Objective: Hepatic encephalopathy (HE) is challenging to identify in children with acute liver failure (ALF), and was not a requirement for enrollment into the Pediatric ALF Study Group (PALFSG). The outcomes of PALFSG participants presenting with and without HE are presented. Methods: PALFSG participants were classified based on daily assessment of HE during the first 7 days following study enrollment: Group1 - never developed HE; Group2 - no HE at enrollment with subsequent HE development; and Group 3 - HE at study enrollment. Clinical and biochemical parameters and outcomes of death, spontaneous recovery (SR), or liver transplantation (LT) were compared between groups. Results: Data from 769PALFSG (54% male; median age 4.2 years; range 0-17.9 years) participants were analyzed, with 277 in Group 1 (36%), 83 in Group 2 (11%) and 409 in Group 3 (53%). Mortality occurred in 11% of all participants and was highest among Group 3 participants who demonstrated persistent grade III-IV HE (55%) or showed progression of HE (26%). Eleven (4%) Group 1 participants died within 21 days of enrollment. SR was highest in Group 1 (79%) and lowest in Group 2 (25%; p
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