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

Maria AlShurman, Bara’ Abdallah AlShurman, Hibah Sehar, Amy Evans, Tala Alzoubi, Christina Mac, Zahid Ahmad Butt
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Abstract

Abstract 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.
揭示病因不明的儿童严重急性肝炎的潜在原因:综合综述
背景自2021年10月以来,多个国家报告了多例非由甲型戊型肝炎病毒引起的儿童不明病因严重急性肝炎(SAHUA)病例。截至2022年9月14日,在37个国家和地区报告了约1296例SAHUA疑似病例。本研究的目的是全面了解此次暴发,包括其起源、当前病例、临床体征、可能的假设和潜在的治疗方法。方法在PubMed和Medline数据库中检索2021年10月至2023年9月的文献。检索了其他网站,包括WHO、CDC、ECDC和UKHSA,以获取进一步的相关数据。结果常见临床症状为黄疸、呕吐、白便、腹泻、腹痛、恶心,发热少见。谷丙转氨酶和谷丙转氨酶普遍升高,大多数病例腺病毒检测呈阳性。然而,肝组织免疫组化染色对腺病毒的检测结果通常为阴性,从而挑战了腺病毒是确定病因的假设。最近一项令人信服的假设表明,在涉及AAV-2异常复制产物和免疫介导的肝病的儿科病例中,AAV-2可能是SAHUA的病因。低免疫原性、组织亲和性和免疫反应的证据支持这一假设。SARS-CoV-2的作用也得到了探讨。一些SAHUA病例即使在PCR检测阴性的情况下也有SARS-CoV-2 IgG阳性,从而提示沉默的既往感染。西多福韦是一种建议用于免疫功能低下患者严重人腺病毒感染的治疗方法,但在两例患者中并未降低腺病毒载量。值得注意的是,据报告有29人死亡,55人需要或接受了肝移植。结论儿童SAHUA是一个复杂的挑战,可能与AAV-2和免疫介导因素有关。SARS-CoV-2可能影响疾病的严重程度,这种可能性需要进一步调查。治疗方案包括诊断、支持性护理、抗病毒药物和免疫抑制。预防依赖于感染控制措施,管理需要先进的诊断方法和国际合作。SAHUA仍然是一个谜,因此强调需要继续研究和适应新出现的传染性威胁。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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