Liver and Bile
J Hepatol. 2023;78(5):971–8
Acute severe non-A-E-hepatitis of unknown origin in children – A 30-year retrospective observational study from North-West Germany
Background and aims: The etiology of the current acute severe non-A-E hepatitis epidemic in children remains unclear. The authors aimed to describe the occurrence and outcomes of acute severe hepatitis in pediatric patients in North-West Germany over a period of more than 30 years and in the context of the current epidemic.
Methods: They analyzed all cases of acute severe hepatitis in childhood, as defined by the World Health Organization, at Hannover Medical School from 1990 and at the University Hospital of Essen from 2009 to May 16, 2022, and separated cases into a historic cohort (1990–2018) and a COVID-19 era cohort (2019–2022).
Results: After application of exclusion criteria, 107 patients with acute severe hepatitis were identified (2.32 cases/center/year). Annual incidence per center rose significantly from 2.2 (historic cohort until 2018) to 4.25 per center and year (from 2019, p = 0.002). Of all cases, 75.7% pre-sented with jaundice, while 53.3% had clinical signs of infection. Two cases of adenovirus were proven (2004/2016), other pathogens detected were human herpes virus (HHV)-6 (4), cytomegalovirus (CMV), herpes simplex virus (HSV), Epstein-Barr virus (EBV) (3). 69 patients (64.5%) met the criteria of pediatric acute liver failure, with 44 requiring liver transplantation. In the current cohort, patients with infection, gastrointestinal symptoms and higher alanine aminotransferase had a better chance of transplant-free survival, whereas hepatic encephalopathy, higher inter-national normalized ratio and bilirubin predicted a poor outcome. 25 patients developed hepatitis-associated aplastic anemia and 19 patients (17.8%) died.
Conclusions: Acute non-A-E-hepatitis (NAEH) in children is a rare but severe entity, often leading to acute liver failure. Clinical presentation in this current cohort resembles 2022 NAEH cases, with improved outcomes compared to historic controls. The rising incidence of NAEH in the authors’ centers since 2019, in the absence of adenoviral infection, indicates other potential triggers of similar NAEH cases.