End-stage Liver Disease-sodium Score Research Articles

Patients With Cirrhosis Who Have a Model for End-stage Liver Disease Sodium Score of 8 or Greater Are at Increased Risk of Poor Outcomes in Operatively Treated Tibia Fractures.

The purpose of this study was to compare 30-day readmission rates for cirrhotic and non-cirrhotic patients after tibia fracture fixation by retrospectively identifying all surgically managed tibial plateau, tibial shaft, and pilon fractures from 2010 through 2018 in the National Surgical Quality Improvement Program database (N=14,028). The primary outcome measure was 30-day readmission rates. Secondary outcome measures included 30-day rates of reoperation, length of stay, pulmonary embolism, deep venous thrombosis, and wound complications, including deep or superficial infection. Cirrhotic patients (n=665) and non-cirrhotic patients (n=13,363) were identified using the aspartate aminotransferase to platelet ratio index test. Cirrhotic patients were more likely to have preoperative ascites, renal failure, bleeding disorders, and preoperative transfusions. No differences were reported between the two groups in readmission rate or any of the secondary outcome measures, except that cirrhotic patients' length of stay was longer by 0.5 day. Stratification of the cirrhotic cohort demonstrated that a Model for End-stage Liver Disease sodium (MELD-Na) score of 8 or greater was associated with a 4.1-fold increase in the rate of readmission (5.9% vs 1.5%; P<.01). No other differences were identified based on MELD-Na score stratification. Patients with advanced cirrhosis (MELD-Na score ≥8) have an increased risk of 30-day readmission after tibia fracture surgery. Cirrhosis associated with a lower MELD-Na score might not significantly increase the risk of 30-day complications in patients with tibia fractures. [Orthopedics. 2022;45(2):79-85.].

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.

BICEPS another score for the assessment of severity of liver cirrhosis

Background and Aim: The clinical assessments using the Child-Turcotte-Pugh (CTP) and model for end-stage liver disease-sodium (MELD-Na) scores are heterogeneous. The present study aims to collate most relevant markers of chronic liver disease as a new score BICEPS (Bilirubin, INR, Creatinine, Encephalopathy, Platelet and Sodium) an alternate to CTP and MELD-Na in patients diagnosed with liver cirrhosis.

The COVID-19 Pandemic Highlights Opportunities to Improve Hepatocellular Carcinoma Screening and Diagnosis in a National Health System.

We evaluated the coronavirus disease 2019 (COVID-19) pandemic's impact on hepatocellular carcinoma (HCC) screening and diagnosis among patients with cirrhosis in the Veterans Health Administration. Rates and predictors of screening and diagnosis were reviewed September 1, 2019-February 29, 2020 ("pre-COVID-19," N = 94,612) and April 1, 2020-September 30, 2020 ("post-COVID-19," N = 88,073). Screening and diagnosis rates declined by 44% and 13%, respectively, after the COVID-19 pandemic. Screening declined irrespective of liver disease severity, but diagnosis declined only in Model for End Stage Liver Disease-Sodium score <20 or Fibrosis-4 score <3.25. Fibrosis-4 score ≥3.25 and HCC risk ≥1.5%/year strongly predicted HCC diagnosis but only moderately predicted receipt of screening. Screening and diagnosis rates declined after the COVID-19 pandemic. Prioritizing screening for patients at greatest risk for HCC may reduce delays in diagnosis.

Development of the AI-Cirrhosis-ECG Score: An Electrocardiogram-Based Deep Learning Model in Cirrhosis.

Cirrhosis is associated with cardiac dysfunction and distinct electrocardiogram (ECG) abnormalities. This study aimed to develop a proof-of-concept deep learning-based artificial intelligence (AI) model that could detect cirrhosis-related signals on ECG and generate an AI-Cirrhosis-ECG (ACE) score that would correlate with disease severity. A review of Mayo Clinic's electronic health records identified 5,212 patients with advanced cirrhosis ≥18 years who underwent liver transplantation at the 3 Mayo Clinic transplant centers between 1988 and 2019. The patients were matched by age and sex in a 1:4 ratio to controls without liver disease and then divided into training, validation, and test sets using a 70%-10%-20% split. The primary outcome was the performance of the model in distinguishing patients with cirrhosis from controls using their ECGs. In addition, the association between the ACE score and the severity of patients' liver disease was assessed. The model's area under the curve in the test set was 0.908 with 84.9% sensitivity and 83.2% specificity, and this performance remained consistent after additional matching for medical comorbidities. Significant elevations in the ACE scores were seen with increasing model for end-stage liver disease-sodium score. Longitudinal trends in the ACE scores before and after liver transplantation mirrored the progression and resolution of liver disease. The ACE score, a deep learning model, can accurately discriminate ECGs from patients with and without cirrhosis. This novel relationship between AI-enabled ECG analysis and cirrhosis holds promise as the basis for future low-cost tools and applications in the care of patients with liver disease.

One-year outcome of patients with cirrhosis who developed spontaneous bacterial empyema: A cohort study.

This study aimed to evaluate outcomes in cirrhotic patients diagnosed with spontaneous bacterial empyema (SBE) compared with those without this complication. We performed a retrospective cohort study of cirrhotic patients from a tertiary care center. The primary outcome was time to death or liver transplantation (LT) within one year after diagnosis of infection. We integrated three groups: patients with SBE (group A), patients with spontaneous bacterial peritonitis (SBP; group B), and cirrhotic patients without SBP or SBE (group C), matched by age, model for end-stage liver disease-sodium (MELD-Na) score and year of infection. Outcomes were analyzed using a Cox regression model adjusted for cardiovascular risk factors and MELD-Na score. Between January 1999 and February 2019, 4829 cirrhotic patients were identified. Among them, 73 (1.5%) had hepatic hydrotorax, of whom 22 (30.1%) were diagnosed with SBE. Median age in group A was 58 years, 50% were men, and median MELD-Na was 21.5. Compared with group C, the hazard ratio of death or LT during the first year after infection was 2.98 (95% confidence interval [CI] 1.43-6.22, P = 0.004) for group A and 1.23 (95% CI 0.65-2.32, P = 0.522) for group B. Our results suggest that patients with SBE have a worse outcome during the first year after infection is diagnosed. Patients who develop SBE should be promptly referred for transplant evaluation. SBE may emerge as new indication that could benefit from MELD exception points.

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.

Alcohol use disorder treatment and outcomes among hospitalized adults with alcoholic hepatitis

Purpose: The burden of alcohol-associated liver disease (ALD) in the United States (US) has continued to worsen in the background of rising rates of alcohol use disorder. Patients with ALD present to care at a late stage, often with the sequela of liver decompensation, such as gastrointestinal bleeding and infection. ALD is now the leading indication for liver transplantation. We aimed to measure the quality of care delivered to hospitalized patients with alcoholic hepatitis (AH) across 3 domains: 1) alcohol-use disorder (AUD) care, 2) inpatient cirrhosis care, and 3) alcohol-associated liver disease (ALD) care—and observe associations between quality of care and outcomes. Methods: We included hospital encounters between January 1, 2016 and January 1, 2019 to a large, diverse integrated health system for AH with active alcohol use within the prior 60 days. The diagnosis of AH was determined based on previously published clinical and laboratory criteria. Quality indicator (QI) pass rates were calculated as the proportion of patients eligible for each indicator who received the QI within the timeframe specified. We then evaluated the association between the receipt of all QIs and 6-month mortality, as well as AUD-specific QIs and 30-day readmission. Results: Of the 179 patients, the median age was 47 years-old, 59.2% were male and 49.2% were non-Hispanic White. The median Model for End-Stage Liver Disease-Sodium score was 25, while the median discriminant function was 33. Patients were followed for an average of 21 months. Overall, 14% of patients died during the index hospitalization while 17.3% died following discharge and 24.8% were re-admitted within 30-days. QI pass-rates were variable across the different domains. Few patients received AUD care—pass rates for receipt of pharmacotherapy and behavioral therapy at 6 months were only 19.1% and 35.1%, respectively. There was a significant association between receiving behavioral therapy and 6-month mortality—3% vs 18%, p = 0.05. Conclusion: The quality of care received during hospital encounters for AH is variable, and AUD-specific therapy is low. Future quality of care initiatives are warranted to link patients to AUD treatment to ensure optimal care and maximize patients survival in this at-risk population.

Symptom Classes in Decompensated Liver Disease

Patients with decompensated liver disease have been categorized by disease severity. This analysis sought to classify patients with end-stage liver disease based on symptoms rather than disease state and to identify distinct severity classes of physical and psychological symptoms. Patients with a model for end-stage liver disease-sodium score of 15 or higher were recruited from liver clinics in 2 health care organizations. They completed the Condensed Memorial Symptom Assessment Scale, Revised Ways of Coping Checklist, Patient Health Questionnaire, Life Orientation Test-Revised, and the Short-Form Health Survey. Cross-sectional data were analyzed using latent class mixture modeling. The sample (N= 191; age, 56.6 ± 11.1 y; 33.5% ETOH; 28.3% nonalcoholic fatty liver disease; 13.1% autoimmune/primary biliary cholangitis/primary sclerosing cholangitis) was predominantly male (64.2%), Child-Turcotte-Pugh class C (49.5%), with an average model for end-stage liver disease-sodium score of 18.7 ± 4.9. Three distinct classes of symptoms were identified, as follows: mild (26.7%), moderate (41.4%), or severe (31.9%) symptoms. Symptom classes were independent of disease severity and demographic characteristics, except age. All Condensed Memorial Symptom Assessment Scale symptoms and Patient Health Questionnaire scores were significantly different across the 3 classes (P &lt; .05). The symptom classes also differed significantly in physical and mental quality of life, optimism, and avoidance coping behaviors (all P &lt; .001). Patient-reported symptom severity occurred independent of disease severity, contrary to common assumptions. Focusing on the moderate and severe symptom classes as well as patient history of end-stage liver disease complications may enhance providers' ability to improve symptom management for this population.

MELD-Na > 16 is associated with high peri-procedural and short-term mortality in patients with ruptured hepatocellular carcinoma treated with emergent transarterial embolization.

To evaluate prognostic factors associated with peri-procedural (30days) and short-term (90days) mortality in the United States cohort of patients following emergent transarterial embolization for ruptured hepatocellular carcinoma. Patients with ruptured hepatocellular carcinoma treated with emergent TAE between January 2001 and December 2019 were retrospectively identified (n = 24). Average age was 62years (range, 23-78year); 15 (62.5%) were men. Univariate and Cox proportional hazard modeling were used to determine independent predictors of overall survival (OS) following TAE. OS stratified by Model for End-Stage Liver Disease-Sodium score was assessed using Kaplan-Meier analysis. Twenty-one patients (88%) died during a mean clinical follow-up period of 328 ± 139days. MELD-Na score (HR 1.22 per 1-unit increase; 95% CI 1.06-1.46; p = 0.005) and pre-rupture ECOG PS score (HR 8.1; 95% CI 1.28-51.2; p = 0.026) were independent predictors of decreased overall survival. There was no significant association between overall survival and presence of cardiovascular co-morbidities (p = 0.60), hemorrhagic shock on presentation (p = 0.16), portal vein thrombus (p = 0.08), vasopressor support required (p = 0.79), intubation required (p = 0.40), acute kidney injury (p = 0.58), and number of packed red blood cell transfusions (p = 0.22). The median OS was 64days. Median OS was significantly greater in patients with a MELD-Na score ≤ 16 as compared to those with a MELD-Na score > 16 (166.5days vs 9days, p = 0.011). Cumulative OS rates in those with a MELD-Na score ≤ 16 at 30, 60, 90, and 360days were 79%, 64%, 64%, and 25%, respectively, vs 33%, 33%, 11%, and 0%, respectively, in those with a MELD-Na score > 16. MELD-Na > 16 is associated with very high peri-procedural (67% at 30days) and short-term (89% at 90days) mortality in patients with ruptured HCC treated with emergent transarterial embolization. A better understanding of these prognostic factors may help guide treatment decisions and provide realistic expectations when counseling patients and their families.

Hepatic Encephalopathy and Liver Transplantation: The Past, Present, and Future Toward Equitable Access.

Cirrhosis is a debilitating chronic disease with high morbidity and mortality, with the only real cure being liver transplantation (LT). Currently, we allocate organs for transplantation based on the Model for End-Stage Liver Disease-Sodium (MELD-Na) score that does not account for hepatic encephalopathy (HE). HE affects patients, families, and the health care system because of high rates of recurrence and major readmission burden. Moreover, HE casts a long shadow even after LT. Accounting for HE and incorporating it into the current allocation system has many proponents, but the framework to do this is currently lacking because of differences in consensus or in operationalization parameters. We review the latest evidence of the burden of HE, management of HE before and after LT, and evaluate pros and cons of several methods of diagnosing HE objectively to ensure early and equitable access to LT in this underserved population.

Takotsubo syndrome after liver transplantation: An association with intraoperatively administered epinephrine and fentanyl.

Takotsubo syndrome (TTS) can develop after liver transplant (LT), but its predisposing factors are poorly understood. In this study, we aimed to determine if perioperative factors were associated with posttransplant TTS. Adult patients who underwent primary LT between 2006 and 2018 were included. Patients with and without TTS were identified and matched by propensity scores. Of 2181 LT patients, 38 developed postoperative TTS with a mean left ventricular ejection fraction of 25.5% (±7.8%). Multivariable logistic regression revealed two preoperative risk factors (alcoholic cirrhosis and model for end-stage liver disease-sodium scores) for TTS. Post-propensity match analyses showed that TTS patients had significantly higher doses of epinephrine and lower doses of fentanyl during LT compared with non-TTS patients. A higher dose of epinephrine and a lower dose of fentanyl was associated with a higher predicted probability of TTS. All TTS patients had full recovery of cardiac function and had comparable 1-year survival. In conclusion, TTS occurred at a rate of 1.7% after LT and was associated with two pretransplant risk factors. The higher doses of epinephrine and lower doses of fentanyl administered during LT were associated with posttransplant TTS. More studies on the relationship between intraoperative medications and TTS are warranted.

The Addition of C-Reactive Protein and von Willebrand Factor to Model for End-Stage Liver Disease-Sodium Improves Prediction of Waitlist Mortality.

Background and AimsPatients with cirrhosis on the liver transplant (LT) waiting list may die or be removed because of complications of portal hypertension (PH) or infections. von Willebrand factor antigen (vWF‐Ag) and C‐reactive protein (CRP) are simple, broadly available markers of these processes.Approach and ResultsWe determined whether addition of vWF‐Ag and CRP to the Model for End‐Stage Liver Disease‐Sodium (MELD‐Na) score improves risk stratification of patients awaiting LT. CRP and vWF‐Ag at LT listing were assessed in two independent cohorts (Medical University of Vienna [exploration cohort] and Mayo Clinic Rochester [validation cohort]). Clinical characteristics, MELD‐Na, and mortality on the waiting list were recorded. Prediction of 3‐month waiting list mortality was assessed by receiver operating characteristics curve (ROC‐AUC). In order to explore potential mechanisms underlying the prognostic utility of vWF‐Ag and CRP in this setting, we evaluated their association with PH, bacterial translocation, systemic inflammation, and circulatory dysfunction. In the exploration cohort (n = 269) vWF‐Ag and CRP both improved the predictive value of MELD‐Na for 3‐month waitlist mortality and showed the highest predictive value when combined (AUC: MELD‐Na, 0.764; MELD‐Na + CRP, 0.790; MELD‐Na + vWF, 0.803; MELD‐Na + CRP + vWF‐Ag, 0.824). Results were confirmed in an independent validation cohort (n = 129; AUC: MELD‐Na, 0.677; MELD‐Na + CRP + vWF‐Ag, 0.882). vWF‐Ag was independently associated with PH and inflammatory biomarkers, whereas CRP closely, and MELD independently, correlated with biomarkers of bacterial translocation/inflammation.ConclusionsThe addition of vWF‐Ag and CRP—reflecting central pathophysiological mechanisms of PH, bacterial translocation, and inflammation, that are all drivers of mortality on the waiting list for LT—to the MELD‐Na score improves prediction of waitlist mortality. Using the vWFAg‐CRP‐MELD‐Na model for prioritizing organ allocation may improve prediction of waitlist mortality and decrease waitlist mortality.

Prognostic Role of Liver Biopsy in Patients With Severe Indeterminate Acute Hepatitis

Severe indeterminate acute hepatitis (sIAH) is a poorly understood rare disease with no specific therapy. This study aims to define the clinicopathological characteristics of sIAH and the role of liver biopsy in determining prognosis. Patients with sIAH admitted to a single center between 2010 and 2019 were included. Histopathological patterns of liver biopsies were reviewed by 2 histopathologists, and key findings further were specified by multiplex immunofluorescence. Patients that died or underwent liver transplantation were analyzed as nonsurvivors. Of 294 patients with acute hepatitis, 43 with sIAH were included. Seventeen (39.5%) underwent liver transplantation and 7 (16.2%) died within 3 months. Multilobular necrosis was the predominant histopathological feature, being significantly more frequent in nonsurvivors (62.5% vs 21.1%; P= .016). Necrotic areas showed low HNF4α and Ki67 expression but high expression of CK19 and cell death markers identifying areas of severe tissue injury and inadequate regenerative response. Patients with multilobular necrosis had higher international normalized ratio, Model for End-Stage Liver Disease, and Model for End-Stage Liver Disease-Sodium scores compared with those without (P values for all markers <.05). Multivariate Cox analysis revealed that multilobular necrosis (hazard ratio, 3.675; 95% confidence interval, 1.322-10.211) and lower body mass index (hazard ratio, 0.916; 95% confidence interval, 0.848-0.991) independently predicted death or transplantation. The results of this study provide novel insights into the important role of liver biopsy in sIAH patients, suggesting that the presence of multilobular necrosis is an early indicator of poor prognosis.

Associations Among Different Domains of Quality Among US Liver Transplant Programs

US liver transplant programs have traditionally been evaluated on 1-year patient and graft survival. However, there is concern that a narrow focus on recipient outcomes may not incentivize programs to improve in other ways that would benefit patients with end-stage liver disease. To determine the correlation among different potential domains of quality for adult liver transplant programs. This retrospective cohort study was conducted from 2014 to 2019 among adult liver transplant programs included in the United Network for Organ Sharing and Scientific Registry of Transplant Recipients program-specific reports. Liver transplant programs in the United States completing at least 10 liver transplants per year were included. Data were analyzed from March 2 to August 13, 2020. The potential domains of quality examined included recipient outcomes (1-year graft and patient survival), aggressiveness (ie, marginal graft use, defined as the rate of use of donors with body mass index [calculated as weight in kilograms divided by height in meters squared] greater than 40, age older than 65 years, or deceased by cardiac death), and waiting list management (ie, waiting list mortality). The correlation among measures, aggregated at the center level, was evaluated using linear regression to control for mean Model for End Stage Liver Disease-Sodium score at organ allocation. The extent to which programs were able to achieve high quality across multiple domains was also evaluated. Among 114 transplant programs that performed a total of 44 554 transplants, the mean (SD) 1-year graft and patient survival was 90.3% (3.0%) with a total range of 75.9% to 96.6%. The mean (SD) waiting list mortality rate was 16.7 (6.1) deaths per 100 person-years, with a total range of 6.3 to 53.0 deaths per 100 person years. The mean (SD) marginal graft use rate was 15.8 (8.8) donors per 100 transplants, with a total range of 0 to 49.3 donors. There was no correlation between 1-year graft and patient survival and waiting list mortality (β = -0.053; P = .19) or marginal graft use (β = -0.007; P = .84) after correcting for mean allocation Model for End Stage Liver Disease-Sodium scores. There were 2 transplant programs (1.8%) that performed in the top quartile on all 3 measures, while 4 transplant programs (3.6%) performed in the bottom quartile on all 3 measures. This cohort study found that among US liver transplant programs, there were no correlations among 1-year recipient outcomes, measures of program aggressiveness, or waiting list management. These findings suggest that a program's performance in one domain may be independent and unrelated to its performance on others and that the understanding of factors contributing to these domains is incomplete.

Efficacy and Safety of Endoscopic Balloon Placement for Weight Loss in Patients With Cirrhosis Awaiting Liver Transplantation.

The efficacy and safety of a fluid-filled intragastric balloon (IGB) for weight loss in patients with cirrhosis on the liver transplantation (LT) waiting list is unknown. We enrolled stable compensated patients with body mass index >35 kg/m2 and on the waiting list for IGB placement endoscopically for a maximum of 6months. A total of 8 patients (7 men) aged mean ± SD, 56 ± 4.6 years with Model for End-Stage Liver Disease-sodium (MELD-Na) scores 14.1±3.4 experienced weight reduction (146±22.2 kg versus 127±21.6kg [P=0.005] with IGB in place and 130±24.6kg [P=0.014] at 6months), with a total body weight loss of 12.2%±8.8% with IGBs in place and 10.9%±8.9% at 6months. Body fat decreased from 48.6%±5.8% to 40.6%±6.4% (P=0.001) and lean mass increased from 51.3%±6% to 59.4%±6.4% (P=0.001). No change in MELD-Na scores occurred (P=0.770). Early balloon retrieval was attributed to accommodative symptoms (n=2) and liver decompensation (n=1). Mallory Weiss tears (n=3), but no portal hypertensive bleeding, occurred. Liver decompensation and/or hepatocellular carcinoma (HCC) developed in 3 patients. A total of 4 patients with LT ± sleeve gastrectomy maintained overall weight loss. Of 4 patients who did not receive transplants, 2 experienced weight regain. IGB results in short-term weight loss in patients with cirrhosis awaiting LT, with body fat loss without lean mass loss. Adverse effects were common. Decompensation and HCC did occur, with uncertainty of the relation to weight loss, and thus careful patient selection and close follow-up are required.

Effect of Direct-Acting Antiviral Treatment on Decompensated Hepatitis C Virus Cirrhosis

Goals: The goal of the study is to assess the effect of direct-acting antivirals (DAAs) on the model for end-stage liver disease-sodium (MELD-Na) score and on specific decompensations related to hepatitis C virus (HCV) cirrhosis. The aim of our study was to identify a specific cohort of patients with cirrhosis, if any, that should be targeted for treatment with DAAs. Background: The development of DAAs has provided safe and well-tolerated treatment options for patients with advanced liver disease. However, controversy remains in terms of optimal timing of treatment and whether this treatment should be offered before or following liver transplantation. Methods: We identified all patients with HCV cirrhosis who initiated treatment with DAA therapy at Johns Hopkins Hospital between July 2014 and June 2016. We identified a subset of patients who had decompensated cirrhosis and recorded their MELD-Na scores and decompensations pre- and post-treatment. Results: Fifty-six patients achieved sustained virologic response with decompensated HCV cirrhosis. The group demonstrated a significant decrease in median MELD-Na score following treatment from 12 to 10.5. Furthermore, a significant percentage of patients experienced resolution of ascites following DAA therapy with 19 patients (35.2%) clearing their ascites posttreatment. Of the 19 patients who cleared ascites, MELD-Na score decreased from a median of 12 (interquartile range [IQR] 11–18) to 11 (IQR 8–14), P = 0.01. Conclusions: Our findings suggest that patients with ascites as their main decompensation should be considered for the treatment with DAAs, while awaiting liver transplant given that the MELD-Na score showed only modest improvement and thus would not affect liver transplant (LT) listing priority.

Copeptin (CTproAVP) - A Biomarker of a Circulatory Impairment in Liver Transplant Recipients? A Prospective, Observational Study

Copeptin, an easily measured and stable surrogate marker of arginine vasopressin, is a biomarker of a homeostasis disorder and a circulatory impairment in a wide spectrum of morbidities. The aim of this study was to evaluate the potential of copeptin as a biomarker of a circulatory impairment in patients undergoing liver transplantation (LT). This was a prospective, observational study. Blood samples were obtained from 38 patients undergoing LT. Serum copeptin level was measured by means of a sandwich immunoassay pre-, intra-, and postoperatively up to 21 days after the operation. The mean concentration of copeptin remained in the range of values slightly below 1000 pg/mL during the analyzed observation period and remained higher than the values observed in healthy individuals. Intraoperative and immediately postoperative copeptin levels did not correlate with hemodynamic parameters. There was also no correlation between preoperative copeptin levels (C1) and preoperative Model for End-Stage Liver Disease scores, serum creatinine levels, plasma transaminase levels, international normalized ratio, or hematocrit (Spearman ρ, P > .05). Preoperative copeptin levels are elevated in most LT recipients and remain elevated for 21 days after surgery. There was no correlation between the concentration of copeptin and the Model for End-Stage Liver Disease-Sodium score or the cause of a hepatic failure. It cannot be concluded that copeptin is a biomarker of a circulatory impairment in patients with transplanted liver in the perioperative period. The secretion of vasopressin, as measured by copeptin concentration during and after LT, requires further study.

Cryptococcosis in patients with liver cirrhosis: Death risk factors and predictive value of prognostic models

BackgroundLiver cirrhosis is associated with immune deficiency, which causes these patients to be susceptible to various infections, including cryptococcus infection. Mortality in cirrhotic patients with cryptococcosis has increased. The present study was to explore the risk factors of mortality and the predictive ability of different prognostic models. MethodsForty-seven cirrhotic patients with cryptococcosis at a tertiary care hospital were included in this retrospective study. Data on demographics, clinical parameters, laboratory exams, diagnostic methods, medication during hospitalization, severity scores and prognosis were collected and analyzed. Student's t test and Mann-Whitney test were used to compare characteristics of survivors and non-survivors at a 90-day follow-up and cerebrospinal fluid (CSF) manifestations of cryptococcal meningitis. Multivariate Cox regression analysis was used to identify the independent risk factors for mortality. Kaplan-Meier curves were used to analyze patient survival. Receiver operating characteristic (ROC) curves were used to evaluate the different prognostic factors. ResultsThe 30- and 90-day survival rates were 93.6% and 80.9%, respectively, in cirrhotic patients with cryptococcosis. Cryptogenic liver diseases [hazard ratio (HR) = 7.567, 95% confidence interval (CI): 1.616-35.428, P = 0.010], activated partial thromboplastin time (APTT) (HR = 1.117, 95% CI: 1.016-1.229, P = 0.022) and Child-Pugh score (HR = 2.146, 95% CI: 1.314-3.504, P = 0.002) were risk factors for 90-day mortality in cirrhotic patients with cryptococcosis. Platelet count (HR = 0.965, 95% CI: 0.940-0.991, P = 0.008) was a protective factor. APTT (HR = 1.120, 95% CI: 1.044-1.202, P = 0.002) and Child-Pugh score (HR = 1.637, 95% CI: 1.086-2.469, P = 0.019) were risk factors for 90-day mortality in cirrhotic patients with cryptococcal meningitis. There was significant difference in the percentage of lymphocytes in CSF between survivors and non-survivors [60.0 (35.0-75.0) vs. 95.0 (83.8-97.2), P < 0.001]. The model of end-stage liver disease-sodium (MELD-Na) score was more accurate for predicting 30-day mortality both in patients with cryptococcosis [area under curve (AUC): 0.826, 95% CI: 0.618-1.000] and those with cryptococcal meningitis (AUC: 0.742, 95% CI: 0.560-0.924); Child-Pugh score was more useful for predicting 90-day mortality in patients with cryptococcosis (AUC: 0.823, 95% CI: 0.646-1.000) and those with cryptococcal meningitis (AUC: 0.815, 95% CI: 0.670-0.960). ConclusionsThese results showed that cryptogenic liver diseases, APTT and Child-Pugh score were associated with mortality in cirrhotic patients with cryptococcosis and cryptococcal meningitis. MELD-Na score was important for predicting 30-day mortality, and Child-Pugh score was critical for predicting 90-day mortality.

Cirrhotic Patients with Bacterial Infection and Negative Cultures Have a More Advanced Disease and an Increased Short-Term Mortality Rate.

The negative clinical impact of bacterial infections (BI) in patients with cirrhosis is well documented. In cirrhotic patients, failure to isolate the pathogen is a frequent event, occurring in 30-40% of cases. The aim of this study was to compare the clinical characteristics, early (30-day) and short-term (90-day) mortality rates, in a cohort of cirrhotic patients with BI, between those with positive (C-pos) and those with negative (C-neg) microbiological cultures. We retrospectively enrolled 279 consecutive hospitalized cirrhotic patients with BI. Survival and predictors of 30-day and 90-day mortality were assessed by Kaplan-Meier curves and logistic regression analysis, respectively. Cultures tested negative in 108/279 (38.7%) patients. C-neg patients were more frequently males (p = 0.035), had higher Child-Pugh-Turcotte (CPT; p = 0.007) and model for end-stage liver disease-sodium (MELD-Na; p = 0.043) scores, and had more frequently decompensated liver disease (p = 0.04). Mortality rate was higher in C-neg than in C-pos patients, both at 30days (22.2% versus 11.7%, p = 0.024) and 90days (46.3% versus 33.3%, p = 0.030). MELD-Na score and non-selective beta-blockers (NSBBs) were independent risk factors for 30-day and 90-day mortality. In particular, the use of NSBBs was independently associated with a lower 30-day and 90-day mortality risk (OR 0.41, CI95% 0.17-0.94, p = 0.040; and OR 0.43, CI95% 0.25-0.75, p = 0.003, respectively). Cirrhotic patients with BI and negative microbiological cultures have significantly higher mortality compared to those with positive cultures. Early mortality and short-term mortality are mainly influenced by the underlying severity of liver disease. In this contest, therapy with NSBBs has a positive impact on short-term survival.