McKenzie Rebecca B, Berquist William E, Nadeau Kari C, Louie Christine Y, Chen Sharon F, Sibley Richard K, Glader Bertil E, Wong Wendy B, Hofmann Lawrence V, Esquivel Carlos O, Cox Kenneth L
Division of Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, Stanford School of Medicine, Stanford, CA, USA.
Pediatr Transplant. 2014 Aug;18(5):503-9. doi: 10.1111/petr.12296. Epub 2014 Jun 14.
In the majority of children with ALF, the etiology is unknown and liver transplantation is often needed for survival. A patient case prompted us to consider that immune dysregulation may be the cause of indeterminate acute hepatitis and liver failure in children. Our study includes nine pediatric patients treated under a multidisciplinary clinical protocol to identify and treat immune-mediated acute liver injury. Patients with evidence of inflammation and no active infection on biopsy received treatment with intravenous immune globulin and methylprednisolone. Seven patients had at least one positive immune marker before or after treatment. All patients had a CD8+ T-cell predominant liver injury that completely or partially responded to immune therapy. Five of the nine patients recovered liver function and did not require liver transplantation. Three of these patients subsequently developed bone marrow failure and were treated with either immunosuppression or stem cell transplant. This series highlights the importance of this tissue-based approach to diagnosis and treatment that may improve transplant-free survival. Further research is necessary to better characterize the immune injury and to predict the subset of patients at risk for bone marrow failure who may benefit from earlier and stronger immunosuppressive therapy.
在大多数急性肝衰竭儿童中，病因不明，往往需要进行肝移植才能存活。一个病例促使我们考虑免疫失调可能是儿童不明原因急性肝炎和肝衰竭的病因。我们的研究纳入了9名接受多学科临床方案治疗以识别和治疗免疫介导性急性肝损伤的儿科患者。活检显示有炎症证据且无活动性感染的患者接受了静脉注射免疫球蛋白和甲泼尼龙治疗。7名患者在治疗前或治疗后至少有一项免疫指标呈阳性。所有患者均以CD8 + T细胞为主的肝损伤，对免疫治疗有完全或部分反应。9名患者中有5名肝功能恢复，无需进行肝移植。其中3名患者随后发生骨髓衰竭，接受了免疫抑制或干细胞移植治疗。该系列研究突出了这种基于组织的诊断和治疗方法的重要性，这种方法可能会提高无移植生存率。有必要进行进一步研究，以更好地描述免疫损伤特征，并预测可能从早期更强免疫抑制治疗中获益的骨髓衰竭高危患者亚组。
