Background: Pediatric Acute Liver Failure (PALF) is an acute-onset, high-mortality disease that affects children of all ages. Its etiology includes drug toxicity, infections, genetic disorders, autoimmune hepatitis, and metabolic diseases1. The etiology is a crucial determinant in guiding treatment and prognosis2. Technological advancements have decreased the proportion of cases with indeterminate causes3.
Aims: This study aims to investigate the potential causes of indeterminate PALF and determine whether it is associated with viral infections.
Methods: We conducted a retrospective analysis of the clinical data of PALF patients treated at our center from September 2015 to November 2024. Liver tissue samples were subjected to metagenomic next-generation sequencing (mNGS).
Results: A total of 72 pediatric patients were included in the study, among which 36 cases (50%) were of indeterminate etiology (IND-PALF). Of IND-PALF patients, 26 cases underwent mNGS on liver tissue samples. Except for 2 cases with negative results, human herpesvirus-6 (HHV-6) was detected in 23 patients, including 22 cases of HHV-6B and 1 case of HHV-6A. 4 patients had HHV-6B as a sole infection. In contrast, the remaining 19 patients had mixed infections, including cytomegalovirus, Epstein-Barr Virus, HHV-7, adenovirus, and human polyomavirus type 2. 3 patients had concomitant bacterial infections, including Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis (Fig.1). 21 patients underwent liver transplantation (LT), while 2 patients improved after pharmacological treatment. The average HHV-6 replicative copies per milliliter (RPM) in the LT group was 531 copies/mL, significantly higher than that in the non-LT group (56 copies/mL).
Conclusion: The number of IND-PALF patients remains relatively high. The mNGS can explore the etiology by detecting a broad spectrum of potentially infectious agents. HHV-6 may be an essential factor in the development of PALF, in which viral replication levels appear to impact patient prognosis. Further investigation is needed to explore the mechanisms through which HHV-6 induces liver failure.