Introduction

Liver biopsy remains the gold standard for fibrosis diagnosis and liver elastography is an accurate method for non-invasive evaluation, although often unavailable. FIB-4, a fibrosis index based on age, AST, ALT and platelet count, is increasingly used to predict advanced fibrosis, mostly in primary care. There are different cut-offs, however considering Non-Alcoholic Fatty Liver Disease (NAFLD) patients FIB-4 <1.30 was able to exclude advanced fibrosis, while FIB-4 >2.67 presented good positive predictive value. For populations older than 65years old, a cut off of 2.0 was advocated.

Aims & Methods

We aim to evaluate this tool on a tertiary hospital.
Using a tertiary hospital database of blood workup we selected the 3575 blood collections in ambulatory patients between 1^st-31^st august 2021 with laboratory data for FIB-4 calculation. We excluded patients under 18 years, those followed on Haematology, and those with AST or ALT >100 UI/L. We considered only the first blood collection for each patient in this period. On our study we compared patients according to FIB-4 value respective of their association with chronic renal disease, dyslipidaemia and altered glucidic metabolism. We investigated what percentage of those with FIB-4 >1.3 were followed on Gastroenterology.

Results

During the study period, among 3213 blood collections that fulfilled the criteria, 1290 (40.1%) had a FIB-4 >1.3. Male gender (51.4% vs 37.7%, p<0.001) and older age (70.1 vs 49.4, p>0.001) were significantly associated with FIB-4 >1.3. FIB-4 >1.3 associated with glomerular filtration rate (GFR) <90ml/min/1.73m² (p<0.001), chronic renal disease (GFR<60ml/min/1.73m²) (p<0.001), serum cholesterol >200mg/dL (p=0.22) and serum glucose >130 mg/dL. (p=0.003). There was no difference in ALT values (p=0.513) but on AST (p=0.001). Only 12.9% of patients with FIB-4>1.3 had a Gastroenterology appointment in our institution.
On a subgroup analysis for patients older than 65 years old, 405 (31.4%) patients had a FIB4 >2.0 among 1286. Male gender (48.8% vs 57.1%, p=0.005) and age (73.3 vs 80.0, p=0.005) significantly associated with FIB-4 >2.0. FIB-4>2.0 associated with GFR <90ml/min/1.73m² (p<0.001), GFR <60ml/min/1.73 (p=0.003) and cholesterol >200mg/dL (p=0.001) but no difference on glucose >130mg/dL (p=0.192). There was no difference in ALT values (p=0.695) but on AST (p=0.001).

Conclusion

Using the lower cut-off for FIB4, it is frequently elevated in referrals to a tertiary hospital. FIB-4 is associated with declining GFR and disturbances on lipid and glucose metabolism. Awareness of FIB-4 tool, may help recognizing the risk of advanced liver disease in patients and suspect renal disease or diabetes, as part of NAFLD phenotype.

Introduction

Renal disorders are among the extra-intestinal manifestations of inflammatory bowel disease (IBD), and treatments may also lead to renal failure. However, the incidence of end-stage renal disease (ESRD), defined as the need for renal replacement therapy (dialysis and/or renal transplantation (RT)), is poorly known. The primary objective of our study was to assess the incidence of ESRD in IBD patients, and to compare it with the general health insurance scheme population.

Aims & Methods

We conducted a prognostic cohort study based on data from the French National Health Insurance Database(SNDS). Prevalent cases of IBD affiliated to the general health insurance scheme during the period 2011-2020 were identified on the basis of declarations long-term diseases ALD 24 or the presence of 2 hospital stays for IBD with ICD-10 codes or a single stay with reimbursement of specific treatments. Incident cases of ESRD were identified on the basis of a stay with a RT or a period with dialysis sessions for at least 45 days. Crude incidence rates of ESRD were calculated over the period for the IBD and the non-IBD population, with their 95% confidence intervals.

Results

A total of 280,283 IBD patients were included in the study over the period 2011-2020, 134,567 with ulcerative colitis(UC) and 145,716 with Crohn’s disease(CD). The mean age at study inclusion was 39.8 (± 17.1) years. The M/F sex ratio was 0.9. The mean age at incidence of ESRD in the non-IBD population was 65.0 (±17.0) years, the M/F sex ratio cases was 1.7.
Among IBD patients, 534 patients began replacement therapy by dialysis or RT, they were younger than non-IBD patients (60.3(±16.7)years, P<0.001).The mean incidence rate of ESRD over the period was 26.4 per 100,000 person-years (IC95% 23.1-29.6), 480 (89.9%) patients entered ESRD by dialysis, and 54 (10.1%) by preemptive RT. In the non-IBD population the mean rate of ESRD was 15.9 per 100,000 person-years (IC95% 14.8- 17.1; P<0.0001 compared with IBD): 79,606 (94.5%) patients entered ESRD by dialysis, and 4,634 (5.5%) by RT (as compared with IBD,P<0.001). In subgroup analysis, the mean incidence rate of ESRD was 22.8 per 100,000 person-years (IC95% 18.9-26.7) in UC patients and 29.5 (IC95% 25.3-33.6) in CD patients (P<0,0001). The rates of preemptive RT were 12.4% in UC patients (87.6% dialysis) and 8.6% in CD patients (91.4% dialysis).
Over a median follow-up of 6.8 years, the survival rate after ESRD was 40.8% in ESRD-IBD patients VS 34.2% in ESRD non-IBD patients (P<0.001). This difference remained significant for patients under 65 (p<0.0073).
No significant difference for the risk of re-hospitalization after RT (p=0.84), of retransplantation during the follow-up period in RT patients (p=0.67), or for the risk of hospitalization for severe infection (p=0.97) after RT in patients from the general population compared with IBD patients. The same was true for the type of severe infections after RT (p= 0.068) and for the risk of solid and haematological cancer after RT (p=0.48). However, there was a significant difference in the type of first severe infection after RT(p=0.003), but we are waiting for the results to tell us which one.

Conclusion

The incidence of ESRD is significantly higher in IBD than in the general data base population, confirming the need for regular monitoring of renal function in our patients.
Survival after ESRD onset, is higher in IBD patients.
The high incidence of RT in the IBD population confirms that access to transplantation is not restricted in this
population.

References

Kirchgesner et al, Gastroenterology 2018
Meyer et al, Aliment Pharmacol Ther. 2020
Tuppin et al, Nephrol Ther 2016

Introduction

Fecal microbiota transplantation (FMT) has been successfully used in a series of diseases in recent years. Most studies have focused on short-term risks, which are mild and generally associated with delivery methods. There have been no reports of FMT safety in the treatment of multiple diseases and long follow-up periods.

Aims & Methods

We performed a retrospective analysis of 11025 patients who underwent FMT in the Tenth People’s Hospital of Tongji University between January 2012 and December 2023. We included patients with various gastrointestinal diseases and patients with extraintestinal diseases that involved intestinal dysfunction. A questionnaire was administered to the included patients during follow-up (2 weeks, 3 months, 1 year, and 5 years after FMT) via telephone and health portal software Haodaifu app).

Results

Most adverse events during short-term follow-up (2 weeks) were related to the method of delivery. The main adverse events in the nasogastric tube group were tube-related respiratory difficulty (40.6%,include sore throat 14.1%, nasal congestion 8.7%, nasal irritation due to nasogastric intubation 17.8%) and nausea/vomiting (12.6%). In the oral capsules group, nausea and vomiting (8.9%) occurred during oral administration because the capsules are associated with a fecal smell and taste, both of which are difficult to remove completely. For colonoscopy and enema routes, the main adverse events were diarrhea (10.7%, 9.9%) and perianal discomfort (15.3%, 8.4%), respectively. Two cases in the colonoscopy group and one case in the enema group were complicated with colon perforation, but remission with conservative treatment. The most frequently reported adverse events were mild or moderate in severity and transient. Those symptoms associated with nasogastric tube administration disappeared after tube removal at the completion of treatment. Several other new symptoms were reported during short-term follow-up, although none occurred in >1% of patients. The most common symptom reported was bloating/flatulence. Although more adverse events were reported in the nasogastric tube group, most were mild. Additionally, patients are more comfortable with the upper gastrointestinal route because they could use it for enteral nutrition support or gastrointestinal imaging according to their medical needs. Based on our clinical experience, we proposed the “Tongji FMT Requirements”and implemented them in our clinic (beginning in 2019) to standardize the indications and timing of FMT treatment and to improve FMT safety. After the implementation of these requirements for 2 years, we compared safety data collected before and after implementation; The application of the requirements has effectively reduced adverse events. The short-term (mainly FMT-related diseases) incidence rate significantly decreased from 32.6% in 2017–2019 to 17.2% in 2019–2021.

Table 1.Tongji FMT Requirements

Conclusion

FMT appears safe during both short-term and long-term follow-up. The patient group that received FMT did not exhibit an increased incidence of new diseases, and the risk of infection transmission appears to be low. Considering the widespread use of FMT, there is a need for the establishment of a national clinical and patient-reported FMT safety collection system in future.

References

• 1) Kelly CR, Yen EF, Grinspan AM, et al. Fecal microbiota transplantation is highly effective in real-world practice: initial results from the fmt national registry. Gastroenterology 2021;160:183-192
• 2) Mullish BH, Quraishi MN, Segal JP, et al. The use of faecal microbiota transplant as treatment for recurrent or refractory clostridium diffificile infection and other potential indications: Joint british society of gastroenterology (BSG) and healthcare infection society (HIS) guidelines. Gut 2018;67:1920e41
• 3) Saha S, Mara K, Pardi DS, et al. Long-term Safety of Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection. Gastroenterology 2021;160:1961-1969
• 4) Zhang S, Chen Q, Kelly CR, et al. Donor Screening for Fecal Microbiota Transplantation in China: Evaluation of 8483 Candidates. Gastroenterology 2022;162:966-968
• 5) Parenteral and Enteral Nutrition Branch of Chinese Medical Association, et al. Chinese experts consensus on standardized methodology and clinical application of fecal microbiota transplantation. Zhonghua Wei Chang Wai Ke Za Zhi 2020;23:5-13
• 6) Wang S, Kou C, Liu Y, et al. Rural-urban differences in the prevalence of chronic disease in northeast China. Asia Pac J Public Health 2015;27:394-406

Introduction

Patients with IBD often have related anxiety and depression which may negatively impact disease activity and have been consistently highlighted as an unmet need by patient groups. Timely access to psychiatric and psychological support can be difficult and costly. We investigated the effectiveness of a novel cognitive behavioural therapy (CBT) program delivered by a trained mental health nurse in place of a formal psychologist.

Aims & Methods

A retrospective review of all CBT referrals made for adult patents between Sep 2019 – Dec 2022 in a tertiary IBD Centre. Referrals were from IBD Consultants, senior medical Trainees, IBD Nurses and a liaison psychiatrist. Patients are offered high-intensity CBT for up to 8 consecutive weeks as per local protocol of a minimum 4 sessions. The CBT took place virtually; over the phone or video call via MS Teams. Patients who completed at least 4 sessions of CBT were included in this review.
Our primary measure was to assess if there was an improvement in mental health using CORE-10, a brief validated psychometric questionnaire, completed at the start and end of therapy. A score of greater than 11 was an indicator of psychological distress, and a reduction of 6 points is clinically meaningful[i].

Results

96 patients were referred to the inflammatory bowel disease CBT service. Of those 47 patients went on to complete at least 4 sessions of CBT, with an average age of 33. 91% of referrals were for either anxiety or depression. With other cited indications including; anger management, PTSD and functional pain.
15 patients (32%) had UC, 31 patients (66%) had Crohn’s disease and 1 patient had indeterminate colitis. The majority of patients had 8 sessions of CBT of which all were completed virtually. The average disease duration was least 8 years at the time of referral.
26 (55%) of patients were on biologics at the time of initiating CBT, with 23% patient of patients referred having undergone at least one surgery prior to referral. Physician global assessment at the initiation of CBT showed 25 (56%) patients were in clinical remission. 21 (45%) patients were in clinical remission following their course of CBT.
Following the completed CBT sessions 37 patients had some improvement in their CORE-10 score with a mean reduction for all patients of 7.6. 20 patients had a CORE-10 reduction of at least 6. 33 patients (70%) had a CORE10 score of >11 at baseline, indicating significant psychological distress. Of the 33 patients with an initial score >11, 20 patients 61% showed reliable clinical improvement.
10 patients (21%) referred for CBT showed, either an increase (8 patients) or no change (2 patients) in their CORE10 score following at least 4 sessions of CBT.

Conclusion

Studies have consistently demonstrated a high burden of anxiety amongst patients with IBD which can have a detrimental effect on quality of life and disease outcomes. CBT delivered by a trained mental health nurse is an effective and relatively low-cost intervention for patients with IBD, delivering beneficial treatment outcomes, and maintaining good levels of engagement; including those with a severe phenotype of disease.
CBT did not significantly influence disease activity as measured by physician global assessment.

References

[i] Barkham, M., Bewick, B., Mullin, T., Gilbody, S., Connell, J., Cahill, J., Mellor-Clark, J., Richards, D., Unsworth, G. and Evans, C. (2013b). The CORE-10: A short measure of psychological distress for routine use in the psychological therapies. Counselling and Psychotherapy Research, 13(1), pp.3–13. doi:https://doi.org/10.1080/14733145.2012.729069.

Disclosure

nil

Introduction

Clinical trials are ongoing to develop novel therapies for ulcerative colitis (UC), aiming to break the existing therapeutic ceiling. Mirikizumab, a monoclonal antibody targeting the p-19 subunit of IL-23, was evaluated in a phase-II clinical trial for the treatment of moderate-to-severe UC. Identifying predictive variables for response to therapy is still an unmet need and would serve as a valuable asset in clinical trials and clinical practice to guide therapeutic strategies.

Aims & Methods

This post-hoc data analysis aimed to identify variables predicting response to mirikizumab in UC patients from a phase II clinical trial. One-hundred and six randomly selected patients from the induction phase were considered: 26 (24.5%) were assigned to receive mirikizumab 50mg IV Q4W, 37 to 200mg IV Q4W (34.9%), 30 to 600mg IV Q4W (28.3%) and 13 to placebo (12.3%). In the maintenance phase, 44 received 200mg SC Q12W (42.3%), 47 received 200mg SC Q4W (45.2%), and 13 received placebo (12.5%). Patients who did not achieve clinical remission (14, 13.2%) were excluded from the analysis related to the maintenance phase. A stepwise analysis was conducted, initially using a principal coordinate analysis (PCoA) with permutational multivariate analysis of the variance (PERMANOVA), followed by a univariate analysis (Fisher’s or Wilcoxon signed-rank test) to select significant variables (p<.05). Further, a country-nested, three-visit repeated-measured generalized mixed ordinal logistic regression model (GLM) using significant PCoA variables was conducted. For both models the endpoint was histological remission at weeks 12 and 52, defined as Geboes score <2.

Results

At week 12, histological remission was achieved in 34 patients (32.1%) while at week 52 in 42 patients (39.6%). PCoA, PERMANOVA and univariate analysis considered histological remission to be significantly predicted by faecal calprotectin, endoscopic remission (Mayo 0, UCEIS <1) and induction therapy at weeks 12 and 52 (p<.05). Also, at week 52, the 32-IBD Questionnaire (systemic symptoms and social function), Physician Global Assessment, partial and total Mayo scores, and maintenance treatment were significant. Considering these as explanatory variables for the GLM, we confirmed the following as significant predictors of histological remission: faecal calprotectin <250 µg/g (Odds Ratio 0.26; 95% CI 0.12-0.58; p<0.001), endoscopic remission (OR 0.16; 95% CI 0.04-0.57; p=.005), induction treatment with mirikizumab 200mg IV Q4W (OR 0.09; 95% CI 0.02- 0.45; p=.004), 600 mg IV Q4W (OR 0.09; 95% CI 0.01-0.50; p=.006) and maintenance with 200 mg SC Q4W (OR 0.05; 95% CI 0.01-0.30; p=.001). A more severe Physician Global Assessment predicted histological activity (OR 2.29; 95% CI 1.03- 5.11; p=.043).

Conclusion

Our predictive model identified faecal calprotectin, endoscopic remission, and Physician Global Assessment as predictive factors for response to therapy. Notably, our model identified the most effective therapeutic strategies to achieve histological remission during induction and maintenance phases, showing promising ability to guide therapeutic choices in clinical trials and clinical practice. Additional investigation utilizing a larger clinical dataset would further enhance the ability of this model to identify variables predictive of response to therapy.

Introduction

MACE is a new, non-invasive technology which approaches the diagnostic sensitivity of OGD in gastric focal lesion detection in patients with dyspepsia. [Li et al., CGH 2016] This study compared the two in the detection of focal and diffuse lesions in patients referred for the investigation of anaemia.

Aims & Methods

MACE was performed within one week before OGD using the AnX Robotica magnet system and Navicam capsule (single camera capsule, frame rate 6/sec: Wuhan, China). Following a fast, simethicone and gastric distension using 0.5-1L water, patients swallowed the capsule semi-recumbent on the left lateral side before lying supine to allow approximation of the magnet to the chest. The examination protocol included a sequence of magnet movements and patient position changes. Inspection of an anatomical location was considered complete if sufficient to exclude any significant pathology. Endoscopists performing OGD were blinded to the MACE outcome and all findings were recorded from a pre-identified diagnostic list. Data was analysed using SPSS.

Results

45 of 81 (55.5%; median age 63 (IQR 45.5- 72), 60% male) patients had pathology identified by MACE, OGD or both. Complete views were obtained by MACE in the oesophagus (72.4%), proximal stomach (93.8%), distal stomach (93.8%) and duodenum(79.6%, p<0.001) and mean examination time was 22 minutes. Findings were concordant in 17 (37.8%: gastric erosions (n=6), ulcers (n=5), oesophagitis (n=2), eroded polyps (n=2) and gastric antral vascular ectasia (n=2)). MACE alone identified pathology in 24 (53.3%: gastric erosions (n=17), angioectasia (n=4), ulcers (n=2, oesophageal and duodenal), eroded polyp (n=1) and both angioectasia and erosions (n=1). OGD identified a distal body ulcer (n=1), small (n=1) and large (n=1) oesophageal varices and oesophageal ulcers (n=1) missed by MACE and in one patient MACE identified only an oesophageal ulcer and OGD only a duodenal ulcer, each missing the pathology detected by the other. Diagnostic yield was higher for MACE than OGD (P<0.001).

Conclusion

The improved diagnostic yield of MACE compared to OGD is accounted for mainly by minor mucosal abnormalities which could, nonetheless, contribute to occult bleeding and anaemia. Although speculative this could be because of better tolerance of MACE and a longer examination time. An increased frame capture rate, with or without a second camera, is needed to improve oesophageal visualisation.

Disclosure

I herwith declare that the magnetic capsules for the study were provided by Ankon

Introduction

Metabolic Associated Steatotic Liver Disease (MASLD) affects 25-30% of the European population and is projected to rise further. These patients are at increased risk for liver-related complications and higher overall mortality, emphasizing the need for early detection to improve outcomes. While abdominal ultrasound serves as the primary imaging modality for suspected liver disease, its sensitivity for diagnosing mild steatosis is inadequate, and gold-standard methods for quantifying liver steatosis infiltration, such as magnetic resonance imaging or liver biopsy are impractical for widespread use.

Aims & Methods

This study aimed to assess the diagnostic accuracy of the Attenuation Coefficient (ATT) as a complementary method to B-mode ultrasound for early detection of hepatic steatosis. Consecutive patients referred for transient elastography were prospectively enrolled. Liver steatosis was graded using a 4-point scale (normal, mild, moderate, or severe) in B-mode ultrasound for each patient, and ATT was measured in accordance with manufacturer quality criteria instructions (Fujifilm®). Additionally, the Hepato-Renal Index (HRI) was calculated for each patient, and Controlled Attenuation Parameter (CAP, Fibroscan®) was measured.

Results

A total of 128 patients, 61.7% male, with a mean age of 56.8±12.8 years, were included. Among them, 78.1% exhibited at least one cardiometabolic risk factor. The main referral indications were fibrosis assessment in viral hepatitis (42.2%), MASLD (21.9%), and alcoholic liver disease (11.7%). The median vibration-controlled elastography result was 5.8kPa. B-mode ultrasound steatosis assessment classified 44.5% as normal, 10.2% with mild steatosis, 21.1% with moderate steatosis, and 24.2% with severe steatosis. The area under the ROC curve for steatosis detection was 0.796 for HRI, 0.894 for ATT, and 0.896 for CAP, highlighting robust diagnostic performance, particularly for the latter two methods. There was a strong correlation between ATT and CAP (r=0.710). Using a CAP>248dB/m to define steatosis, the area under the ROC curve for ATT was 0.890. For an ATT cutoff value ≥0.66, Sensitivity, Specificity, Negative Predictive Value, and Positive Predictive Value were 82.7%, 77.3%, 72.3%, and 86.1%, respectively. The sensitivity of B-mode ultrasound for steatosis detection was 79.5%, increasing to 90.4% when combined with ATT measurement.

Conclusion

ATT demonstrated excellent accuracy for steatosis detection, comparable to CAP and superior to HRI. Importantly, combining B-mode ultrasound with ATT significantly improved the diagnostic sensitivity. These findings suggest that ATT has the potential to become a valuable non-invasive tool alongside ultrasound for early detection of hepatic steatosis, aiding in earlier intervention and improved patient outcomes.

References

Tamaki N, Koizumi Y, Hirooka M, et al. Novel quantitative assessment system of liver steatosis using a newly developed attenuation measurement method. Hepatol Res. 2018;48(10):821-828. doi:10.1111/hepr.13179
Bozic D, Podrug K, Mikolasevic I, Grgurevic I. Ultrasound Methods for the Assessment of Liver Steatosis: A Critical Appraisal. Diagnostics. 2022;12(10):2287. doi:10.3390/diagnostics12102287