Patients Undergoing Evaluation For Liver Transplantation Research Articles

Patient-Reported Outcome Screens for Cognitive Dysfunction and Predicts Admissions in Cirrhosis

IntroductionHepatic encephalopathy (HE) is a frequent complication of cirrhosis, leading to preventable hospitalizations and increased mortality. Despite the availability of validated neuro-psychometric tests to diagnose HE, only 10% of clinicians regularly screen for HE due to lack of time, equipment, and trained personnel. Materials and MethodsWe studied the association between patient-reported cognitive function and the National Institutes of Health Toolbox Cognition Battery (a validated measure of HE) in patients with cirrhosis. A single-center prospective study of adult patients undergoing liver transplantation evaluation was performed from 10/2020 to 12/2021. Cognition was assessed using the National Institutes of Health Toolbox Cognition Battery and a brief Patient-Reported Outcomes Measurement Information System (PROMIS) survey. ResultsTwenty-three liver transplantation candidates were enrolled; the mean age was 56.4 (±9.7) years, 39% were female and the most common etiologies of cirrhosis were primary biliary cirrhosis/primary sclerosing cholangitis/overlap syndrome (30%), hepatitis C (22%) and alcohol-associated liver disease (22%). The mean MELD-Na was 14.9 (±6.4). The mean PROMIS Cognitive Function T-score (PROMISCF) was 49.2 (±9.6). The mean T-scores for the List Sort Working Memory test, Flanker Inhibitory Control and Attention test, and Pattern Comparison Processing Speed test were 46.4 (±9.9), 37.8 (±6.2), and 50.22 (±16.4), respectively. PROMISCF correlated with the List Sort Working Memory test (r = 0.45, P = .03). The mean hospitalization rate was 1.6 days admitted per month. On adjusted multivariate analysis, PROMISCF predicted total hospitalization days (P < .001), hospital admissions (P = .01), and hospitalization rate (P < .001). ConclusionsA brief survey can screen for HE and predict hospitalizations in patients with cirrhosis.

Approach to the patient with decompensated cirrhosis and aortic stenosis during liver transplantation evaluation.

Aortic stenosis (AS) is the most common valvular disease and is reported to be present in 2%-7% of people over the age of 65. Risk factors for aortic stenosis and NASH overlap; thus, as the population ages, there is an increased likelihood that patients undergoing liver transplantation evaluation may have severe aortic stenosis. There is a high mortality rate associated with cardiac surgeries in patients with cirrhosis. Further, there are no guidelines that assist in the decision making process for patients with cirrhosis and AS. In this review, we highlight key studies that compare transcatheter aortic valve implantation (TAVI) with surgical aortic valve replacement (SAVR) in patients with cirrhosis. We propose an algorithm as to how to approach the patient with aortic stenosis and considerations unique to patients with cirrhosis (i.e., anticoagulation, EGD for variceal assessment; need to determine timing after TAVI before listing).

Increasing prevalence of obesity and diabetes among patients evaluated for liver transplantation in a Swiss tertiary referral center: a 10-year retrospective analysis.

Non-alcoholic fatty liver disease (NAFLD) is now the first cause of chronic liver disease in developed countries. We aimed to assess trends in the prevalence of obesity, type 2 diabetes mellitus (T2DM) and NAFLD in patients undergoing liver transplantation evaluation and to assess whether obese patients were less likely to be listed or had an increased drop-out rate after listing. We conducted a retrospective study of all consecutive patients who underwent liver transplantation evaluation at a Swiss tertiary referral centre between January 2009 and March 2020. A total of 242 patients were included, 83% were male. The median age was 59 years (IQR, 51-64 years). The most common causes of end-stage liver disease were viral hepatitis (28%), alcoholic liver disease (21%) and NAFLD (12%). Obesity was present in 28% of our cohort, with a significant increase over time. Prevalence of type 2 diabetes mellitus followed the same trend (p = 0.02). The proportions of non-listed and listed obese patients did not differ (21% vs. 30% respectively; p = 0.3). The prevalence of obesity and type 2 diabetes mellitus significantly increased over our study period. Obese patients had similar chances of being listed. The landscape of liver transplantation indications is shifting towards NAFLD, highlighting the urgent need to prevent NAFLD progression.

Utility of Framingham Score for Optimizing Preoperative Evaluation Among Patients Undergoing Liver Transplant Evaluation

Cardiac testing of candidates for liver transplant (LT) requires balancing risks and benefits of cardiac procedures. The goal of this study was to evaluate the utility of the Framingham score (FS) for optimizing preoperative risk stratification for coronary artery disease (CAD). In this single-center retrospective study of 615 adults undergoing LT evaluation from 2016 to 2019, data of preoperative evaluation, post-LT 1-year mortality, and post-LT cardiac events were reviewed. Patients >30 years of age with normal echocardiogram underwent FS calculation. Elevated FS (≥35%) patients were triaged to undergo angiogram for CAD evaluation; FS <35% patients underwent stress testing as initial CAD evaluation. Of 615 patients referred for LT, 481 underwent cardiac testing. Ninety-five were excluded from the FS pathway because of age, abnormal baseline echocardiogram, or known CAD. Of the remaining 386 patients in the FS pathway, 342 had a low FS and 44 had a high FS. In patients with low FS, 90% underwent stress testing as initial test; 16% underwent invasive testing at some time. In those with elevated FS, 59% underwent invasive testing as initial test. Listing rate and posttransplant outcomes were similar between patients with low and high FS. We demonstrated the feasibility of a simple algorithmic evaluation process using FS for optimizing pre-LT risk stratification for CAD. Although exceptions to the protocol occur, the proposed protocol allows for a streamlined approach by prioritizing testing based on cardiac risk. This approach may maximize diagnostic yield while limiting invasive procedures.

Clinical implications of inducible left ventricular outflow tract obstruction among patients undergoing liver transplant evaluation

IntroductionPatients with end stage liver disease (ESLD) have a hyperdynamic state due to decreased systemic vascular resistance and increased cardiac output. Preoperative evaluation with dobutamine stress echocardiography (DSE) is used to risk-stratify patients prior to liver transplant. We sought to identify the impact of inducible left ventricular outflow tract obstruction (LVOTO) on DSE on post-operative liver transplant outcomes. MethodsPatients with ESLD who underwent liver transplant at Cleveland Clinic between January 2007 and August 2016 were identified. Pre-operative DSE data, and post-operative intensive care unit (ICU) data were extracted. Patients with inducible LVOTO were compared to those without LVOTO. ResultsOf the 515 patients identified who underwent DSE prior to liver transplant, 165 (30%) were female, and 95 (18%) had LVOTO. There were no major differences in baseline characteristics between the two groups. In the LVOTO group, rest gradients were 10.8 ± 3 mm Hg while peak gradients were 90 ± 48.2 mm Hg. No significant differences in ICU length of stay or duration of mechanical ventilation between both groups were noted. There were 21 deaths at 30 days. There were 2 (2.1%) deaths in the LVOTO group, versus 19 (4.5%) deaths in the non LVOTO group (p = 0.28). Higher Model for End Stage Liver Disease (MELD) scores predicted longer duration of mechanical ventilation and ICU length of stay. ConclusionInducible LVOTO on DSE does not adversely affect the short-term outcomes post liver transplant. Presence of inducible LVOTO should not be the mere reason to deny liver transplant among patients with ESLD.

95 Prevalence of Intrapapillary Mucinous Neoplasm in Patients With Chronic Kidney Disease

INTRODUCTION: The prevalence of intraductal papillary mucinous neoplasm (IPMN) in the general population ranges from 3.3%–9.8%. In patients undergoing liver transplant evaluation, overall prevalence is documented to be 6.6%. So far, the suggested risk factors for IPMN include diabetes, family history of pancreatic adenocarcinoma, and tobacco use. We aim to study the prevalence and risk factors for IPMN formation in patients with chronic kidney disease (CKD). METHODS: We performed a retrospective cross-sectional study of patients with CKD who had MRIs of the abdomen performed between the dates of 1/2018 and 12/2018. Independent chart review was conducted and various demographic, clinical, and imaging metrics were extracted. Overall, the prevalence of IPMN was calculated. A student's t-test and chi-square test were used to compare the IPMN group to non-IPMN group. RESULTS: A total of 400 patients were reviewed. The total prevalence of IPMN in CKD patients was 13.7% (55/400). In 68% of the study patients, the MRI was done for a kidney transplant evaluation. The average age of patients in the study was 58 ± 14 years, 59% were male and 52% patients were on dialysis. Diabetes and Hypertension accounted for 26% and 45% of CKD respectively. In patients with IPMNs, the average size was 10 ± 5.7 mm; 45% were located in the head, 33% in the body and 22% in the tail. Notably, 16% were main duct IPMNs, 80% were side branch IPMNs and 4% patients had mixed (MD + SB) IPMNs. Amongst the patients with IPMNs, 7.5% of patients had associated high-risk features and were referred for endoscopic ultrasound. Comparison of the IPMN group to non-IPMN group is shown in Table 1. IPMNs were most commonly observed in elderly patients. Gender, dialysis status, etiology of CKD, smoking and alcohol intake did not seem to impact the prevalence of IPMN in CKD patients. CONCLUSION: Patients with CKD have a higher prevalence of IPMNs than the general population. We further aim to confirm this interval data with our age and gender matched control group without CKD.

Application of Prescription Drug Monitoring Program to detect underreported controlled substance use in patients evaluated for liver transplant.

Presurgical controlled substance use predicts postoperative complications, increased readmissions, and mortality. We aimed to examine if a Prescription Drug Monitoring Program (PDMP) would detect underreported controlled substance use in patients undergoing liver transplant evaluation. We performed a retrospective cohort study at a tertiary referral center of patients undergoing liver transplant evaluation in 2017. PDMP reviews were performed on all 360 patients and urine drug screen (UDS) results were reviewed when available to evaluate dispensed controlled substances. These results were compared to the patient's self-reported medication list at evaluation to identify any underreporting. The primary outcome was the number of self-reported controlled substance discrepancies on the medication list identified by PDMP and UDS at the time of evaluation. Among the 360 patients, 87 (24%) had a discrepancy where PDMP revealed a controlled substance prescription that the patient did not report on their medication list. Seventy-seven (67/87) of these discrepancies involved opiates. Of the 360 patients, 219 (61%) had a negative UDS, but 70 (32%) of these patients had at least one controlled substance listed on PDMP. PDMP is a promising screening tool when used in conjunction with the UDS for detecting underreported controlled substance use in liver transplant candidates.

03:18 PM Abstract No. 210 Association between modified BALAD score and locoregional therapy response in transplant waitlist patients with hepatocellular carcinoma: prospective, observational analysis at a high-volume transplant center

The BALAD score, a risk index combining threshold values for bilirubin, albumin, α-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP), and Lens culinaris agglutinin-reactive α-fetoprotein (AFP-L3), has been useful in predicting survival and recurrence risk in hepatocellular carcinoma (HCC). This study seeks to correlate BALAD score with durable locoregional treatment response to doxorubicin-eluting bead transarterial chemoembolization (DEB-TACE). A single-center, prospective analysis was performed on patients undergoing liver transplant evaluation with HCC who were selected for down-staging or bridge-to-transplantation LRT with DEB-TACE. Blood was collected immediately prior to DEB-TACE in all patients. Plasma levels of AFP, DCP, and AFP-L3 were measured using the μTASWako i30 autoanalyzer. DEB-TACE was performed with 100-300μ LC beads mixed with 50mg Doxorubicin to near-complete stasis. Tumor response to DEB-TACE was calculated by mRECIST at 30-day and 3-month follow-up imaging. Cohort demographics were median age of 60, 69% male, 78% hepatitis C cirrhosis etiology, 88% within Milan criteria with an average MELD-Na score of 10. Median BALAD components were as follows: bilirubin 1.5 mg/dL, albumin 3.2 g/dL, AFP 7 ng/mL, AFP L3% 8, and DCP 2.8 ng/mL. Median follow up imaging for durable tumor response was 112 days. Fifty-percent of cohort had a complete response to DEB-TACE. Univariate analysis revealed BALAD score was associated with response to DEB-TACE (P=0.04), with 73% of patients with BALAD ≥ 2 not responding to DEB-TACE. BALAD component analysis revealed tumor biomarker thresholds poorly modeled to the dataset. The BALAD biomarker cutoffs were modified from AFP 400ng/mL to 20ng/mL, AFP-L3% from 15% to 10%, and DCP 1.9ng/mL to 7.5ng/mL decreasing the corresponding P-value (0.04 to 0.02) between BALAD and treatment response. Waitlist dropout after DEB-TACE for patients with modified-BALAD ≤ 1 was 5%. By combining metrics for liver synthetic function with biomarkers of HCC aggressiveness, the BALAD can identify HCC resistance to embolization therapy and risk of waitlist dropout.

Coronary artery disease in decompensated patients undergoing liver transplantation evaluation.

Coronary artery disease (CAD) is an important contributor to morbidity and mortality in patients undergoing liver transplantation (LT). However, the current literature is limited by sampling bias and nondefinitive assessment of CAD. The current study examines the prevalence of CAD via per protocol coronary angiography and its relationship to etiology of liver disease in patients undergoing liver transplantation evaluation (LTE). Data on 228 patients were prospectively collected who had coronary angiography as part of LTE between 2011 and 2014. Coronary angiography was done in all patients age ≥50 years or with CAD risk factors. CAD was defined as any coronary artery stenosis, whereas stenosis ≥ 70% in distribution of 1 or 3 major coronary arteries was considered as single- or triple-vessel disease. CAD was detected in 36.8% of patients, with the highest prevalence among nonalcoholic steatohepatitis (NASH) patients with cirrhosis (52.8%). Prevalence of single-vessel disease was higher among patients with NASH compared with hepatitis C virus (HCV) and alcoholic cirrhosis (15.1% versus 4.6% versus 6.6%; P = 0.02). Similarly, patients with NASH were more likely to have triple-vessel disease when compared with HCV and alcoholic cirrhosis (9.4% versus 0.9% versus 0%; P = 0.001). While adjusting for traditional risk factors for CAD, only NASH as etiology of liver disease remained significantly associated with CAD. Complications from diagnostic coronary angiography or percutaneous coronary intervention were low (2.6%). In conclusion, patients undergoing LTE have a high prevalence of CAD, which varies widely depending on etiology of liver cirrhosis. The procedural complications from coronary angiography are low. Liver Transplantation 24 333-342 2018 AASLD.

CORRELATION BETWEEN ECHOCARDIOGRAPHIC PULMONARY ARTERY PRESSURE ESTIMATES AND RIGHT HEART CATHETERIZATION MEASUREMENTS IN PATIENTS UNDERGOING LIVER TRANSPLANT EVALUATION: A SINGLE CENTER STUDY

Background: Pulmonary hypertension is a major adverse outcome indicator in patients undergoing liver transplant evaluation. We aim to examine the correlation between pulmonary artery systolic pressure calculated from echocardiography (ePASP) and measurement from right heart catheterization (cPASP)

Portal Hypertension Complications Are Frequently the First Presentation of NAFLD in Patients Undergoing Liver Transplantation Evaluation.

Nonalcoholic fatty liver disease (NAFLD) is likely to replace Hepatitis C as the leading cause of cirrhosis resulting in liver transplantation (LT) within a few years. Unfortunately, due to the lack of established guidelines for the screening of NAFLD in high-risk populations, many patients present with portal hypertension complications as their first manifestation of NAFLD require a LT evaluation. We aimed to investigate what proportion of patients who underwent LT for NAFLD-cirrhosis had knowledge of their liver disease prior to presenting with portal hypertension complications and to identify differences in clinical parameters between those with and without knowledge of preexisting NAFLD. Consecutive patients who underwent LT for NAFLD-cirrhosis at a tertiary referral center were included in the study. Demographic and clinical data at the time of the first LT evaluation visit were collected, and patient knowledge of previous NAFLD was documented. Ascites, variceal bleeding, hepatic encephalopathy, and thrombocytopenia leading to diagnosis of underlying cirrhosis were considered as the presenting symptoms of portal hypertension. A p<0.05 was considered statistically significant. A total of 124 subjects who received LT for NAFLD-cirrhosis were included, 58% (n=72) were male. At the time of the first LT evaluation visit, 60% had diabetes, the mean body mass index was 33.2 [28.6, 37.6] kg/m(2), and the mean Model for End-Stage Liver Disease (MELD) score was 14.0 [11.0, 19.0]. More importantly, 85/124 patients (68.5%) had no knowledge of preexisting NAFLD prior to presentation with symptoms of portal hypertension. The presenting symptoms were new-onset ascites in 61%, hepatic encephalopathy in 25%, variceal bleeding in 18%, thrombocytopenia in 9%, and other in 9% (non-exclusive). Patients with no prior knowledge of NAFLD were less likely to have a diagnosis of hypercholesterolemia (30 vs. 50%, p=0.035) and had a trend toward having higher MELD scores at the time of the first LT evaluation visit (15 vs. 13.5, p=0.05) and presenting with encephalopathy (25 vs. 10%, p=0.06) compared to those with previous knowledge of NAFLD diagnosis. The majority of patients undergoing liver transplant evaluation for NAFLD-cirrhosis are not aware of underlying NAFLD until they present with features of portal hypertension. New guidelines should consider screening for NAFLD in certain high-risk groups as more effective treatments for NAFLD are emerging.

Portal Hypertension Complications Are Frequently the First Presentation of NAFLD in Patients Undergoing Liver Transplantation Evaluation

Portal Hypertension Complications Are Frequently the First Presentation of NAFLD in Patients Undergoing Liver Transplantation Evaluation

Sa1035 Is Underlying Liver Disease a Risk Factor for Coronary Artery Disease Among Patients Undergoing Liver Transplant Evaluation?

Sa1035 Is Underlying Liver Disease a Risk Factor for Coronary Artery Disease Among Patients Undergoing Liver Transplant Evaluation?

Utility of Serum YKL-40 as a Tumor-Specific Marker of Hepatobiliary Malignancies

Serum YKL-40 has been linked to several human cancers. We investigated the potential role of serum YKL-40 as a marker of hepatobiliary malignancies. Archived serum samples of patients undergoing liver transplantation evaluation at the Mayo Clinic Rochester were used to measure YKL-40 levels. Patients were divided into three groups: hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and end-stage liver disease (ESLD) without malignancies. The Model for ESLD (MELD) score was used to quantify the severity of liver disease. The median serum YKL-40 level was highest in the ESLD group at 296 ng/mL, compared to 259 ng/mL in the HCC group and 80 ng/mL in the CCA group (p<0.01). There was a significant correlation between the MELD score and serum YKL-40 level (r=0.50, p<0.01). In a multivariate analysis, there was no significant difference in serum YKL-40 level between ESLD and HCC. CCA was associated with lower YKL-40 levels, a finding that was attributable to a lower prevalence of cirrhosis. The serum YKL-40 level has little utility as a cross-sectional screening tool for hepatobiliary malignancies, namely HCC and CCA. The role of YKL-40 as a surveillance marker in the follow-up of individual patients remains to be determined.

Pulmonary Complications of Cirrhosis

Pulmonary vascular complications of liver disease comprise two distinct clinical entities: hepatopulmonary syndrome (HPS-microvascular dilatation and angiogenesis) and portopulmonary hypertension (POPH-vasoconstriction and remodeling in resistance vessels). These complications occur in similar pathophysiologic environments and may share pathogenic mechanisms. HPS is found in 15% to 30% of patients with cirrhosis and its presence increases mortality and the risks of liver transplantation, particularly when hypoxemia is present. Contrast echocardiography and arterial blood gas analysis are required to establish the diagnosis. No medical therapies are available, although liver transplantation is effective in reversing the syndrome. POPH is found in 4% to 8% of patients undergoing liver transplantation evaluation, and the presence of moderate to severe disease significantly increases perioperative transplant mortality. Transthoracic echocardiography is recommended for screening and right-heart catheterization is required to establish the diagnosis. Medical therapies are increasingly effective in improving pulmonary vascular hemodynamics in POPH and may result in better perioperative outcomes.

Elevated Myostatin Levels in Patients with Liver Disease

Loss of skeletal muscle mass is a poorly understood complication of end-stage liver disease (ESLD). Based on recent stem cell literature, we hypothesized that the potent negative regulator of muscle mass, myostatin, could play a role in the muscle loss associated with ESLD. In this preliminary investigation, we measured myostatin levels in patients undergoing liver transplant evaluation, using a novel enzyme-linked immunosensitivity assay. Myostatin levels were significantly elevated in patients with ESLD compared with healthy controls. These data suggest that myostatin deserves further investigation as a target for therapies designed to preserve muscle mass in patients with ESLD.

463 Dobutamine Stress Echocardiography (Dse) Is a Poor Predictor of Coronary Artery Disease in Patients Undergoing Liver Transplant Evaluation

463 Dobutamine Stress Echocardiography (Dse) Is a Poor Predictor of Coronary Artery Disease in Patients Undergoing Liver Transplant Evaluation

Use of contrast-enhanced echocardiography (bubble echocardiogram) as routine screen for asymptomatic hepatopulmonary syndrome in patients undergoing liver transplant evaluation: Dianne L Rudow, Micheal Goldstein, Steven Lobritto, Lori Rosenthal, Mark W Russo, Patricia Harren, Jean Emend, Robert S Brown Jr., Columbia University College of Physicians & Surgeons, New York, NY

Use of contrast-enhanced echocardiography (bubble echocardiogram) as routine screen for asymptomatic hepatopulmonary syndrome in patients undergoing liver transplant evaluation: Dianne L Rudow, Micheal Goldstein, Steven Lobritto, Lori Rosenthal, Mark W Russo, Patricia Harren, Jean Emend, Robert S Brown Jr., Columbia University College of Physicians & Surgeons, New York, NY

Prospective evaluation of a 3.1-mm battery-powered esophagoscope in screening for esophageal varices in cirrhotic patients

Objective Standard esophagogastroduodenoscopy (EGD) is costly and uses conscious sedation that cirrhotic patients may tolerate poorly. This study aimed to determine the feasibility and acceptance of unsedated esophagoscopy with an ultrathin battery-powered endoscope (BPE) in cirrhotic patients for diagnosing esophageal varices (EV). Methods We first studied the prevalence of significant gastroduodenal pathology that could be missed if only esophagoscopy were performed in cirrhotic patients undergoing liver transplant evaluation. A prospective study was then done to evaluate a BPE in EV screening. Unsedated per-oral endoscopy was first done by a single endoscopist using a BPE, followed by EGD by a second endoscopist who was masked to the BPE result. A visual analog score was used to determine patient tolerance. Patients were asked about their preference for endoscopy in the future. A paired Student t test and the κ statistic were used in the statistical analysis. Results In the retrospective study, 199 patients were reviewed; three patients (1.5%) had gastric ulcers, and two patients (1%) had duodenal ulcers. In the prospective study, 28 cirrhotic patients (16 women) were evaluated. EV were diagnosed in 14 patients with a BPE, and 13 were confirmed by standard EGD (sensitivity and negative predictive value 100%, specificity and positive predictive value 93%, κ = 0.93). EV were graded as large in one and small in 13 patients with a BPE, but small varices diagnosed in one patient were not confirmed on EGD. Both procedures were well tolerated by all patients. Twenty-seven of 28 patients preferred unsedated endoscopy with a BPE over EGD. Conclusions Unsedated endoscopy with a BPE is safe and well tolerated. The diagnostic accuracy of a BPE for diagnosing EV is the same as by EGD. Esophagoscopy with a BPE is a potential alternative to EGD for EV screening.

Dobutamine stress echocardiography in patients undergoing liver transplantation evaluation.

Coronary artery disease has an important impact on perioperative morbidity and mortality in patients undergoing liver transplantation. To assess the role of dobutamine stress echocardiography (DSE) in these patients, DSE was included in the preoperative evaluation. Patients under consideration for liver transplantation underwent detailed clinical history, electrocardiography, and echocardiography. Patients with documented coronary disease or symptoms of myocardial ischemia underwent angiography. The remaining patients with cardiac risk factors, atypical chest pain, or age > or = 60 years underwent DSE. These 121 patients (77 men and 44 women) ranged in age from 34 to 73 years (mean 53). Among the 61 patients who underwent liver transplantation, DSE was normal in 25, nondiagnostic in 34 because of inadequate heart rate response, and abnormal in two patients. Major perioperative events occurred in eight patients, all with normal or nondiagnostic DSE studies (negative predictive value 86%). In patients with low to moderate risk of cardiac disease, DSE performed as part of an evaluation for liver transplantation is a poor predictor of major perioperative events.