Introduction

There are a growing number of drugs approved for IBD. Despite this, there remains a subset of patients with IBD who do not respond to conventional medical treatment, which can result in significant morbidity and detrimentally impact quality of life. In these refractory cases, biologics or small molecules may be combined and the aim was to report the experience of IBD patients treated with such combination therapies in our tertiary-centre.

Aims & Methods

This was a retrospective single-centre cohort study evaluating adult IBD patients receiving combination therapy, which was defined as either two biologics or one biologic and a small molecule simultaneously. All patients received combination therapy to treat refractory IBD. Baseline patient characteristics, IBD phenotype and combinations used were reported. Response to combination therapy was based on overall evaluation, comprising clinical, biochemical, endoscopic and radiological measures, where appropriate. Steroid use during combination therapy was documented. Safety outcomes were recorded for each patient and included infection, development of cancer and hospitalisation. Worsening of IBD was not included as an adverse event as this was not felt to be directly related to combination therapy.

Results

We identified 13 patients (all with Crohn’s disease) that were treated with combination therapy. One patient received two combinations. Combinations included: Vedolizumab and Adalimumab (n=3), Ustekinumab and Adalimumab (n=5), Ustekinumab and Infliximab (n=1), Vedolizumab and Infliximab (n=2), Upadacitinib and Vedolizumab (n=1), Upadacitinib and Infliximab (n=1), Vedolizumab and Ustekinumab (n=1). The median duration of combination therapy was 182 days (interquartile range 277) and duration of follow up was 11.4 patient years. Response to combination therapy was observed in 9 of the 13 patients (69%), with a steroid-free response in 7 patients (54%). Three patients (23%) had worsening of their IBD and in 1 patient (8%) combination therapy was started too recently to be able to meaningfully measure response. During follow up, one patient on Infliximab and Upadacitinib required hospitalisation for active luminal symptoms and developed mild nosocomial COVID-19 infection, but he was also receiving steroids concomitantly and had previously received Methotrexate earlier on during the period of combination therapy. The same patient also required intestinal surgery for medically refractory IBD during the hospital admission. No other patients developed adverse events during follow up. Combination therapy is currently being continued in 10 out of 13 patients (77%).

Conclusion

In this small cohort, combination therapy led to improvement in IBD in the majority of patients. Those that had worsening of their IBD whilst on combination therapy all had complex, multi-focal Crohn’s disease, including the one patient who required surgery. Only one patient (8%) developed an adverse event. Combination therapy was shown in our single-centre experience to be a successful way to treat refractory IBD in high-risk phenotypes and is likely to be the future of treating these groups of patients. Two of our patients were treated with Upadacitinib as part of their combination therapy, which is a newly approved small molecule for IBD. Additional studies on different combinations of biologics and small molecules are needed, especially with more IBD drugs on the horizon.

Disclosure

Dr Kamal Patel has received honoraria for educational meetings and speaker fees from Abbvie, Janssen, Takeda, DrFalk, PredictImmune, Ferring and Pfizer and has received advisory board fees from Abbvie, Galapagos, Janssen and Pfizer.

Introduction

Diarrhea after cholecystectomy is a well-known complication that worsens the quality of life of the patient and may become a real challenge for the doctor.
Both changes in the bile acids spectrum (BAsS) and possible changes in microbiota and Small Intestinal Bacterial Overgrowth (SIBO) may have a major impact. What is primary in this circle is not fully understood.

Aims & Methods

The aim was to assess BAsS and SIBO in patients prior to cholecystectomy, three and twelve months after cholecystectomy.
Methods: Initially, the bile of the patients was obtained directly from the gallbladder after it was removed during the surgery. For the second and third time, the bile of the same patients after cholecystectomy was obtained in 3 and 12 months postoperatively, after the intubation of the duodenum under ultrasound control. The spectrum of BA was assessed using photocalorimetry. To assess the possible influence of SIBO, all the patients underwent a hydrogen breath test before cholecystectomy, and if SIBO was confirmed, they were not included in the study. Successive hydrogen breath tests were performed 3 and 12 months after cholecystectomy to all the patients who were included. The data were analyzed using parametric and non-parametric methods of evaluating the results through the Statistica program (StatSoft Inc, USA).

Results

14 patients, predominantly women (71.4%) were enrolled in the study. The spectrum of BA three months after cholecystectomy showed a tendency for secondary BA (deoxycholic acid) to predominate over primary BA (cholic acid) (P>0.05). After 12 months, the BAs pool returned to the baseline in most of the patients (P>0.05). SIBO was not registered in patients 3 months after cholecystectomy, but it was detected in 50% of cases (P>0.05) after 12 months.

Conclusion

The predominance of secondary BA in the early postoperative period probably indicates an increase in the number of bacteria, for the transformation of primary BA in the ileum, but the breath test is not sensitive enough to determine this.
Over time, if the equilibrium in a complex mechanism of BA homeostasis is not achieved (the amount of bile in the ileum, bacteria, FXR, etc.), this may lead to the SIBO development.

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