本期文章：《新英格兰医学杂志》：Online/在线发表

美国阿拉巴马大学伯明翰分校L. Helena Gutierrez Sanchez团队对儿童急性肝炎和人类腺病毒感染病例系列进行了分析。该项研究成果发表在2022年7月13日出版的《新英格兰医学杂志》上。

人类腺病毒通常会导致健康儿童的自限性呼吸道、胃肠道和结膜感染。2021年末至2022年初，几名先前健康的儿童被确诊为急性肝炎和人类腺病毒血症。

研究组使用国际疾病分类第10次修订版代码来识别2021年10月1日至2022年2月28日期间入住阿拉巴马州儿童医院的所有肝炎儿童（<18岁）；病例系列包括那些通过全血定量聚合酶链反应（PCR）检测出人类腺病毒阳性的急性肝炎患者。人口统计学、临床、实验室和治疗数据来自医疗记录。剩余的血液样本被送往诊断确认和人类腺病毒分型。

共有15名儿童被确定患有急性肝炎，其中6名（40%）患有已确定原因的肝炎，9名（60%）患有未知原因的肝炎。8名（89%）不明原因肝炎患者检测出人类腺病毒阳性。这8名患儿加上另外1名转诊到该机构进行随访的患儿被纳入本病例系列（中位年龄2岁11个月）。

肝活检显示6名儿童中有轻度至中度活动性肝炎，有些儿童有胆汁淤积，有些没有胆汁淤积，但在免疫组化检查或电子显微镜下没有显示人类腺病毒的证据。3名儿童（50%）肝组织腺病毒PCR检测呈阳性。对5名儿童的标本进行测序，结果显示有三种不同的人类腺病毒41型六邻体变体。两名儿童接受了肝移植；所有其他患者在支持性护理下康复。

2021年10月1日至2022年2月28日，阿拉巴马州儿童医院收治的大多数不明原因急性肝炎儿童中存在人类腺病毒血症，但人类腺病毒是否是病因尚不清楚。测序结果表明，若人类腺病毒是致病性的，则这起疫情非单一菌株引起。

附：英文原文

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

Author: L. Helena Gutierrez Sanchez, M.D.,, Henry Shiau, M.D.,, Julia M. Baker, Ph.D.,, Stephanie Saaybi, M.D.,, Markus Buchfellner, M.D.,, William Britt, M.D.,, Veronica Sanchez, Ph.D.,, Jennifer L. Potter, M.P.H.,, L. Amanda Ingram, M.P.H.,, David Kelly, M.D.,, Xiaoyan Lu, M.S.,, Stephanie Ayers-Millsap, M.P.H.,, Wesley G. Willeford, M.D.,, Negar Rassaei, M.D.,, Julu Bhatnagar, Ph.D.,, Hannah Bullock, Ph.D.,, Sarah Reagan-Steiner, M.D.,, Ali Martin, B.S.,, Michael E. Rogers, D.O., M.P.H.,, Anna M. Banc-Husu, M.D.,, Sanjiv Harpavat, M.D., Ph.D.,, Daniel H. Leung, M.D.,, Elizabeth A. Moulton, M.D., Ph.D.,, Daryl M. Lamson, B.S.,, Kirsten St. George, Ph.D.,, Aron J. Hall, D.V.M.,, Umesh Parashar, M.D.,, Adam MacNeil, Ph.D.,, Jacqueline E. Tate, Ph.D.,, and Hannah L. Kirking, M.D.

Issue&Volume: 2022-07-13

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 International Classification of Diseases, 10th Revision, 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.

DOI: 10.1056/NEJMoa2206294