Introduction

Non-alcoholic Fatty Liver Disease (NAFLD), is a state of hyperinflammation which is associated with release of pro-inflammatory cytokines. Obesity, diabetes and metabolic syndrome, which are usually accompanied by hepatosteatosis, are risk factors for severe Covid-19 infection.

Aims & Methods

We aimed to investigate the association of hepatosteatosis and liver fibrosis by non-invasive markers (FIB-4 and APRI) with the prognosis of Covid-19 disease among hospitalized patients. In this retrospective and observational study, 500 patients with the diagnosis of Covid-19 between March 2020 and March 2022 and underwent Thorax Computed Tomography (CT) were included. Demographics, clinical characteristics and laboratory data at admission were recorded. Liver-spleen attenuation value difference (CT _L-S) was obtained from CT images and non-invasive fibrosis markers as APRI and FIB-4 scores were calculated (1). Advanced fibrosis was defined as FIB-4>2.67, APRI≥1. Severe outcomes were defined as either intensive care unit (ICU) admission or mortality.

Results

Among the patients, 129 (25.8%) were admitted to the ICU, and mortality occurred in 53 (10.3%) cases. According to CT _L-S value, hepatosteatosis was in 32.6% of the cases. 82.8% of cases with hepatosteatosis were male, mean age was 52.6±13.5, 82% were overweight or obese. Hypertension and diabetes were the most common comorbidities. Among ICU patients, hepatosteatosis was found in 41.8% and ICU admission was associated with hepatosteatosis (p=0.002). Of the patients with hepatosteatosis, 58% of patients have FIB-4>1.3 and of these, FIB-4 and APRI score were significantly high in patients with ICU admission and mortality (p=0,001). Of the patients both with hepatosteatosis and advanced fibrosis, 71% were admitted to the ICU, mortality was seen in 32.5%. Mortality was significantly higher in patients with hepatosteatosis and advanced fibrosis according to the FIB-4 score (p=0.001). In the ROC analysis, combination of FIB-4 score and attenuation had highest sensitivity (sensitivity: 88.37%; Negative Predictive Value 90.85%; p=0.001) in determining the need for ICU need. The need for ICU follow-up was found to be 5 times higher in patients with a high FIB-4 score and low attenuation value [(Odds ratio (OR) 5.101; 95% Confidence Interval (CI): 2.865-9.083)]. The risk factors for the need for intensive care in patients with hepatosteatosis were advanced age, presence of fibrosis, high ferritin and IL-6 level in univariate analysis, whilst only high ferritin level was defined as a risk factor in multivariate analysis. Inflammation markers such as IL-6 and ferritin were significantly higher in patients with hepatosteatosis and fibrosis.

Conclusion

Hepatosteatosis and fibrosis determined by non-invasive tests were found to be associated with severe Covid-19 infection. Hepatosteatosis and fibrosis may increase inflammation-related markers such as ferritin and IL-6 and may create a synergistic effect with infectious conditions. Likewise high ferritin level in Covid-19 patients with hepatosteatosis is a risk factor for severe disease. CT_L-S and fibrosis scores have strong negative predictive value in the diagnostic evaluation for severity of Covid-19 disease.

References

1. Byun J, Lee SS, Sung YS, Shin Y, Yun J, Kim HS, et al. CT indices for the diagnosis of hepatic steatosis using non-enhanced CT images: development and validation of diagnostic cut-off values in a large cohort with pathological reference standard. European Radiology. 2019 Aug 1; 29(8):4427–35.

Introduction

PEUGIC (Post-Endoscopy Upper Gastrointestinal Cancer) is defined as carcinoma in the upper gastrointestinal (GI) tract which was preceded by negative upper endoscopy in the last 3 years. According to current knowledge, the rate of PEUGIC is an important parameter of quality and should not exceed 10 %. The aim of this study was to evaluate the occurrence and risk factors of PEUGIC at non-university hospital in Frydek-Mistek (Czech Republic) between 2013 and 2023.

Aims & Methods

This is a retrospective analysis of the patients diagnosed with upper GI cancer from January 2013 to December 2023. The data analyzed included family history of upper GI cancer, indications of the examination, therapy, tumor location and histological type. Risk factors for PEUGIC were calculated using the Chi-squared test and Fisher's exact test, with p <0,05 considered significant.

Results

During the study period, a total of 22727 gastroscopies were performed in total, and 122 patients were diagnosed with upper GI cancer (88 men and 34 women), including 35 esophageal tumors, 80 gastric tumors, and 7 duodenal tumors. Family history of upper GI tumor was reported in 10 patients. PEUGIC was identified in 12 patients (9,84%, 9 men and 3 women, mean age 69,25 years), including 6 in the esophagus, 5 in the stomach, and 1 in the duodenum. Two patients had early detection as part of adequate surveillance (Barrett's esophagus, post-polypectomy). Thus, we can evaluate 10 patients as true PEUGIC (8,20%). The rate of PEUGIC was 17,14 % (6/35) in the esophagus, 6,25 % (5/80) in the stomach, and 14,3 % (1/7) in the duodenum. Tumor location (for esophagus p=0,086, for stomach p=0,065, for duodenum p=0,525), histology (for adenocarcinoma p=0,332, for spinocelular cancer p=0,402, for neuroendocrine tumor p=0,25), male gender (p=0,815), or family history of upper GI tumor (p=0,335) were not statistically significant risk factors for detecting PEUGIC.

Conclusion

The overall rate of PEUGIC at our institution over the 11-year study period was 9,86 %, without early detected lesions as part of adequate surveillance, it was 8,20 %. Early detection of PEUGIC, which indicate poorer endoscopy quality, need to be distinguished from early detection of carcinoma within adequate surveillance.

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

Computer Aided Detection (CADe) systems have the potential to enhance the detection of early neoplasia in Barrett's Esophagus (BE) patients during endoscopic procedures. In this study, we aimed to evaluate a recently developed CADe system during live endoscopic procedures.

Aims & Methods

The CADe system was developed using a large and diverse training data set from 15 international endoscopy centers, comprising 6,237 neoplastic images from 1,304 patients and 7,595 non-dysplastic images from 1,103 patients. Multiple extensive ex-vivo benchmarking studies were performed for validation. The CADe system displayed consistent and reliable performance, leading to a significant improvement in the detection rate of neoplasia by endoscopists.
During this pilot study, the CADe system was evaluated in live endoscopic procedures of BE patients with neoplastic lesions or non-dysplastic Barrett's esophagus (NDBE) in two tertiary hospitals. The protocol involved a series of white light endoscopy videos obtained by an expert endoscopist with real-time evaluation and feedback provided by the CADe system. First, the Barrett's segment was comprehensively visualized using a standardized "pullback video", spanning from the gastric folds to the maximum extent of the Barrett's segment. Subsequently, at 2 centimeter intervals, a series of 10-second "level videos" was recorded, starting from the retrograde position. Ground truth, referring to the presence or absence of visible abnormalities requiring targeted biopsy, was determined by the endoscopist prior to starting the protocol. This was followed by post-hoc histopathological confirmation through targeted biopsies, endoscopic resection, or acquisition of random biopsies. The primary outcome measure focused on the standalone performance of the CADe system, which was evaluated in terms of per-patient sensitivity and specificity.

Results

A total of 15 neoplastic patients and 15 NDBE patients were included in the study (mean age of 67 years; mean Barrett length of C7M9; 25 males; no significant differences between groups). The CADe system exhibited a 100% sensitivity on a per patient basis, correctly identifying all neoplastic lesions. 14 out of 15 visible lesions were correctly diagnosed in the pullback videos. The initially missed lesion was detected in the subsequent level video. The system incorrectly predicted neoplasia in 8 NDBE patients. If applied in a clinical setting, this would result in a maximum of one additional targeted biopsy per patient, compared to the 16 random biopsies dictated by the mean Barrett length in this study. Histopathological examination confirmed neoplasia in 13 cases, with 11 cases being adenocarcinoma and 2 cases being high-grade dysplasia. Two cases did not contain any dysplasia. Additionally, in 4 cases from the non-dysplastic group, low-grade dysplasia was found through the random biopsy protocol.

Conclusion

This study represents one of the first evaluations of a CADe system for real-time detection of neoplasia in Barrett's esophagus in the endoscopy suite. The system accurately detected all neoplastic lesions, with an acceptable number of false positive detections.

Disclosure

This study received financial and logistical support from Olympus Tokyo.