Society: AGA

Introduction:
Acute variceal bleeding (AVB) is a major cause of death in cirrhotic patients. We developed and internally validated a pragmatic model to predict the individualized risk of 30-day readmission with recurrent AVB in liver cirrhosis patients.

Methods:
Hospitalizations with a primary diagnosis of esophageal AVB were identified using the 2019's Nationwide Readmission Database (NRD). We utilized the NRD as it recognizes the same patient's index admissions and recognition of readmissions. Patients were excluded if aged <18 years, had non-AVB, end-stage renal disease, solid organ transplants, anticoagulation use, immunosuppression, para/quadriplegics, lymphomas/leukemias, or malignant tumors. We used supervised machine learning to input variables with increased association with recurrent AVB readmissions to undergo Least Absolute Shrinkage and Selection Operator (LASSO) penalized regression for selecting the best predictors. Receiver operating characteristic (ROC) curves assessed predictive power for each selected predictor and those with a poor threshold of discrimination [area under the curve (AUC <0.60)] were eliminated. The remaining predictors were utilized to develop a variceal AVB nomogram. The nomogram was internally validated using 10 fold cross validation, and ROC curves were generated along with bootstrapped Bias corrected (BC) 95% confidence intervals (CI) for the AUC. The Brier score was used to report measures of overall performance.

Results:
The prevalence of recurrent AVB readmissions was 2.65%. For the model predicting the risk, five predictors were included: Chronic pulmonary disease history (AUC 0.84± 0.003 ), Age >=50 years (AUC 0.61 ± 0.002), Transjugular intrahepatic portosystemic shunt (TIPS) during index hospitalization (AUC 0.89±0.003 ), Obesity (AUC 0.84± 0.002), history of cardiac arrhythmia (AUC 0.84± 0.002) (Figure 1). These variables were used to develop a nomogram that displayed outstanding discrimination AUC 0.91 (Bootstrap Bias Corrected 95%CI 0.90-0.92), correlating to a 91% probability of the model correctly assigning a higher score to patients at risk of recurrent variceal bleed readmission within 30 days of discharge (Figure 2A, 2B). Liu's index was used to determine the cut-off (21 points). Therefore patients with a score ≥ 21 were deemed at high risk for recurrent AVB readmission. For high-risk patients, with a sensitivity of 80.44% and a negative predictive value of 99.47%, the specificity was 100.00% with a positive predictive value of 100.00%. The Brier score was 0.005, indicating the good overall performance of the nomogram.

Conclusions:
The proposed nomogram score can be used to identify such patients with a risk for recurrent variceal bleed readmission within 30 days of discharge.

<b>Figure 1: </b>Individual Receiver operating characteristic (ROC) curves of selected predictors by penalized regression (LASSO) with acceptable discriminative power (ROC curve >0.60)

Figure 1: Individual Receiver operating characteristic (ROC) curves of selected predictors by penalized regression (LASSO) with acceptable discriminative power (ROC curve >0.60)

<b>Figure 2: </b>(A) The proposed risk nomogram; (B) ROC curve with mean cross validated area under the curve (CvAUC) after 10 fold cross validation. AUC: 0.91 (Bootstrap Bias Corrected 95%CI 0.90-0.92)

Figure 2: (A) The proposed risk nomogram; (B) ROC curve with mean cross validated area under the curve (CvAUC) after 10 fold cross validation. AUC: 0.91 (Bootstrap Bias Corrected 95%CI 0.90-0.92)

Background & Objective
Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment for portal hypertension complications. Still, the role of adjuvant variceal embolization is a matter of debate. Thus, we aim to evaluate the efficacy and safety of TIPS with variceal embolization versus TIPS alone to prevent variceal rebleeding.
Methods
We used PubMed, CENTRAL, and OVID to search for all randomized controlled trials (RCTs) and comparative observational studies up to June 17^th, 2022. We pooled binary outcomes using risk ratios (RRs) presented with 95% confidence intervals (CIs) using RevMan 5.4. We prospectively published our protocol in PROSPERO with ID: CRD42022341354.
Results
We included 11 studies (two RCTs and 9 observational studies) with 1024 patients. Pooled RR favored TIPS with embolization in preventing variceal rebleeding (RR: 0.58 with 95% CI [0.44, 0.76]], p=0.0001); however, we found no difference between both groups regarding shunt dysfunction (RR: 0.92 with 95% CI [0.68, 1.23], p=0.57), encephalopathy (RR: 0.88 with 95% CI [0.70, 1.11], p=0.28), or death (RR: 0.97 with 95% CI [0.77, 1.22], p=0.78).
Conclusions
TIPS with embolization significantly prevented variceal rebleeding; however, there was no difference regarding shunt dysfunction, encephalopathy, or death. TIPS with embolization can be an effective strategy, especially in patients with cardio-fundal varices. Finally, more large-scale randomized controlled trials comparing TIPS plus embolization with balloon-occluded retrograde transvenous obliteration or endoscopic variceal ligation are still required.

Effect of TIPS plus embolization versus TIPS alone on A) variceal rebleeding; B) shunt dysfunction; C) Encephalopathy; and D) death.

Effect of TIPS plus embolization versus TIPS alone on A) variceal rebleeding; B) shunt dysfunction; C) Encephalopathy; and D) death.

BACKGROUND:
Frailty is a clinically recognizable state of increased vulnerability due to age-related decline in reserve and function across multiple physiologic systems that compromises the ability to cope with acute stress. We aimed to assess hospital mortality and morbidity in patients with decompensated cirrhosis within this cohort.

METHOD:
We conducted a retrospective study using the Nationwide Inpatient Sample (NIS) database. ICD-10 codes were used to inquire for patients admitted with decompensated cirrhosis between September 2015 through December 2018. ICD-10 codes corresponding to the Hospital Frailty Risk Score (HFRS) were used to divide the study sample into 2 cohorts; low risk (<5 points) and intermediate or high risk (>5 points). To calculate the points, we fitted a logistic regression model that included membership of the frail group as the binary dependent variable (frail vs. non-frail) and the set of ICD-10 codes as binary predictor variables (1 = present, 0 = absent for each code). To simplify the calculation and interpretation, we multiplied regression coefficients by five to create a points system, so that a certain number of points are awarded for each ICD-10 code and added together to create the final frailty risk score. Multivariate regression analysis was performed to find adjusted mortality.

RESULTS:
A total of 767,794 patients were admitted with decompensated cirrhosis, and 472,193 (61.5%) were identified as intermediate and high risk (>5 points) (study cohort) and 295,601 (39.5%) as low risk (<5 points). The mean age was 65.8 ± 12.6 in the study cohort and 60.6 ± 9.5 in the low-risk group. The predominant gender was male in both the study cohort (60.4%) and low-risk group (52.5%), and the predominant race was Caucasian in both the study cohort (63.6%) and low-risk group (61.9%) (Table 1). The primary outcome was in-hospital mortality, which was significantly higher in the study cohort as compared to the low-risk group (5.3% vs 2.8%, p<0.0001). The age-adjusted Odds ratio of mortality was 1.59 (95% CI 1.31 – 1.80, p<0.0001). When compared between the two groups, median length of stay (8.7 vs 6.1); hospitalization cost ($87,486 vs $79,193); disposition to a skilled nursing facility (SNF) (29.0% vs 13.6%); and need for home health care (HHC) was significantly higher in the study cohort. Complications such as septicemia, septic shock, and acute kidney injury were also significantly higher in the study cohort (Table 2).

CONCLUSION:
Using frailty to identify those who are at greater risk for adverse outcomes, can help formulate interventions to target individualized reversible factors to improve outcomes in patients with decompensated cirrhosis. Future large-scale prospective studies are warranted to understand the dynamic and longitudinal relationship between cirrhosis and frailty.

Patient level characteristic in the study group.

Patient level characteristic in the study group.

Outcomes

Background:
Literature regarding outcomes associated with LAAO device procedure in patients with atrial fibrillation (A fib) and cirrhosis is limited.

Objective:
We aim to evaluate the in-hospital clinical outcomes and 30-day readmissions among patients with A fib with cirrhosis, stratified by presence or absence of LAAO device procedure.

Methods:
We performed a retrospective study of all A fib with cirrhosis hospitalizations, stratified by Child-Pugh score, using the Nationwide Readmissions Database (NRD) from January 1, 2016 to December 31, 2019. Primary outcomes were in-hospital mortality outcomes and 30-day readmissions.

Results:
A total of 207,443 index hospitalizations of cirrhosis and A-fib (Mean age 68.99±11.20; female 36.2%) were reported in NRD. Of these, 767 (3.7/1000) had LAAO procedure. A total of 15,397 (7.45%) patients died during the principal hospitalization, all among the non-LAAO subgroup (p<0.001). When patients with cirrhosis were separated based on Child-Pugh Classification, there were 437 (57%) patients in Class A, 253 (33%) in Class B, and 77 (10%) in Class C. Gastrointestinal bleeding occurred in 20,901 patients and was statistically lower in LAAO (4.2%) versus non-LAAO patients (10.1%; p<0.001). The following outcomes were statistically lower in the LAAO patients compared to the non-LAAO patients: coagulopathy, need for blood transfusion or plasma transfusion, and ICU encounters (Table 1). Of the patients discharged, a total of 52,589 (27.39%) patients were readmitted in 30-days of discharge, 65 (8.47%) among LAAO vs 52,524 (27.39%) among non-LAAO; p<0.001. It was also found that patients with CHADVASc 6 or greater had higher 30-day readmissions among the LAAO device patients.

Conclusion:
LAAO was associated with significantly better in-hospital outcomes and 30-day readmissions. Regardless of the Child Pugh class, there was no death in the LAAO patients compared to non-LAAO patients. This suggests that the presence of cirrhosis, regardless of the Child Pugh class, should not deter clinicians from performing LAAO procedure in patients with compensated cirrhosis and atrial fibrillation.

<b>Table 1: </b>Baseline characteristics and in-hospital clinical outcomes associated with Cirrhosis with Atrial fibrillation encounters, stratified by presence or absence of LAAO device.

Table 1: Baseline characteristics and in-hospital clinical outcomes associated with Cirrhosis with Atrial fibrillation encounters, stratified by presence or absence of LAAO device.

Introduction: EUS injection of cyanoacrylate (CYA) into gastric varices (GV) is typically performed in cirrhotic patients. This study aims to evaluate safety and efficacy of the procedure in non-cirrhotics.
Methods: We identified consecutive patients who underwent EUS-guided CYA treatment of GV between 11/2012 and 12/2021 at our hospital. CYA was injected in 0.5-1.5 mL aliquots and coils inserted at the discretion of the endoscopist. At follow-up EUS (EUS #2), GV were considered eradicated with minimal or absent doppler flow; otherwise repeat injection and/or coil placement was performed. GV were graded by the Sarin classification and adverse events (AE) by the Cotton classification. Endoscopic techniques and outcomes were reviewed from local and statewide EMRs and compared between non-cirrhotic (NCG) and cirrhotic (CG) groups. Data was reviewed until patients met one of the following endpoints: a) loss to follow-up; b) GV bleeding; c) IR or surgery decompression; d) death or comfort care.
Results: 119 patients (61 M, mean 59±12 yrs.; Table 1) with (n=105) or without (n=14) cirrhosis underwent EUS for secondary (n=95) or primary GV prophylaxis (n=24). Compared to the CG, the NCG were younger (p=0.013) and had smaller GV (p=0.026). The groups were otherwise similar.
For the NCG group, 4 (29%) mild or moderate post EUS AEs occurred including one splenic infarct. No post-procedure GV bleeding occurred between EUS #1 and EUS #2. 12 of 14 patients had a follow-up EUS a mean 10.1±12.1 months after the index procedure. During the EUS #2, 2 (17%) had a persistent GV and one was retreated with CYA and coils. Within 30 days of EUS #2, no post-procedural AE were noted. Bleeding from GV after the second EUS occurred in one non-cirrhotic patient 7 months after the procedure.
Compared to the CG, mean time between index and surveillance EUS was longer in the NCG (10.1 vs 4.1 months, p=0.006). However, there was no difference in rate of GV eradication (p=1), rate and severity of AE (including thromboembolic complications) and GV bleeding rate after index (p=1) and interval (p=0.563) EUS between the two groups (Table 2).
Conclusion: In this single center study of GV treated with EUS, non-cirrhotic patients were younger and had smaller varices compared to cirrhotics. Post-procedural GV bleeding and AE rates were similar between the two groups. These findings suggest that EUS may be considered for non-cirrhotic GV bleeding, however further studies with a larger population should be completed to better assess outcomes in these patients.

<u>Table </u><u>1.</u><u> Demographics and outcomes of index EUS</u>

Table 1. Demographics and outcomes of index EUS

<u>Table </u><u>2</u><u>. Post-procedure adverse events after index and surveillance endoscopy</u>

Table 2. Post-procedure adverse events after index and surveillance endoscopy

Aditya Gutta

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