Evaluation of a Scoring System for Assessing Prognosis in Pediatric Acute Liver Failure

doi:10.1016/j.cgh.2008.05.013

Clinical Gastroenterology and Hepatology

Volume 6, Issue 10, October 2008, Pages 1140-1145

https://doi.org/10.1016/j.cgh.2008.05.013 Get rights and content

Background & Aims

Pediatric acute liver failure (PALF) results in death or need for liver transplantation (LT) in up to 50% of patients. A scoring system for predicting death or LT (Liver Injury Units [LIU] score) in PALF was previously derived by our group, and used peak values during hospital admission of total bilirubin, prothrombin time/international normalized ratio, and ammonia as significant predictors of outcome. The aims of this study were to test the predictive value of the LIU score in a subsequent validation set of patients and to derive a hospital admission LIU (aLIU) score predictive of outcome.

Methods

Data were obtained from 53 children admitted with PALF from 2002 to 2006. Outcome was defined at 16 weeks as alive without LT, death, or LT.

Results

Survival without LT at 16 weeks for each LIU score quartile was 92%, 44%, 60%, and 12%, respectively (P < .001). The receiver operating characteristic C index for predicting death or LT by 4 weeks was 86.3. An admission LIU score was derived using admission total bilirubin and prothrombin time/international normalized ratio. Survival without LT at 16 weeks for each quartile using the aLIU score was 85%, 77%, 69%, and 31% (P = .001). The receiver operating characteristic C index for predicting death or LT by 4 weeks was 83.7.

Conclusions

The original LIU score is a valid predictor of outcome in PALF. The aLIU score is promising and needs to be validated in subsequent patients.

Section snippets

Methods

The demographics and clinical course of all children admitted to The Children's Hospital in Denver who met criteria for PALF from January 2002 to December 2006 were entered prospectively into a database. This group is referred to as the validation set. The training set refers to the original data set from which the LIU score was derived. This study was reviewed and approved by the Colorado Multiple Institutional Review Board. PALF was defined as acute onset of severe liver dysfunction plus the

Clinical and Outcome Data

Fifty-three patients (31 males, 22 females) were identified with PALF over 5 years. The cause of PALF was indeterminate (n = 14), sepsis/ischemia-reperfusion injury (n = 14), viral infection (n = 8), metabolic disease (n = 5), acetaminophen toxicity (n = 4), hematology/oncology-related (n = 4), and other causes (n = 4). Thirteen percent (n = 7) underwent LT, 23% (n = 12) died without LT, with an overall transplant-free survival rate of 64% at 16 weeks. There were no significant differences in

Discussion

In this study, using a second independent validation cohort of children with PALF at a single institution, the previously derived LIU score was shown to be strongly predictive of death or LT (C index, 86.3). In the validation set, the second and third quartiles showed overlap when compared with the training set of data; however, the lowest and highest quartiles clearly reflected patients with low and high likelihoods of death or LT. The predictive value was better for the LIU score using INR

References (28)

P. Durand et al.
Acute liver failure in infancy: a 14-year experience of a pediatric liver transplantation center
J Pediatr
(2001)
L. Nicolette et al.
Transplantation for acute hepatic failure in children
J Pediatr Surg
(1998)
E. Liu et al.
Characterization of acute liver failure and development of a continuous risk of death staging system in children
J Hepatol
(2006)
M.B. Zaman et al.
MELD score as a prognostic model for listing acute liver failure patients for liver transplantation
Transplant Proc
(2006)
A.O. Shakil et al.
Acute liver failure: clinical features, outcome analysis, and applicability of prognostic criteria
Liver Transpl
(2000)
M. Peláez-Luna et al.
Utility of the MAYO End-Stage Liver Disease score, King's College Criteria, and a new in-hospital mortality score in the prognosis of in-hospital mortality in acute liver failure
Transplant Proc
(2006)
S.W. Biggins et al.
Evidence-based incorporation of serum sodium concentration into MELD
Gastroenterology
(2006)
R.H. Squires et al.
Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group
J Pediatr
(2006)
A. Baker et al.
Hepatic failure and liver transplant: working group report of the Second Work Congress of Pediatric Gastroenterology, Hepatology, and Nutrition
J Pediatr Gastroenterol Nutr
(2004)
G. Ostapowicz et al.
Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States
Ann Intern Med
(2002)

F.V. Schiødt et al.

Etiology and outcome for the 295 patients with acute liver failure in the United States

Liver Transpl Surg

(1999)

W.S. Lee et al.

Etiology, outcome and prognostic indicators of childhood fulminant hepatic failure in the United Kingdom

J Pediatr Gastroenterol Nutr

(2005)

A. Dhawan et al.

Approaches to acute liver failure in children

Pediatr Transplant

(2004)

M. Ciocca et al.

Prognostic factors in pediatric acute liver failure

Arch Dis Child

(2008)

Cited by (46)

Dynamic risk score modeling for multiple longitudinal risk factors and survival
2024, Computational Statistics and Data Analysis
Modeling disease risk and survival using longitudinal risk factor trajectories is of interest in various clinical scenarios. The capacity to build a prognostic model using the trajectories of multiple longitudinal risk factors, in the presence of potential dependent censoring, would enable more informed, personalized decision making. A dynamic risk score modeling framework is proposed for multiple longitudinal risk factors and survival in the presence of dependent censoring, where both events depend on participants' post-baseline clinical progression and form a competing risks structure. The model requires relatively few random effects regardless of the number of longitudinal risk factors and can therefore accommodate multiple longitudinal risk factors in a parsimonious manner. The proposed method performed satisfactorily in extensive simulation studies. It is further applied to the motivating registry study on pediatric acute liver failure to model death using the trajectories of multiple clinical and biochemical markers. Once established, the model yields an easily calculable longitudinal risk score that can be used for disease monitoring among future patients.
Acute Liver Failure in Children
2022, Pediatric Clinics of North America
Emergencies in paediatric hepatology
2022, Journal of Hepatology
Citation Excerpt :
The available prognostic markers include those indicating degree of liver dysfunction, extrahepatic dysfunction, systemic inflammatory response syndrome, age and aetiology.23,25,27,28,30,95–98 The various parameters known to affect outcomes and the scoring systems (combining these parameters) that are validated in PALF are detailed in Tables S2 and S3.23–25,27,28,30,95,97–102 Median waiting times for LT vary among centres.
The aetiology of several liver diseases in children is age specific and many of these conditions have significant and potentially long-term clinical repercussions if not diagnosed early and managed in a timely fashion. We address 5 clinical scenarios that cover most of the diagnostic and therapeutic emergencies in children: infants with liver disease; acute liver failure; management of bleeding varices; liver-based metabolic disorders; and liver tumours and trauma. A wide spectrum of conditions that cause liver disease in infants may present as conjugated jaundice, which could be the only symptom of time-sensitive disorders – such as biliary atresia, metabolic disorders, infections, and haematological/alloimmune disorders – wherein algorithmic multistage testing is required for accurate diagnosis. In infantile cholestasis, algorithmic multistage tests are necessary for an accurate early diagnosis, while vitamin K, specific milk formulae and disease-specific medications are essential to avoid mortality and long-term morbidity. Management of paediatric acute liver failure requires co-ordination with a liver transplant centre, safe transport and detailed age-specific aetiological work-up – clinical stabilisation with appropriate supportive care is central to survival if transplantation is indicated. Gastrointestinal bleeding may present as the initial manifestation or during follow-up in patients with portal vein thrombosis or chronic liver disease and can be managed pharmacologically, or with endoscopic/radiological interventions. Liver-based inborn errors of metabolism may present as encephalopathy that needs to be recognised and treated early to avoid further neurological sequelae and death. Liver tumours and liver trauma are both rare occurrences in children and are best managed by a multidisciplinary team in a specialist centre.
Prognostic parameters of pediatric acute liver failure and the role of plasma exchange
2019, Pediatrics and Neonatology
This study investigated the prognostic parameters and beneficial effects of repeat plasma exchange in children with acute liver failure (ALF).
Twenty-three patients under 18 years of age admitted to National Taiwan University Hospital due to ALF from 2003 to 2016 were included in this retrospective analysis.
Among the patients, 11 (48%) had native liver recovery (NLR), 9 (39.1%) died without liver transplant, and 3 (12.9%) received liver transplantation. The NLR group showed a lower proportion of idiopathic cases, lower peak ammonia level, higher peak alpha fetoprotein (AFP) level, and they had plasma exchange fewer times than the other groups. Receiver operating characteristic curve analyses yielded optimal cutoff values of plasma exchange (≤6 times), peak ammonia level (<190 μmol/L), and peak AFP level for predicting NLR in children with ALF.
Pediatric ALF with idiopathic etiology, high peak ammonia level, and low peak AFP level are associated with fewer cases of NLR. Plasma exchange for more than six times probably offers little benefit with regard to patient survival if liver transplantation is not performed promptly.
Aetiology, outcomes and prognostic indicators of paediatric acute liver failure
2018, Anales de Pediatria
El fallo hepático agudo (FHA) es una enfermedad multisistémica con afectación severa de la función hepática de aparición brusca. La puntuación Pediatric End-stage Liver Disease (PELD) es un predictor de mortalidad en hepatopatías crónicas, siendo la experiencia en FHA limitada.
Evaluar las características etiológicas y la evolución de niños con FHA en un centro con trasplante hepático (TH) infantil e investigar la validez del PELD como indicador pronóstico.
Estudio retrospectivo de pacientes con FHA en nuestro centro de 2000 a 2013 según criterios del grupo de trabajo de FHA.
Se reclutaron 49 pacientes (0-14 años). Las etiologías más frecuentes fueron la indeterminada (36,7%) y la metabólica (26,5%). Los pacientes que requirieron TH fueron el 42,8%, y el 16,3% fallecieron. Los pacientes con cifras elevadas de bilirrubina, INR o que desarrollaron encefalopatía tuvieron más probabilidades de presentar una evolución tórpida, obteniéndose una OR para el INR de 1,93. Un punto de corte de 27 en el PELD según la curva ROC mostró una sensibilidad del 86% y una especificidad del 85% de presentar evolución desfavorable (ABC: 0,90; p < 0,001). La supervivencia de FHA sin necesidad de TH fue más probable en aquellos con valores de PELD bajos y que no desarrollaron encefalopatía, con un RR de 0,326.
Los pacientes con FHA que presentaron un PELD elevado junto con encefalopatía tuvieron peor evolución. El valor del PELD puede ayudar a establecer el momento óptimo para inclusión en lista de TH; sin embargo son necesarios estudios a mayor escala.
Acute liver failure (ALF) is a multisystem disease with severe impairment of liver function of acute onset. The Paediatric End-stage Liver Disease (PELD) score is used as a predictor of mortality in chronic liver disease, however experience is limited in ALF.
To evaluate the aetiology and outcomes of children with ALF in a Children's Liver Transplant Centre, and to investigate the validity of PELD as a prognostic indicator.
A retrospective study was conducted on patients diagnosed with ALF in our hospital from 2000 to 2013 using the criteria of the Paediatric ALF Study Group.
The study included 49 patients with an age range 0-14 years. The most frequent aetiologies were: indeterminate (36.7%) and metabolic (26.5%). Liver transplant (LT) was required by 42.8%, and there were 16.3% deaths. Patients with higher levels of bilirubin, INR, or encephalopathy were more likely to require a liver transplant, yielding an OR for INR 1.93. A cut-off of 27 in the PELD score according to the ROC curve showed a sensitivity of 86% and a specificity of 85%, predicting a worse outcome (AUC: 0.90; P < .001). The survival of patients with ALF without transplantation seems more likely in those who have low values of PELD and absence of encephalopathy, with a RR of 0.326.
ALF patients with a high PELD score and the presence of encephalopathy had worse outcomes. The PELD score could be a useful tool to establish the optimum time for inclusion in the transplant list, however further studies are still needed.
Clinical Course among Cases of Acute Liver Failure of Indeterminate Diagnosis
2016, Journal of Pediatrics
Citation Excerpt :
Distilling multiple clinical and biochemical measures into a practical model that can be used at the bedside for each decision interval remains a challenge. Previous predictive models for ALF in adults and children have included clinical and biochemical measures that are objective (eg, INR, bilirubin, ammonia, age) or subjective (eg, jaundice, encephalopathy) at the time of admission to hospital, the highest recorded or “peak” value,13,14 or combinations of these data elements.2,15-17 Measures obtained only at admission are limited by their inability to account for disease progression or improvement during the ensuing days.
To investigate the heterogeneity in clinical course among those with pediatric acute liver failure (PALF) of indeterminate disease etiology.
We studied participants enrolled in the PALF registry study with indeterminate final diagnosis. Growth mixture modeling was used to analyze participants' international normalized ratio, total bilirubin, and hepatic encephalopathy trajectories in the first 7 days following enrollment. Participants with at least 3 values for 1 or more of the measurements were included. We examined the association between the resulting latent subgroup classification with participants' characteristics and disease outcomes. Data from participants with PALF of specified etiologies were used to investigate the potential diagnostic value of the latent subgroups.
In this sample of 380 participants with indeterminate final diagnosis, 115 (30%) experienced mild and quickly improving disease trajectories and another 48 (13%) started with severe disease but improved by day 7. The majority of participants (216, 57%) had disease trajectories that worsened over time. The identified patterns of disease trajectories are predictive of outcome (P < .001). The trajectory patterns are associated with the underlying disease etiology (P < .001) for the 488 participants with PALF of specified etiologies.
The clinical courses of participants with PALF of indeterminate disease etiology exhibit distinct trajectory patterns, which have important prognostic and potentially diagnostic value.

View all citing articles on Scopus

: B.R.L. is supported by a National Institutes of Health training grant (5T32DK067009).

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Original article—liver, pancreas and biliary tractEvaluation of a Scoring System for Assessing Prognosis in Pediatric Acute Liver Failure

Background & Aims

Methods

Results

Conclusions

Section snippets

Methods

Clinical and Outcome Data

Discussion

J Pediatr

J Pediatr Surg

J Hepatol

Transplant Proc

Liver Transpl

Transplant Proc

Gastroenterology

Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group

J Pediatr

Hepatic failure and liver transplant: working group report of the Second Work Congress of Pediatric Gastroenterology, Hepatology, and Nutrition

J Pediatr Gastroenterol Nutr

Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States

Ann Intern Med

Etiology and outcome for the 295 patients with acute liver failure in the United States

Liver Transpl Surg

Etiology, outcome and prognostic indicators of childhood fulminant hepatic failure in the United Kingdom

J Pediatr Gastroenterol Nutr

Approaches to acute liver failure in children

Pediatr Transplant

Prognostic factors in pediatric acute liver failure

Arch Dis Child

Original article—liver, pancreas and biliary tract
Evaluation of a Scoring System for Assessing Prognosis in Pediatric Acute Liver Failure