https://pubmed.ncbi.nlm.nih.gov/36572350/ hepatitis

J Hepatol. 2022 Dec 23;S0168-8278(22)03464-X.
doi: 10.1016/j.jhep.2022.12.012.Online ahead of print.

Acute severe non-A-E-hepatitis of unknown origin in children - a 30-year retrospective observational study from north-west Germany

Christoph Leiskau 1, Sofia Tsaka 2, Lena Meyer-Ruhnke 1, Frauke Elisabeth Mutschler 3, Eva-Doreen Pfister 3, Elke Lainka 2, Ulrich Baumann 4

Abstract

Background and aims: The etiology of acute severe non-A-E hepatitis in children still remains unclear. We aimed to describe occurrence and outcome of pediatric patients with acute severe hepatitis in North-West Germany over a period of more than 30 years and to compare the features to the cases of the current endemic.

Methods: Analysed were all cases of acute severe hepatitis in childhood as defined by WHO at Hannover Medical School from 1990 and at the University Hospital of Essen from 2009 to 16 May 2022. We separated a historic cohort (1990-2018) and compared it to recent cases (2019-2022).
Results: After application of exclusion criteria, 107 patients with acute severe hepatitis were identified (2.32 cases/centre/year). Annual incidence per centre rose significantly from 2.2 (historic cohort until 2018) to 4.25/centre/year (from 2019, p=0.002). 75.7 % presented with jaundice, 51.4% in context of infection. Two cases of Adenovirus were proven (2004/2016), other pathogens detected were HHV-6 (4), CMV, HSV, EBV(3). 69 patients (64.5%) met criteria of pediatric acute liver failure, 44 needed liver transplantation. Patients of the current cohort, patients with infection, gastrointestinal symptoms and higher ALT had a better chance of transplant-free survival, whereas hepatic encephalopathy, higher INR and bilirubin predicted a poor outcome. 25 patients developed hepatitis associated aplastic anemia. 19 patients (17.8 %) died.

Conclusions: Acute non-A-E-hepatitis in children is a rare but severe entity, often leading to acute liver failure. Clinical presentation in our current cohort resembles 2022 NAEH cases, and outcome has improved compared to historic controls. The rising incidence in our centres since 2019 without adenoviral infection, shortly before and during SARS-CoV-2-pandemia, indicates other potential triggers than Adenovirus for comparable NAEH cases.

Impact and implications: As the current epidemic of severe acute non-A-E-hepatitis cases in children highlights our limited understanding in the field, we aim to improve clinicians´ comprehension and ultimately their clinical management of this disease by the description of current cases, characterisation of the presentation over time, and definition of similarities and discrepancies, before and during the COVID-19 pandemic. Our data show a rising incidence of comparable non-A-E-hepatitis cases since the beginning of the COVID-19 pandemic, without association to adenoviral infections, possibly suggesting the recently described accumulation of Adenovirus infections in relationship to hepatitis as a new trigger for a known phenomenon, rather than a new disease entity. Therefore, the role of protective isolation and subsequent lack of contact to trivial infections in children during the pandemic should be the subject of further examinations. We expect our data to contribute to a better understanding of severe acute hepatitis in childhood, an increased vigilance for this potentially lethal disease beyond the current epidemic, and ultimately improved clinical diagnosis and care.