Shotgun metagenomics detects Human Pegivirus complete genome in a pediatric patient with acute hepatitis of unknown etiology: a case report

Roberta Vazzana^1*Alessandra Mularoni²Claudia Vaiana¹Andrea Cona²Giovanni Mulè²Caterina Amato¹Giusy Ranucci³Pier Giulio Conaldi¹Valentina Agnese¹Nicola Cuscino¹Alessia Gallo¹

• ¹Department of Research, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Palermo, Italy
• ²Unit of Infectious Diseases, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Palermo, Italy
• ³Pediatric Department for the treatment and study of abdominal diseases and abdominal transplantation, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Palermo, Italy

Human Pegivirus (HPgV) is a positive-sense single strand RNA virus belonging to the Flaviviridae family. Although not conclusively linked to a specific disease, an increasing number of studies are recently reporting as association between this virus and different human pathologies. Here we present a 6-months old female admitted to the hospital for severe acute hepatitis. Her clinical history started with a one-week of fever and diarrhea treated with paracetamol and amoxicillin-clavulanate for a total of four days. Persistence of the symptoms, high levels of transaminases, coagulopathy, increased lymphocytosis and C reactive protein (CRP) in the blood, suggested an acute hepatitis episode. Serological and molecular biology tests for hepatotropic and non-hepatotropic viruses, including Hepatitis B virus (HBV), Hepatitis A virus (HAV), Hepatitis C virus (HCV), Hepatitis E virus (HEV), Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), Herpes Simplex Virus (HSV), enterovirus and adenovirus, were tested negative. Metabolic and genetic alterations, deficiency of alpha-1 antitrypsin and Wilson's disease were ruled out following negative results. The child was thus treated with supportive therapy. Metagenomic Next Generation Sequencing (mNGS), performed to identify other possible infective agents undetected with the classical tests, showed the presence of the complete genome of Human HPgV-1. This case provides further evidences supporting the hypothesis of the pathogenic role of HPgV-1 and warrants a particular attention, especially in the pediatric population. Moreover, here we confirmed the diagnostic power of metagenomic-NGS in the detection of unusual pathogens.