Acute Hepatitis of Unknown Origin in Children: Two Cases in a Portuguese Hospital

Costa, Ricardo Craveiro; Esteves, Catarina Schrempp; Flores, P.; Varandas, Luís

doi:10.20344/amp.18690

Cited by 3 publications

(2 citation statements)

References 6 publications

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“…Інші дослідження описували або невелику групу пацієнтів [11,17], або окремі випадки [18][19][20][21] та були з інших регіонів світу (Китай, Японія, Нідерланди). Результати, описані в цих публікаціях, були суперечливими.…”

Section: аналіз повідомлень про етіологію гострого гепатитуunclassified

“…Результати, описані в цих публікаціях, були суперечливими. Одні підтримували гіпотезу аденовірусу [11,21], інші більше схилялись на користь SARS-CoV-2 [17,18,20].…”

Section: аналіз повідомлень про етіологію гострого гепатитуunclassified

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Acute hepatitis of unknown origin in children: analysis of probable etiologies

Boyarchuk,

Pavlyshak

2023

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Background. An outbreak of hepatitis of unknown origin in children aged 1 month — 16 years was first reported by the WHO in April 2022. It was accompanied by a high frequency of acute liver failure, and up to 5 % of children required liver transplantation. The purpose of the review was to determine probable etiological factors and mechanisms of acute hepatitis of unknown origin based on a systematic analysis of literary sources. Materials and methods. We conducted a search for studies on cases or case series of acute hepatitis of unknown origin in the PubMed between January 2022 and February 2023. A combination of the following terms was used for the search: “unknown hepatitis”, “hepatitis of unknown origin”, “non-A-E hepatitis”, “hepatitis of unknown etiology” and “children”. Results. According to the search results, 312 publications were found. After the selection, 14 publications were included in the review. A systematic analysis of 1,188 cases of acute hepatitis of unknown origin, which corresponded to the identified case, showed a high variability of causative agents. However, most children were tested positive for adenovirus (almost 57 %), and 14 % of children had a positive PCR for SARS-CoV-2. Among other viruses detected in children, viruses of the herpes family should be noted, especially human herpesvirus 7 (34.2 %), human herpesvirus 6 (20 %), Epstein-Barr virus (18.2 %), cytomegalovirus (9.2 %). Rhinovirus (40.7 %), enterovirus/rhinovirus (28.7 %), parainfluenza virus (15.4 %), streptococcal infection, and other pathogens were also found. Conclusions. Viruses, genetic predisposition and other factors that change the body’s immune response play an important role in the development of an outbreak of severe hepatitis. Systematic analysis has shown that human adenovirus most often acts as a helper for adeno-associated virus 2, which plays a major role in initiating an immune response in genetically predisposed individuals, causing acute hepatitis and acute liver failure. SARS-CoV-2 infection probably also plays a certain role in immune activation and in the development of hyperinflammation, as do other viruses that act as helpers for adeno-associated virus 2. Continued collection of detailed clinical, microbiological, and epidemiological data on probable cases, as well as well-planned and coordinated follow-up studies are necessary to identify risk factors and other etiological factors associated with this disease.

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Section: аналіз повідомлень про етіологію гострого гепатитуunclassified

Acute hepatitis of unknown origin in children: analysis of probable etiologies

Boyarchuk,

Pavlyshak

2023

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Uncovering the Underlying Causes of Severe Acute Hepatitis of Unknown Aetiology in Children: A Comprehensive Review

AlShurman,

Sehar

et al. 2023

Dr. Sulaiman Al Habib Med J

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Background Since October 2021, multiple paediatric cases of severe acute hepatitis of unknown aetiology (SAHUA) not caused by hepatitis A–E viruses have been reported by multiple countries. As of 14 September 2022, approximately 1296 probable cases of SAHUA in 37 countries and regions had been reported. Objectives The purpose of this study was to present a complete picture of this outbreak, including its origin, current cases, clinical signs, possible hypotheses, and potential treatments. Methods A thorough search for literature from October 2021 to September 2023 was performed in the PubMed and Medline databases. Additional websites, including the WHO, CDC, ECDC, and the UKHSA, were searched for further relevant data. Results Common clinical symptoms include jaundice, vomiting, pale stools, diarrhoea, abdominal pain, and nausea, whereas fever is infrequent. Elevated AST and ALT are prevalent, and most cases test positive for adenovirus. However, immunohistochemical staining on liver tissue often yields negative results for adenovirus, thus challenging the hypothesis that adenovirus is a definitive cause. A recent compelling hypothesis has implicated AAV-2 as a likely etiologic agent of SAHUA in paediatric cases involving abnormal AAV-2 replication products and immune-mediated hepatic disease. Evidence of low immunogenicity, tissue tropism, and immune responses supports this hypothesis. SARS-CoV-2's role has also been explored. Some SAHUA cases have SARS-CoV-2 IgG positivity even when PCR tests are negative, thereby suggesting silent prior infections. Cidofovir, a suggested treatment for severe human adenovirus infection in immunocompromised patients, has not decreased adenoviral load in two cases. Notably, 29 deaths have been reported, and 55 cases have required or received liver transplant. Conclusion SAHUA in children presents a complex challenge with potential involvement of AAV-2 and immune-mediated factors. SARS-CoV-2 may affect disease severity—a possibility warranting further investigation. Treatment options include diagnostics, supportive care, antivirals, and immunosuppression. Prevention relies on infection control measures, and management requires advanced diagnostics and international collaboration. SAHUA remains an enigma, thus underscoring the need for continued research and adaptability to emerging infectious threats.

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