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.

Clinical Case Summary

Visceral artery aneurysms and pseudoaneurysms ruptures are a rare cause of haemobilia, associated with congenital or acquired vascular malformations; anyway, they are associated with high morbidity and mortality caused by their life-threatening complications, such as haemorrhage.
We present a video reporting a case of haemobilia secondary to the rupture of an inferior pancreaticoduodenal pseudoaneurysm identified after a necrotizing pancreatitis with a coexisting celiac artery stenosis.
A patient with hepatic alcoholic cirrhosis with severe prolongation of INR (⁓2) patient was admitted for acute pancreatitis; several days after, melena occurred and a one point hemoglobin drop was observed. An emergency upper gastrointestinal endoscopy was performed, revealing active bleeding coming from the duodenal papilla.
The emergency computed tomography scan of the abdomen showed a pancreatic pseudocyst with an adjacent aneurism, with active bleeding; computer tomographic angiography revealed a pancreatic-duodenal artery aneurysm with fistulization with pancreatic duct through pseudocyst wall; angiography coil embolization of the pseudoaneurysm was performed, successfully. Unfortunately, embolization of splenic artery lead to splenic infarction as a complication which caused further decompensation of cirrhosis and death after ten days.
Rupture of post-pancreatitis arterial aneurism into pancreatic pseudocyst is a rare, dreadful event which can precipitate the natural history of liver cirrhosis.

Introduction

Most of the data concerning the epidemiology of inflammatory bowel disease (IBD) in Asia originated from the Eastern population and there are limited studies conducted in the Middle East. We aimed to describe the clinical phenotype, disease course, and medication usage of IBD cases from Iran in the middle east.

Aims & Methods

We conducted a cross-sectional study of registered IBD patients in the Iranian Registry of Crohn’s and Colitis (IRCC) recruited from 2017 until 2022. IRCC is a nationwide registry with at least one center in every province of Iran.¹ More than 400 gastroenterologists collaborated with IRCC, which was reported as approximately 87% of total gastroenterologists working in Iran. Demographics characteristics, past medical history, family history of IBD, disease extent and location, clinical behavior, extraintestinal manifestations, IBD medications, IBD activity using the IBD-control-8 questionnaire and the Manitoba IBD index, admissions in the past 3 months, emergency visits in the past 12 months, history of colon cancer, and IBD-related surgeries were gathered.

Results

Overall, 9746 patients with confirmed IBD, including 7793 patients with ulcerative colitis (UC) and 1953 patients with Crohn’s disease (CD) were reported. The ratio of UC to CD patients was 3.99. The median age at diagnosis was 29.2 (IQR: 22.6,37.6) and 27.6 (IQR: 20.6,37.6) for patients with UC and CD, respectively. 17.9% of patients with UC had a positive family history. Majority of patients with UC had pancolitis (47%). The most common treatment received by patients was 5-ASA (93.5%) followed by immunomodulator, prednisolone, and anti-TNF. Among patients who received immunomodulators, 96.2% was azathioprine followed by 6-mercaptopurine (2.8%) and methotrexate (1%). Of patients who used anti-TNF, 68.8% were adalimumab and 31.2% were infliximab. Among patients with CD, only one peak was observed in the distribution of age at diagnosis at 30-40 years. Male to female ratio was 1.28 in patients with CD. Patients with CD most commonly had ileocolonic involvement (43.7%) and stricturing behavior prevalence was 4.6%. Moreover, 38.4% of patients with CD had been treated with anti-TNF. Among patients who received immunomodulators, 90.4% was azathioprine followed by 6-mercaptopurine (4.6%) and methotrexate (5%). Of patients who used anti-TNF, 71.9% were adalimumab and 28.1% were infliximab.

Conclusion

This first report of IBD behavior, clinical outcome, and medication usage from the Iranian Registry of Crohn’s and Colitis as a representative population of the Middle East highlights the differences in IBD characteristics based on geographical location.

References

1. Malekzadeh MM, Sima A, Alatab S, et al. Iranian Registry of Crohn's and Colitis: study profile of first nation-wide inflammatory bowel disease registry in Middle East. Intest Res. 2019;17(3):330-339

Introduction

The Janus kinase inhibitor (JAKi) upadacitinib (UPA) is approved for the treatment of moderate-to-severe ulcerative colitis (UC). However, safety warnings from the US Food and Drug Administration and the European Medicines Agency recommend caution when using JAKis in certain at-risk patients. These drug-class warnings are based on data from the ORAL Surveillance (OS) study, a safety outcomes trial comparing risk of cardiovascular (CV) events with the JAKi tofacitinib plus methotrexate vs a tumor necrosis factor inhibitor (TNFi) plus methotrexate in patients with rheumatoid arthritis (RA) who were ≥50 years of age with ≥1 CV risk factor.¹ An OS study post hoc analysis observed higher major adverse CV event risk with tofacitinib vs TNFi in patients with RA plus a history of atherosclerotic CV disease (ASCVD).² CV risk profiles may be different for patients with UC vs RA.

Aims & Methods

This analysis aimed to describe the CV risk profile for patients with UC relative to the CV risk profile for patients with RA included in the OS study. Patients with UC enrolled in the placebo-controlled UPA U-ACHIEVE and U-ACCOMPLISH induction trials³ were evaluated for the OS study inclusion criteria (age ≥50 years, ≥1 CV risk factor [CV event history, hypertension, diabetes mellitus, smoking/tobacco use, and high-density lipoprotein cholesterol <1.034 mmol/L]). In addition, history of coronary artery disease or ASCVD and 10-year CV disease risk for patients with UC with no prior CV disease were estimated using the American College of Cardiology ASCVD risk score calculation.

Results

Overall, 268/1097 (24.4%) patients with UC met the OS criteria and 624 (56.9%) had ≥1 CV risk factor, regardless of age. Few patients with UC (30; 2.7%) had a history of ASCVD, in contrast to the RA population (640/4362; 14.7%). The distribution of 10-year ASCVD risk scores for patients with UC was similar between the placebo and UPA treatment arms, but markedly different from patients with RA (Table). Most patients with UC were categorized as low risk (938; 85.5%), with another 52 (4.7%) categorized as borderline risk, 51 (4.6%) as intermediate risk, and 26 (2.4%) as high risk.

Conclusion

The majority of patients in the UC trials had low estimated CV risk, while the majority of patients with RA included in the OS study were at intermediate or high CV risk. Caution should be used when extrapolating adverse events data from patients with RA to risk discussions for patients with UC.

References

1. Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med 2022;386:316-326.
2. Charles-Schoeman C, Buch MH, Dougados M, et al. Risk of major adverse cardiovascular events with tofacitinib versus tumour necrosis factor inhibitors in patients with rheumatoid arthritis with or without a history of atherosclerotic cardiovascular disease: a post hoc analysis from ORAL Surveillance. Ann Rheum Dis 2023;82:119-129.
3. Danese S, Vermeire S, Zhou W, et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. Lancet 2022;399:2113-2128.

Disclosure

L Peyrin-Biroulet has received personal fees from Galapagos, AbbVie, Janssen, Genentech, Alimentiv, Ferring Pharmaceuticals, Tillotts Pharma, Celltrion, Takeda, Pfizer, InDex Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Inotrem, Allergan, MSD, Roche, Arena Pharmaceuticals, Gilead, Amgen, Bristol Myers Squibb, CSL Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, OSE Immunotherapeutics, Enthera, Theravance Biopharma, Pandion Therapeutics, Gossamer Bio, Viatris, and Thermo Fisher Scientific; grants from AbbVie, MSD, Takeda, and Fresenius Kabi; and stock options from CTMA.
RK Cross is an advisory board member and consultant for AbbVie, Adiso, BMS, Fresenius Kabi, Fzata, Janssen, Magellan Health, Pfizer, Samsung Bioepis, Sebela, and Takeda; and a member of the Executive Committee for the IBD Education Group and Scientific Co-Director of CorEvitas.
KM De Felice is an advisory board member and honorary speaker for AbbVie and BMS.
D Ilo, B Duncan, J Liu, and CTJ Holweg are employees of AbbVie Inc. and may hold AbbVie stock and/or stock options.
R Chowdhury has no conflicts of interest to declare.
This study was funded by AbbVie. Medical writing and editorial assistance were provided by Jeffrey Kohn, PhD, and Lauren Smith, BA (Hons), from Complete HealthVizion, an IPG Health Company, funded by AbbVie.

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

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

Per-Oral Endoscopic Myotomy (POEM) was introduced in clinical practice few years ago, and quickly become one of the first line treatments of esophageal motility disorders. We report on the outcomes of the first 1000 patients treated with POEM in a single tertiary referral center during 11 years.

Aims & Methods

The first 1000 patients treated with POEM between May 2011 and September 2022 were identified from a prospective database and included in this study.
Demographics, clinical and technical aspects and follow-up data were collected and analysed. After treatment, patients underwent a regular follow-up, after 6 month, 2 years, 5 years and 10 years. Additional follow-up visits were performed, if clinically indicated. Timed Barium Esophagram, EGD, and esophageal manometry were performed before endoscopic treatment and during post-operative follow-up; a 24-hour esophageal pH monitoring study was performed 6 months after POEM.
Clinical failure was defined by and Eckardt score > 3 and by the need for additional treatments.

Results

Mean age of patients was 51.5 years; 36 patients were younger than 18 years and 157 older than 70 years. Four-hundred ninety-eight patients were male. One hundred seventy-seven patients had received previous treatments for achalasia (110 pneumodilation, 46 surgical myotomy; 21 botulinum toxin injection).
A total of 141 patients had a type I achalasia, 626 a type II, 111% a type III, 30 non-achalasia spastic esophageal motility disorders; in 92 patients achalasia type were not adequately classified. A sigmoid-type esophagus was present in 45 patients.
Mean symptoms duration before POEM was 24±64.6 months.
POEM was technically successful in 979 patients.
The median length of myotomy was 8.0 cm (range 4-22 cm) in the esophagus and 3.1 cm (range 0-7 cm) in the stomach. An anterior myotomy was performed in the 83% of patients. Mean operative time was 50.4 minutes (11–180 minutes).
Length of hospital stay was a mean of 2.5 days (range 1 to 48 days) after POEM.
Mild or moderate complications occurred in 28 patients (2.8%) and were managed conservatively. Severe complications occurred in 2 patients and required prolongation of hospital stay and other interventional treatment. There were no perioperative deaths in our series.
A mean follow-up of 30.4 months (3–130 months) was available for 93.8% of patients. Overall clinical success rate (Eckardt score ≤ 3) was 95.1%. Clinical success was 97.3%, 95.2%, 90.8% and 82% after 6 months, 2 years, 5 years and 10 years, respectively.
Thirty-three patients (70.2 %) with clinical failure underwent pneumodilation (78.8% with persisting clinical benefits); 5 patients (10.6% underwent surgery), one (2.1%) underwent re-POEM.
Clinical success was 93.4% in achalasia-patients and 83.3% in those with spastic motility disorders (p=0.1742).
An altered esophageal pH-study was documented in 32.6% patients; esophagitis rate was 34% (88% grade A/B; 12% grade C/D). At the date of the last follow-up, 38% of patients was receiving daily proton-pump inhibitors for gastroesophageal reflux. Two patients underwent antireflux surgery. Non cases of post-operative Barrett esophagus were identified.

Conclusion

Our results confirm the efficacy of POEM in a large cohort of patients. Benefits of POEM seem durable; adverse events are rare and no specific mortality was reported. Prevalence of GERD is relatively high, but well controlled by medications in the vast majority of patients.