Acute severe hepatitis associated with active human herpesvirus 6 (HHV-6) infection is a rare life-threatening condition with unclear clinical course and histopathology. In this study, we retrospectively analyzed 5 patients with indeterminate acute severe hepatitis found to have active hepatic HHV-6 infection during care. All patients were previously healthy children presenting with a nonspecific prodrome. Four developed acute liver failure (ALF) and 3 received liver transplantation. The explanted livers and biopsies demonstrated a centrilobular pattern of necroinflammation characterized by moderate to marked central perivenulitis and confluent centrilobular to panlobular necrosis in 4 cases, accompanied by marked hepatocellular swelling and milder portal inflammation in 3. Central perivenulitis was more prominent in comparison to a control of group of ALF without HHV-6 (P=0.01). When compared with the children with acute severe hepatitis associated with adenovirus encountered in the recent outbreak, both central perivenulitis and centrilobular necrosis were significant predictors for association with HHV-6 (P<0.01). Liver immunohistochemistry detected HHV-6 structural protein in biliary epithelium in all cases and a predominance of CD8+ T cells in the perivenular inflammatory infiltrate. Among the 4 patients with ALF, one received early anti-HHV-6 therapy and had transplant-free survival, while the other 3 received either general prophylactic antiviral treatment only (n=2) or late anti-HHV-6 therapy (n=1) and needed liver transplantation. Our findings were similar to those in previously reported cases. In summary, acute severe hepatitis associated with HHV-6 tends to affect children, progress to ALF, and exhibit characteristic centrilobular necroinflammation which likely represents an immune-mediated process.

中文翻译：

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与人类疱疹病毒 6 感染相关的急性重症肝炎的临床和组织病理学特征。


与活动性人类疱疹病毒 6 (HHV-6) 感染相关的急性重症肝炎是一种罕见的危及生命的疾病，其临床病程和组织病理学尚不明确。在这项研究中，我们回顾性分析了 5 例在护理过程中发现患有活动性肝脏 HHV-6 感染的不确定性急性重症肝炎患者。所有患者都是先前表现出非特异性前驱症状的健康儿童。 4 名患者出现急性肝衰竭 (ALF)，3 名患者接受了肝移植。移植的肝脏和活检显示小叶中心坏死性炎症，其中 4 例表现为中度至显着的中央静脉周围炎和汇合性小叶中心至全小叶坏死，3 例伴有明显的肝细胞肿胀和较轻的门静脉炎症。与对照相比，中央静脉周围炎更为突出不含 HHV-6 的 ALF 组（P=0.01）。与最近爆发的腺病毒相关急性重型肝炎儿童相比，中央静脉周围炎和小叶中心坏死都是与HHV-6相关的显着预测因子（P<0.01）。肝脏免疫组织化学检测到所有病例的胆道上皮中均存在 HHV-6 结构蛋白，并且在小静脉周围炎症浸润中均检测到 CD8+ T 细胞为主。 4 例 ALF 患者中，1 例接受早期抗 HHV-6 治疗并实现无移植生存，而另外 3 例仅接受一般预防性抗病毒治疗（n=2）或晚期抗 HHV-6 治疗（n= 1）需要肝移植。我们的发现与之前报道的病例相似。 总之，与 HHV-6 相关的急性重症肝炎往往会影响儿童，进展为 ALF，并表现出特征性的小叶中心坏死性炎症，这可能代表免疫介导的过程。