title: Clinical Course among Cases of Acute Liver Failure of Indeterminate Diagnosis.
abstract: OBJECTIVE
  To investigate the heterogeneity in clinical course among those with pediatric acute liver failure (PALF) of indeterminate disease etiology.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The clinical courses of participants with PALF of indeterminate disease etiology exhibit distinct trajectory patterns, which have important prognostic and potentially diagnostic value.
authors.affiliation: Department of Biostatistics, University of Texas School of Public Health, Houston, TX.
authors.forename: Ruosha
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Belle
authors.affiliation: Division of Gastroenterology, Seattle Children's Hospital, Seattle, WA.
authors.forename: Simon
authors.initials: S
authors.lastname: Horslen
authors.affiliation: Department of Statistics, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Ling-wan
authors.initials: LW
authors.lastname: Chen
authors.affiliation: Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA. Electronic address: squiresr@upmc.edu.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Squires
mesh_terms: D001663:Bilirubin / Q000097:blood; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016208:Databases, Factual; D018450:Disease Progression; D005260:Female; D006501:Hepatic Encephalopathy / Q000175:diagnosis / Q000453:epidemiology; D006801:Humans; D007223:Infant; D019934:International Normalized Ratio; D017114:Liver Failure, Acute / Q000628:therapy*; D008297:Male; D015233:Models, Statistical; D011379:Prognosis; D012042:Registries; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001663:Bilirubin
references.citation: Pediatr Transplant. 2013 Jun;17(4):362-8
references.pmid: 23586473
references.citation: Med Decis Making. 2010 Jul-Aug;30(4):474-83
references.pmid: 20044582
references.citation: Alcohol Clin Exp Res. 2000 Jun;24(6):882-91
references.pmid: 10888079
references.citation: Int J Behav Dev. 2009;33(6):565-576
references.pmid: 23885133
references.citation: J Hepatol. 2006 Jan;44(1):134-41
references.pmid: 16169116
references.citation: Biometrics. 1999 Jun;55(2):463-9
references.pmid: 11318201
references.citation: J Pediatr. 2006 May;148(5):652-658
references.pmid: 16737880
references.citation: J Pediatr Gastroenterol Nutr. 2005 May;40(5):575-81
references.pmid: 15861019
references.citation: Clin Gastroenterol Hepatol. 2008 Oct;6(10):1140-5
references.pmid: 18928939
references.citation: J Pediatr. 2009 Dec;155(6):801-806.e1
references.pmid: 19643443
references.citation: J Pediatr. 2013 Feb;162(2):319-23.e1
references.pmid: 22906509
references.citation: Gastroenterology. 1989 Aug;97(2):439-45
references.pmid: 2490426
references.citation: Hepatology. 2013 Apr;57(4):1542-9
references.pmid: 22886633
references.citation: Pediatr Transplant. 2013 Sep;17(6):535-42
references.pmid: 23802584
references.citation: Gut. 2012 Jul;61(7):1068-75
references.pmid: 22337947