bluuebunny/crossref_metadata_2025 huggingface dataset:
A255 COMMUNICATING NEEDS AND FEATURES OF IBD EXPERIENCES (CONFIDE) SURVEY: PATIENT PERSPECTIVES ON EXPERIENCE OF ULCERATIVE COLITIS SYMPTOMS IN CANADA
Authors: Glass J , Panaccione R , Bessissow t , Hunter Gibble T , Atkinson C , Braun M , Ellis H , Dewar T , Jairath V
Published: February 2024

Background

Moderate-to-severe ulcerative colitis (UC) can be associated with impairment in quality of life (Kawalec, 2016).

Aims

The Communicating Needs and Features of IBD Experiences (CONFIDE) study aims to increase understanding of patients’ experiences and the impact of IBD on their lives in the United States, Europe, Japan, and Canada. These data focus on Canadian patients.

Methods

An online, quantitative, cross-sectional survey was conducted (panel recruitment) between February and March 2023 in patients diagnosed with active moderate-to-severe UC in Canada. Moderate-to-severe UC was defined using criteria based on previous treatment, steroid use, and/or hospitalization. Data collected included patient perspectives on their experiences with UC, including symptom burden. Results were summarised descriptively.

Results

The survey was completed by 82 (of 373 contacted – 22% response) patients (65% male, mean age 43.5 years (SD 12.6), mean time since diagnosis 6.3 years (SD 7.6, range 1-33 years)). The top 3 patient-reported symptoms experienced in the past month were diarrhea (39%, n=32), bowel urgency (BU, 31%, n=25), and fatigue/tiredness (29%, n=24). Overall 73% (n=60/82) were receiving advanced therapies (biologic or novel oral therapy), and BU was currently experienced by 28% (n=17) of these patients. Over half of patients had ever experienced BU (56%, n=46); of these, 48% (n=22) reported doing so at least once a week in the past 3 months. Due to fear/anticipation of bowel urgency related accidents, 68% (n=56) of patients with UC reported wearing diaper/pad/protection at least once in the past 3 months. Of those who had worn diaper/pad/protection, 32% (n=18) reported that they suffered from BU in the past month. Due to fear of BU-related accidents, 31% (n=25) of patients declined participating in work/school, 34% (n=28) declined participating in social events, and 26% (n=21) declined participating in sports/physical exercise in the last 3 months.

Conclusions

Out of the top 3 symptoms reported by patients, BU was the second-most common in patients with moderate-to-severe UC in this study of Canadian patients. A substantial proportion of patients with moderate-to-severe UC continue to report BU, despite receiving advanced therapies; with two-thirds requiring to wear diapers or pads. Further work is needed to understand the pathophysiology of urgency and the efficacy of medical therapies to improve urgency using validated outcome measures.

References

Kawalec P. Indirect costs of inflammatory bowel diseases: Crohn's disease and ulcerative colitis. A systematic review. Arch Med Sci. 2016 Apr 1;12(2):295-302

Funding Agencies

Eli Lilly and Company
A256 NAVIGATING IBD CARE : HEALTHCARE PROVIDERS’ INSIGHTS ON IMPLEMENTATION OF NURSE NAVIGATOR-LED IBD FLARE PATHWAY
Authors: Reuangrith J , Jones J , Rohatinsky N , Nguyen G
Published: February 2024

Background

Disparities in access to healthcare for persons living with inflammatory bowel disease (IBD) persist. An IBD nurse navigational role promises to improve access to evidence-based specialist care by minimizing inequities in access to care. Little is known about how to implement a provincial nurse navigational role in the Canadian health system.

Aims

This study aims to explore healthcare providers' perceptions of barriers and facilitators to the implementation of an evidence-based IBD flare pathway through a provincial nurse navigational role.

Methods

This was a national qualitative study performed in collaboration with the CCC PACE Program, in which two virtual semi-structured group interviews were conducted in 2022. One group interview was with six IBD nurses from three provinces, and the second was with five gastroenterologists from five provinces. Participants were purposefully recruited. The Consolidated Framework for Implementation Research (CFIR) and the Capability, Opportunity, Motivation, and Behaviour (COM-B) frameworks informed the interview script development. Data were transcribed verbatim and subjected to content analysis, with major themes categorized into the COM-B domains. The results of preliminary data analysis are presented.

Results

While IBD nurses emphasized the critical role of effective communication tools, standardized referral systems, strong administrative support and patient education and engagement as facilitators, they also highlighted challenges like patient resistance, variability of training and the necessity for tailored patient care. Other barriers identified were the medical complexity of managing overlapping conditions, remote vs in-person considerations and the perception and definition of a flare. On the other hand, IBD-focused gastroenterologists emphasized the potential of integrating pathways into electronic medical records and the value of empowering nurse navigators. However, they pointed out concerns regarding the inherent variability in disease presentation, entrenched medical beliefs, comfort levels with nurse-led pathways and the inherent diversity in medical practices. Both groups identified resource constraints as a barrier and an effective triage process as a facilitator.

Conclusions

This study sheds light on the multifaceted perceptions of healthcare providers concerning the implementation of an evidence-based IBD flare pathway through a provincial nurse navigational role. These insights underline the complexity of implementing a nurse navigational role and the need for targeted interventions and resources to address the identified barriers while leveraging the facilitators.

Funding Agencies

CCC
A258 ULTRASOUND ASSESSMENT OF CROHN’S DISEASE PATIENTS FOLLOWING RISANKIZUMAB INITIATION; BASELINE, 3 AND 6 MONTH FOLLOW UP
Authors: Rosentreter R E , Ingram R , Ma C , Chan M , Shukla T , Devlin S , Kaplan G G , Seow C , Panaccione R , Novak K , Lu C
Published: February 2024

Background

Risankizumab (RIS), an interleukin-23 inhibitor specific to the p19 subunit, was approved for the treatment of moderate to severe Crohn’s Disease (CD) in December 2022. Intestinal ultrasound (IUS) is an accurate and well-tolerated modality for evaluating response to therapy.

Aims

We aim to assess IUS response at 3 and 6 months following RIS therapy.

Methods

Consecutive patients initiating RIS for CD were recruited to be evaluated by IUS at baseline (within 14 days of initiation), 3 months, and 6 months. Baseline demographics, medication exposure, surgical history, and inflammatory biomarkers were obtained. IUS response (decrease in bowel wall thickness (BWT) ≥ 25%)) and transmural remission (TR) (normalization of BWT normalization, color doppler signal (CDS, modified Limberg (ML) score 0), wall stratification, inflammatory fat) for each segment were evaluated. Paired t-tests compared values at baseline, 3 and 6 months.

Results

Thirty-three (20, 60.6% female) patients were recruited; 30 completed baseline and 3 month IUS, while 18 patients have 6 month IUS. Median age was 55 years (IQR 39-63), with a 12 year median CD duration (IQR 5-28). Five had inflammatory, 19 stricturing, and 6 fistulizing behaviour. CD distribution was 18 ileal, 1 colonic, and 11 ileocolonic. 20% (6/30) were bio-naïve, while 30% (9/30) had failed ≥ 3 biologics. Baseline mean CRP (4.1 ± 4.9 mg/L) did not significantly differ at 3 months (5.0 ± 6.8 mg/L, p=0.16), nor at 6 months for patients with values available (6.2mg/L ± 8.3, p = 0.38). Of patients with FC concentrations, 3 month mean FC (129.4 ±70 mcg/g) (9 patients) had significantly decreased from baseline (427.6 ± 271 mcg/g) (p=0.008), and similarly at 6 months (9 patients; baseline 396 ± 299 vs. 129 ± 75, p = 0.02). 80.0% (4/5) patients with colonic BWT ampersand:003E 3mm had IUS response (baseline mean BWT 5.6 ±1.4mm vs 3.5 ± 0.8mm at 3 months (p=0.011). IUS response was not achieved in those with ileal CD at 3 months (BWT 6.3 ± 2.1mm vs 3 month 6.0 ± 2.5mm (p=0.31). However, 21.4% (3/14) of ileal CD patients had an IUS response at 6 months. There is a non-significant ileal BWT reduction (5.4 ± 1.6mm) from baseline (6.0 ± 1.7mm) at 6 months. Of the 9 with moderate to severe CDS, 55% (5/9) had reduction to mild CDS by 3 months. TR was achieved by one patient with ileal CD at 6 months.

Conclusions

IUS response was achieved in 80.0% of CD patients with colonic disease at 3 months follow RIS initiation. IUS response was not detected for ileal CD at 3 months, but detected in 21.4% at 6 months A significant FC reduction by 3 and 6 months was attained. Further prospective patient recruitment and IUS at 6 and 12 months to assess preliminary results and longer-term response is needed.

Funding Agencies

None
A263 IRONING OUT THE DETAILS: CROHN’S DISEASE PATIENT DERIVED MACROPHAGES ARE MORE SUSCEPTIBLE TO FERROPTOSIS
Authors: Sousa J A , Callejas Pina B E , Munazza Y , Wang A , Raman M , McKay D
Published: February 2024

Background

Death of intestinal epithelial cells is ubiquitous in Crohn’s disease (CD) but the death of immune cells such as macrophages is less explored. We have found that monocyte derived macrophages from patients with active CD are more susceptible to H2O2-induced cytotoxicity but the form of regulated cell death these cells undergo remains to be elucidated. Selenium (Se)—a common micronutrient deficiency in patients with CD—is used in the synthesis of selenoproteins that have antioxidant properties (e.g., glutathione peroxidases (GPx)) and are highly expressed in macrophages. Whether Se deficiency plays a role in the increased cytotoxicity also remains to be elucidated.

Aims

To determine the form of cell death of macrophages in response to H2O2-induced cytotoxicity and whether selenium deficiency plays a role in the increased susceptibility to H2O2-induced cytotoxicity.

Methods

Blood collected from healthy volunteers and patients with active CD was analyzed for serum GPx activity. Monocytes isolated by plastic adherence were treated with M-CSF (10ng/ml, 7d) to derive macrophages. Macrophages were treated with H2O2 (500μm, 2h) and lactate dehydrogenase release was measured. GPX1, SLC7A11 and PTGS2 mRNA expression were determined by qPCR. The presence of cleaved caspase 3 was determined by immunoblotting and IL-1β by ELISA. Lipid peroxidation a marker of ferroptosis was assessed by staining macrophages with Bodipy C-11 (± liproxstatin-1, an inhibitor of ferroptosis).

Results

CD macrophages were two times more susceptible to H2O2-evoked cell death. In response to H2O2 macrophages did not express cleaved caspase 3 or IL-1β, but there was an induction of ferroptosis markers (SLC7A11 and PTGS2). Moreover, lipid peroxidation was induced and could be blocked with liproxstatin-1. Dietary Se intake did not differ between groups but serum GPx activity was greater in patients with CD compared to control. In contrast, GPX1 mRNA expression and GPx1 protein expression were decreased in CD macrophages compared to healthy controls.

Conclusions

Macrophages derived from patients with CD are inherently more sensitive to ferroptosis potentially through reduced GPx1 expression. Future studies warrant testing if GPx1 prevents ferroptotic macrophage cell death and if it holds therapeutic relevance in CD pathophysiology.

Funding Agencies

Helmsley Charitable Trust, Crohn's and Colitis Foundation of America
A266 TISSUE-SPECIFIC FUNCTION OF THE CIRCADIAN GENE, BMAL1, DURING COLITIS RECOVERY
Authors: Taleb Z , Carmona-ALcocer V , Wan R , Karpowicz P
Published: February 2024

Background

The circadian clock is a self-sustained molecular oscillator which drives 24-hour physiological rhythms in nearly every cell of the body. It consists of the genes Bmal1 and Clock that positively regulate Cry and Per, their negative regulators, resulting in a 24-hour transcription/translation feedback cycle. Shift work, which causes disruptions to 24-hour physiological rhythms, has been linked with an increased incidence of inflammatory bowel disease (IBD).

Aims

We have previously established that mice lacking the non-redundant circadian regulator, Bmal1, exhibit more severe colitis compared to controls. The loss of Bmal1 also negatively impacts post-colitis regeneration and recovery. However, the role of Bmal1 in specific cell types remains unknown in regard to regenerative capacity following colitis. The intestinal stem cell niche includes stromal cells that provide signaling factors to regulate the proliferation of epithelial cells in the colonic crypt.

Methods

To test the role of the circadian clock in these cell types, we conditionally disrupted Bmal1 in intestinal epithelial versus stromal cells using VilCre/+;Bmal1flox/flox and PdgfraCre/+;Bmal1flox/flox mice, respectively. Dextran Sulfate Sodium (DSS) was applied to induce acute colitis, disease progression was evaluated, and regeneration at different stages of recovery was analyzed. We hypothesize that the cell-specific disruption of Bmal1 in both intestinal epithelial and stromal cells negatively impacts the regenerative capacity following colitis, leading to delayed recovery and increased inflammation.

Results

No differences in survival and colitis disease activity were observed between Vil+/+;Bmal1flox/flox control and VilCre/+;Bmal1flox/flox but increases in lesion number, inflammation, and disrupted recovery are evident in VilCre/+;Bmal1flox/flox colons histologically. Whereas control animals are able to recover two weeks following DSS treatment, regenerative proliferation is still present in conditional knockouts. Thus, Bmal1 is required in intestinal epithelial cells for efficient repair. Preliminary results in the PdgfraCre/+;Bmal1flox/flox conditional stromal mutanats do not show differences in survival or disease severity, and we are currently evaluating effects on regeneration.

Conclusions

Our results support a critical role for Bmal1 in intestinal epithelial cells during post-colitis regeneration and recovery.

Funding Agencies

CCC, CIHR
A267 RECENT IMMIGRANTS WITH INFLAMMATORY BOWEL DISEASE HAVE SIGNIFICANT HEALTH-CARE UTILIZATION FROM PRECONCEPTION TO POSTPARTUM: A POPULATION-BASED COHORT STUDY
Authors: Tandon P , Huang V , Feig D , Saskin R , Maxwell C , Fell D , Seow C , Snelgrove J , Nguyen G
Published: February 2024

Background

Previous studies have demonstrated an increase in health-care utilization, such as hospitalizations and emergency department (ED) visits, in immigrant people with IBD compared to non-immigrants. This may be even higher from preconception to postpartum due to heightened provider and patient concerns, though this remains to be confirmed.

Aims

To characterize differences in health-care utilization from preconception to postpartum amongst immigrant and non-immigrant women with IBD.

Methods

We accessed administrative databases to identify women (age 18-55) with IBD with a singleton pregnancy between 2003-2018. Immigration status was defined as recent (ampersand:003C 5 years of date of conception), remote (ampersand:003E5 years since date of conception), and none. Differences in ambulatory, ED, hospitalization and endoscopic visits during 12-months preconception, pregnancy and 12-months postpartum were characterized. World region of immigration origin was also ascertained. Adequate prenatal care was defined by using the validated R-GINDEX which assesses the date of first prenatal visit and total number of prenatal visits. Multivariable negative binomial regression was used to report adjusted incidence rate ratios (aIRR) and modified Poisson regression with quasi-likelihood models and robust error variance procedures were used to report adjusted relative risks (aRR) with 95% confidence intervals (95% CI).

Results

8880 pregnancies were included, 8304 in non-immigrants, 96 in recent immigrants, 480 in remote immigrants. Compared to non-immigrants, recent immigrants had the highest rates of IBD-specific ambulatory visits during preconception (aIRR 3.06, 95% CI, 1.93-4.85), pregnancy (aIRR 2.15, 95% CI, 1.35-3.42), and postpartum (aIRR 2.21, 1.37-3.57) and the greatest rates of endoscopy visits during preconception (aIRR 2.69, 95% CI, 1.64-4.41) and postpartum (aIRR 2.01, 95% CI, 1.09-3.70). There were no differences in ED and hospitalization visits between groups. Compared to non-immigrants, immigrant women were much less likely to have a first trimester prenatal visit (remote: aRR 0.78, 95% CI, 0.65-0.93; recent: aRR 0.61, 95% CI, 0.42-0.88) or receive adequate prenatal care (remote: aRR 0.67, 95% CI, 0.46-0.98; recent: aRR 0.46, 95% CI, 0.22-0.96). Those immigrating from the Americas, Africa, or the Middle East were the most likely to be hospitalized during pregnancy, have a postpartum endoscopy visit, and receive inadequate prenatal care.

Conclusions

There remain significant disparities in health-care utilization amongst immigrant women with IBD from preconception to postpartum. Health policy endeavors are required to provide standardized and equitable care to all women with IBD during these otherwise high risk periods.

Funding Agencies

CCC, CIHR
A274 COVID-19 INFECTION RISK BETWEEN VACCINATED PATIENTS WITH ULCERATIVE COLITIS AND CROHN’S DISEASE : A RETROSPECTIVE COHORT STUDY IN TAIWAN
Authors: WU Y , Chou J
Published: February 2024

Background

The effectiveness of coronavirus disease 2019 (COVID-19) vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with inflammatory bowel disease (IBD) is well established, but it is not clear whether patients with ulcerative colitis (UC) and Crohn’s disease (CD) have different risks of COVID-19 infection after vaccination.

Aims

The aim of this study was to compare the risk of COVID-19 infection after vaccination in patients with UC and CD. Moreover, we also investigated risk factors related to COVID-19 infection and collected data on any adverse events and disease symptoms.

Methods

We conducted a retrospective cohort study in adult IBD patients who had received at least two doses of COVID-19 vaccination and compared the prevalence of infection between UC patients and CD patients using the medical records of China Medical University Hospital between 1 January 2020 and 31 March 2023. All data management and odds ratios calculations were performed using version 9.4 of SAS software (SAS Institute, Cary, NC, USA).

Results

Total 169 IBD patients (96 with UC, 73 with CD) were included in this study. UC patients were older than CD patients (44.92±13.72 vs. 37.27±15.27 years, p=0.0008)(Table 1). A high proportion were male (IBD 70.41%; UC 65.63%, and CD 76.71%). Most (57.4%) received three doses of COVID-19 vaccines. Azathioprine, steroid, and mesalazine medication histories were different between the groups (pampersand:003C0.05). COVID-19 infection prevalence was 49.11% (UC 56.25%, CD 39.73%; p=0.0333) (Figure 1). Logistic regression analysis suggested UC patients had an odds ratio of 1.95 (95% CI=1.05-3.62) and adjusted odds ratio of 2.78 (95% CI=1.20-6.44) for COVID-19 infection compared to CD patients, indicating a 1.95-fold to 2.78-fold higher risk (Figure 2). There was a trend towards a decreasing risk of COVID-19 infection with increasing number of vaccine doses. Medication was not identified as a risk factor. (Figure 3)

Conclusions

Our study identified a greater risk of COVID-19 infection in vaccinated patients with UC than those with CD. However, most patients who became infected with COVID-19 did not have severe symptoms and only one case was hospitalized. The mortality rate of COVID-19 in IBD patients is not specifically higher than the general population. Supporting the view that SARS-CoV-2 vaccination is effective in patients with IBD.

Odds ratios (95% confidence interval) for logistic regression model predicting COVID-19 infection among vaccinated IBD patients

Figure 1. The medications used before COVID-19 infection between vaccinated patients with ulcerative colitis (UC) and Crohn’s disease (CD).

Figure2. The prevalence of COVID-19 infection between vaccinated patients with ulcerative colitis (UC) and Crohn's disease (CD).

Figure 3. The symptoms after COVID-19 infection between vaccinated patients with ulcerative colitis (UC) and Crohn's disease (CD).

Funding Agencies

None
A277 SYNOPTIC REPORTING IN INFLAMMATORY BOWEL DISEASE
Authors: Yu R , Smith B C , Loomes D
Published: February 2024

Background

Inflammatory bowel disease is a chronic medical condition requiring regular clinical assessment and evaluation. Specialist involvement often occurs regularly to determine disease activity, progression, and consider therapeutic changes for disease control. The rapid advancement of scientific evidence and addition of novel medications have combined to make IBD care increasingly complex. Moreover, evolving standards of care have led to an increased burden of documentation.

Synoptic reporting is a novel documentation method that standardizes the input of clinical data and generates comprehensive reports based on that data. It has yet to be widely accepted throughout medicine, but is commonly used in surgery and diagnostics. Advancements within IBD have amplified the need for meticulous reporting of patients' previous therapies and preventative health care: areas synoptic reporting excels in.

Aims

We analyzed for the presence of disease-related, treatment-based, and preventative health elements in consultation reports across standard of care and synoptic reporting methods.

Methods

We identified consecutive IBD consultations from Jan 1 2023 onwards for participating gastroenterologists, up to 10 reports for most clinicians, if available. Each report was labeled synoptic or standard reporting. Manual review was used to determine whether each element was present and coded in binary fashion, except for female reproductive health, which was absent, present, or N/A. For analysis, data was partitioned based on whether synoptic reporting was used, with the percentage of reports including each element being calculated based on this data. Comparisons for inclusion were then completed between the groups.

Results

We identified a total of 62 consultations with 19 utilizing synoptic reporting. Reporting methods fared similarly for age, sex, year of diagnosis, and summary of course. Synoptic reporting performed significantly better in reporting vaccinations, marijuana use, as well as B12, vitamin D, and ferritin levels. Differences exceeding 20% were found in the reporting of EIMs, CRC screening, and female reproductive health, though these were not at a level of statistical significance in this preliminary study.

Conclusions

We found through our analysis that synoptic reporting is a simple tool that creates reports with a greater inclusion of elements important for disease management and health maintenance. Relaying this information back to patients' practitioners can theoretically improve outcomes through better preventative care, active monitoring, and awareness of patients’ disease history by future consultants. Future research will focus on expanding the study population as well as gaining further insight into the utility of synoptic reporting in improving clinical communication and disease management.

Funding Agencies

None
A280 HEPATOBILIARY DISEASE IN INDIVIDUALS LIVING WITH FRAGILE X SYNDROME: A CASE SERIES
Authors: Alalool A , Hirschfield G , Leung K
Published: February 2024

Background

Fragile X syndrome is a genetic disorder known to cause intellectual disability through decreased or absent FMR protein (FMRP). Basic science studies have identified potential associations with hepatobiliary inflammation. Clinical reports of liver disease in Fragile X syndrome are however infrequent.

Aims

We describe 3 individuals living with Fragile X syndrome and chronic liver disease.

Methods

A case series and literature review were performed.

Results

The 1st person is a woman with concurrent Fragile X and autosomal recessive polycystic kidney disease, initially seen by Hepatology at 18 y.o. with evidence of hepatic fibrosis on abdominal ultrasound with normal liver enzymes (Table 1). She subsequently developed liver cirrhosis and portal hypertension, as well as biliary duct dilatation seen on MRI. Her overall presentation was thought to be in keeping with Caroli syndrome and congenital hepatic fibrosis, and she is currently pending genetic screening for hepatorenal ciliopathy.

The 2nd person is a woman with Fragile X syndrome and ulcerative colitis, who initially presented to Hepatology at 24 y.o. with mixed liver enzyme abnormalities. Lab tests over time revealed immunology suggestive of autoimmune hepatitis (AIH) (Table 1). Subsequent investigations demonstrated primary sclerosing cholangitis (PSC) with cirrhosis. Her disease is currently managed as AIH/PSC overlap syndrome with ursodeoxycholic acid (UDCA), tacrolimus, mycophenolate, and budesonide.

The 3rd person is a man with Fragile X syndrome who initially presented to Hepatology at 17 y.o. with acute hepatitis with AIH immunology (Table 1). Liver biopsy at the time demonstrated findings suggestive of early PSC as well as possible AIH. He continued to have progressive cirrhosis as well as overt PSC on subsequent abdominal imaging and is currently managed as AIH/PSC overlap syndrome with UDCA, azathioprine, and budesonide.

A review of literature revealed that asides from known intellectual, behavioral, and physical effects of Fragile X syndrome, there are minimal reports of other associated medical complications including liver problems or autoimmune conditions including IBD. There are however reports of autoimmunity in those with altered FMR1 (Fragile X Mental Retardation 1) gene mutations.

Conclusions

These 3 cases of liver disease in Fragile X highlight young age of presentation for chronic liver disease with both biliary and immune-mediated characteristics, along with progression to cirrhosis. Additional review for liver manifestations in people living with Fragile X would help understand if this association is incidental or causal.

Investigations of individuals with Fragile X syndrome and liver disease

Funding Agencies

None
A281 CASE REPORT: STEATOTIC LIVER DISEASE DIAGNOSED IN A 24-YEAR-OLD FEMALE WITH RETT SYNDROME
Authors: Albino L G , Halloran B , Thiesen A , Adatia A , Dong V , Moctezuma Velázquez C
Published: February 2024

Background

Rett syndrome (RTT) is a rare, severe neurodevelopmental disorder seen almost exclusively in females that is caused by spontaneous loss-of-function mutations in the methyl CpG binding protein 2 (MECP2) gene. Girls with RTT typically demonstrate normal development for the first 6-18 months of life before displaying evidence of variable levels of developmental milestone regression and physical disability. Although perturbed lipid metabolism in the nervous system is the main contributor to the pathophysiology of RTT, mutations to the MECP2 gene also contribute to disease burden by causing perturbations to peripheral systems, leading to consequences such as dyslipidemia (DLD) and steatotic liver disease (SLD). Although DLD has been described in human cell lines and girls with RTT, SLD has only been described in RTT mouse models.

Aims

This report aims to present a case of a patient with RTT who was diagnosed with SLD on liver biopsy in the context of DLD but without insulin resistance or other comorbidities associated with metabolic syndrome.

Methods

Retrospective review of one patient.

Results

A 24-year-old woman with genetically proven RTT (T158M point mutation to MECP2) complicated by several physical disabilities was seen at a tertiary care center clinic for evaluation of abnormal liver enzymes (ALT 163, AST 51, ALP 258, total bilirubin 6). Abdominal ultrasound demonstrated moderately echogenic liver parenchyma consistent with hepatic steatosis. Additional investigations for an etiology were unremarkable and the patient had no history of alcohol misuse or the use of new medications or supplements. Regarding risk factors for SLD, her homeostatic model assessment for insulin resistance (HOMA-IR) score was 1.8, hemoglobin A1c was 4.8%, and her lipid profile demonstrated elevated triglycerides and LDL, in keeping with DLD. The decision was made to proceed with a liver biopsy. This demonstrated moderate steatosis and no ballooning, categorized as grade A1 and stage F1.

Conclusions

This case demonstrates that RTT patients have similar lipid metabolism perturbations to those seen in MECP2-null mouse models, resulting in similar metabolic abnormalities such as DLD and SLD. The absence of insulin resistance and other comorbidities associated with metabolic syndrome further support these perturbations are caused by a pathophysiologic mechanism specific to RTT. This demonstrates the importance of screening RTT patients for DLD and SLD despite their young age to detect these conditions before complications arise. It also demonstrates that MECP2-null mice can be used as reliable models to identify future therapies for RTT, such as ketogenic diet, ω-3 PUFAs supplementation, and lipid-lowering statin therapy.

Funding Agencies

None
A283 HETEROGENEITY OF TREATMENT RESPONSE TO BETA-BLOCKERS IN THE TREATMENT OF PORTAL HYPERTENSION RELATED TO CIRRHOSIS
Authors: Alsaeid M , Abraldes J
Published: February 2024

Background

Non-selective beta-blockers (BB) improve clinical outcomes in patients with cirrhosis and portal hypertension. However, it has been suggested that only a proportion of patients treated with BB benefit from them. Indeed, patients who achieve a ampersand:003E20% reduction in Hepatic Venous Pressure Gradient (HVPG) with BB have an excellent prognosis, but only 30-50% achieve such response. This has been suggested as a reason for not using BB where no HVPG measurements are available.

Aims

In this study we aimed to quantify how heterogeneous is the response to BB in patients with cirrhosis, by analyzing trials in which the effects of BB on HVPG were compared with those of placebo.

Methods

For assessing the potential heterogeneity of treatment response to BB we conducted a meta-analysis of differences in variance between trial arms. The degree of heterogeneity of HVPG response to BB was quantified with the pooled variability ratio (VR) (SD of the HVPG at the end of the trial in the BB group divided by that in the placebo group).

Results

Our systematic search yielded 18 studies. Figure 1 shows a forest plot with the meta-analysis of the variability ratios (VR) in final HVPG. Pooled VR was 0.99 (95% CI 0.87-1.14). This indicates that there was no evidence for a higher average variability in the final HVPG in the beta-blocker treatment groups as compared to placebo groups, and hence there was no evidence to support that patients with cirrhosis exhibit a heterogeneous response to beta-blockers (i.e. there is no evidence to support that some patients responded to beta-blockers and others did not).

Conclusions

In conclusion, the analysis of RCTs comparing the HVPG response of beta-blockers with placebo in patients with cirrhosis does not suggest a heterogeneous hemodynamic response to beta-blockers. This, together with the fact that in most RCTs demonstrating the clinical benefits of beta-blockers treatment was not adjusted based on HVPG response, further supports the concept that there is no need to perform portal pressure measurements to guide treatment with beta-blockers.

Funding Agencies

None
A284 EVALUATING THE INCIDENCE OF MAJOR GASTROINTESTINAL BLEEDING IN PATIENTS WITH CIRRHOSIS ON ANTICOAGULATION THERAPY: A TERTIARY SINGLE CENTRE EXPERIENCE
Authors: Bualbanat H , Teriaky A , Hudson D , Qumosani K
Published: February 2024

Background

Patients with chronic liver disease, especially those with cirrhosis, face an increased risk of bleeding and thrombosis due to hemostasis dysregulation. In such cases, prescribing anticoagulation therapy requires a cautious approach, given the inherent risk-reduction in thrombosis alongside a suspected elevated bleeding risk.

Aims

Perform a retrospective study to evaluate anticoagulation safety and gastrointestinal bleeding incidence in cirrhotic patients.

Methods

A retrospective study was conducted at the University Hospital of London Health Sciences Centre, involving patients who attended outpatient hepatology clinics between 2010 and 2022. To be eligible, patients had to be 18 years or older and have confirmed cirrhosis through imaging, radiology, or pathology. They were monitored for up to 5 years for the primary outcome, which was major gastrointestinal bleeding requiring hospitalization. Exclusions included patients with underlying hematologic or thrombotic conditions contributing to abnormal hemostasis beyond cirrhosis and those who underwent liver transplantation. Descriptive statistics were provided, such as means and standard deviations for continuous variables, and proportions/percentages for categorical ones. Group comparisons utilized the Student's t-test for continuous variables and chi-squared tests for categorical variables. Univariate and multivariate logistic regression were employed to calculate odds ratios and their associated 95% confidence intervals for the primary outcome

Results

We retrospectively enrolled 300 patients, with 34.0% having cirrhosis and anticoagulation history. The average age was 63.1 years [95% CI 61.7 – 64.6], and 43.7% were female. Atrial fibrillation was the primary reason for anticoagulation (53.9%). Cirrhotic patients on anticoagulation had a 13.1% bleeding rate, while those without had 18.6% (p-value = 0.207, not significant). Univariate analysis suggested a possible link between anticoagulation and bleeding risk (OR 1.51 [95% CI 0.79 – 2.89]). No covariates predicted bleeding in univariate logistic regression. In multivariate analysis adjusting for age and sex, the odds ratio remained at 1.50 [95% CI 0.78 – 2.88].

The study hints at a higher bleeding risk in cirrhotic patients on anticoagulation, but more statistical power is needed, either through a larger sample or a multicenter approach.

Conclusions

To further investigate the association between anticoagulation and bleeding risk in cirrhotic patients, a larger multicentre study with increased enrollment is required. Nonetheless, interim findings do suggest the potential existence of an associated bleeding risk in cirrhotic patients undergoing anticoagulation therapy, albeit with a small observed effect size and uncertain clinical significance.

Funding Agencies

None
A285 COMPARISON OF ADVERSE OUTCOMES IN PATIENTS WITH COMBINED INFLAMMATORY BOWEL DISEASE AND PRIMARY SCLEROSING CHOLANGITIS VERSUS ISOLATED PRIMARY SCLEROSING CHOLANGITIS
Authors: Dahiya M , Bedi H , Fetz A , Yoshida E , Ko H , Salh B , Chahal D
Published: February 2024

Background

Primary sclerosing cholangitis (PSC) results in progressive inflammation and fibrosis of bile ducts causing chronic cholestasis. PSC is associated with an increased risk of malignancy [hepatobiliary and colorectal cancers (CRC)] compared to the general population, in addition to an increased risk of developing end-stage liver disease, often requiring liver transplantation at a relatively young age. The increased risk of adverse outcomes confers an increased risk of premature death of patients with PSC. PSC is commonly associated with IBD, particularly ulcerative colitis (UC), which in itself carries a higher rate of CRC. A study of the impact of PSC with IBD on development of cancer and survival outcomes is imperative.

Aims

To compare the risk of cancer, liver transplantation, and mortality in PSC-IBD versus isolated PSC.

Methods

Retrospective data from PSC patients from two hospital sites in Vancouver, British Columbia was analyzed to compare the relative risk of death, transplantation, and malignancy in PSC-IBD versus isolated PSC.

Results

169 patients with PSC were included in the analysis [mean age of diagnosis of PSC 37 (SD 16.92) years, 41.4% (70) female]. Out of the 169 patients with PSC, 102 had IBD [29.4% (30) with Crohn’s Disease (CD); 70.6% (72) with UC]. The mean age of IBD diagnosis was 28.96 (SD 14.46) years. Death occurred in 31 [64.5% (20) with IBD; RR 1.19, 95% CI 0.61-2.32, p=0.60] patients, 35 [57.1% (20) with IBD; RR 0.88, 95% CI 0.48-1.59, p=0.66] patients developed cancer, and 33 [66.7% (22) with IBD; RR 1.31, 95% CI 0.68-2.52, p=0.41] patients required liver transplantation. The cause of death was malignancy in 15 [53.3% (8) with IBD] patients, liver failure in 5 [80% (4) with IBD] patients, sepsis in 2 [100% (2) with IBD] patients, and unknown cause of death in 9 [77.7% (7) with IBD] patients. For malignancy types, 16 [68.75% (11) with IBD] patients had cholangiocarcinoma (CCA), 4 [50% (2) with IBD] had CRC, 2 [50% (1) with IBD] had gallbladder cancer, 1 [0% (0) with IBD] had pancreatic cancer, 1 [0% (0) with IBD] had esophageal cancer, and 11 [54.5% (6) with IBD] had other malignancies not involving the hepatobiliary or gastrointestinal system. Of the patients who died due to malignancy, 73.3% (11) had CCA.

Conclusions

Although we do not observe any statistically significant difference in risk of cancer, transplantation, or all-cause mortality in patients with PSC-IBD when compared to isolated PSC, we do observe that 59% of all-included patients experienced one or more adverse outcome. It is important for clinicians to recognize the high rates of adverse outcomes in PSC-IBD and isolated PSC patients, potentially warranting earlier or more frequent screening for outcomes such as malignancy and liver dysfunction.

Funding Agencies

None
A286 MYO5B MUTATIONS AS A CAUSE OF CHOLESTASIS IN A CHILD WITHOUT MICROVILLOUS INCLUSION DISEASE
Authors: Fahmy Doaa M , Kamath Binita M
Published: February 2024

Background

Biallelic Myosin Vb (MYO5B) mutations are identified in the majority of patients with microvillus inclusion disease (MVID) that requires life-long parenteral nutrition and eventually cholestatic liver disease. Biallelic MYO5B mutations have also been reported in a few children with predominant early-onset cholestatic liver disease.

Aims

To report on a patient with MYO5B mutations and progressive familial intrahepatic cholestasis PFIC-like phenotype and normal serum GGT without intestinal disease.

Methods

We describe a 2-year and 8-month-old girl, who is the first child of healthy non- consanguineous parents from the Phillipines with no family history of liver disease. She presented at the age of 10 months for evaluation of mild jaundice, which was noticed at the age of 6 months. Other symptoms included pruritus, slowly weight gain, intermittent pale stools and dark urine. Laboratory investigations revealed AST 99, ALT 87, GGT 27, conjugated bilirubin 13 and INR 0.8. Fasting abdominal ultrasound was normal apart from a possibly hypoplastic gallbladder and mild splenomegaly. Additional investigations revealed normal thyroid-stimulating hormone, cortisol, galactosemia screening and sweat chloride, but bile acids were elevated 391.6 umol/L. A liver biopsy was performed and a cholestasis genetic panel sent. The patient was started on ursodiol, hydroxyzine, rifampicin and vitamin D.

Results

Liver biopsy revealed moderate hepato-canalicular cholestasis, bile duct injury without prominent ductopenia, small caliber bile ducts with no features of obstructive cholangiopathy, mild periportal and pericentral fibrosis stage 1-2/ 4. Electron microscopy demonstrated cytoplasmic and canalicular bile accumulation. The bile canaliculi were variably distended by coarse granular bile. Immunohistochemical staining for BSEP and MDR3, showed canalicular staining in zones 1 and absence of staining in zones 2 and 3. Genetic analysis revealed one pathogenic variant and one variant of uncertain significance in MYO5B. No mutations in ABCB11 or ATP8B1 genes were identified. On follow-up, the jaundice improved, pruritus was managed with the medications described above. Her growth has improved and she is growing on the 25th centiles. She has not developed any gastrointestinal symptoms.

Conclusions

We present a patient with MYO5B mutations who presented with normal GGT cholestasis and a liver biopsy consistent with PFIC, without any evidence of intestinal disease. Because MYO5B mutations disrupt the intracellular trafficking of brush border proteins in the intestine, it has been assumed that it similarly disrupts the trafficking of the canalicular bile acid transporting and bilirubin transporting proteins in the liver. This case highlights the broad phenotype associated with MYO5B variants.

Funding Agencies

None
A287 LEVERAGING MACHINE LEARNING TO IMPROVE THE DIAGNOSTIC ACCURACY OF ULTRASOUND SCREENING FOR HEPATOCELLULAR CARCINOMA
Authors: Govardhanam V , ZEGHAL M , Cheung A
Published: February 2024

Background

Ultrasound screening stands out as the gold standard for hepatocellular carcinoma (HCC) detection, attributed to its broad accessibility, patient-friendly, and cost-efficient nature. Nevertheless, the five-year survival rate for HCC currently rests at 32.7%, with suboptimal screening being a key contributor to this. The recent years have witnessed the rise of machine learning models, powered by artificial neural networks. Among these, convolutional neural networks (CNNs) have taken the lead in revolutionizing medical image analysis, offering unprecedented success in predictive tasks and giving us hope for a brighter future in the fight against HCC

Aims

To train and test a machine learning algorithm using pre-trained CNNs to improve early detection of HCC through ultrasound screening.

Methods

In this retrospective study, 1835 charts of patients with chronic liver disease were reviewed: 346 with histologically confirmed HCC and 1457 with ultrasounds without HCC. A diagnosis of HCC was confirmed pathologically on biopsy or surgical resection, and/or radiographically with a Liver Imaging Reporting and Data System (LI-RADS) score of five on CT and/or MRI. Patients with benign lesions were required to have at least two ultrasounds three years apart that confirmed benign characteristics. Cases were excluded if they had a prior history of treated HCC, post-transplant HCC, or HCC with Barcelona Clinic Liver Cancer (BCLC) Stage B and above. All ultrasound images were reviewed by experienced radiologists, and segmented as liver lesions (HCC versus benign) and surrounding liver.

Results

A total of 149 patients have been included to date, comprising 72 with benign lesions, 73 with HCC, and four with both benign and malignant lesions. 224 lesions have been segmented, consisting of 87 HCC and 137 benign lesions. Candidate networks are under development and evaluation for the classification of liver lesions. Imaging pre-processing was performed such that the liver region of interest (ROI) and the lesion ROI were standardized, with 2-channel greyscale images on two separate channels. The algorithm was constructed using a per-lesion analysis. Initial testing has achieved an area under the curve (AUC) of 73.3%, 95% CI [68.6, 77.0] with 2 repetitions of 10-fold cross-validation.

Conclusions

Enhancing ultrasound screening for HCC is imperative for improving patient care. Analysis of remaining cases is ongoing. Future studies will be essential, including prospective evaluation and external validation.

Funding Agencies

None
A288 ALCOHOL RELAPSE AND ADVERSE OUTCOMES IN EARLY VERSUS ROUTINE LIVER TRANSPLANT FOR ALCOHOL-ASSOCIATED LIVER DISEASE IN THE PROVINCE OF BRITISH COLUMBIA
Authors: Hemy A R , Fetz A , Jayakumar S
Published: February 2024

Background

Liver transplant is a life-saving treatment for patients with alcohol-associated liver disease (ALD) resulting in decompensated cirrhosis or severe alcoholic hepatitis, significantly reducing mortality compared to supportive treatment. Despite its previous wide acceptance, there is a lack of strong evidence to justify a 6-month abstinence period. In 2019, BC Transplant policies were updated to allow liver transplant within 6-months of alcohol use in carefully selected patients with limited life expectancy and favorable multidisciplinary psychosocial assessment.

Aims

This study aims to assess alcohol relapse rates and adverse outcomes in patients who received an early liver transplant for ALD.

Methods

A retrospective chart review was performed on all adult patients who underwent liver transplant in the province of British Columbia between January 1, 2020, and December 31, 2022. Follow up data was extracted until May 31, 2023. Patients were included if they had alcohol documented as a contributing factor to their liver disease prior to transplant. Early transplant was defined as alcohol abstinence of 179-days or less and routine transplant as 180-days or more. Alcohol use and time to alcohol use were determined by patient history, random biochemical testing, and health-care utilization for an alcohol-associated complication. Graft dysfunction or rejection resulting in a change in therapeutic management, noncompliance determined by clinician documentation, rehospitalization, and death were recorded as adverse events.

Results

278 patients underwent liver transplant during the study period. 81 patients were classified as alcohol-related, and 15 received early transplant. The mean follow-up period was 20.5 months. Early transplant recipients were more likely to be younger (median 45 vs. 58 years, p = 0.003) and have a higher MELD score at the time of transplant (median 37 vs. 17, p ampersand:003C 0.001). There was no significant difference in post-transplant alcohol relapse (13 vs. 15%, hazard ratio = 0.78, 95% CI [0.17, 3.55], p = 0.74). Graft dysfunction was increased in patients who received early transplant (53 vs. 25%, relative risk = 2.17, 95% CI [1.15, 4.10]). There was no significant difference between rates of noncompliance (0 vs. 9%), rehospitalization (53 vs. 56%), or death (0 vs. 2%).

Conclusions

Alcohol relapse is similar between early and routine liver transplant. Graft dysfunction is increased in early transplant, although other adverse events including medication noncompliance, rehospitalization, and death are not significant different. These results are favorable for the continued use of early liver transplant for ALD, providing an effective treatment for ALD and significantly reducing mortality in patients with a limited life expectancy.

Funding Agencies

None
A289 MAJOR ADVERSE CARDIAC EVENTS (MACE) IN PATIENTS WITH A HISTORY OF LIVER TRANSPLANTATION: A NATIONWIDE ANALYSIS USING THE NATIONAL INPATIENT SAMPLE
Authors: Hussain M , Teriaky A , Hudson D
Published: February 2024

Background

Liver transplantation is the preferred treatment for end-stage liver disease. However, in around one-third of transplant recipients cardiovascular disease remains to be a significant contributor to morbidity and mortality.

Aims

Using data from the national inpatient sample (NIS), this study aimed to assess the prevalence and patient characteristics of MACE in those who underwent liver transplantation.

Methods

The study used a cross-sectional design to analyze NIS data, comparing MACE prevalence in hospitalized liver transplant patients. MACE included heart-related events. Patients with MACE and liver transplant history were identified using 2013 NIS data and ICD-9-CM codes. Baseline characteristics were compared, and association strength was assessed via logistic regression.

Results

Out of 33,725 post-liver transplant patients, 26.1% (8,805) had prior MACE. Those with MACE had higher rates of comorbidities: type 2 diabetes (odds ratio (OR) 1.90, 95% CI 1.69-2.13, p ampersand:003C 0.001), hypertension (OR=2.07, 95% CI 1.83-2.34, pampersand:003C 0.001), dyslipidemia (OR=2.27, 95% CI 1.97-2.60, pampersand:003C 0.001), and morbid obesity (OR=1.69, 95% CI 1.39-2.04, pampersand:003C 0.001). Smoking wasn't significantly linked (p = 0.738). Hospitalization with MACE increased in-hospital mortality (3.25%, p ampersand:003C 0.001).

Conclusions

These findings highlight the importance of proactive cardiovascular risk factor management to minimize the morbidity and mortality of MACE in this patient population.

1: Baseline characteristics of patients admitted to hospital with or without MACE after liver transplantation.

Funding Agencies

None