bluuebunny/crossref_metadata_2025_split huggingface dataset:
A206 EVOLUTION OF PEDIATRIC AUTOIMMUNE CHOLANGITIS AND PRIMARY SCLEROSING CHOLANGITIS INTO ADULTHOOD
Authors: Willems P , Hercun J , Vincent C , Alvarez F 
Published: March 2021

Abstract

Background
The natural history of primary sclerosing cholangitis (PSC) in children seems to differ from PSC in adults. However, studies on this matter have been limited by short follow-up periods and inconsistent classification of patients with autoimmune cholangitis (AIC) (or overlap syndrome). Consequently, it remains unclear if long-term outcomes are affected by the clinical phenotype.

Aims
The aims of this is study are to describe the long-term evolution of PSC and AIC in a pediatric cohort with extension of follow-up into adulthood and to evaluate the influence of phenotype on clinical outcomes.

Methods
This is a retrospective study of patients with AIC or PSC followed at CHU-Sainte-Justine, a pediatric referral center in Montreal. All charts between January 1998 and December 2019 were reviewed. Patients were classified as either AIC (duct disease on cholangiography with histological features of autoimmune hepatitis) or PSC (large or small duct disease on cholangiography and/or histology). Extension of follow-up after the age of 18 was done for patients followed at the Centre hospitalier de l’Université de Montréal. Clinical features at diagnosis, response to treatment at one year and liver-related outcomes were compared.

Results
40 patients (27 PSC and 13 AIC) were followed for a median time of 71 months (range 2 to 347), with 52.5% followed into adulthood. 70% (28/40) had associated inflammatory bowel disease (IBD) (78% PSC vs 54% AIC; p=0.15). A similar proportion of patients had biopsy-proven significant fibrosis at diagnosis (45% PSC vs 67% AIC; p=0.23). Baseline liver tests were similar in both groups.
At diagnosis, all patients were treated with ursodeoxycholic acid. Significantly more patients with AIC (77% AIC vs 30 % PSC; p=0.005) were initially treated with immunosuppressive drugs, without a significant difference in the use of Anti-TNF agents (0% AIC vs 15% PSC; p= 0.12). At one year, 55% (15/27) of patients in the PSC group had normal liver tests versus only 15% (2/13) in the AIC group (p=0.02).
During follow-up, more liver-related events (cholangitis, liver transplant and cirrhosis) were reported in the AIC group (HR=3.7 (95% CI: 1.4–10), p=0.01). Abnormal liver tests at one year were a strong predictor of liver-related events during follow-up (HR=8.9(95% CI: 1.2–67.4), p=0.03), while having IBD was not (HR=0.48 (95% CI: 0.15–1.5), p=0.22). 5 patients required liver transplantation with no difference between both groups (8% CAI vs 15% CSP; p=0.53).

Conclusions
Pediatric patients with AIC and PSC show, at onset, similar stage of liver disease with comparable clinical and biochemical characteristics. However, patients with AIC receive more often immunosuppressive therapy and treatment response is less frequent. AIC is associated with more liver-related events and abnormal liver tests at one year are predictor of bad outcomes.

Funding Agencies
None
A207 DE NOVO DONOR-SPECIFIC ANTIBODY FORMATION IN LIVER TRANSPLANTS: RISK FACTORS FOR DEVELOPMENT AND IMPACT ON GRAFT SURVIVAL.
Authors: Wang C , Montano-Loza A J , Campbell P M , Bain V 
Published: March 2021

Abstract

Background
Antibody mediated rejection (AMR) is an area of great importance in solid organ transplantation. Donor-specific antibodies (DSA) have emerged as relevant biomarkers in predicting graft function and survival. DSA detected post-transplant may either be preformed or de novo and emerging evidence suggests de novo DSA, in particular, is associated with inferior graft outcomes. In contrast to the clear role that AMR plays in renal and thoracic organ transplantation, its importance in liver transplants remains controversial.

Aims
The aim of this study was to determine the risk factors associated with de novo DSA formation and to evaluate its role in determining clinical outcomes after liver transplantation.

Methods
This single-center retrospective study compiled data on liver transplants performed between 2005 and 2019 in Edmonton, Canada. Data collected from medical charts included gender, age at transplant, reason for transplant, and immunosuppressive regimens, among several others. The presence of DSA was determined by single antigen flow beads until 2009 and by Luminex thereafter. Potential predictors of DSA formation were evaluated using Cox proportional hazard models. Graft survival estimates were obtained using the Kaplan-Meier method and comparisons between patient groups were conducted using the log-rank test.

Results
Between 2005–2019, 131 patients had measurements of DSA both before and after liver transplantation. In this cohort, 17 patients (13%) tested negative on DSA screening before transplant but developed new antibodies against either Class I or Class II molecules post-transplant. Risk factor analysis revealed transplants performed in the setting of autoimmune liver disease (PSC, PBC, and autoimmune hepatitis) had higher risks of developing de novo DSA post-transplant (p=0.002. See Table 1). Graft survival probability at 5- and 10-years was 72% and 61% in those with de novo DSA formation, compared to 93% and 89% in patients without de novo DSA formation (p=0.04. See Figure 1). Overall patient survival was similar between the two groups.

Conclusions
In this single-center study, a transplant done in the setting of autoimmune liver disease had a higher risk of de novo DSA formation. Furthermore, de novo DSA formation lead to a decreased graft survival time in liver transplant patients but overall patient survival was not significantly decreased. A standard approach to DSA monitoring, especially in high risk populations, is required to better understand its prevalence and impact in liver transplantation.

Funding Agencies
None
A213 OUTCOMES OF INCIDENTAL CHOLANGIOCARCINOMA IN LIVER TRANSPLANT PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS
Authors: JAMES L J , Kulai T , MCLEOD M , PELTEKIAN K , Yoshida E M , Zhu J 
Published: March 2021

Abstract

Background
Primary sclerosing cholangitis (PSC) is a predisposing factor for cholangiocarcinoma(CCA).Patients with CCA have poor outcomes post-transplant.Intrahepatic CCA is difficult to detect pre-operatively in cirrhosis.Few outcomes are reported among PSC transplant patients where CCA was incidental.

Aims
To determine the incidence of incidental CCA (iCCA) in PSC liver explants and the impact of iCCA on post-transplant survival for patients with PSC

Methods
This was a retrospective cohort study in which the medical records of PSC patients who underwent transplant at QEII Health Sciences Center in Halifax between January 1987 to March 2020 were reviewed. The incidence of iCCA was calculated. Survival analysis was performed to determine the mean time to survival among iCCA and non-iCCA groups

Results
A total of 94 patients were transplanted for PSC during the study period.The mean age was 43 years.Twenty-six percent were women and 74% were men.Three were iCCA, one hilar and two intrahepatic CCA. All iCCAs occurred prior to 2008.
All iCCA patients had contrast enhanced CT, ERCP with cholangiogram and MRI.Two of the ERCPs reported CBD related strictures and the brushings had no evidence of malignancy.CA19-9 level was measured in one and reported as normal.Contrast enhanced MRI was not available prior to 2007.
The PSC patients had 1, 5, and 10-year survival rates of 93.8%, 88.6% and 81.9% respectively.One patient required re-transplant for graft failure and died within 3 months post-transplant due to complications. In all other cases the cause of death was not identified.
Among patients with iCCA, two deaths were due to metastatic cholangiocarcinoma and the other due to surgical complication in the immediate post-transplant period. None survived beyond 2 years.

Conclusions
Observed PSC survival in this cohort was above national average in the same period.The 3 iCCA cases identified occurred before the availability of contrast enhanced MRI. Patients with iCCA and liver transplant had poor survival at 1 and 2 years.There were no iCCA identified after 2007.These findings suggest incidental cholangiocarcinoma was effectively reduced by the advent of high-resolution imaging modality, and improvements in pre-transplant screening, including tumor marker CA19-9 and stringent patient selection. Further study involving multiple centres is necessary to draw a definite conclusion.

Funding Agencies
None
A214 BARIATRIC SURGERY PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE HAVE DIFFERENT VISCERAL ADIPOSE TISSUE GENE EXPRESSION COMPARED TO THOSE WITH NORMAL LIVER
Authors: Keshavjee S , Yadav J , Schwenger K , Fischer S , Jackson T D , Okrainec A , Allard J 
Published: March 2021

Abstract

Background
Non-alcoholic fatty liver disease (NAFLD) includes simple steatosis (SS) and nonalcoholic steatohepatitis (NASH). It affects 74–98% of individuals with morbid obesity undergoing bariatric surgery (BSX). Among several factors contributing to NAFLD pathogenesis, adipokines secreted by visceral adipose tissue (VAT) can play a role by regulating glucose/lipid metabolism and inflammation.

Aims
This study aims to determine if visceral adipose tissue adipokine and cytokine gene expression are associated with NAFLD (SS and NASH) at the time of BSX.

Methods
Patients were recruited from the Toronto Western Hospital Bariatric Clinic. Demographic data was recorded. The VAT and liver biopsies were collected at the time of bariatric surgery. VAT adipokines and other mediators were assessed by RT-PCR and included markers of thermogenic capacity, inflammation, fibrosis, adipokines, and others. Liver histology was assessed by a pathologist using the Brunt system and individuals were diagnosed as either SS, NASH, or having a healthy liver (HL). Blood samples were collected pre-BSX to measure liver and metabolic syndrome related parameters, including HOMA-IR, HbA1c, liver enzymes, and lipid profile. Anthropometry was also assessed. Groups were compared using Kruskal-Wallis test followed by Wilcoxon ranked sum, or chi-square and Fisher’s exact test as necessary. Data was considered to be statistically significant with a p-value less than 0.05.

Results
We are presenting data on 126 patients, 80.2% females with a median age of 49 and a body mass index (BMI) of 46.9. Fifty-seven patients had SS, 34 had NASH and 35 had a healthy liver (HL). BMI, age, and sex did not differ between the three groups. First, we found that those with NASH had significantly higher VAT expression of fibrosis (Loxl2), inflammation (CCL4 and TGFb1) and proliferation markers (E2F1) and significantly lower expression of adipokines (TNFa and resistin) compared to HL. Also, we found that SS had significantly higher fibrosis (Col3a1, Col6a1, Loxl2, CD9 and Acta2), inflammation (Nox2, TGFb1, IFNg and Clec10a), browning (PPARa, PPARg and Glut1) and proliferation (E2F1) marker expression compared to HL.

Conclusions
Results show that there is a significant difference in the expression pattern of VAT fibrotic and inflammatory markers between HL, SS and NASH patients. The observed increase of inflammatory markers in NAFLD is in line with prior research outlining the ability of inflammatory mediators from VAT to contribute to liver pathology via portal circulation. The relationship between VAT characteristics and NAFLD are important in understanding the widespread metabolic effects of obesity.

Funding Agencies
CIHRCanadian Liver foundation
A221 CLINICAL CHARACTERISITICS OF PORTAL VEIN THROMBOSIS AMONG AN INPATIENT COHORT WITH CIRRHOSIS
Authors: Dadgar K , Kelly E M 
Published: March 2021

Abstract

Background
Portal vein thrombosis (PVT) has a reported prevalence ranging from 0.6 to 26% in cirrhotic patients and yet optimal management in these patients remains unclear [1]. PVT can lead to poor outcomes including increased risk of bleeding, intestinal injury, and deterioration in liver function. Conversely, treatment of PVT in cirrhotic patients increases their risk of bleeding complications, particularly in patients with known varices.

Aims
The aim of this study is to better characterize the prevalence and impact of PVT in cirrhotic inpatients.

Methods
We conducted a retrospective cohort study based on data collected on adult patients admitted to the Ottawa Hospital between January 1, 2011 and December 31, 2015. We included patients with a diagnosis of cirrhosis either before or during index admission. Patients with a radiology report indicating a PVT were compared to those without PVT. Non-Ontario residents were excluded and where there were multiple admissions per patient one admission was randomly selected to be used. Ethics approval was obtained from the Research Ethics Board at the University of Ottawa.

Results
This study found 34 patients with cirrhosis diagnosed with PVT during their hospitalization (3.73%). Of the patients with PVT, 23 were acute and 11 were chronic based on radiologic appearance. Mean age was similar between groups (PVT: 61.7, SD=9.8; No PVT: 62.3, SD=12.3). The mean Na-MELD was also similar (PVT: 17.6, no PVT: 17.3, p=0.82). Among patients with PVT, 11 patients presented with ascites, 10 with hepatic encephalopathy (HE), 5 with abdominal pain and 5 with an upper GI bleed. Spontaneous bacterial peritonitis (SBP) occurred in 11.76% of patients with PVT as compared to 3% of patients without PVT (p value= 0.006). There also seemed to be a trend towards more HE in the cohort with PVT (20.6% vs 10.7%, p value= 0.07). With regards to screening for varices, 2 patients had an EGD in the 6 months prior to admission, 11 had an EGD on admission, 1 after anticoagulation due to bleeding, and 18 had no screening in the 6 months prior to admission. Twelve patients were treated for PVT, 17 were untreated and 5 did not have documentation about treatment. Of the patients that were not treated, 9 were due to palliative goals of care, 1 due to bleeding, 1 due to thrombocytopenia, 2 due to chronicity on imaging and 4 did not have reasons documented.

Conclusions
PVT is a known complication of cirrhosis, however the clinical significance and optimal management of patients with PVT is poorly understood. Although prevalence of PVT was low in this cohort, our data suggests some possible association between liver related complications and PVT, including SBP and HE. Further research is needed to determine how to best manage patients with PVT.
1. Garcia-Pagan JC, Valla DC. Portal vein thrombosis: a predictable milestone in cirrhosis? Journal of hepatology. 2009 Oct 1;51(4):632–4.

Funding Agencies
None
A222 ASSOCIATION BETWEEN PROTON PUMP INHIBITOR USE AND DEVELOPMENT OF HEPATIC ENCEPHALOPATHY AND SPONTANEOUS BACTERIAL PERITONITIS IN HOSPITALIZED PATIENTS WITH CIRRHOSIS
Authors: Tan P , Yau K , Ukos M , Miller C , Lombardi J , Kelly E 
Published: March 2021

Abstract

Background
Proton pump inhibitors (PPIs) are commonly prescribed medications which are indicated in various different gastrointestinal (GI) diseases, including peptic ulcer disease, gastroesophageal reflux disorder and upper GI bleeding. There is some evidence to suggest that PPI use in cirrhosis may predispose to the development of hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP), albeit with some controversy.

Aims
We aim to conduct a retrospective epidemiological analysis of the association between PPI use in hospitalized patients with cirrhosis and prevalence of HE and SBP.

Methods
This was a retrospective cohort study of 953 adult patients (mean age 62.3 (SD=12.2)) with cirrhosis admitted to the Ottawa Hospital between January 1, 2011 and December 31, 2015. A chart review was conducted and relevant information extracted.

Results
Average MELD-Na on admission was 17.4 (SD = 7.5) with no significant differences when stratified by in-hospital PPI use (p=0.53). 14.7% of patients had a prior history of HE, 5.4% SBP, 31.6% ascites, 9.3% hepatocellular carcinoma and 1.2% hepatorenal syndrome. 26.4% of patients had a history of varices, of which 34.4% had previous variceal bleeding. 45.4% of patients were on a PPI prior to admission and 69.8% during their hospitalization. Patients with a previous history of HE (16.8% vs. 9.6% p=0.006), varices (31.4% vs. 14.2% p&lt;0.001) and variceal bleed (11.6% vs. 3.1% p&lt;0.001) were more likely to be exposed to a PPI in-hospital. Mortality rate during index admission was 19.4%.
There was no significant association noted between the incidence of HE (31.2% vs. 25.0% p=0.06) or SBP (10.4% vs. 8.0% p=0.25) and in-hospital PPI use. There was also no significant association between PPI use and infectious complications, including bacteremia (8.6% vs. 7.6% p=0.63), pneumonia (12.7% vs. 12.5% p=0.95), urinary tract infections (9.2% vs. 6.6% p=0.19) and clostridium difficile (3.8% vs. 2.1% p=0.18). Patients on a PPI had greater in-hospital mortality (22.0% vs. 13. 5% p=0.002), although there was no significance between cause of death (p=0.31) nor death from infectious complications (18.5% vs. 23.1% p=0.52) between groups. Length of stay (LOS) was longer in patients exposed to PPI (median (IQR) 7 (4–17) vs 6 (3–13) p=0.03). Similar findings were noted on subgroup analysis of decompensated patients.

Conclusions
We did not observe a significant difference in HE, SBP or infectious complications among this cohort of cirrhotic patients by in-hospital PPI use. However, there was a significantly higher mortality rate noted in hospital and longer LOS, despite similar baseline MELD-Na and causes of death. Further study and judicious PPI prescribing practices in this vulnerable population of patients is warranted.

Funding Agencies
None
A227 UMBILICAL HERNIA INCARCERATION IN LIVER CIRRHOSIS: A RARE COMPLICATION OF PARACENTESIS
Authors: LAGROTTERIA A , Aruljothy A , Tsoi K 
Published: March 2021

Abstract

Background
Patients with decompensated liver cirrhosis with ascites frequently have umbilical hernias with a prevalence of 20% and are managed with large volume paracentesis (LVP). Common complications of LVP include hemorrhage, infection, and bowel perforation that occur infrequently with a frequency of less than 1%. However, incarceration of umbilical hernias has been reported as a rare complication of LVP and is speculated to be from ascitic fluid decompression that reduces the umbilical hernia ring diameter resulting in entrapment of the hernia sac. It is unclear whether the quantity or the fluid removal rate increases the herniation risk. Based on case series, this rare complication occurs within 48 hours of the LVP and requires emergent surgical repair and involves a high risk of morbidity and mortality due to potential infection, bleeding, and poor wound healing.

Aims
We describe a case report of an incarcerated umbilical hernia following a bedside large-volume paracentesis.

Methods
Case report

Results
A 59-year-old Caucasian male presented to the emergency department with a 24-hour history of acute abdominal pain following his outpatient LVP. His medical history included Child-Pugh class C alcoholic liver cirrhosis with refractory ascites managed with biweekly outpatient LVP and a reducible umbilical hernia. He reported the onset of his abdominal pain 2-hours after his LVP with an inability to reduce his umbilical hernia. Seven liters of clear, straw-coloured asitic fluid was drained. Laboratory values at presentation revealed a hemoglobin of 139 g/L, leukocyte count of 4.9 x109 /L, platelet count of 110 xo 109 /L, and a lactate of 2.7 mmol/L His physical exam demonstrated an irreducible 4 cm umbilical hernia and bulging flanks with a positive fluid wave test. Abdominal computed tomography showed a small bowel obstruction due to herniation of a proximal ileal loop into the anterior abdominal wall hernia, with afferent loop dilation measuring up to 3.4 cm. He was evaluated by the General Surgery consultation service and underwent an emergent laparoscopic hernia repair. There was 5 cm of small bowel noted to be ecchymotic but viable, with no devitalized tissue. He tolerated the surgical intervention with no post-operative complications and was discharged home.

Conclusions
Ultrasound-guided bedside paracentesis is a common procedure used in the management of refractory ascites and abdominal wall hernia incarceration should be recognized as a potential rare complication. To prevent hernia incarceration, patients with liver cirrhosis should be examined closely for hernias and an attempt should be made for external reduction prior to LVP. A high index of suspicion for this potential life-threatening condition should be had in patients who present with symptoms of bowel obstruction following a LVP.

Funding Agencies
None
A232 AUTONOMIC FUNCTION ANALYSIS VIA HEART RATE VARIABILITY ASSOCIATED WITH PROPULSIVE MOTOR PATTERNS OF THE HUMAN COLON
Authors: Ali M , Liu L , Chen J , Huizinga J D 
Published: March 2021

Abstract

Background
Although parasympathetic activity is the primary driver of colonic propulsive activity, and sympathetic activity a major inhibitor of colonic motility, they are rarely measured and almost play no role in diagnosis of dysfunction or standard treatments.

Aims
Our aim was to develop assessment of autonomic nervous system activity associated with the major propulsive motor patterns, an essential part of defecation reflexes in the human colon orchestrated by neural reflexes.

Methods
One hundred and forty-five motor patterns were recorded from eleven healthy volunteers using high resolution colonic manometry (HRCM) with concurrent electro- and impedance cardiography to evaluate changes in parameters of heart rate variability (HRV).

Results
High-amplitude propagating pressure waves (HAPWs) that often start in the proximal colon, traverse distally and end with anal sphincter relaxation, were associated with a 8.2% (P&lt;0.02) increase in the respiratory sinus arrhythmia (RSA) value, a 24.6% increase in the root mean square of successive differences of beat to beat intervals (RMSSD), indicated a strong parasympathetic reactivity that subsided within 2 min of termination of the HAPW (Figure 1). The measure of sympathetic reactivity to motor patterns was best reflected by the Baevsky Stress Index (or Sympathetic Index, SI) that reduced by 45% (P&lt;0.02). We developed a measure of autonomic balance, the SI/RSA ratio that changed from 18.8 to 8.7 (54%; P&lt;0.01) during motor activity and recovered to 16.1 immediately after (P&lt;0.005). The SI/RMSSD reduced by 65% (P&lt;0.01). When HAPWs occurred in quick succession, the parasympathetic activity showed rhythmicity at the HAPW frequency that slowly terminated when motor activity stopped. During motor activity, the heart rate did not significantly change.

Conclusions
The major propulsive motor pattern of the human colon, the HAPW as measured by HRCM that is part of the major defecation reflexes, is associated with marked changes in parasympathetic and sympathetic activity that is reflected and measurable as heart rate variability parameters. This opens the way to evaluate autonomic dysfunction in patients with colon motor disorders.

Funding Agencies
CIHRNSERC, Farncombe Institute