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Development of an organ failure score in acute liver failure for transplant selection and identification of patients at high risk of futility.

ABSTRACT: King's College Hospital criteria are currently used to select liver transplant candidates in acetaminophen-related acute liver failure (ALF). Although widely accepted, they show a poor sensitivity in predicting pre-transplant mortality and cannot predict the outcome after surgery. In this study we aimed to develop a new prognostic score that can allow patient selection for liver transplantation more appropriately and identify patients at high risk of futile transplantation.We analysed consecutive patients admitted to the Royal Free and Beaujon Hospitals between 1990 and 2015. Clinical and laboratory data at admission were collected. Predictors of 3-month mortality in the non-transplanted patients admitted to the Royal Free Hospital were used to develop the new score, which was then validated against the Beaujon cohort. The Beaujon-transplanted group was also used to assess the ability of the new score in identifying patients at high risk of transplant futility.152 patients were included of who 44 were transplanted. SOFA, CLIF-C OF and CLIF-ACLF scores were the best predictors of 3-month mortality among non-transplanted patients. CLIF-C OF score and high dosages of norepinephrine requirement were the only significant predictors of 3-month mortality in the non-transplanted patients, and therefore were included in the ALF-OFs score. In non-transplanted patients, ALF-OFs showed good performance in both exploratory (AUC = 0.89; sensitivity = 82.6%; specificity = 89.5%) and the validation cohort (AUC = 0.988; sensitivity = 100%; specificity = 92.3%). ALF-OFs score was also able to identify patients at high risk of transplant futility (AUC = 0.917; sensitivity = 100%; specificity = 79.2%).ALF-OFs is a new prognostic score in acetaminophen-related ALF that can predict both the need for liver transplant and high risk of transplant futility, improving candidate selection for liver transplantation.

SUBMITTER: Figorilli F

PROVIDER: S-EPMC5716582 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Development of an organ failure score in acute liver failure for transplant selection and identification of patients at high risk of futility.

Figorilli Francesco F Putignano Antonella A Roux Olivier O Houssel-Debry Pauline P Francoz Claire C Paugam-Burtz Catherine C Soubrane Olivier O Agarwal Banwari B Durand François F Jalan Rajiv R

PloS one 20171205 12

<h4>Introduction</h4>King's College Hospital criteria are currently used to select liver transplant candidates in acetaminophen-related acute liver failure (ALF). Although widely accepted, they show a poor sensitivity in predicting pre-transplant mortality and cannot predict the outcome after surgery. In this study we aimed to develop a new prognostic score that can allow patient selection for liver transplantation more appropriately and identify patients at high risk of futile transplantation.< ...[more]

PMID: 29206839

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Project description:Background & aimsSex disparities in liver transplantation (LT) for chronic liver disease have been described. It is unclear if similar disparities exist for acute liver failure (ALF).MethodsAdults waitlisted for LT from 2002 to 2016 with ALF were investigated using the United Network of Organ Sharing database. Clinical characteristics and causative aetiologies were compared between men and women who were waitlisted Status-1. Differences in LT, waitlist removal, and 1-year post-transplant survival were explored.ResultsOf 8,408 patients waitlisted for LT with ALF, 41.3% of men and 63.9% of women were waitlisted Status-1 (p <0.001). Women had significantly higher international normalised ratio, higher frequency of grade 3-4 hepatic encephalopathy, and different aetiologies of ALF than men. On univariable analysis, women were less likely to undergo LT (subdistribution hazard ratio [SHR] 0.90; 95% CI 0.84-0.97) and were more likely to die or be removed from the waitlist as a result of clinical deterioration (SHR 1.14; 95% CI 1.002-1.30) than men. The disparities in LT (HR 0.95; 95% CI 0.87-1.03) and death/clinical deterioration (SHR 1.13; 95% CI 0.99-1.29) were no longer significant on multivariable analysis. On multivariable analysis, there was no difference in 1-year post-transplant survival between men and women.ConclusionsWomen with ALF are more likely to be waitlisted Status-1 than men. There were no clear disparities in LT or waitlist removal. Sex differences in LT and waitlist removal were attenuated on fully adjusted models, suggesting that these disparities may in part be mitigated by Status-1 listing.Lay summaryWomen with acute liver failure appear to be sicker than men and more often require urgent Status-1 waitlisting. There were no sex disparities in waitlist removal because of clinical deterioration or liver transplantation. This is in contrast to chronic liver disease, where sex disparities exist. The Status-1 waitlisting that women with acute liver failure receive may in part mitigate sex disparities in liver transplantation.

Project description:Patients with acute liver failure (ALF) have a high risk of death that can be substantially reduced with liver transplantation. It is a challenge to predict which patients with ALF will survive without liver transplant because available prognostic scoring systems are inadequate. We devised a mathematical model, using a large dataset collected by the Acute Liver Failure Study Group, which can predict transplant-free survival in patients with ALF.We performed a retrospective analysis of data from 1974 subjects who met criteria for ALF (coagulopathy and hepatic encephalopathy within 26 weeks of the first symptoms, without pre-existing liver disease) enrolled in the Acute Liver Failure Study Group database from January 1, 1998 through June 11, 2013. We randomly assigned the subjects to development and validation cohorts. Data from the development cohort were analyzed to identify factors associated with transplant-free survival (alive without transplantation by 21 days after admission to the study). Statistically significant variables were used to create a multivariable logistic regression model.Most subjects were women (70%) and white (78%); acetaminophen overdose was the most common cause (48% of subjects). The rate of transplant-free survival was 50%. Admission values of hepatic encephalopathy grade, ALF etiology, vasopressor use, and log transformations of bilirubin and international normalized ratio were significantly associated with transplant-free survival, based on logistic regression analysis. In the validation cohort, the resulting model predicted transplant-free survival with a C statistic value of 0.84, 66.3% accuracy (95% confidence interval, 63.1%-69.4%), 37.1% sensitivity (95% confidence interval, 32.5%-41.8%), and 95.3% specificity (95% confidence interval, 92.9%-97.1%).Using data from the Acute Liver Failure Study Group, we developed a model that predicts transplant-free survival of patients with ALF based on easily identifiable hospital admission data. External validation studies are required.

Project description:Acute liver failure (ALF) is a syndrome characterized by an intense systemic inflammatory response (SIRS) and multi-organ system failure (MOSF). Platelet-derived microparticles increase in proportion to the severity of the SIRS and MOSF, and are associated with poor outcome. We investigated whether patients with ALF develop thrombocytopenia in proportion to the SIRS, MOSF, and poor outcome.In a retrospective study, we collected data on the post-admission platelet counts of 1598 patients included in the ALF Study Group Registry from 1998 through October 2012. We investigated correlations between platelet counts and clinical features of ALF, laboratory test results, and outcomes. Of the patients studied, 752 (47%) survived without liver transplantation, 390 (24%) received liver transplants, and 517 (32%) died.In patients with SIRS, platelet counts decreased 2 to 7 days after admission, compared with patients without SIRS (P ? .001). Patients with abnormal levels of creatinine, phosphate, lactate, or bicarbonate had significantly lower platelet counts than patients with normal levels of these laboratory values (all P ? .001). The decrease in platelets during days 1 to 7 after admission was proportional to the grade of hepatic encephalopathy and requirement for vasopressor and renal replacement therapy. Although platelet numbers decreased after admission in the overall population, platelets were significantly lower 2 to 7 days after admission in patients with outcomes of death or liver transplantation than in patients who made spontaneous recoveries and survived. In contrast, international normalized ratios over time were not associated with SIRS, laboratory test results associated with poor outcomes, grade of hepatic encephalopathy, or requirement for renal replacement therapy.The development of thrombocytopenia in patients with ALF is associated with the development of MOSF and poor outcome. We speculate that SIRS-induced activation of platelets, yielding microparticles, results in clearance of platelet remnants and subsequent thrombocytopenia.

Project description:Rationale: Acute liver failure (ALF) causes severe liver injury and a systemic inflammatory response, leading to multiorgan failure with a high short-term mortality. Bioartificial liver (BAL) therapy is a promising approach that is hampered by the lack of appropriate bioreactors and carriers to retain hepatic cell function and poor understanding of BAL treatment mechanisms in ALF and extrahepatic organ injury. Recently, we used a fiber scaffold bioreactor (FSB) for the high-density, three-dimensional (3D) culture of primary porcine hepatocytes (PPHs) combined with an absorption component to construct a BAL and verified its function in a D-galactosamine (D-gal)-induced ALF porcine model to evaluate its protective effects on the liver and extrahepatic organs. Methods: Male pigs were randomized into standard/supportive therapy (ST), ST+no-cell BAL (ST+Sham BAL) and ST+BAL groups and received treatment 48 h after receiving a D-gal injection. Changes in blood chemistry and clinical symptoms were monitored for 120 h. Tissues and plasma were collected for analysis by pathological examination, immunoblotting, quantitative PCR and immunoassays. Results: PPHs cultured in the FSB obtained sufficient aeration and nutrition for high-density, 3D culture and maintained superior viability and functionality (biosynthesis and detoxification) compared with those cultured in flasks. All the animals developed ALF, acute kidney injury (AKI) and hepatic encephalopathy (HE) 48 h after D-gal infusion and received corresponding therapies. Animals in the BAL group showed markedly improved survival (4/5; 80%) compared with those in the ST+Sham BAL (0/5; p < 0.001) and ST (0/5; p < 0.001) groups. The levels of blood ammonia and biochemical and inflammatory indices were alleviated after BAL treatment. Increased liver regeneration and attenuations in the occurrence and severity of ALF, AKI and HE were observed in the ST+BAL group compared with the ST (p = 0.0009; p = 0.038) and ST+Sham BAL (p = 0.011; p = 0.031) groups. Gut leakage, the plasma endotoxin level, bacterial translocation, and peripheral and neuroinflammation were alleviated in the ST+BAL group compared with those in the other groups. Conclusions: BAL treatment enhanced liver regeneration and alleviated the systemic inflammatory response and extrahepatic organ injury to prolong survival in the ALF model and has potential as a therapeutic approach for ALF patients.

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Development of an organ failure score in acute liver failure for transplant selection and identification of patients at high risk of futility.

Publications

Development of an organ failure score in acute liver failure for transplant selection and identification of patients at high risk of futility.

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