小兒肝炎與腺病毒 41 之間的關聯仍不清楚

資料來源：露西.希克斯 / Medscape / 2022 年 7 月 13 日

雖然兩項新研究重申了腺病毒 41 與兒童不明原因急性肝炎之間可能存在的關係，但這些感染是否重要或僅僅是旁觀者仍不清楚。

    在兩項研究中——一項在美國阿拉巴馬州進行，另一項在英國進行——研究人員發現，90% 患有不明原因急性肝炎的兒童其腺病毒 41 型檢測呈陽性。該病毒亞型並非罕見感染，但在兒童中通常會導致腸胃炎。

阿拉巴馬大學伯明翰分校兒科肝移植計畫的醫學主任 Helena Gutierrez 醫學博士在接受 Medscape Medical News 採訪時說：「在全世界，腺病毒仍然是這些兒科肝炎病例中的常見訊號」。 .她領導了一項研究。她說，需要更多的數據來了解這種病毒在這些病例中可能扮演的角色。

11 月，阿拉巴馬州公共衛生處和美國疾病控制與預防中心 (CDC) 開始在伯明翰的阿拉巴馬州兒童醫院調查一群組嚴重的兒科肝炎病例；這些兒童（在腺病毒檢測中也呈陽性）。4 月，英國宣布他們正在調查類似病例，而美國疾病預防控制中心在全國範圍內擴大了搜索範圍。截至 7 月 8 日止，全球有35 個國家已向世界衛生組織報告了1,010 例的病例。根據最新統計，英國有 263 例確診病例，美國 CDC 正在調查 332 例病例。  

這兩項研究都發表在今天的《新英格蘭醫學雜誌》上，提供了一些關於這些神秘肝炎病例的額外臨床數據。 Gutierrez 的研究觀察了 10 月 1 日至 2 月 28 日期間因不明原因肝炎入院的 9 名兒童。患者的中位數年齡為 2 歲 11 個月，其中兩人需要肝移植，但沒有人死亡。

9 名患者中有 8 名 (89%) 的腺病毒檢測呈陽性，所有 5 份質量足以進行基因測序的樣本都檢測出腺病毒 41 陽性。曾進行的 6 次肝活檢均未發現腺病毒感染跡象，但三名患者的肝臟組織樣本透過 PCR 檢測為腺病毒陽性。

第二項研究涉及今年 1 月 1 日至 4 月 11 日期間轉診至英國肝移植中心的 44 名兒童。患者的中位年齡為 4 歲。六名兒童需要肝移植，沒有人死亡。在接受腺病毒分子檢測的 30 名患者中，27 名（90%）腺病毒 41 陽性。9 名兒童的肝臟樣本（3 名來自活檢組織，6 名來自移植下的肝臟）的腺病毒抗體檢測均為陰性。

然而，在這兩項研究中，需要移植的患者的腺病毒病毒載量中位數值遠高於不需要肝移植的兒童的病毒載量。

儘管這些病例的大多數臨床特徵和檢測結果顯示可能與腺病毒有關，但組織學的陰性結果是「引人注意及興趣的」，英國伯明翰婦女兒童醫院兒科肝病學顧問醫師 Chayarani Kelgeri在一封電子郵件中告訴Medscape。她是英國研究的主要作者。「不論這是否是因我們看到的肝損傷是病毒感染的後果，抑或損傷機制是免疫介導的，以及是否涉及其他共同輔助因子均正在探索」，她補充說。「英國衛生安全局正在進行的進一步調查將增加我們對這種疾病的了解」。

「儘管這些病例中的腺病毒陽性率很高，但還沒有足夠的證據顯示腺病毒 41 是以前健康兒童中小兒肝炎的新病因」，美國喬治亞州亞特蘭大埃默里大學醫學院的肝病學和營養學之兒科胃腸病學科主任 Saul Karpen 醫學博士說；他正是新英格期刊本期評論這二篇文章社論的作者。

他告訴 Medscape，根據最近的一項分析，美國CDC 尚未發現兒童肝炎病例有所增加，儘管英國今年發現病例有所增加。此外，兩篇文章中強調的病例均未顯示肝活檢中有腺病毒的組織學證據。 「這與我們通常在可能相當嚴重的腺病毒肝炎中所看到的完全相反」，他說；並補充說道，一般在受影響的肝臟中會有可檢測到的病毒顆粒和抗原。

「這兩份重要報告向兒科肝病學領域內外的人們顯示，兒童急性肝炎的登記和臨床研究非常需要」，Karpen 在社論中寫道。 「如果能更加關注從患有急性肝炎的兒童身上收集病例和生物樣本上的數據，我們將能夠確定這種病毒——人類腺病毒 41，是否與兒童中這種重要而嚴重的疾病有關」。

Link Between Pediatric Hepatitis and Adenovirus 41 Still Unclear

Lucy Hicks / Medscape / Jul 13, 2022. 

While two new studies reiterate a possible relationship between adenovirus 41 and acute hepatitis of unknown cause in children, whether these infections are significant or merely bystanders remains unclear.  

    In both studies — one conducted in Alabama and the other conducted in the United Kingdom — researchers found that 90% of children with acute hepatitis of unknown cause tested positive for adenovirus 41. The virus subtype is not an uncommon infection, but it usually causes gastroenteritis in children. 

“Across the world, adenovirus continues to be a common signal,” in these pediatric hepatitis cases, said Helena Gutierrez, MD, the medical director of the Pediatric Liver Transplant Program at the University of Alabama at Birmingham, in an interview with Medscape Medical News. She led one of the studies. More data is necessary to understand what role this virus may play in these cases, she said. 

In November, the Alabama Department of Public Health and the US Centers for Disease Control and Prevention (CDC) began investigating a cluster of severe pediatric hepatitis cases at the Children’s of Alabama hospital in Birmingham. These children (in also tested positive for adenovirus. In April, the United Kingdom announced they were investigating similar cases, and the CDC expanded their search nationally. As of July 8, 1010 cases in 35 countries have been reported to the World Health Organization. There are 263 confirmed cases in the UK and 332 cases under investigation by the CDC in the US, according to the most recent counts. 

The two studies, both published today in the New England Journal of Medicine, provide additional clinical data on a number of these mysterious hepatitis cases. Gutierrez’s study looked at nine children admitted for hepatitis of unknown origin between October 1 and February 28. Patients had a median age of 2 years 11 months, two required liver transplants, and there were no deaths. 

Eight out of nine patients (89%) tested positive for adenovirus, and all five of the samples that were of sufficient quality for gene sequencing tested positive for adenovirus 41. None of the six liver biopsies performed found signs of adenovirus infection, but the liver tissue samples of three patients tested positive for adenovirus via PCR. 

The second study involved 44 children referred to a liver transplantation center in the United Kingdom between January 1 and April 11 of this year. The median age for patients was 4 years. Six children required liver transplants and there were no deaths. Of the 30 patients who underwent molecular adenovirus testing, 27 (90%) were positive for adenovirus 41. Liver samples of nine children (3 from biopsies and 6 from explanted livers) all tested negative for adenovirus antibodies.

In both studies, however, the median adenovirus viral load of patients needing a transplant was much higher than the viral loads in children who did not require liver transplants. 

Although most of the clinical features and test results of these cases suggest that adenovirus may be involved, the negative results in histology are “intriguing,” Chayarani Kelgeri, MD, a consultant pediatric hepatologist at the Birmingham Women’s and Children’s Hospital, UK, told Medscape in an email. She is the lead author of the UK study. “Whether this is because the liver injury we see is an aftermath of the viral infection, the mechanism of injury is immune mediated, and if other cofactors are involved is being explored,” she added. “Further investigations being undertaken by UK Health Security Agency will add to our understanding of this illness.

” Although there is a high adenovirus positivity rate amongst these cases, there is not enough evidence yet to say adenovirus 41 is a new cause of pediatric hepatitis in previously healthy children, said Saul Karpen, MD, PhD, the division chief of pediatric gastroenterology, hepatology, and nutrition at Emory University School of Medicine in Atlanta, Georgia. He wrote an editorial accompanying the two NEJM studies. 

The CDC has not yet found an increase in pediatric hepatitis cases, according to a recent analysis, though the UK has found an uptick in cases this year, he told Medscape. Also, the cases highlighted in both articles showed no histological evidence of adenovirus in liver biopsies. “That’s completely opposite of what we generally see in adenoviral hepatitis that can be quite severe,” he said, adding that in general, there are detectable viral particles and antigens in affected livers. 

“These two important reports indicate to those inside and outside the field of pediatric hepatology that registries and clinical studies of acute hepatitis in children are sorely needed,” Karpen writes in the editorial; “It is likely that with greater attention to collecting data on cases and biospecimens from children with acute hepatitis, we will be able to determine whether this one virus, human adenovirus 41, is of relevance to this important and serious condition in children.” 

Cite this: Link Between Pediatric Hepatitis and Adenovirus 41 Still Unclear – Medscape – Jul 13, 2022.