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儿童急性肝炎与人类腺病毒感染病例系列

A Case Series of Children with Acute Hepatitis and Human Adenovirus Infection.

机构信息

From the Division of Pediatric Gastroenterology, Hepatology, and Nutrition (L.H.G.S., H.S., S.S.) and the Division of Pediatric Infectious Diseases, (M.B., W.B., V.S., J.L.P.), Department of Pediatrics, and the Department of Pathology (D.K.), University of Alabama at Birmingham, Children's of Alabama (L.H.G.S., H.S., S.S., M.B., D.K.), and Jefferson County Department of Health (S.A.-M., W.G.W.), Birmingham, and the Alabama Department of Public Health, Montgomery (L.A.I., A. Martin) - all in Alabama; the Division of Viral Diseases (J.M.B., X.L., A.J.H., U.P., A. MacNeil, J.E.T., H.L.K.), the Epidemic Intelligence Service (J.M.B.), and the Division of High-Consequence Pathogens and Pathology (N.R., J.B., H.B., S.R.-S.), Centers for Disease Control and Prevention, Atlanta, and Synergy America, Duluth (H.B.) - both in Georgia; the Department of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center (M.E.R.), and the Department of Pediatrics, University of Cincinnati College of Medicine (M.E.R.) - both in Cincinnati; the Division of Pediatric Gastroenterology, Hepatology and Nutrition (A.M.B.-H., S.H., D.H.L.) and the Division of Pediatric Infectious Diseases (E.A.M.), Texas Children's Hospital, and the Department of Pediatrics, Baylor College of Medicine (A.M.B.H., S.H., D.H.L., E.A.M.) - both in Houston; and the Wadsworth Center, New York State Department of Health (D.M.L., K.S.G.), and the Department of Biomedical Sciences, University at Albany (K.S.G.) - both in Albany.

出版信息

N Engl J Med. 2022 Aug 18;387(7):620-630. doi: 10.1056/NEJMoa2206294. Epub 2022 Jul 13.

Abstract

BACKGROUND

Human adenoviruses typically cause self-limited respiratory, gastrointestinal, and conjunctival infections in healthy children. In late 2021 and early 2022, several previously healthy children were identified with acute hepatitis and human adenovirus viremia.

METHODS

We used , codes to identify all children (<18 years of age) with hepatitis who were admitted to Children's of Alabama hospital between October 1, 2021, and February 28, 2022; those with acute hepatitis who also tested positive for human adenovirus by whole-blood quantitative polymerase chain reaction (PCR) were included in our case series. Demographic, clinical, laboratory, and treatment data were obtained from medical records. Residual blood specimens were sent for diagnostic confirmation and human adenovirus typing.

RESULTS

A total of 15 children were identified with acute hepatitis - 6 (40%) who had hepatitis with an identified cause and 9 (60%) who had hepatitis without a known cause. Eight (89%) of the patients with hepatitis of unknown cause tested positive for human adenovirus. These 8 patients plus 1 additional patient referred to this facility for follow-up were included in this case series (median age, 2 years 11 months; age range, 1 year 1 month to 6 years 5 months). Liver biopsies indicated mild-to-moderate active hepatitis in 6 children, some with and some without cholestasis, but did not show evidence of human adenovirus on immunohistochemical examination or electron microscopy. PCR testing of liver tissue for human adenovirus was positive in 3 children (50%). Sequencing of specimens from 5 children showed three distinct human adenovirus type 41 hexon variants. Two children underwent liver transplantation; all the others recovered with supportive care.

CONCLUSIONS

Human adenovirus viremia was present in the majority of children with acute hepatitis of unknown cause admitted to Children's of Alabama from October 1, 2021, to February 28, 2022, but whether human adenovirus was causative remains unclear. Sequencing results suggest that if human adenovirus was causative, this was not an outbreak driven by a single strain. (Funded in part by the Centers for Disease Control and Prevention.).

摘要

背景

人类腺病毒通常在健康儿童中引起自限性呼吸道、胃肠道和结膜感染。2021 年末和 2022 年初,一些以前健康的儿童被诊断出患有急性肝炎和人腺病毒血症。

方法

我们使用 ICD-10 代码来确定 2021 年 10 月 1 日至 2022 年 2 月 28 日期间在阿拉巴马儿童医院住院的所有(<18 岁)肝炎患儿;那些通过全血定量聚合酶链反应(PCR)检测为人腺病毒阳性的急性肝炎患儿被纳入我们的病例系列。从病历中获取人口统计学、临床、实验室和治疗数据。保留血样用于诊断确认和人腺病毒分型。

结果

共确定了 15 名患有急性肝炎的儿童-6 名(40%)有明确病因的肝炎和 9 名(60%)病因不明的肝炎。8 名(89%)病因不明的肝炎患儿检测出人腺病毒阳性。这些 8 名患儿和另外 1 名转介至本机构进行随访的患儿被纳入本病例系列(中位年龄为 2 岁 11 个月;年龄范围为 1 岁 1 个月至 6 岁 5 个月)。6 名患儿的肝活检显示为轻度至中度活动性肝炎,其中一些伴有和不伴有胆汁淤积,但在免疫组织化学检查或电子显微镜检查中未显示人腺病毒的证据。3 名患儿的肝组织 PCR 检测人腺病毒阳性(50%)。对 5 名患儿的标本进行测序显示有 3 种不同的人腺病毒 41 型六邻体变体。2 名患儿接受了肝移植;其余所有患儿均通过支持治疗康复。

结论

2021 年 10 月 1 日至 2022 年 2 月 28 日期间,阿拉巴马儿童医院收治的病因不明的急性肝炎患儿中,大多数患儿存在人腺病毒血症,但人腺病毒是否为致病原因尚不清楚。测序结果表明,如果人腺病毒是致病原因,这不是由单一菌株引起的暴发。(部分由疾病控制和预防中心资助)。

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