{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T14:41:05Z","timestamp":1781534465932,"version":"3.54.5"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>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 have recently reported an association between this virus and different human pathologies. In this study, we present a 6-month-old female infant 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\u2013clavulanate for a total of 4\u00a0days. The 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\u2013Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV), enterovirus, and adenovirus, were negative. Metabolic and genetic alterations, deficiency of alpha-1 antitrypsin, and Wilson\u2019s 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 evidence supporting the hypothesis of the pathogenic role of HPgV-1 and warrants particular attention, especially in the pediatric population. Moreover, here we confirmed the diagnostic power of metagenomic-NGS in the detection of unusual pathogens.<\/jats:p>","DOI":"10.3389\/fgene.2025.1653082","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T04:12:24Z","timestamp":1757563944000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Shotgun metagenomics detects the human pegivirus complete genome in a pediatric patient with acute hepatitis of unknown etiology: a case report"],"prefix":"10.3389","volume":"16","author":[{"given":"Roberta","family":"Vazzana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Mularoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Vaiana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Cona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Mul\u00e8","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Amato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giusy","family":"Ranucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Giulio","family":"Conaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Agnese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Cuscino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Gallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.3201\/eid2410.180161","article-title":"Human pegivirus in patients with encephalitis of unclear etiology, Poland","volume":"24","author":"Bukowska-Osko","year":"2018","journal-title":"Emerg. 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