Paediatric acute liver failure: A prospective, nationwide, population-based surveillance study in Germany

Dominic Lenz; Muhammad Abdulaziz; Bianca Peters; Matias Wagner; Lea D Schlieben; Victor M Corman; Ulrich Baumann; Philip Bufler; Tal Dattner; Rainer Ganschow; Kristin Genzel; Nicole Hammann; Steffen Hartleif; Bianca Hegen; Stephan Henning; André Hoerning; Martin Jankofsky; Norman Junge; Simone Kathemann; Birgit Knoppke; Martina Kohl-Sobania; Martin Laass; Elke Lainka; Eberhard Lurz; Michael Melter; Hanna Müller; Denisa Pilic; Markus Ries; Lisa Schiefele; Tobias Schwerd; Ekkehard Sturm; Mechtild Wegner; Michael S Urschitz; Sven F Garbade; Daniel Wenning; Christian Drosten; Alexander Fichtner; Stefan Kölker; Georg F Hoffmann; Holger Prokisch; Christian Staufner

doi:10.1002/jpn3.70149

Paediatric acute liver failure: A prospective, nationwide, population-based surveillance study in Germany

J Pediatr Gastroenterol Nutr. 2025 Jul 7. doi: 10.1002/jpn3.70149. Online ahead of print.

Authors

Dominic Lenz¹, Muhammad Abdulaziz^{1

2}, Bianca Peters¹, Matias Wagner^{3

4}, Lea D Schlieben^{3

4}, Victor M Corman^{5

6}, Ulrich Baumann⁷, Philip Bufler⁸, Tal Dattner¹, Rainer Ganschow⁹, Kristin Genzel¹⁰, Nicole Hammann¹, Steffen Hartleif¹¹, Bianca Hegen¹², Stephan Henning⁸, André Hoerning¹³, Martin Jankofsky¹², Norman Junge⁷, Simone Kathemann¹⁴, Birgit Knoppke¹⁵, Martina Kohl-Sobania¹⁶, Martin Laass¹⁷, Elke Lainka¹⁴, Eberhard Lurz¹⁸, Michael Melter¹⁵, Hanna Müller^{19

20}, Denisa Pilic¹⁴, Markus Ries¹, Lisa Schiefele²¹, Tobias Schwerd¹⁸, Ekkehard Sturm¹¹, Mechtild Wegner²², Michael S Urschitz²³, Sven F Garbade¹, Daniel Wenning¹, Christian Drosten^{5

6}, Alexander Fichtner¹, Stefan Kölker¹, Georg F Hoffmann¹, Holger Prokisch^{3

4}, Christian Staufner¹

Affiliations

¹ Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Division of Pediatric Neurology and Metabolic Medicine, Heidelberg University, Heidelberg, Germany.
² Clinic for Pediatrics I, University Children's Hospital Essen, University Duisburg-Essen, Essen, Germany.
³ School of Medicine, Institute of Human Genetics, Technical University of Munich, Munich, Germany.
⁴ Helmholtz Zentrum München, Institute of Neurogenomics, Computational Health Center, Neuherberg, Germany.
⁵ Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.
⁶ German Centre for Infection Research (Deutsches Zentrum für Infektionsforschung), Berlin, Germany.
⁷ Department of Paediatric Kidney, Division for Paediatric Gastroenterology and Hepatology, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany.
⁸ Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité Universitätsmedizin Berlin, Berlin, Germany.
⁹ Department of Pediatrics, University Hospital Bonn, Bonn, Germany.
¹⁰ Pediatrics, HELIOS Klinikum Erfurt, Erfurt, Germany.
¹¹ Paediatric Gastroenterology and Hepatology, University Children's Hospital, Eberhard Karls University Tubingen, Tubingen, Germany.
¹² Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹³ Department of Pediatrics, University Hospital Erlangen, Friedrich Alexander University of Erlangen-Nürnberg, Erlangen, Germany.
¹⁴ Department of Pediatric Gastroenterology, Hepatology, and Transplant Medicine, Children's Hospital, University Duisburg-Essen, Essen, Germany.
¹⁵ KUNO University Children's Hospital, University Hospital Regensburg, Regensburg, Germany.
¹⁶ Department of General Pediatrics, University Medical Center Schleswig-Holstein, Kiel, Germany.
¹⁷ Children's Hospital, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
¹⁸ Department of Pediatrics, Division of Gastroenterology and Hepatology, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.
¹⁹ Department of Pediatrics, Division of Neonatology and Pediatric Intensive Care, University Hospital Marburg Baldingerstraße, Marburg, Germany.
²⁰ Neonatology, University Children's Hospital, Eberhard Karls University Tubingen, Tubingen, Germany.
²¹ Department of Pediatrics and Adolescent Medicine, Division of Neonatology and Pediatrics, University Medical Center Ulm, Ulm University, Ulm, Germany.
²² Department of Pediatrics, University Hospital Greifswald, Greifswald, Germany.
²³ German Paediatric Surveillance Unit (ESPED), Division of Paediatric Epidemiology, Institute of Medical Biostatistics, Epidemiology, and Informatics (IMBEI), University Medical Centre of the Johannes Gutenberg University, Mainz, Germany.

PMID: 40621689
DOI: 10.1002/jpn3.70149

Abstract

Objectives: Paediatric acute liver failure (PALF) is a rare but life-threatening condition, yet comprehensive epidemiological data in Germany are lacking. Our study aimed to systematically analyse incidence, aetiology, and outcome of PALF in Germany.

Methods: In a nationwide, population-based surveillance study, cases of PALF (defined following the PALF study group inclusion criteria) were queried from 2016 to 2018 through the German Paediatric Surveillance Unit (ESPED). Demographic, clinical, laboratory, therapeutic, and outcome data were collected and analysed. In case of unexplained aetiology, whole exome and virus sequencing was offered as a complementary diagnostic.

Results: Over the 3-year period, 148 cases were reported, yielding an estimated incidence of 3.7 per 1 million children per year. Neonates and infants were predominantly affected (45% of the cases); median age at PALF was 1.2 years (range: 0-17.9 years). Metabolic/genetic diseases were the most common cause (23%), followed by infectious causes (17%). The overall diagnostic yield was 73%, diagnosis remained unknown in 40 cases. Clinical outcome was age-dependent: new-borns showed a significant higher lethality (42%), followed by infants (29%), toddlers (15%), and school children (12%). Liver transplantation was reported in 22% of cases.

Conclusions: This study provides comprehensive insights into PALF epidemiology in Germany. Metabolic/genetic causes and infectious diseases were most common. Advances in standardised diagnostic work-up and genetic analysis have enhanced diagnostic yield, yet mortality remains substantial, particularly among neonates. Further research is warranted to improve diagnostic accuracy, therapeutic outcomes, and overall management of PALF.

Keywords: ESPED; PALF; aetiology; incidence; outcome.

© 2025 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Abstract

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