Introduction

Performance of liver ultrasound (US) in the detection of fibrosis has been compared in the past with histology, however non-invasive tests are today’s standard of care. Additionally, most of these studies were conducted in a controlled setting with dedicated sonographers, which does not reflect clinical practice. We aim to determine the specificity and diagnostic accuracy of routine clinical ultrasound surrogate markers in the staging of liver fibrosis against fibroscan, in the real-world setting.

Aims & Methods

Retrospective cohort study of patients who underwent liver US and Fibroscan (Echosens®) within 3 months of each other, in the last 6 months. Patients with clinical signs of decompensated cirrhosis were excluded. Ultrasonographic keywords of chronic liver disease were collected and their accuracy, specificity, and AUROC for liver fibrosis was calculated.

Results

251 patients met the inclusion criteria. Mean age was 58,2 (±13,05) years, and 73% were male. The most common etiologies were MASLD (34,5%), MetAld (19,2%), Alcohol (15,1%), followed by HCV (12,8%) and HBV (12,4%). In our cohort 25,9% of patients had advanced fibrosis(>10Kpa). The most specific signs were severe coarseness of the parenchymal texture 100% (98,02-100%); major structural changes (parenchymal atrophy or left liver lobe/caudate lobe hypertrophy): 96.17% (92.28%-98.45%) and severe steatosis: 89,87% (84,34%-93,67%). The simultaneous presence of an altered liver edge and any degree of coarseness showed a specificity of 82,07% (75,75%-87,32%). Splenomegaly, hepatomegaly/globose liver, steatosis, or coarseness of any degree showed a specificity under 75%. The most accurate signs (considering a prevalence of 2,85% of advance fibrosis) were severe coarseness 97,42% (94,59-99,01%, AUC 93,7%); major structural changes 93.94% (90.23%-96.55%, AUC 66,4%), severe steatosis: 87,30% (82,50%-91,17%, AUC of 51,5%) and the combined presence of an altered liver edge/any degree of coarseness 82,49% (77,18%-87,01%, AUC 69.5%). BMI and the presence of diabetes were strongly correlated with advanced fibrosis.

Conclusion

In summary, ultrassound surrogate markers of fibrosis remain accurate in predicting advanced fibrosis, even in a real-world setting

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

Loss of parietal cells causes the development of spasmolytic polypeptide-expressing metaplasia (SPEM) through transdifferentiation of chief cells. Slc26a9 is a member of Slc26a family with highly expression in the parietal cells to maintain gastric mucosal homeostasis (Liu et al., DDW 2019, 2020 and 2022). Our previous study showed that SLC26A9 deficiency causes gastric intraepithelial neoplasia in mice. (Liu et al., Cellular oncology 2022). However, the role of Slc26a9 in SPEM is never investigated.

Aims & Methods

Explore the role of Slc26a9 in SPEM. Slc26a9^fl/fl mice were crossed with Atp4b-Cre to generate parietal cell-specific Slc26a9 knockouts in Slc26a9^fl/fl/Atp4b-Cre mice in a mixed genomic background. Histopathology, immunohistochemistry (IHC), immunofluorescence (IF), Flow cytometry analysis, qPCR and single-cell sequencing were performed in Slc26a9^fl/fl mice and Slc26a9^fl/fl/Atp4b-Cre mice. Macrophage polarization markers and cytokine-related markers were detected by qPCR and Western-blot. Slc26a9 was overexpressed by adeno-associated virus and chronic SPEM model was established by using IL-33.

Results

Compared with Slc26a9^fl/fl mice, Slc26a9^fl/fl/Atp4b-Cre mice exhibited autoimmune gastritis (strongly loss of parietal cells, oxyntic atrophy followed with lymphocyte infiltration) at 1month, accompanied with H⁺/K⁺-ATPaseb and intrinsic factor lost. Flow cytometry analysis showed that CD4⁺T cells that infiltrated the Slc26a9^fl/fl/Atp4b-Cre stomach expressed the TCR (TCRVa2/TCRVb2) specific for the H⁺/K⁺-ATPase peptide. With advanced of age, Slc26a9^fl/fl/Atp4b-Cre mice displayed SPEM and hypergastrinemia at 6 months, followed with gastric alarmin IL-33 released and upregulation of SPEM markers, TFF2 and MUC6. Identification of gastric epithelial cell lineages using scRNA-seq and unbiased clustering showed that a variety of immune cell types. qPCR revealed significantly upregulation of macrophage molecular markers (F4/80, CD86, CD163), followed with the significantly upregulation of polarization markers of M2 macrophages and related chemokines in Slc26a9^fl/fl/Atp4b-Cre mice, including Arg1, Klf4, Fizz1, Ym1, Mrc1, CCL24 and CCL22 when compared with Slc26a9^fl/fl mice. Moreover, double immunofluorescence confirmed that M2 polarized markers F4/80⁺CD163⁺ cells were significantly accumulated in Slc26a9^fl/fl/Atp4b-Cre mice. At the same time, there was a corresponding increase in M2 macrophages capable of secreting IL-33. Notably, overexpression of Slc26a9 in IL-33-induced chronic SPEM model reduced SPEM formation and suppressed IL-33 downstream immune signaling as well as decreased M2 macrophages polarization. These results suggested that parietal cell-selective Slc26a9 deletion in mice caused SPEM development by promoting polarization of M2 macrophages via IL-33 upregulation.

Conclusion

Parietal cell-selective Slc26a9 deficiency in mice lead to the development of SPEM via IL-33 signaling. We speculated that Slc26a9 plays an important protective role in stabilizing gastric mucosal immunity and gastric epithelial cell homeostasis.

Introduction

Endoscopy is the gold standard for detecting mucosal inflammation in order to differentiate between Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) as well as for monitoring mucosal inflammation in diagnosed IBD patients. Fecal calprotectin has been established as an excellent surrogate biomarker of intestinal inflammation as it correlates well with endoscopic and histological disease activity. Most IBD diagnosis and treatment guidelines recommend using fecal calprotectin as an aid in diagnosis and to measure it routinely to follow the disease course in IBD patients. As there is no international standard to date, fecal calprotectin assay manufacturers rely on their own internal calprotectin standardization. Assays can be based on various technologies from traditional enzyme-linked immunosorbent assays (ELISA), particle enhanced turbidimetric high throughput assays (PETIA), to rapid lateral flow assays (LFA). LFAs can be read by conventional tabletop lateral flow readers or by everyday smartphone applications using the phone’s camera to acquire an image, detect the test cassette and calculate a quantitative result. It is essential that the biomarker is measured comparably across all assay methods. In this work, different assay methods were compared with clinical samples using a clinically relevant assay range.

Aims & Methods

128 raw stool samples from patients with signs and symptoms suggesting intestinal inflammation and who underwent endoscopic evaluation to determine if patients had IBD or IBS were used in this study. Samples were extracted using the BÜHLMANN CALEX Cap stool extraction device. Each extract was measured on the BÜHLMANN fCAL ELISA, fCAL turbo (PETIA), Quantum Blue fCAL extended lateral flow assay and smartphone based IBDoc fCAL home test. For the home test two phones, iPhone 11 and Samsung Galaxy S7, were used to measure the test cassettes. Each sample was measured one time on each assay and a Receiver Operating Characteristic (ROC) curve analysis was performed.

Results

ROC curves for each method were calculated in respect of differentiating between IBS and IBD with area under the curve (AUC) values ranging from 0.827 (Samsung Galaxy S7)) to 0.835 (fCAL turbo). There was no significant difference between the methods. BÜHLMANN uses a cut-off of 80 µg/g and 160 µg/g for IBS/IBD differentiation and 100 µg/g and 300 µg/g for IBD monitoring. For all methods, the sensitivity at the cut-off level of 80 µg/g was 90.8 % and specificity at 160 µg/g ranged from 67.3% to 71.2 %. Sensitivity at a cut-off of 100 µg/g ranged from 85.5% to 88.2% and specificity at 300 µg/g ranged from 82.7% to 86.5%.

Conclusion

This study shows that all BÜHLMANN fecal calprotectin assays are very comparable. They show an excellent clinical performance irrespective of the assay method performed. This allows for the use of the methods interchangeably, depending on the needs of the patients and their care team.

Disclosure

Authors are employee of BÜHLMANN Laboratories AG

Introduction

​The gut microbiota is often altered in chronic liver diseases and hepatocellular carcinoma (HCC), and increasing evidence suggests that it may influence response to cancer immunotherapy. Strategies to modulate the gut microbiome (i.e., fecal microbiota transplant (FMT)) may help to improve efficacy of immune checkpoint inhibitors (ICIs) or even overcome resistance to ICIs.

Aims & Methods

​In this single-center phase II pilot study (ClinicalTrials.gov ID: NCT05750030), we plan to include 12 patients with advanced HCC who progressed on atezolizumab/bevacizumab. Patients will receive atezolizumab/bevacizumab every 3 weeks in combination with a single FMT via colonoscopy from donors with HCC who responded to PD-(L)1-based immunotherapy. The primary endpoint is safety, measured by incidence and severity of treatment-related adverse events (TRAEs). The main secondary endpoint is best overall response (BOR) according to RECISTv1.1 and mRECIST. Here, we report results of a preplanned interim analysis.

Results

Of 6 patients included so far, 5 were male, 5 had BCLC stage C, and 5 had Child-Pugh class A. All patients underwent successful FMT without any periinterventional complications. TRAEs related to FMT were all low-grade (grade 1-2) and included bloating (n=2), constipation (n=2), and diarrhea (n=1). TRAEs related to atezolizumab included one grade 2 pruritus, and TRAEs related to bevacizumab included arterial hypertension (one grade 3 and two grade 2) and proteinuria (one grade 3 and one grade 1). All patients had at least one follow-up imaging. Two patients had partial response, 3 patients had stable disease, and 1 patient had progressive disease as BOR according to both RECISTv1.1 and mRECIST, which corresponds to an objective response rate of 33% and a disease control rate of 83%.

Conclusion

Based on acceptable safety and promising efficacy results, the decision to continue recruitment in this trial was made. An update with longer follow-up will be presented at the meeting, including analyses of the gut microbiome.

Disclosure

AF received travel support from Takeda and Amgen, he received speaker honoraria from AbbVie
KP has nothing to disclose.
BS received travel support from AbbVie, AstraZeneca, Gilead and Ipsen, speaker honoraria from Eisai as well as grant support from AstraZeneca and Eisai.
BL received speaker honoraria from Chiesi and Gilead.
LP has nothing to disclose.
AK has nothing to disclose.
KR has nothing to disclose.
KZ has nothing to disclose.
MT received speaker honoraria from Albireo, BMS, Falk Foundation, Gilead, Intercept, Madrigal and MSD; he has advised for Abbvie, Albireo, BiomX, Boehringer Ingelheim, Falk Pharma GmbH, Genfit, Gilead, Hightde, Intercept, Ipsen, Jannsen, MSD, Novartis, Phenex, Pliant, Rectify Regulus, Siemens and Shire. He further received travel grants from Abbvie, Falk, Gilead Intercept and Jannsen and research grants from Albireo, Almylam, Cymabay, Falk, Gilead, Intercept, MSD, Takeda and Ultragenyx. He is also co-inventor of patents on the medical use of NorUDCA filed by the Medical Universities of Graz and Vienna.
DT served as a speaker and/or consultant and/or advisory board member for Siemens, Roche, Sanova, Bristol-Myers Squibb and received travel support from Bayer and Siemens.
CG nothing to disclose.
MP received speaker honoraria from Bayer, BMS, Eisai, Ipsen, Lilly, MSD, and Roche; he is a consultant/advisory board member for AstraZeneca, Bayer, BMS, Eisai, Ipsen, Lilly, MSD, and Roche; he received grants from AstraZeneca, Bayer, BMS, and Roche; he received travel support from Bayer, BMS, Ipsen, and Roche.

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