bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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
A290 ILLICIT SUBSTANCE USE AND ITS IMPACT ON ALCOHOL-ASSOCIATED HEPATITIS IN LATIN AMERICA
Authors: Islam A H , Diaz L A , Idalsoaga F , Ayares G , Arnold J , Alcayaga B , Maldonado K , Arab J 
Published: February 2024

Abstract

Background
Concomitant substance use is frequent among patients with alcohol use disorder (AUD), but its impact on alcohol-associated hepatitis (AH) is unknown.

Aims
To assess the prevalence and impact of substance use in patients hospitalized for AH in a multinational cohort in Latin America.

Methods
Multicenter prospective cohort study including patients with AH between 2015-2022. We recorded sociodemographic and clinical information, including data on alcohol and drug use. We assessed the impact of substance consumption using competing-risk models.

Results
We included 405 patients from 24 centers in 8 countries (Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Mexico, and Peru). The mean age was 49.6±12.2 years, 345 (85.4%) were men, 210 (57.5%) had a previous diagnosis of cirrhosis, and the median MELD at diagnosis was 25 [20–31] points. Around 74% of patients fulfilled ACLF criteria (ACLF-1: 11.1%, ACLF-2: 11.6%, ACLF-3: 49.6%). A total of 82 (20.3%) reported active substance use, while 22 (5.4%) were former substance users. The most common drugs used at admission were marijuana (11.1%), cocaine (10.4%), methamphetamine (4.4%), and heroin (0.5%). Out of the total, 35.7% died, and only 2.5% underwent liver transplantation during follow-up. Active substance use was higher in younger patients (users 44.4±16.1 years vs. non-users 51.0±10.6 years; pampersand:003C0.001) and in men compared to women (22.0% vs 10.2%, p=0.036). In a competing-risk model adjusted by age, sex, history of cirrhosis, MELD, and ACLF grade, active substance use was independently associated with mortality (subdistribution Hazard Ratio [sHR] 1.53, 95%CI:1.01–2.32; p=0.043). Also, active cocaine (sHR 1.69, 95%CI:1.07–2.70; p=0.025) and marijuana use (sHR 1.83, 95%CI:1.11–3.04; p=0.018) were independently associated with mortality in adjusted competing-risk analyses.

Conclusions
Active drug use is common in AH patients. Marijuana and cocaine were the most frequent substances and were independently associated with increased mortality. Substance use should be screened in patients with AUD, and integrated management with addiction specialists and psychiatrists could impact survival in AH.

Funding Agencies
None
A294 CHOLESTASIS SECONDARY TO XANTHOGRANULOMATOUS CHOLANGITIS: A CASE REPORT
Authors: Labib K A , Bishay K 
Published: February 2024

Abstract

Background
An 86-year-old female presented with four weeks of intermittent abdominal pain, postprandial nausea with an associated 10 lbs weight loss. Initial labs demonstrated a predominantly cholestatic liver enzyme elevation. Imaging revealed a thickened gallbladder with dilated CBD up to 15mm with no calculi, obstruction or pancreatic mass. EUS demonstrated a prominent ampulla with an area of hyperechogenicity, and ERCP was completed with sphincterotomy and biopsy of the ampulla. A cholangiogram showed a prominent common bile duct and a smooth distal taper without filling defects. Tumor markers, ampullary biopsy, and cytology of CBD brushings were negative for malignancy. Repeat ERCP for non-resolving symptoms with an extension of the sphincterotomy, brushings and insertion of a metal stent was completed without improvement in liver enzymes and a standard hepatitis workup returned negative. Her clinical course was further complicated by recurrent gram-negative bacteremia with CT findings of innumerable abscesses or metastasis in the liver. A US-guided targeted liver biopsy revealed large duct periductal tissue expansion by foamy macrophages with admixed neutrophils, eosinophils, plasma cells, and lymphocytes. These features were consistent with xanthogranulomatous cholangitis. We were planning to start ursodiol given the small duct disease however the patient succumbed to recurrent bacteremia and passed away.

Aims
Review of methods to attain diagnosis of xanthogranulomatous cholangitis.

Methods
Case Report.

Results
Diagnosis of xanthogranulomatous cholangitis can be attained from targetted US-guided biopsy, surgical excision, or EUS-guided CBD biopsy.

Conclusions
Xanthogranulomatous cholangitis is an extremely rare entity described in limited case reports, frequently mimicking neoplastic disease. Pathology is difficult to attain and historically case reports required surgical resections. One recent case reported diagnosis confirmed via EUS-guided FNA of the CBD. In our case, we attained the diagnosis through a targeted liver biopsy. Pathology of xanthogranulomatous cholangitis typically demonstrates foamy histiocytes, lipid-laden macrophages, eosinophils, lymphocytes, plasma cells, and fibrosis indicating xathogranulomas. The pathogenesis is thought to be an extension of xanthogranulomatous cholecystitis in which bile is extravasated into the gallbladder wall through Rokitansky-Aschoff sinuses or ulceration of the mucosa resulting in an inflammation caused by fibroblasts and macrophages as they phagocytose the lipids in bile, resulting in the formation of xanthoma cells. Given the rarity of the disease, there is no guideline on management and a majority of patients reported underwent surgical excision. This case demonstrates the utility of liver biopsy to establish this rare diagnosis, allowing for better detection and subsequently better-studied management.

Funding Agencies
None
A297 EXAMINING THE IMPACT OF INFLAMMATORY BOWEL DISEASE IN PRIMARY SCLEROSING CHOLANGITIS PATIENTS POST LIVER TRANSPLANTATION
Authors: Malhi G , Diaz L A , Punchhi G , Mortuza R , Khan M , Brahmania M , Jairath V , Arab J 
Published: February 2024

Abstract

Background
Primary sclerosing cholangitis (PSC) is an immune-mediated disease that is characterized by biliary inflammation and fibrosis. It is associated with inflammatory bowel disease (IBD) in 80% of cases. To date, the impact of IBD in liver transplantation (LT) recipients is not completely understood.

Aims
To assess the impact of IBD in individuals with PSC who underwent liver transplantation (LT) in terms of graft survival, infections, and mortality.

Methods
This was a retrospective cohort study that included individuals with PSC who received a LT between 1999–2021. Statistical analysis included Kaplan-Meier survival curves, a binary logistic regression to estimate infection risk, and a competing-risk analysis to estimate post-LT mortality (with re-transplantation being a competing risk).

Results
122 LT recipients were included. Mean age at LT was 44.9±12.6 years old. The median MELD-Na at LT was 22 [17–28]. Twenty-nine (23.8%) LT recipients died during follow-up (median 1,248 [413–3,857] days) and 5 (4.1%) required re-transplantation (median 1,460 [923–2,563] days). Estimated graft survival was 93.2% (95%CI: 86.9%–96.6%) at 1 year and 81.3% (95%CI: 72.5%–87.6%) at 5 years. An adjusted competing-risk model demonstrated that increasing age (sHR 1.05, 95%CI: 1.01–1.10; p=0.018), baseline MELD-Na (sHR 1.07, 95%CI: 1.02–1.12; p=0.005), and ERCP requirements before LT (sHR 6.33; 95%CI: 1.63–24.65; p=0.008) were associated with higher post-LT mortality, while IBD was not associated with post-LT mortality (sHR 1.02, 95%CI: 0.38–2.70; p=0.962). The incidence of infections after LT was 50.8% at 30 days. IBD was not associated with development of infections at 30 days (OR 1.01, 95%CI: 0.98–1.04; p=0.615) post-LT.

Conclusions
Based on this retrospective review, an older age, higher MELD-Na at LT and prior ERCP requirements were independently associated with a higher mortality post-LT in PSC patients. However, a background history of IBD was not associated with higher mortality or with infections post-LT.
Table 1: Baseline Demographics

Funding Agencies
None
A298 HIGH MORTALITY NOTED AMONG PATIENTS ADMITTED WITH ALCOHOL ASSOCIATED HEPATITIS: A DESCRIPTIVE STUDY
Authors: Malhi G , McChesney C , Hudson D , Stephenson E , Almahanna Y , Arab J 
Published: February 2024

Abstract

Background
Alcohol associated hepatitis is a syndrome related to alcohol use disorder characterized by jaundice, malaise, decompensated liver disease, and coagulopathy. This is associated with bacterial infections, the development of chronic liver failure, and high short-term mortality. However, the rates at which these events occur is less understood, with a broad range of estimates reported.

Aims
To understand the demographic profile of those admitted with alcohol associated hepatitis assess its impact on resource utilization, complications in hospital, and mortality.

Methods
This study examined a subset of individuals with alcohol associated hepatitis who were admitted to the GI and Medicine Wards between 2010 and 2023.

Results
70 encounters were identified and interpreted. The average age at admission was 48.3 ± 11.4 years old. 62.8% were male and 22% reported cannabis use. 54% had a previous reported history of alcohol use disorder. The average MELD-Na score at the time of admission was 25.9 ± 7.7.
The Median length of stay was 8.5 days (IQR 4.5,15). 63% were provided steroids in hospital and 33.3% developed infectious complications. 36.3% of patients had a GI bleed reported during admission. 4% of patients underwent a transplantation during follow-up. Approximately 44.3% experienced mortality with a 30-day mortality rate found to be 28.6%.

Conclusions
Alcohol associated hepatitis patients are prone to developing infections and bleeding during admission. This diagnosis also carries a high mortality rate, particularly within the first 30 days. Further studies examining the global impact of alcohol associated hepatitis should be considered.
Table 1: Baseline Demographics

Funding Agencies
None
A301 RELATIONSHIP BETWEEN INTRAHEPATIC IMMUNE CELL PROFILE AND MICROBIOME ACCORDING TO DISEASE SEVERITY IN OBESE PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE
Authors: Schwenger K J , Ghorbani Y , Chen L , Fischer S , Jackson T 
Published: February 2024

Abstract

Background
Non-alcoholic fatty liver disease (NAFLD) includes histology ranging from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. The pathogenesis of NAFLD is multifactorial and includes several immune cell-mediated inflammatory processes. Recent research suggests a potential relationship between NAFLD, disease severity and the intestinal microbiome (IM). In particular, our previous work in NAFLD showed that lower abundance of fecal Faecalibacterium prausnitzii was associated with liver histology and gene expression. In addition, we found that Kupffer cell markers, hematopoietic cell marker cluster of differentiation and B cells were associated with liver histology.

Aims
Knowing that F prausnitzii may have anti-inflammatory effect, we seek to determine if there was any association between fecal F prausnitzii and hepatic immune cells.

Methods
Biochemical and anthropometric measurements as well fecal samples for IM analysis were collected in those with obesity undergoing bariatric surgery. Fecal shotgun metagenome sequencing to profile the intestinal microbiome Liver histology was assessed using Brunt scoring system. The frequency, location and phenotype of 8 immune cell subtypes were analyzed by multiplex immunofluorescence. Spearman correlation coefficients and partial Spearman correlation coefficients were used to evaluate the association between significant hepatic immune cells and fecal F. prausnitzii.

Results
113 patients had both hepatic immune and IM data. Of the 113 patients, 30 had normal liver obese (NLO), 41 had SS and 42 had NASH. With regards to hepatic immune cells, those with NAFLD (SS and NASH) or NASH had significantly higher Helper T, CD4 and B cells and lower activated macrophages compared to NLO. In those with NAFLD or NASH, F. prausnitzii was significantly negatively correlated with Helper T cells (NAFLD, R= -0.25, p-value 0.009; NASH, R= -0.25, p-value 0.038). In those with NASH, F. prausnitzii was also significantly negatively correlated with CD4 cells (R= -0.31, p-value 0.009).

Conclusions
Specific hepatic immune cells were associated with NAFLD and NASH with Helper T and CD4 cells being negatively correlated with F. prausnitzii. Knowing that these immune cells contribute to NAFLD pathogenesis, the relationship between fecal IM, hepatic immune cells and NAFLD require further exploration.

Funding Agencies
CIHRCanadian Liver Foundation
A302 NON-INVASIVE BIOMARKERS PREDICTING THE PROGRESSION OF MASLD TO ADVANCED FIBROSIS: A PROSPECTIVE COHORT STUDY
Authors: Song Y , Mortuza R , Arab J , Khan M 
Published: February 2024

Abstract

Background
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects around 30% of the global population and is one of the most prevalent non-communicable diseases. Due to its high prevalence, it is becoming the most common cause of liver-related mortality in all populations worldwide. Current standards of care for the treatment of MASLD encompass mostly lifestyle measures that are nonspecific and difficult for clinicians to ensure compliance. Although not all patients with MASLD progress to more advanced disease, the high prevalence of MASLD in the general population means the absolute number of “at risk” individuals are substantial and places a significant burden on the healthcare system. As a result, MASLD is currently viewed as a heterogeneous disease with varying rates of disease progression.

Aims
We aim to elucidate the predictors of disease progression in MASLD to develop and guide interventions while the disease is reversible.

Methods
Prospective chart review on patients seen in MASLD clinic at LHSC on CERNER from Sept. 2021 – Apr. 30, 2023. A REDCap database was constructed pertaining to a) basic patient information b) basic medical history c) patient lifestyle habits d) InBody bioimpedance analysis if available f) laboratory data g) elastography, including liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). Collected data were exported into a spreadsheet to allow for analysis. IBM SPSS was used to analyze descriptive statistics and regression analyses.

Results
A total of 116 encounters were reviewed, including both enrolment and follow-ups. HbA1c percent is positively correlated with LSM (r=0.28, pampersand:003C0.05). The longer that the patient has been diagnosed with NAFLD (current age minus age of initial diagnosis), the more likely the patient has higher LSM scores (r= 0.23, pampersand:003C0.05). Platelet levels are negatively correlated with LSM (r=-0.28, pampersand:003C0.05). There is no difference between cannabis users and non-users in the degree of CAP or LSM. Only n=15 InBody bioimpedance analyses were included; preliminary results showed Trunk Reactance at 250kHz is correlated with LSM with (r=0.593 pampersand:003C0.05).

Conclusions
Patients with higher HbA1c, lower platelets and longer duration of disease are at higher risk for developing advanced fibrosis. This can allow the development of a better predictive model to find F2-F3 patients without using FibroScan or a liver biopsy, which is helpful in the primary care setting, given the prevalence of MASLD. InBody bioimpedance studies are a useful tool to predict LSM, although more data is needed to ensure the correlation is sufficiently powered. Phenotyping patients would lead to more accurate prognostication, facilitate better monitoring to prevent decompensation and allow for the development of precision-based, personalized management plans.

Funding Agencies
None
A303 SAFETY AND EFFICACY OF DIRECT ORAL ANTICOAGULANTS IN PATIENTS WITH LIVER CIRRHOSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Tham D , Yu W , Zhao L , Kou R , Kherani J , Li P , Sreeraman S , Eshaghpour A , Li A , Crowther M 
Published: February 2024

Abstract

Background
Direct oral anticoagulants (DOACs) are widely used for treatment of venous thromboembolism (VTE) and stroke prophylaxis in patients with atrial fibrillation. Liver cirrhosis increases the risk of conditions necessitating anticoagulation, but also increases bleeding risks, complicating anticoagulation use. DOACs may be suitable for chirrotic patients as their reliance on hepatic elimination is reduced compared to traditionally used anticoagulants such as low molecular weight heparin (LMWH) or vitamin K antagonists (VKAs). However, safety data on DOACs in cirrhosis patients is limited as severe Child-Pugh (CP) classes are historically underrepresented in major trials. Various guidelines currently classify severe CP classes as contraindications to DOACs.

Aims
To synthesize primary evidence on the safety profile of DOACs in patients with severe liver cirrhosis.

Methods
A literature search of MEDLINE and Embase from inception to Jan 2023 identified randomized controlled trials (RCTs) and cohort studies comparing DOACs to LMWH or VKAs in cirrhosis patients. Two reviewers screened and extracted data at title/abstract, and full-text levels. Baseline patient characteristics, CP class, and anticoagulation regimens were extracted. The primary outcome was major bleeding per ISTH criteria, stratified by CP B&C, and CP Unspecified (primary study did not report/stratify by CP class) subgroups. Data were meta-analyzed using the Mantel-Haenszel random-effects model and presented as odds ratios with corresponding 95% confidence intervals.

Results
Of 794 articles screened, 17 articles (2 RCTs, 15 cohorts) were included for analysis (n = 5046). Overall, DOACs were associated with a lower risk of major bleeding compared to controls (OR=0.63 [0.45, 0.89]). This result was consistent in the CP B&C Exclusive subgroup (OR=0.42 [0.29, 0.62], 5 studies) but not in the CP Unspecified subgroup (OR=0.71 [0.48, 1.08], 12 studies). One large study (n=3213), Lawal 2023, in the CP B&C group, favored DOACs in reduction of major bleeding (OR=0.37, 95%CI [0.24,0.57]). Removal of this study in post-hoc sensitivity analysis led to no significant differences in major bleeding overall or in any subgroup.

Conclusions
In this analysis comparing DOACs to LMWH/VKAs in patients with liver cirrhosis, DOACs were associated with a statistically significant reduction in the risk of major bleeding overall and in more advanced subgroups (CP B&C). Future analysis will stratify by DOAC agent, duration, dosage, and include secondary efficacy outcomes.
Table 1. Summary of the major bleeding effect size in all subgroups.

Figure 1. Major bleeding in Child-Pugh B&C and Child-Pugh Unspecified groups with DOAC vs VKA

Funding Agencies
None