A NEW nationwide study in Germany has provided the first comprehensive epidemiological assessment of paediatric acute liver failure (PALF), a rare but life-threatening condition in children. Drawing on data from the German Paediatric Surveillance Unit (ESPED), the study recorded 148 cases of PALF, estimating an incidence of 3.7 cases per million children per year, comparable to other ultrarare paediatric conditions such as arterial ischaemic stroke.
The study aimed to improve understanding of PALF’s aetiology, incidence, and outcomes, especially in cases previously labelled as indeterminate. Importantly, 73% of cases received a specific diagnosis through an enhanced diagnostic protocol that included whole exome sequencing (WES), advanced metabolic profiling, and virological analysis. Of 47 unsolved cases that underwent WES, 13 were diagnosed, highlighting the value of genetic testing in identifying hidden metabolic or monogenic causes.
Metabolic and genetic disorders emerged as the most frequent aetiological group, reflecting broader diagnostic capabilities compared to earlier studies. Infections were the second most common cause, with viruses such as CMV, HSV, influenza, and adenovirus identified. No cases of classical galactosemia were found, likely due to routine newborn screening in Germany. The role of infections as potential triggers for PALF, especially in genetically predisposed children, remains a focus for future research.
Surprisingly, a high number of gestational alloimmune liver disease cases were reported, a finding that requires further investigation. Toxic causes, including paracetamol overdose, were less common than in US data, possibly due to restricted over-the-counter availability in Germany.
Clinical symptoms did not significantly vary by cause, but high ALT/AST levels were linked to better outcomes, while high INR, ammonia, and bilirubin levels, along with the need for intensive interventions, predicted poorer prognosis. Although liver biopsies were performed in select cases, their utility remains controversial due to risks involved.
This study demonstrates that incorporating advanced genetic and virological tools into diagnostic workflows can significantly improve the identification of PALF causes, potentially guiding more targeted treatments and timely decisions about liver transplantation.
Reference
Lenz D et al. Paediatric acute liver failure: a prospective, nationwide, population-based surveillance study in Germany. J Pediatr Gastroenterol Nutr. 2025;DOI:10.1002/jpn3.70149.
