Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center.
Department of Pathology and Laboratory Medicine, Children's of Alabama.
Am J Surg Pathol. 2023 Sep 1;47(9):977-989. doi: 10.1097/PAS.0000000000002084. Epub 2023 Jun 26.
A recent increase in reports of severe acute hepatitis of unknown etiology in children is under investigation. Although adenovirus has been frequently detected, its role remains unclear, and systematic histopathologic analysis is lacking. We conducted a retrospective study of 11 children hospitalized between October 2021 and May 2022 with unexplained acute hepatitis and concurrent adenovirus infection. Liver biopsies collected shortly after admission demonstrated moderately to severely active hepatitis in 8/11 (73%) cases, characterized by marked portal mixed inflammation, moderate-to-severe interface activity, and milder lobular inflammation. Clusters of plasma cells were present in 6/11 (55%) cases, mimicking autoimmune hepatitis. Semiquantitative scoring of 17 discrete histologic features found that greater degrees of portal inflammation, interface activity, bile duct injury, bile ductular reaction, lobular inflammation, Kupffer cell activation, and hepatocyte focal necrosis were significantly more common in these cases in comparison to the control group of unexplained acute severe hepatitis without adenovirus infection. Liver biopsy immunohistochemistry was negative for adenovirus in all cases. Polymerase chain reaction testing of liver tissue was positive for the enteric adenovirus serotypes 41 (species F) in 10/11 (91%) cases. An immunoprofile study of hepatic infiltrating lymphocytes in 1 patient revealed the presence of large numbers of CD3 + and CD4 + lymphocytes. Nine patients received supportive treatment without steroids and recovered without the need for liver transplantation. In summary, liver injury in children with severe acute hepatitis and adenovirus infection is characterized by a hepatitic pattern that resembles severe autoimmune hepatitis and may represent an immune-mediated process associated with viral infection.
近期，不明病因儿童严重急性肝炎病例报告有所增加，目前正在调查中。虽然腺病毒频繁被检测到，但它的作用仍不清楚，且缺乏系统的组织病理学分析。我们对 2021 年 10 月至 2022 年 5 月期间因不明原因急性肝炎且同时感染腺病毒而住院的 11 名儿童进行了回顾性研究。入院后不久采集的肝活检显示，11 例中有 8 例（73%）表现为中度至重度活跃性肝炎，其特征为显著的门管区混合炎症、中重度界面活动和较轻的肝小叶炎症。6 例（55%）存在浆细胞簇，类似于自身免疫性肝炎。对 17 种离散组织学特征进行半定量评分发现，与无腺病毒感染的不明原因急性重症肝炎对照组相比，这些病例的门管区炎症、界面活动、胆管损伤、胆管反应、肝小叶炎症、枯否细胞激活和肝细胞局灶坏死程度更严重。所有病例肝活检免疫组化均为腺病毒阴性。11 例中有 10 例（91%）的肝组织聚合酶链反应检测到肠道腺病毒 41 型（种 F）。对 1 例患者的肝浸润淋巴细胞进行免疫表型研究显示，存在大量 CD3+和 CD4+淋巴细胞。9 例患者未接受类固醇治疗，仅接受支持治疗，无需肝移植即可康复。总之，腺病毒感染所致儿童严重急性肝炎的肝损伤表现为类似于重度自身免疫性肝炎的肝炎模式，可能代表与病毒感染相关的免疫介导过程。
