bluuebunny/crossref_metadata_2025_split huggingface dataset:
A277 SYNOPTIC REPORTING IN INFLAMMATORY BOWEL DISEASE
Authors: Yu R , Smith B C , Loomes D 
Published: February 2024

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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