Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kanazawa University, Ishikawa, Japan.
Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kanazawa University, Ishikawa, Japan.
Transplant Proc. 2023 Oct;55(8):1946-1950. doi: 10.1016/j.transproceed.2023.06.011. Epub 2023 Aug 1.
Hemophagocytic lymphohistiocytosis (HLH) is a rare but lethal complication of liver transplantation (LT). HLH is characterized by pathologic macrophage activation with hypercytokinemia, excessive inflammation, and tissue destruction, resulting in progressive organ dysfunction. HLH is also known as macrophage activation syndrome (MAS) when complicated by rheumatic or autoinflammatory diseases. Measuring several serum cytokines could be helpful in diagnosing HLH and MAS. Cytokines related to macrophage activation: neopterin, interleukin-18 (IL-18), and soluble tumor necrosis factor receptors (sTNF-R) I and II have not been assessed in patients with HLH complicated by LT. In this case, these cytokines were evaluated in the perioperative period of LT. The patient was a 24-year-old woman who underwent living-donor LT for acute worsening of autoimmune hepatitis. On postoperative day 12, the patient was diagnosed with HLH on the basis of the criteria. Plasma exchange, steroid pulse therapy, intravenous immunoglobulin and granulocyte-colony stimulating factor effectively inhibited progression to lethal HLH. When HLH occurred after LT, cytokine analysis showed that neopterin, IL-18, sTNFR-I, and II were elevated: cytokine storm. Of note, cytokine analysis on hospital admission also revealed elevated cytokine levels. Particularly, IL-18 levels were markedly elevated, suggesting that activation of the innate immune system was involved. These results revealed that a cytokine storm and macrophage activation developed before LT. Based on these findings, cytokine analysis related to macrophage activation may be useful for diagnosing and predicting HLH and MAS in patients with LT.
噬血细胞性淋巴组织细胞增生症（HLH）是肝移植（LT）后罕见但致命的并发症。HLH 的特征是病理性巨噬细胞激活伴有细胞因子血症、过度炎症和组织破坏，导致进行性器官功能障碍。当伴有风湿性或自身炎症性疾病时，HLH 也称为巨噬细胞活化综合征（MAS）。测量几种血清细胞因子有助于诊断 HLH 和 MAS。与巨噬细胞活化相关的细胞因子：新蝶呤、白细胞介素-18（IL-18）和可溶性肿瘤坏死因子受体（sTNF-R）I 和 II 尚未在 LT 并发 HLH 的患者中进行评估。在这种情况下，评估了 LT 围手术期这些细胞因子。患者为 24 岁女性，因自身免疫性肝炎急性加重而行活体供肝 LT。术后第 12 天，根据标准诊断为 HLH。血浆置换、激素冲击治疗、静脉注射免疫球蛋白和粒细胞集落刺激因子有效抑制了致命 HLH 的进展。当 LT 后发生 HLH 时，细胞因子分析显示新蝶呤、IL-18、sTNFR-I 和 II 升高：细胞因子风暴。值得注意的是，入院时的细胞因子分析也显示细胞因子水平升高。特别是 IL-18 水平显著升高，提示先天免疫系统被激活。这些结果表明，细胞因子风暴和巨噬细胞活化在 LT 之前就已经发生。基于这些发现，与巨噬细胞活化相关的细胞因子分析可能有助于诊断和预测 LT 患者的 HLH 和 MAS。
