{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:12:20Z","timestamp":1785402740432,"version":"3.56.0"},"reference-count":15,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University\u2014Plovdiv","award":["20\/2026"],"award-info":[{"award-number":["20\/2026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Acute hepatitis B virus (HBV) infection is rare during infancy, and severe symptomatic HBV-associated hepatitis is even less common. We describe two siblings who developed severe HBV-associated liver injury during infancy, two years apart, but experienced markedly divergent clinical outcomes. Clinical, laboratory, virological, microbiological, imaging, therapeutic, and follow-up data were retrospectively reviewed. Household members were subsequently tested for HBV and HDV. The first infant, a 5-month-old girl, presented with HBsAg positivity, negative serological markers for HAV, HCV, and HEV, and severe acute liver injury with a fulminant clinical course that resulted in death. Because anti-HBc IgM, HBV DNA, repeat HBsAg testing, and follow-up serology were unavailable, acute HBV infection could not be confirmed, and the episode was therefore classified as presumed HBV-associated fulminant hepatitis. The rapidly fatal clinical course precluded a comprehensive etiological evaluation, and the available medical records did not fully document the diagnostic work-up. The second patient, a 4-month-old boy, presented with serological and molecular evidence of acute HBV infection, including low-level HBV DNA, total anti-HDV positivity of uncertain clinical significance, and positive CMV IgM\/IgG serology. He also had a urinary tract infection (UTI) caused by extended-spectrum \u03b2-lactamase (ESBL)-producing Escherichia coli. Without HDV RNA and CMV DNA testing, active HDV infection and clinically significant CMV disease could not be definitively confirmed, while passive transfer of maternal anti-HDV antibodies could not be excluded. The patient required prolonged hospitalization, during which he received supportive, replacement, and antimicrobial therapy. He recovered, and long-term follow-up demonstrated HBsAg clearance with undetectable HBV DNA. Testing of household members revealed chronic HBV infection in the mother and maternal grandmother, both of whom had detectable HDV RNA, consistent with ongoing HBV\/HDV circulation within the family. However, without viral sequence data from the infants, the source, route, timing, and direction of transmission could not be established. These cases illustrate the potential severity of HBV-associated hepatitis during infancy and its highly variable clinical outcomes. They also underscore the importance of antenatal HBV screening, timely immunoprophylaxis, and cautious interpretation of suspected viral coinfections when molecular confirmation is unavailable.<\/jats:p>","DOI":"10.3390\/pathogens15080804","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T08:09:42Z","timestamp":1785398982000},"page":"804","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Severe HBV-Associated Hepatitis in Infants from the Same Family: Two Clinical Cases with Different Outcomes"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0573-9889","authenticated-orcid":false,"given":"Petar","family":"Vasilev","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Parasitology and Tropical Medicine, Faculty of Medicine, Medical University, 4002 Plovdiv, Bulgaria"},{"name":"Clinic of Infectious Diseases, University Multipurpose Hospital for Active Treatment \u201cSveti Georgi\u201d, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhelyazko","family":"Badarov","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Parasitology and Tropical Medicine, Faculty of Medicine, Medical University, 4002 Plovdiv, Bulgaria"},{"name":"Clinic of Infectious Diseases, University Multipurpose Hospital for Active Treatment \u201cSveti Georgi\u201d, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Todev","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Parasitology and Tropical Medicine, Faculty of Medicine, Medical University, 4002 Plovdiv, Bulgaria"},{"name":"Clinic of Infectious Diseases, University Multipurpose Hospital for Active Treatment \u201cSveti Georgi\u201d, 4002 Plovdiv, Bulgaria"},{"name":"Center for Emergency Medical Care, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2223-9058","authenticated-orcid":false,"given":"Petya","family":"Argirova","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Parasitology and Tropical Medicine, Faculty of Medicine, Medical University, 4002 Plovdiv, Bulgaria"},{"name":"Department of Infectious Diseases, Pulmed University Hospital, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6239-4418","authenticated-orcid":false,"given":"Velina","family":"Stoeva","sequence":"additional","affiliation":[{"name":"Section of Epidemiology, Department of Epidemiology and Disaster Medicine, Faculty of Public Health, Medical University, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boriana","family":"Chopova","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Medical University, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Atanasova","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, University Multipurpose Hospital for Active Treatment \u201cSveti Georgi\u201d, 4002 Plovdiv, Bulgaria"},{"name":"Department of Medical Microbiology and Immunology \u201cProf. Dr. Elisei Yanev\u201d, Faculty of Medicine, Medical University, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Baltadzhiev","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Parasitology and Tropical Medicine, Faculty of Medicine, Medical University, 4002 Plovdiv, Bulgaria"},{"name":"Clinic of Infectious Diseases, University Multipurpose Hospital for Active Treatment \u201cSveti Georgi\u201d, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariyana","family":"Stoycheva-Vartigova","sequence":"additional","affiliation":[{"name":"Research Institute, Medical University, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2026, April 21). Hepatitis B. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hepatitis-b."},{"key":"ref_2","unstructured":"World Health Organization (2017). Global Hepatitis Report 2017, World Health Organization."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1002\/hep.29800","article-title":"Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance","volume":"67","author":"Terrault","year":"2018","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2017). EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J. Hepatol., 67, 370\u2013398.","DOI":"10.1016\/j.jhep.2017.03.021"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"E16","DOI":"10.1046\/j.1440-1746.2000.02096.x","article-title":"Natural history of hepatitis B virus infection in children","volume":"15","author":"Chang","year":"2000","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0140-6736(75)91359-8","article-title":"Severe viral hepatitis type B in infancy","volume":"1","author":"Dupuy","year":"1975","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1097\/INF.0b013e31821e23b3","article-title":"Successful tenofovir treatment for fulminant hepatitis B infection in an infant","volume":"30","author":"Diamanti","year":"2011","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_8","unstructured":"World Health Organization (2020). Prevention of Mother-to-Child Transmission of Hepatitis B Virus: Guidelines on Antiviral Prophylaxis in Pregnancy, World Health Organization."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.rr6701a1","article-title":"Prevention of hepatitis B virus infection in the United States: Recommendations of the Advisory Committee on Immunization Practices","volume":"67","author":"Schillie","year":"2018","journal-title":"MMWR Recomm. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1136\/bmj.38719.435833.7C","article-title":"Effect of hepatitis B immunisation in newborn infants of mothers positive for hepatitis B surface antigen: Systematic review and meta-analysis","volume":"332","author":"Lee","year":"2006","journal-title":"BMJ"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/S1473-3099(20)30586-7","article-title":"Efficacy and safety of antiviral prophylaxis during pregnancy to prevent mother-to-child transmission of hepatitis B virus: A systematic review and meta-analysis","volume":"21","author":"Funk","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1002\/jmv.2057","article-title":"Sequence analysis of hepatitis B virus genomes from an infant with acute severe hepatitis and a hepatitis B e antigen-positive carrier mother","volume":"65","author":"Komatsu","year":"2001","journal-title":"J. Med. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.jpeds.2005.12.051","article-title":"Acute liver failure in children: The first 348 patients in the Pediatric Acute Liver Failure Study Group","volume":"148","author":"Squires","year":"2006","journal-title":"J. Pediatr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/nri.2016.90","article-title":"Sex differences in immune responses","volume":"16","author":"Klein","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Wang, C., Liu, Z., Zou, G., Li, J., and Lu, M. (2019). Host genetic determinants of hepatitis B virus infection. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.00696"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/8\/804\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T08:31:02Z","timestamp":1785400262000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/8\/804"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":15,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["pathogens15080804"],"URL":"https:\/\/doi.org\/10.3390\/pathogens15080804","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]}}}