Development of a Model to Predict Transplant-free Survival of Patients With Acute Liver Failure

Abstract

Background & Aims: 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 (ALFSG),that can predict transplant-free survival in patients with ALF. Methods: 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 ALFSG 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. Results: Most subjects were women (70%) and Caucasian (78%); acetaminophen overdose was the most common etiology (48% of subjects). The rate of transplant-free survival was 50%. Admission values of coma 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 [CI], 63.1%–69.4%), 37.1% sensitivity (95% CI, 32.5%−41.8%), and 95.3% specificity (95% CI, 92.9%−97.1%). Conclusion: Using data from the ALFSG, 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.

Elevated FABP1 serum levels are associated with poorer survival in acetaminophen‐induced acute liver failure

“…The Model for End‐Stage Liver Disease (MELD) is defined as 10 × [0.957 × log(4) + 0.378 × log(bilirubin) + 1.12 × log(INR)] for dialyzed patients and 10 × [0.957 × log(creatinine) + 0.378 × log (bilirubin) + 1.12 × log(INR)] for patients not dialyzed . The ALFSG prognostic index calculates the log odds (logit) for 21‐day transplant‐free survival as 2.67 – 0.95(HE*) + 1.56(etiology*) – 1.25(vasopressor use*) – 0.70(ln bilirubin) – 1.35(ln INR) . For low coma grade use HE insert 0; for high coma grade use insert 1.…”

“…The most widely used prognostic criteria in APAP‐ALF patients are the King's College criteria (KCC) . While initially published in 1989, subsequent studies that have used KCC have shown relatively poor sensitivity of the APAP criteria, ranging 25%‐76% . More recently, the Acute Liver Failure Study Group (ALFSG) prognostic index also demonstrated limited sensitivity (41%) in APAP‐ALF …”

A Model to Predict 1‐Month Risk of Transplant or Death in Hepatitis A–Related Acute Liver Failure

“…However, this study was limited to a small number of patients. More recently, the new ALFSG prognostic index derived from patients with ALF of varying etiologies was developed . This model predicted 21‐day transplant‐free survival with a c‐statistic of 0.84 using five clinical variables (hepatic encephalopathy grade, etiology of ALF, vasopressor use, bilirubin, and INR).…”

“…For predicting outcomes, the King’s College criteria (KCC) for nonparacetamol‐related ALF, the U.S. Acute Liver Failure Study Group (ALFSG) index for fulminant HAV infection (HAV‐ALFSG), the new ALFSG prognostic index published in 2016, the United Network for Organ Sharing–modified Model for End‐Stage Liver Disease (MELD), and MELD including sodium (MELD‐Na) scores according to Organ Procurement and Transplantation Network guidelines were assessed at the time of diagnosis of ALF …”

Recent advances in understanding and managing liver transplantation

“…Commonly used criteria evaluate multiorgan impairment (encephalopathy and metabolic acidosis), etiology, and severity of coagulopathy as the most important factors for listing ALF patients. King's College criteria 41 are the most commonly applied; however, other algorithms have been proposed over time 42, 43 . Nevertheless, several factors, such as recipient age, severity of pre-transplant illness, comorbidities, and the nature of graft used, could affect the outcome of emergency LT 38 .…”