 to 1.074), geographic origin (OR 2.848; 95% CI: 1.585-5.116 for Europe and OR 4.044; 95% CI: 2.205-7.416 for North America), and ADR in the control arms (OR 1.054; 95% CI: 1.031-1.077) as significant predictors of SSLDR, with sample size (OR 0.999; 95% CI: 0.998-1.000) showing a negative correlation. Other factors, such as publication year, number of study centers (single or multiple), study design (parallel or tandem), type of intervention (imaging or mechanical), proportion of screening colonoscopy, and withdrawal time, had no significant effect. In multivariable meta-regression, RCTs conducted in Europe (OR 2.179; 95% CI: 1.242-3.820) and North America (OR 2.664; 95% CI: 1.550-4.580), as well as ADR in control arms (OR 1.035; 95% CI: 1.006-1.065), remained significant predictors of SSLDR, while sample size (OR 0.998; 95% CI: 0.997-0.999) and proportion of screening colonoscopy (OR 0.991; 95% CI: 0.983-0.998) were negatively correlated with SSLDR.

Conclusion

A high level of variability in SSLDR was found in the control groups of RCTs. Standardization of methodological and technical parameters is essential to improve the generalizability and reproducibility of findings from RCTs and enhance SSL detection in colonoscopy.