Severe acute hepatitis of unknown etiology in a large cohort of children

BACKGROUND: We evaluated the proportion, clinical features, and outcomes of previously healthy children presenting to a large Canadian quaternary pediatric center with severe acute hepatitis of unknown etiology. METHODS: All patients with serum alanine aminotransferase (ALT) > 500 U/L or aspartate aminotransferase (AST) > 500 U/L between June 1, 2018, and May 31, 2022, at The Hospital for Sick Children, were identified. Subjects with only AST > 500 U/L were excluded. Clinical characteristics, investigations, and outcomes for patients without clear etiology for ALT > 500 U/L (severe acute hepatitis of unknown etiology) for our study period and from October 1 to May 31 of each year 2018–2021 were reviewed. RESULTS: Of 977 patients with ALT/AST> 500 U/L, 720 had only ALT > 500 U/L. We excluded age below 6 months (n = 99) or above 16 years (n = 66), known pre-existing liver conditions (n = 66), and ALT > 500 U/L in already admitted patients (n = 151). Among the remaining 338 children with ALT > 500 U/L at presentation, an etiology was identified in 303 subjects. 33 (9.8%) children [median age 6.1 y (range 0.5–15.5); 61% male] were confirmed as severe acute hepatitis of unknown etiology. Twenty patients (60.6%) were tested for blood adenovirus by PCR, and 1 (5%) was positive (serotype B7). Liver tissue specimens from 18 patients revealed no evidence of viral inclusions or adenovirus. Twelve (36.3%) presented with pediatric acute liver failure, with 8 (24.2%) requiring liver transplantation. There were no deaths. Hepatitis-associated aplastic anemia occurred in 5 (15%) patients. CONCLUSIONS: Of children presenting with severe acute hepatitis to a quaternary children’s hospital over a 48-month period, 9.8% had unknown etiology with no change over time. Liver transplantation remains an important treatment strategy for those presenting with pediatric acute liver failure phenotype. The frequency of cases associated with human adenovirus infection was noncontributory.