[Metagenomic sequencing-based pathogen analysis in pediatric severe acute non-A-E hepatitis]

Objective: Metagenomic sequencing was employed to analyze the pathogen detection profile in pediatric severe acute non-A-E hepatitis. Methods: Based on the platform of the China Childhood Severe Acute Hepatitis Collaborative Group, a case series study was conducted. This study enrolled 36 children with severe acute non-A-E hepatitis, who were admitted to 17 hospitals between April and July 2022. Clinical data, including etiological test results and liver function tests, were collected, and peripheral blood and nasopharyngeal swab specimens were obtained. Metagenomic next-generation sequencing (mNGS) was performed to detect potential infectious pathogens. Results: Among 36 children, there were 24 males and 12 females, with an onset age of 3.5 (1.1, 9.0) years. Common clinical symptoms were fever in 22 cases (61%), jaundice in 13 cases (36%), vomiting in 12 cases (33%), abdominal pain in 10 cases (28%), rash in 10 cases (28%), and diarrhea in 3 cases (8%). Serum alanine aminotransferase and aspartate aminotransferase levels were 950 (826, 1 404) and 811 (498, 1 295) U/L, respectively. Using PCR, plasma Epstein-Barr virus (EBV)-DNA was tested in 31 cases (86%) and plasma cytomegalovirus (CMV)-DNA in 25 cases (69%), and all results were below 5×10⁵ copies/L. Plasma mNGS was performed on all 36 patients, detecting 11 viruses. These included EBV in 14 cases, CMV in 12 cases, human adenovirus in 2 cases, herpes simplex virus type 1 in 2 cases, adeno-associated virus type 2 (AAV2) in 1 case, and 6 other viruses. No patient tested positive for both human adenovirus and AAV2 simultaneously. Plasma mNGS results showed a viral read count of 4 (2, 10) per 1×10⁸ reads. Nasopharyngeal swab mNGS was performed on 8 cases (22%), detecting 7 viruses. These included human herpesvirus 7 in 4 cases, EBV in 3 cases, and CMV in 3 cases, as well as 4 other viruses. Human adenovirus and AAV2 were not detected. Among the 4 children with human herpesvirus 7, 2 cases were also positive for human herpesvirus 6B, but neither virus was detected in their plasma mNGS. Conclusions: The detection rates of human adenovirus and AAV2 are both low among children with severe acute non-A-E hepatitis, and there are no cases of co-infection with both viruses.