Introduction

Azathioprine and mercaptopurine are commonly used to treat Inflammatory Bowel Disease (IBD), with around 6 in 10 patients being prescribed them at some point. Adherence to treatment is important to maintain disease control, prevent flare ups, reduce the need for steroids and improve wellbeing. A good response to treatment may delay or negate the need to escalate treatment to Biologic medications or surgery. Despite this, treatment non-adherence is a common problem among patients with chronic diseases, averaging at around 50%. In IBD specifically, the data varies widely, but non-adherence to oral therapy has been reported to be as high as 72%.

Aims & Methods

The aim of this study was to determine the adherence to azathioprine and mercaptopurine in IBD patients across the Bristol, North Somerset, South Gloucestershire Integrated Care Board (BNSSG ICB). Primary care records were searched to identify all patients with IBD prescribed azathioprine or mercaptopurine. Demographic data as well as data on disease type, length of treatment and co-prescription with a Biologic treatment was collected. Medication adherence was determined by GP records of pharmacy refill data.

Results

A total of 1313 patients were identified as having IBD and a current prescription for azathioprine or mercaptopurine, from 78 GP surgeries (98% of surgeries within the BNSSG ICB). 154 patients were excluded as they had been on azathioprine for less than 1 year. 59% of the 1159 included patients had Crohn’s disease. 360 patients (31%) were on combination therapy with a Biologic medication. 324 patients (28%) were found to be non-adherent with their medication based on prescription refill data suggesting that they do not have an adequate supply of medication.

Conclusion

Our data suggests that adherence to the immunosuppressant medications azathioprine and mercaptopurine in patients with IBD is comparable or slightly better than in other chronic diseases. However, pharmacy refill data is an indirect measure of medication adherence so adherence may have been overestimated. There remains a substantial proportion of patients who are not adhering to treatment, which is likely to be associated with poorer outcomes.

References

Chan W, Chen A, Tiao D, et al. Medication adherence in inflammatory bowel disease. Intest Res. 2017 Oct;15(4):434-445

Disclosure

No conflicts of interest to declare.

Introduction

Hepatocellular carcinoma (HCC) is an end stage liver disease with increasing morbidity and mortality worldwide. Development of the disease is dependent on various genetic, dietary and environmental factors. While alcohol-related liver disease (ALD/MetALD) remains a major contributor, metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming increasingly relevant in clinical practice. There is increasing evidence for the role of bacteria, for instance, such as Bifidobacterium and Blautia, which were considered protective, while Streptococcus has been associated with disease progression. However, little is known about the alteration of microRNAs (miRNAs) in liver diseases and its interrelationship with microbial environment in view of etiological factors.

Aims & Methods

This study aimed to elucidate gastrointestinal miRNA alterations and explore their relationship with microbiome composition in patients with different stages of liver disease in terms of disease etiology. Multi-omics analyses were performed in a subset of well characterized patients (n=59) with liver disease and healthy controls. Systematic characterization included clinical, laboratory, demographic and imaging characterization and dietary preferences. Patients subclassification included fibrosis stage (no fibrosis, fibrosis, liver cirrhosis(LC)) and etiology (MetALD/ALD vs. MASLD). Fecal miRNAs were extracted using the Qiagen miRNeasy Kit and profiled via Agilent miRNA microarray. Microbiome analyses were performed amplifying the V1-V2 region of the 16S rRNA gene following Illumina sequencing.

Results

For miRNA analysis stringent criteria were applied to identify high quality miRNA targets. From approximately 4,000 candidates filtering resulted in selection of 202 high-quality miRNAs with reliably measurable concentrations. 28 of these miRNAs showed significantly positive alterations in concentration in patients with liver disease and 7 miRNAs significant negative alterations. Specifically, miR-642a-3p, miR-5006, miR-6781, and miR-6849 were elevated in feces in patients with LC. In contrast, miR-6869, miR-4467, and miR-5001 were present in lower concentration in LC patients. Notably, miR-4467 also showed strong negative associations with liver-specific laboratory markers, including gamma-glutamyl transferase (GGT) (r=-0.34; p=0.026) and M65, a marker of apoptosis (r=-0.42; p=0.005). Cross-sectional comparison of miRNA and microbiome data revealed miRNA alterations associated with specific microbial signatures. MiR-6795-5p, which was associated with liver stiffness (r = 0.39, p = 0.01), also correlated positively with the abundance of Streptococcus, a genus linked to disease progression (r=0.29; p=0.047). Conversely, miR-6869, miR-4467, and miR-5001 showed positive correlations with the potentially protective genera Blautia and Bifidobacterium (miR-6869: r_{Bifidobacterium}=0.35; p_{Bifidobacterium}=0.012; r_Blautia=0.37; p_Blautia=0.008; miR-4467: r_Blautia=0.41; p_Blautia=0.002; miR-5001: r_Blautia=0.38; p_Blautia=0.006).

Conclusion

Multi-omics analysis reveals distinct alterations in fecal miRNAs and gut microbiota across different stages of liver disease. Changes in microbial composition were associated with shifts in miRNA profiles, suggesting a functional link in maintaining intestinal homeostasis. These findings highlight the potential of integrated microbiome–miRNA signatures as novel diagnostic and therapeutic targets. Further studies are warranted to validate these associations and explore their clinical applications.

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

The coexistence of HBV and hepatic steatosis is frequent, but its impact on the progression of liver disease remains poorly characterized and much debated.

Aims & Methods

We aim by this study to determine the prevalence, associated factors, consequences of this association and response to treatment.
A retrospective analysis was conducted over 20 years from 2005 to 2025 on a single-center cohort of 124 patients with chronic HBV, of whom 16.1% (n=20) had steatosis (confirmed by imaging). Demographic, virological, metabolic and histological (fibrosis stage) characteristics were compared between the groups with and without steatosis. And statistical tests (Chi², Mann-Whitney, logistic regression) were used.
For the comparison, we defined:
- Group A: combining steatosis and HBV
- Group B: HBV without steatosis.

Results

The prevalence of steatosis in patients with HBV in our series was 16.1%, with a mean age of 52.1 years higher than that of patients with HBV without steatosis, (45.8 years), with a p-value of 0.02. Furthermore, in our work there was a clear female predominance, with a sex ratio of 3 F/H in group A vs 0.9F/H in group B with a p-value of 0.04.
In the history of our patients, we found that 30% of patients had high blood pressure in group A compared with 18% in group B, 10% had diabetes in group A compared with 8% in the other group, and there was no significant difference in smoking habits (15% compared with 12%). Statistical regression did not find any significant correlation in those signs. On the other hand, in the case of dyslipidemia, there was a slight predominance of group A (15% vs. 10%) with a p-value of 0.045.
The analysis of hepatic test didn’t show any big difference between results of GGT, PAL and ASAT but for ALAT there was a higher in patients with steatosis with a median of 62 vs 52,1 and a p-value of 0,02.
Our study also found no difference in serological results: 95% of patients with steatosis were Hbs Ag positive, with the presence of Hbc Ab in all patients at the time of diagnosis. These results were not very different from those of patients without steatosis (Hbs Ag positive in 96.8% and Hbc Ab positive in all patients). Only 10% of patients had a positive Hbe Ag in group A vs 7.2% in group B. The median viral load before treatment was 1870 UI/ml vs 2450 UI/ml with no real difference noted between the 2 groups, confirmed by statistical regression which found a p=0.82 value.
Our study found no real impact on liver disease, showing no worsening of fibrosis (30% F≥2 with steatosis vs 25% without, p=0.62*).
After analysis using the association Chi² test, our study found similar virological responses under treatment (83% in group A vs 78% in group B, p=0.75*).

Conclusion

In this cohort, steatosis in HBV patients (16.1%) was associated with age and female sex. Hepatic test showed a higher ALAT fold among patient with steatosis. However, higher viral load or more severe fibrosis was not demonstrated. Steatosis in HBV does not appear to have a negative influence on the course of the disease. These results suggest that the management of HBV with steatosis should primarily target virological control, without requiring any specific therapeutic adaptation.

Disclosure

no conflict of interest

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

Patients with eosinophilic oesophagitis often experience diagnostic delays. Untreated eosinophilic oesophagitis may result in fibrosis and stricture formation, leading to morbidity and impaired quality of life. Early diagnosis and treatment can potentially prevent these outcomes and reduce emergency admissions with food bolus obstruction. The reasons for these delays have not been examined in primary care previously. This study quantifies the time to eosinophilic oesophagitis diagnosis and examines factors associated with diagnostic delays.

Aims & Methods

A retrospective cohort study of incident eosinophilic oesophagitis patients between 1st Jan 2006 and 31st Dec 2022 was undertaken using Clinical Practice Research Datalink (CPRD AURUM) linked to hospital admission data in Hospital Episode Statistics. Patients were followed from first proton pump inhibitor (PPI) prescription or presentation with eosinophilic oesophagitis related symptoms (food bolus obstruction or dysphagia) identified from SNOMED CT codes for primary care and ICD-10 codes for secondary care to diagnosis. The association between patient level factors and time to eosinophilic oesophagitis diagnosis was examined using a Robust Poisson regression model.

Results

2300 eosinophilic oesophagitis patients were studied (67.7% male; age 38 (IQR 30-49)). Median time to diagnosis was 3.6 years (IQR 0.5-8.7). 80.7% patients had a PPI prescription record in primary care prior to eosinophilic oesophagitis diagnosis with a time to eosinophilic oesophagitis diagnosis of 4.9 years (IQR 1.5- 9.7). Factors associated with more than 3 years to diagnosis included: female sex (adjusted risk ratio 1.18, 95% CI 1.10-1.27); smoking (1.11, 1.01-1.23); compared with baseline of elective endoscopy, urgent endoscopy for dysphagia (1.35, 1.18-1.54), urgent endoscopy for food bolus obstruction (1.26, 1.13-1.41), dysphagia presentation in primary care (1.16, 1.08-1.25), food bolus obstruction presentation in primary care (1.11,1.00-1.23) and PPI prescription in primary care (3.08, 2.58-3.67). 77% of patients had PPI treatment prescribed after eosinophilic oesophagitis diagnosis. 21% patients with no history of asthma or chronic obstructive pulmonary disease were prescribed a steroid inhaler (presumably swallowed) after eosinophilic oesophagitis diagnosis.

Conclusion

Longer time to eosinophilic oesophagitis diagnosis was associated with being female, smoking, food bolus obstruction and dysphagia presentations in primary or secondary care and particularly PPI prescriptions in primary care.

Introduction

Thiopurines (TP) (azathioprine AZA, and 6 mercaptopurine 6MP) are immunosuppressive drugs (IS) used in the treatment of chronic inflammatory bowel diseases (IBD), particularly Crohn's disease (CD). The aim of our work is to see if they still have an indication in monotherapy, in the era of biotherapies and small molecules.

Aims & Methods

This is a retrospective analytical study conducted at the Hepato-Gastroenterology and Proctology Department "Medicine B" from January 2012 to July 2022. 740 patients were followed for CD during this period. 407 patients were put on TP. Age, sex, different characteristics of CD, indication for and type of TP treatment, and course of treatment were collected from all patients. SPSS 20.0 software was used for statistical analysis. The khi-2 test was used to compare categorical variables. The binary logistic regression model was used for multivariate analysis.

Results

There were 375 patients followed up for CD on TP monotherapy (92.13%) and 32 on combination therapy (7.86%). The sex ratio was F/H=1.5. The average age was 39.8 years (15-72). The location was ileal in 69 patients (16.95%), colonic in 78 patients (19.16%), ileocolic in 257 patients (63.14%), 6 patients (1.47%) had upper gastrointestinal tract involvement of CD and 3 patients (0.73%) had anal CD. 99 patients (24.32%) had ano-perineal lesions (APL). The phenotype was stenosing in 47 cases (11.54%), fistulizing in 159 cases (39%), stenosing and fistulizing in 60 cases (14.74%) and inflammatory in 141 cases (34.64%). The type of TP used was AZA in 299 patients (73.46%) and 6MP in 108 patients (26.53%). TP was indicated as maintenance treatment in 270 cases (66.33%), as monotherapy in the absence of biotherapy (which was not available before 2016) in fistulizing forms in 105 cases (25.8%), and in case of cortico-dependency in 32 cases (7.86%).
Clinical remission was obtained with monotherapy in 326 cases (86.93%) and with combotherapy in 24 cases (75%), this difference is statistically non-significant p=0.08. Mucosal healing was noted with monotherapy in 124 cases (33%) in patients who performed a control endoscopy, and with combotherapy in 15 cases (46.87%), this difference is statistically not significant p=0.07.
CRP was negatived in monotherapy in 149 patients (39.73%) and in combination therapy in 27 patients (84.37%), this difference is statistically significant p<0.001. Fecal calprotectin was not always available. Among the patients who had it performed (65: 15.97%), it was negative in 18 cases (41.86%) in monotherapy and 3 cases (13.63%) in combination therapy. This difference is statistically significant p=0.015. Metabolite dosing was also rarely available. In cases where this was done (43 cases: 10.56%), 6-TGN was in the therapeutic range only in 14 cases (32.55%) and in 36 cases (83.72%) for 6-MMP, requiring therapeutic adjustment.
In multivariate analysis and adjusting for the different confounding parameters, it was found that only the combination therapy was a predictive factor for mucosal healing [OR=1.8; [0.8 - 3.9]; p=0.01].

Conclusion

The results of this study show that TPs still have a place in the therapeutic arsenal of CD, but that their combination with biotherapy allows more clinical and biological remission and especially mucosal healing.