Evaluation For Liver Transplantation Research Articles

Diagnostic accuracy of coronary computed tomography angiography-derived fractional flow reserve (CT-FFR) in patients before liver transplantation using CT-FFR machine learning algorithm

ObjectivesLiver transplantation (LT) is associated with high stress on the cardiovascular system. Ruling out coronary artery disease (CAD) is an important part of evaluation for LT. The aim of our study was to assess whether CT-derived fractional flow reserve (CT-FFR) allows for differentiation of hemodynamically significant and non-significant coronary stenosis in patients evaluated for LT.MethodsIn total, 201 patients undergoing LT evaluation were included in the study. The patients received coronary computed tomography angiography (CCTA) to rule out CAD and invasive coronary angiography (ICA) to further evaluate coronary lesions found in CCTA if a significant (≥ 50 % on CCTA) stenosis was suspected. CT-FFR was computed from CCTA datasets using a machine learning–based algorithm and compared to ICA as a standard of reference. Coronary lesions with CT-FFR ≤ 0.80 were defined as hemodynamically significant.ResultsIn 127 of 201 patients (63%), an obstructive CAD was ruled out by CCTA. In the remaining 74 patients (37%), at least one significant stenosis was suspected in CCTA. Compared to ICA, sensitivity, specificity, PPV, and NPV of the CT-FFR measurements were 71% (49–92%), 90% (82–98%), 67% (45–88%), and 91% (84–99%), respectively. The diagnostic accuracy was 85% (85–86%). In 69% of cases (52 of 75 lesions), additional analysis by CT-FFR correctly excluded the hemodynamic significance of the stenosis.ConclusionsMachine learning–based CT-FFR seems to be a very promising noninvasive approach for exclusion of hemodynamic significant coronary stenoses in patients undergoing evaluation for LT and could help to reduce the rate of invasive coronary angiography in this high-risk population.Key Points• Machine learning–based computed tomography-derived fractional flow reserve (CT-FFR) seems to be a very promising noninvasive approach for exclusion of hemodynamic significance of coronary stenoses in patients undergoing evaluation for liver transplantation and could help to reduce the rate of invasive coronary angiography in this high-risk population.

CAQ Corner: Surgical evaluation for liver transplantation.

The evaluation of a liver transplantation candidate is a complex and detailed process that in many cases must be done in an expedited manner because of the critically ill status of some patients with end-stage liver disease. It involves great effort from and the collaboration of multiple disciplines, and during the evaluation several studies and interventions are performed to assess and potentially prepare a patient for liver transplant. Here we review the liver transplantation evaluation from a surgical perspective.

Invasive coronary angiography as a tool in cardiac evaluation for liver transplant candidates

BackgroundCardiovascular assessment is central to evaluation of liver transplant (LT) candidates. However, there is a lack of consensus on the diagnostic algorithm for screening for coronary artery disease (CAD), and the place for invasive coronary angiography (ICA) remains undefined. MethodsWe retrospectively analysed 1201 adults who underwent elective LT assessment over a 5-year period. For patients who underwent LT, survival data to 5 years post-LT was collected. ResultsICA was performed in 259 (21.6%): 134 no CAD, 58 mild, 33 moderate, and 34 severe. Detection of CAD was associated with age (OR 1.08, P < 0.01), current smoking (OR 4.92, P < 0.01) and prior CAD (OR 8.93, P < 0.001). Poor performance on cardiopulmonary exercise test (CPET) was associated with age (OR 1.02, P < .05) and diabetes mellitus (OR 1.54, P < 0.05). 122 (10.2%) patients were declined due to severity of cardiovascular disease.169/779 (21.7%) patients listed for LT had undergone ICA, and CAD was present in 73/169 (43.2%). The non-risk-adjusted all-cause post-LT 5-year survival was 82.6%, with no difference in survival in those with and without CAD on ICA. In patients with CAD, diabetes was associated with reduced survival (OR 3.78, P < 0.05). ConclusionsMulti-modality cardiac evaluation is useful in high-risk patients undergoing LT assessment. ICA can be used with non-invasive assessments and risk factors to delineate candidacy. In selected patients with CAD, LT has been undertaken with comparable post-LT survival.

Essential Tips for Hospice & Palliative Care Clinicians Caring for Patients with Advanced Liver Disease Undergoing Liver Transplant Evaluation (FR252)

Essential Tips for Hospice & Palliative Care Clinicians Caring for Patients with Advanced Liver Disease Undergoing Liver Transplant Evaluation (FR252)

Telemedicine for Liver Transplant Evaluations: The Benefits and Risks.

Content available: Author Interview and Author Audio Recording.

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.

Availability of PEth testing is associated with reduced eligibility for liver transplant among patients with alcohol‐related liver disease

Serum phosphatidylethanol (PEth) is a highly sensitive test to detect alcohol use. We evaluated whether the availability of PEth testing impacted rates of liver transplant evaluation terminations and delistings. Medical record data were collected for patients who initiated transplant evaluation due to alcohol-related liver disease in the pre-PEth (2017) or PEth (2019) eras. Inverse probability weighting (IPW) was used to balance baseline patient characteristics. Outcomes included termination of evaluation or delisting due to alcohol use; patients were censored at receipt of transplant; death was considered a competing risk. The Fine-Gray method was performed to determine whether PEth testing affected risk of evaluation termination/ delisting due to alcohol use. Three hundred and seventy-five patients with alcohol-related indications for transplant (157 in 2017; 210 in 2019) were included. The final IPW-adjusted model for the composite outcome of terminations/delisting due to alcohol use retained two significant variables (P<.05): PEth era and BMI category. Patients evaluated during the PEth era were almost three times more likely to experience an alcohol-related termination/delisting than those in the pre-PEth era (sHR=2.86; 95%CI 1.67-4.97) CONCLUSION: We found that availability of PEth testing at our institution was associated with a higher rate of exclusion of patients from eligibility for liver transplant. Use of PEth testing has significant potential to inform decisions regarding transplant candidacy for patients with alcohol-related liver disease.

Treatment of Portopulmonary Hypertension (PoPH): A review

Portopulmonary Hypertension (PoPH) is a type of pulmonary arterial hypertension that uniquely afflicting patients with underlying liver disease and portal hypertension. The mainstay of treatment centers around the use of targeted pulmonary vasodilator therapy and evaluation for liver transplantation. This review article focuses on the role of targeted pulmonary vasodilator therapy and liver transplantation in the management of PoPH, with special emphasis on the expected hemodynamic and clinical effects of treatment. The relationship between PoPH and Hepatopulmonary Syndrome (HPS), another type of pulmonary vascular disease due to liver disease, is also reviewed.

Successful Liver Transplantation From a SARS-CoV-2 Positive Donor to a Positive Recipient: Potential Role of Monoclonal Antibodies.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic initially resulted in a decline in organ transplantation, including a 35.9% decrease in the United States.1 Although there are many factors contributing to this, potential donors who tested positive for SARS-CoV-2 have been largely excluded from donation. Simultaneously, there was uncertainty about safety of transplanting a recipient with coronavirus disease 2019 (COVID-19). Although there are emerging reports of liver transplantation from SARS-CoV-2-infected deceased donors,2 optimal risk mitigation strategies are unclear. Herein, we report a case of liver transplantation from a SARS-CoV-2 positive deceased donor to a SARS-CoV-2 positive recipient who was managed with anti spike monoclonal antibodies. This report did not require review board approval. Our patient was a 33 y-old female with adult-onset Still’s disease, treated previously with canakinumab, admitted for severe acute-on-chronic liver failure of unclear etiology. She had experienced several months of relapsing elevations in liver biochemistries attributed to lobular hepatitis of unclear etiology. She developed jaundice with progressive encephalopathy over 3 wk, culminating in a clinical scenario consistent with subacute liver failure, with a calculated Model for End-stage Liver Disease-Sodium score of 35. Concurrently, multiple household contacts developed mild upper respiratory symptoms and were diagnosed with COVID-19. She had not undergone SARS-CoV-2 vaccination. Upon admission, the patient was jaundiced, encephalopathic, and coagulopathic, although normoxic, and her chest radiograph did not show infiltrates. Urgent evaluation for liver transplantation was initiated. Nasopharyngeal SARS-CoV-2 polymerase chain reaction was positive (cycle threshold N 33.0, open reading frame 27.6; ARIES SARS-CoV-2 assay, Luminex Corp), and serum SARS-CoV-2 nucleocapsid antibody was negative. Because of high-risk comorbidities and likely impending transplantation, she received casirivimab and imdevimab on hospital day 1. She received an organ offer for liver transplantation on hospital day 4. The donor was incidentally found to have a positive SARS-CoV-2 polymerase chain reaction on routine donor screening without evidence of clinical disease. The donor had died from trauma, and the liver was normal. After shared decision-making, she proceeded with orthotopic liver transplantation and received a 5-d course of remdesivir after transplantation. She received induction immunosuppression with methylprednisolone and maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and prednisone. She did receive augmented prophylactic anticoagulation with enoxaparin 30 mg twice per day; however, this was complicated by perihepatic hematoma requiring reoperation for evacuation and hemostasis on posttransplant day 8. She experienced no thrombotic complications. She was dismissed from the hospital 11 d following transplantation and remained in isolation for 20 d posttransplantation. She did not develop respiratory symptoms or abnormal lung imaging in 30 d of follow-up. There is currently little experience transplanting a SARS-CoV-2 positive donor to a SARS-CoV-2 positive recipient.3 We utilized anti spike monoclonal antibodies to mitigate the risk of progression to severe infection while awaiting transplantation. This treatment has been associated with good outcomes in solid organ transplantation4 and has been utilized as postexposure prophylaxis.5 We propose anti spike monoclonal antibodies may have a role in mitigating the risks of SARS-CoV-2 donor-derived infection and progression to severe disease posttransplantation. Our case highlights that donor SARS-CoV-2 positivity does not necessarily preclude nonlung organ transplantation, and risks of transmission must be balanced with the risk of death while remaining on the transplant waitlist. SARS-CoV-2-directed monoclonal antibody therapy and/or preemptive remdesivir administration may have roles in this setting; however, additional studies on strategies to mitigate donor-derived COVID-19 are necessary.

Expedited evaluation for liver transplantation: A critical look at processes and outcomes.

Most patients are listed for liver transplant (LT) following extensive workup as outpatients ("conventional evaluation"). Some patients undergo urgent evaluation as inpatients after being transferred to a transplant center ("expedited evaluation"). We hypothesized that expedited patients would have inferior survival due to disease severity at the time of transplant and shorter workup time. Patients who underwent evaluation for LT at our institution between 2012 and 2016 were retrospectively reviewed. The expedited and conventional cohorts were defined as above. Living donor LT recipients, combined liver-kidney recipients, acute liver failure patients, and re-transplant patients were excluded. We compared patient characteristics and overall survival between patients who received a transplant following expedited evaluation and those who did not, and between LT recipients based on expedited or conventional evaluation. Five-hundred and nine patients were included (110 expedited, 399 conventional). There was no difference in graft or patient survival at 1year for expedited versus conventional LT recipients. In multivariable analysis of overall survival, only Donor Risk Index (HR 1.97, CI 1.04-3.73, P=.037, per unit increase) was associated with increased risk of death. Patients who underwent expedited evaluation for LT had significant demographic and clinical differences from patients who underwent conventional evaluation, but comparable post-transplant survival.

Impact of hepatopulmonary syndrome in liver transplantation candidates and the role of angiogenesis.

Hepatopulmonary syndrome affects 10-30% of patients with cirrhosis and portal hypertension. We evaluated the serum angiogenic profile of hepatopulmonary syndrome and assessed the clinical impact of hepatopulmonary syndrome in patients evaluated for liver transplantation. The Pulmonary Vascular Complications of Liver Disease 2 study was a multicentre, prospective cohort study of adults undergoing their first liver transplantation evaluation. Hepatopulmonary syndrome was defined as an alveolar-arterial oxygen gradient ≥15 mmHg (≥20 mmHg if age >64 years), positive contrast-enhanced transthoracic echocardiography and absence of lung disease. We included 85 patients with hepatopulmonary syndrome and 146 patients without hepatopulmonary syndrome. Patients with hepatopulmonary syndrome had more complications of portal hypertension and slightly higher Model for End-Stage Liver Disease-Na score compared to those without hepatopulmonary syndrome (median (interquartile range) 15 (12-19) versus 14 (10-17), p=0.006). Hepatopulmonary syndrome patients had significantly lower 6-min walk distance and worse functional class. Hepatopulmonary syndrome patients had higher circulating angiopoietin 2, Tie2, tenascin C, tyrosine protein kinase Kit (c-Kit), vascular cell adhesion molecule 1 and von Willebrand factor levels, and lower E-selectin levels. Patients with hepatopulmonary syndrome had an increased risk of death (hazard ratio 1.80, 95% CI 1.03-3.16, p=0.04), which persisted despite adjustment for covariates (hazard ratio 1.79, 95% CI 1.02-3.15, p=0.04). This association did not vary based on levels of oxygenation, reflecting the severity of hepatopulmonary syndrome. Hepatopulmonary syndrome was associated with a profile of abnormal systemic angiogenesis, worse exercise and functional capacity, and an overall increased risk of death.

Fractional Flow Reserve in End-Stage Liver Disease

Fractional flow reserve (FFR) determines the functional significance of epicardial stenoses assuming negligible venous pressure (Pv) and microvascular resistance. However, these assumptions may be invalid in end-stage liver disease (ESLD) because of fluctuating Pv and vasodilation. Accordingly, all patients with ESLD who underwent right-sided cardiac catheterization and coronary angiography with FFR as part of their orthotopic liver transplantation evaluation between 2013 and 2018 were included in the present study. Resting mean distal coronary pressure (Pd)/mean aortic pressure (Pa), FFR, and Pv were measured. FFR accounting for Pv (FFR-Pv) was defined as (Pd-Pv)/(Pa-Pv). The hyperemic effect of adenosine was defined as resting Pd/Pa-FFR. The primary outcome was all-cause mortality at 1 year. In 42 patients with ESLD, 49 stenoses were interrogated by FFR (90% were <70% diameter stenosis). Overall, the median model for ESLD score was 16.5 (10.8 to 25.5), FFR was 0.87 (0.81 to 0.94), Pv was 8 mm Hg (4 to 14), FFR-Pv was 0.86 (0.80 to 0.94), and hyperemic effect of adenosine was 0.06 (0.02 to 0.08). FFR-Pv led to the reclassification of 1 stenosis as functionally significant. There was no significant correlation between the median model for ESLD score and the hyperemic effect of adenosine (R=0.10). At 1 year, 13 patients had died (92% noncardiac in etiology), and patients with FFR ≤0.80 had significantly higher all-cause mortality (73% vs 17%, p=0.001. In conclusion, in patients with ESLD who underwent orthotopic liver transplantation evaluation, Pv has minimal impact on FFR, and the hyperemic effect of adenosine is preserved. Furthermore, even in patients with the predominantly angiographically-intermediate disease, FFR ≤0.80 was an independent predictor of all-cause mortality.

Evaluation Within 30 Days of Referral for Liver Transplantation is Associated with Reduced Mortality: A Multicenter Analysis of Patients Referred Within the VA Health System.

Successful liver transplantation offers the possibility of improved survival among patients with decompensated cirrhosis. However, there is wide variability in access to care and promptness of the transplant evaluation process in the United States. We performed a multicenter retrospective study of 1118 patients who underwent evaluation for liver transplantation at the 6 Veterans Affairs' transplant centers from 2013 to 2018. Of these, 832 patients were evaluated within 30 d and 286 > 30 d after referral. We studied the differential effects of the time from referral to evaluation on pretransplant and posttransplant mortality and transplant list dropout and explored predictors of early transplant evaluation. Patients in the early evaluation group had a shorter adjusted time from referral to listing by 29.5 d (95% confidence interval [CI] -50.4, -8.5, P < 0.006), and referral to transplantation by 115.1 d (95% CI -179.5, -50.7, P < 0.0001). On a multivariable Cox hazard model, evaluation within 30 d of referral was associated with a significantly lower pretransplant mortality (adjusted hazard ratio [aHR] 0.70, 95% CI 0.54-0.91, P < 0.01), but not associated with transplant list dropout (aHR 0.95, 95% CI 0.65-1.39, P = 0.79) or posttransplant death (aHR 1.88, 95% CI 0.72-4.9, P = 0.20). An early evaluation within 30 d was positively associated with a higher MELD at referral (aHR 1.03, 95% CI 1.01-1.06, P = 0.006) and negatively associated with distance from the transplant center (aHR 0.99, 95% CI 0.99-0.99, P = 0.045). Evaluation of patients referred for liver transplantation within 30 d is associated with a reduction in pretransplant mortality.

Integrating Specialist Palliative Care in the Liver Transplantation Evaluation Process: A Qualitative Analysis of Hepatologist and Palliative Care Provider Views.

Patients undergoing evaluation for liver transplantation face heavy burdens of symptoms, health care use, and mortality. In other similarly ill populations, specialist palliative care has been shown to benefit patients, but specialist palliative care is infrequently used for liver transplantation patients. This project aims to describe the potential benefits of and barriers to specialist palliative care integration in the liver transplantation process. We performed qualitative analysis of transcripts from provider focus groups followed by a community engagement studio of patients and caregivers. Focus groups consisted of 14 palliative care specialists and 10 hepatologists from 11 institutions across the United States and Canada. The community engagement studio comprised patients and caregivers of patients either currently on the liver transplantation waiting list or recently after transplant. The focus groups identified 19 elements of specialist palliative care that could benefit this patient population, including exploring patients' illness understanding and expectations; assessing physical symptoms comprehensively; discussing patient values; and providing caregiver support, a safe space to discuss noncurative options, and anticipatory guidance about likely next steps. Identified barriers included role boundaries, differences in clinical cultures, limitations of time and staff, competing goals and priorities, misconceptions about palliative care, limited resources, changes in transplant status, and patient complexity. Community studio participants identified many of the same opportunities and barriers. This study found that hepatologists, palliative care specialists, patients, and caregivers identified areas of care for liver transplantation patients that specialist palliative care can improve and address.

Psychosocial Assessment Rather Than Severity of Liver Failure Dominates Selection for Liver Transplantation in Patients With Alcohol-Related Liver Disease.

The Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) is a validated interview tool to assess psychosocial well-being in candidates for solid organ transplants, with higher scores indicating greater vulnerability. We hypothesized that patients with alcohol-related liver disease (ALD) undergoing liver transplantation (LT) evaluation would have higher SIPAT scores than candidates with non-ALD, but that only patients with ALD who have low scores would be selected. We analyzed retrospectively consecutive adults undergoing LT evaluation from June 2018 to December 2019. Comparisons between patients with ALD and patients with non-ALD were made using the nonparametric Wilcoxon rank sum test plus a multivariate analysis to determine independent predictors for approval. In the study cohort of 358 patients, there were 199 (56%) patients with ALD with a mean age of 55years, and 133 (67%) were men. There were 159 (44%) patients with non-ALD with a mean age of 57years, and 95 (60%) were men. Mean Model for End-Stage Liver Disease-sodium scores were similar for selected versus not selected patients with ALD (25 versus 25.6) and selected versus not selected patients with non-ALD (18.3 versus 17.4), although the ALD group had substantially higher Model for End-Stage Liver Disease scores. Patients with ALD had higher mean SIPAT composite and individual domain scores compared with their non-ALD counterparts. SIPAT scores were not affected by age or sex. Proportionately more candidates with non-ALD were selected compared to candidates with ALD (68% versus 42%; P<0.001; odds ratio for approval of non-ALD versus ALD, 2.9; 95% confidence interval, 1.8-4.7; P<0.001). Composite SIPAT scores were lower in the selected versus nonselected in both ALD and non-ALD groups, although the SIPAT scores were significantly higher in selected patients with ALD (median, 39) than selected patients with non-ALD (median, 23; P=0.001). Psychosocial assessment has a greater influence than acuity of liver failure on the selection of patients with ALD for LT listing, whereas psychosocial assessment has a minor influence on the selection of non-ALD candidates.

Recovery and outcomes of patients denied early liver transplantation for severe alcohol-associated hepatitis.

Liver transplantation (LT) in alcohol-associated hepatitis (AH) remains controversial, in part because spontaneous recovery (SR) can occur. There is a paucity of data on SR in patients with severe AH who undergo LT evaluation. The purpose of this study was to determine factors associated with SR and survival in patients with severe AH who undergo LT evaluation. This is a retrospective study of ALD patients with Model for End-Stage Liver Disease (MELD) >25 and <90 days abstinence who underwent LT evaluation at a single center between 2012 and 2018. One hundred forty-four patients (median age, 45.5 years; 68.1% male) were included. Forty-nine (34%) underwent LT and 95 (66%) patients did not undergo LT, and of those, 34 (23.6%) experienced SR. Factors associated with recovery were younger age (OR, 0.92; p = 0.004), lower index international normalized ratio (INR; 0.31; p = 0.03), and lower peak MELD (OR, 0.83; p = 0.02). Only 7 patients (20.6%) achieved a compensated state with a MELD <15 and absence of therapy for ascites or HE. Survival was improved in patients who underwent early LT when compared to SR. Survival was impaired in SR following relapse to alcohol use when compared to SR patients who abstained and LT recipients. Among all 6-month survivors of AH, alcohol use trended toward an association with mortality (HR, 2.05; p = 0.17), but only LT was associated with decreased mortality risk (HR, 0.20; p = 0.005). SR from AH after LT evaluation is associated with age, index INR, and lower peak MELD. Most recovered patients continue to experience end-stage complications. LT is the only factor associated with lower mortality.

Introduction of a standardized protocol for cardiac risk assessment in candidates for liver transplant – A retrospective cohort analysis

IntroductionRecommendations on non-invasive imaging to assess pre-operative cardiac risk among liver transplant candidates vary amongst societal guidelines and individual institutional practices. In 2018, a standardized pre-transplant coronary evaluation protocol was established at Beth Israel Deaconess Medical Center, Boston MA, to ensure appropriate and consistent pre-operative testing was performed. MethodsAll patients who underwent liver transplant evaluation between January 1st, 2016 and December 31st, 2019, were retrospectively analyzed and divided into three cohorts; before the introduction of the protocol (prior to 2018), initial protocol favoring invasive coronary angiography (ICA) (2018), and amended protocol favoring coronary computed tomography angiography (CCTA) (post-2018). We described clinical characteristics, candidacy for transplant, and cardiovascular complications during follow-up. As an unadjusted exploratory analysis, the Cochran-Armitage Exact Trend Test was used to examine univariate differences across time. ResultsA total of 462 patients underwent liver transplant evaluation during the study period. Among these, 218 (47.2%) patients underwent stress test, 50 (10.8%) underwent CCTA, and 68 (14.8%) underwent ICA. Across the three time periods, there was an increase in the proportion of CCTAs performed (3%, 6.3%, and 26.3% respectively; p <0.001) and proportion of patients diagnosed with obstructive CAD using CCTA (0%, 30%, and 51.4% respectively; p = 0.04). There was no significant difference in post-transplant cardiac complications among patients evaluated before 2018, during 2018, and after 2018 (5.9% vs. 5.6 vs. 6.0%; p=1.0). ConclusionOur findings suggest it is reasonable to shift practice to a less invasive approach utilizing CCTA or nuclear stress testing when assessing liver transplant candidates at increased cardiovascular risk.

Predictors of Mortality and Outcomes of Liver Transplant in Spur Cell Hemolytic Anemia

BACKGROUND :Spur cell hemolytic anemia (SCHA) is a rare, acquired, non-immune hemolytic anemia of decompensated cirrhosis resulting from abnormal lipid composition of the red cell membrane. Treatment is limited to red cell transfusion. Data describing prognostic impact, outcomes of liver transplant, and clinical hematologic characteristics of SCHA are absent or limited; published data on SCHA are limited to single-patient case reports and small single-center case series. The independent prognostic impact of SCHA on patients with cirrhosis remains unclear, and it is not known if hemolytic anemia severity has a significant impact on survival of these patients. As a result, SCHA is not formally considered during liver transplant evaluation, and patients do not receive MELD exception points for this diagnosis.METHODS :We performed a multicenter, 24-year observational cohort study of patients with SCHA, retrospectively analyzing hepatic and hematologic parameters, independent predictors of mortality, and long-term outcomes of liver transplant. Strict diagnostic criteria for SCHA were applied, requiring all of the following: (1) decompensated cirrhosis; (2) anemia; (3) objective laboratory evidence of hemolysis; (4) no alternate contributing cause of hemolysis or acanthocytosis; and (5) chart documentation of a confirmed diagnosis of SCHA incorporating peripheral blood film examination. The primary outcome was mortality at 3 months after date of SCHA diagnosis. The impact of hemolytic parameters on 3-month mortality was evaluated utilizing multivariable logistic models. Observed mortality vs. expected mortality (per MELD-Na score and Child-Turcotte-Pugh class) was compared using standardized mortality ratios. Given the limited survival of this population, red cell transfusion dependence was defined as 4 or more units of red cells transfused during the 60-day peri-diagnostic period.RESULTS :Patients: 69 patients with SCHA were included (FIGURE 1). The median (interquartile range) age was 53 (42-59) years; 46.4% were female, and 11 (15.9%) received liver transplant. Alcohol contributed to the etiology of cirrhosis in 53 patients (76.8%). The median (IQR) survival from SCHA diagnosis of patients not receiving liver transplant was 58 (23-113) days. 39 patients (56.5%) were red cell transfusion-dependent. Hematologic parameters are described in TABLE 1.Outcomes of Liver Transplant: All 11 patients undergoing transplant had rapid and complete resolution of SCHA, with an improvement in median hematocrit from 22.1% to 34.6% post-transplant (P=0.001) (TABLE 2) and excellent post-transplant outcomes, with 9 patients still alive after 6.1 years median follow-up.Independent Predictors of Mortality in SCHA: In multivariable logistic models adjusting for age, sex, etiology of cirrhosis, active/recent variceal bleeding, and Child-Turcotte-Pugh score, transfusion dependence had an OR for 90-day mortality of 9.14 (95% CI, 2.46-34.00) and reduced pre-transfusion hematocrit had an OR of 4.73 (95% CI, 1.42-15.82) per 6% decrease; increased red cell transfusion requirement, reduced hemoglobin, increased lactate dehydrogenase, and increased indirect bilirubin were also independently predictive of higher 90-day mortality (FIGURE 2).Performance of MELD-Na and Child-Turcotte-Pugh Scores in Estimating 90-Day Mortality: MELD-Na and Child-Turcotte-Pugh scores consistently significantly underestimated 90-day mortality, with standardized mortality ratios (SMRs) >1 across all scores/classes [MELD-Na 20-29, SMR 2.42 (1.18-4.44); Child-Turcotte-Pugh class B, SMR 4.46 (1.64-9.90)], FIGURE 3.CONCLUSIONS :In this largest study of SCHA to date, SCHA was associated with substantial excess mortality than was predicted by MELD-Na or Child-Turcotte-Pugh scores. Several clinical and laboratory parameters of hemolytic anemia severity, including transfusion burden, hemoglobin, and markers of hemolysis were each independent predictors of 90-day mortality in SCHA. Despite its unique morbidity as a complication of decompensated cirrhosis, outcomes of liver transplant were excellent in all 11 patients undergoing this intervention, with total resolution of SCHA and no evidence of recurrence. These findings should promote greater awareness of SCHA as a clinical entity and broader consideration of MELD exception points for afflicted patients when transplant-eligible. [Display omitted] DisclosuresAl-Samkari: Novartis: Consultancy; Amgen: Research Funding; Argenx: Consultancy; Rigel: Consultancy; Dova/Sobi: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Moderna: Consultancy.

Diagnostic Accuracy and Optimal Cut-off of Controlled Attenuation Parameter for the Detection of Hepatic Steatosis in Indian Population

Ultrasound of the liver is not good to pick up mild steatosis. Controlled attenuation parameter (CAP) evaluated in transient elastography (FibroScan) is widely available in India. However, data regarding the diagnostic accuracy and optimal cut-off values of CAP for diagnosing hepatic steatosis are scarce in Indian population. MRI-PDFF is an accurate technique for quantifying hepatic steatosis. Thus, this study examined the diagnostic accuracy and optimal cut-off values of CAP for diagnosing steatosis with MRI-PDFF as reference standard. A total of 137 adults underwent CAP and MRI-PDFF measurements prospectively. A subset of participants (n=23) underwent liver biopsy as part of liver transplantation evaluation. The optimal cut-off values, area under the receiver operating characteristic(AUROC) curves, sensitivity, and specificity for CAP in detecting MRI-PDFF ≥5% and ≥10% were assessed. The mean age and body mass index (BMI) were 44.2±10.4 years and 28.3±3.9kg/m2, respectively. The mean hepatic steatosis was 13.0±7.7% by MRI-PDFF and 303±54dB/m by CAP. The AUROC of CAP for detecting hepatic steatosis (MRI-PDFF ≥5%) was 0.93 (95% CI, 0.88-0.98) at the cut-off of 262dB/m, and of MRI-PDFF ≥10% was 0.89 (95% CI, 0.84-0.94) at the cut-off of 295dB/m. The CAP of 262dB/m had 90% sensitivity and 91% specificity for detecting MRI-PDFF ≥5%, while the CAP of 295dB/m had 86% sensitivity and 77% specificity for detecting MRI-PDFF ≥10%. The optimal cut-off of CAP for the presence of liver steatosis (MRI-PDFF ≥5%) was 262dB/m in Indian individuals. This CAP cut-off was associated with good sensitivity and specificity to pick up mild steatosis.

S1137 The Impact of Electrocardiogram Parameters on Cardiovascular Complications at Time of Liver Transplantation

Introduction: Electrocardiogram (ECG) is an integral component of cardiovascular assessment in patients evaluated for liver transplant (LT). However, despite its centrality, there is paucity of data linking ECG interval and rhythm assessment to peri-LT cardiovascular events. Methods: In this retrospective study, the ECG of all patients receiving LT at our institution between 2010-2018 (n=651) were reviewed independently by two cardiologists blinded to clinical data according to the Minnesota classification. Primary outcome included cardiac arrest, new-onset cardiac arrythmia or known arrhythmia requiring change in medication that occurred within 4 weeks of LT. Results: The mean age was 56±10 years and consisted mainly of males (n=478) and Whites (n=469). Leading etiology of cirrhosis was hepatitis C (n=276), followed by NASH (n=120) and alcohol-related liver disease (n=104). At LT evaluation, 633 patients were in sinus rhythm, while atrial fibrillation or flutter was present in 18 subjects. The most common abnormal ECG findings included prolonged QTc (n=347), left ventricular hypertrophy (n=58), right bundle branch block (n=28), and left bundle branch block (n=6). Patients with NASH were more likely to have atrial fibrillation/flutter (5.8% vs. 2.1%; p=0.03), interventricular conduction delay (13.3% vs. 5.1%; p=0.003), and left anterior fascicular block (5.8% vs. 1.3%; p=0.007). The likelihood of primary outcome was 17.3% with the most common arrhythmia being atrial fibrillation (n=53, 8.1%), followed by bradycardia (n=22, 3.4%), supraventricular tachycardia (n=10, 1.5%), and sinus tachycardia (n=9, 1.4%). Primary outcome was more common among patients with dyslipidemia (24.3% vs. 15.5%, p=0.01) and CAD (23.6% vs. 15.0%, p=0.008). After adjusting for gender, BMI, beta blocker use, diabetes, dyslipidemia, statin use, and presence of CAD, age (HR 1.06, p=0.001) and male gender (HR 1.97, p=0.04) were associated with increased risk of post-LT arrythmias. While aspirin (HR 0.37, P=0.02) and prolonged QRS (HR 0.49, p=0.04) were associated with lower risk of cardiovascular events. Conclusion: ECG abnormalities are common among patients with cirrhosis, particularly NASH cirrhosis. It is likely perturbation the bio-clinical profile (older, diabetic, obese, electrolyte abnormalities) that predispose them to developing peri-transplant arrhythmias. Well designed mechanistic studies are required to better understand the pathophysiology to implement targeted peri-transplant therapy to mitigate this risk.