Department of Medicine, Service of Infectious Disease, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.
Biol Blood Marrow Transplant. 2010 Jan;16(1):46-52. doi: 10.1016/j.bbmt.2009.08.015. Epub 2009 Oct 9.
Voriconazole is increasingly used in allogeneic hematopoietic stem cell transplantation (HSCT) for prophylaxis and treatment of fungal infections. Hepatic dysfunction is common in patients undergoing HSCT and may have an impact on the clinical decision to institute voriconazole. We conducted a retrospective review of all adult and pediatric HSCT recipients who received >2 consecutive doses of voriconazole between January 2005 and February 2008. Clinical hepatotoxicity was defined as the subjective attribution of liver enzyme elevation (even a mild one) to hepatotoxicity because of voriconazole by the treating physician and leading to discontinuation of voriconazole. Biochemical hepatotoxicity was defined as an elevation in one or more liver enzymes to >3 times the upper limit of normal or >3 times the baseline value if abnormal at baseline. Liver enzymes assessed included aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total bilirubin. Simple and multiple logistic regressions were used to define the risks for hepatic dysfunction. The Wilcoxon signed-rank test was used to assess the differences in liver function test values before, during, and after the use of voriconazole. Sixty-eight of 200 patients (34%) developed hepatotoxicity while on voriconazole. The median duration of voriconazole therapy was 72 days (range, 1-804 days). Biochemical hepatotoxicity occurred in 51 patients (75%); clinical hepatotoxicity, in 17 patients (25%). Thirty-five (51%) of the patients with hepatotoxicity required discontinuation of therapy. In simple logistic regression, acute graft-versus-host disease (GVHD) was a risk factor for hepatotoxicity, and receipt of a T-cell depleted allograft was protective. In multiple logistic regression, acute GVHD (P = .002) remained significant. There were no cases of liver failure or death attributed to voriconazole. In this cohort of patients undergoing allogeneic HSCT, the rate of hepatotoxicity while on voriconazole was 34%. In general, the hepatic dysfunction was mild and reversible. Voriconazole therapy with monitoring appears to be reasonably safe for use in HSCT recipients at high risk for invasive fungal infections.
伏立康唑在异基因造血干细胞移植（HSCT）中越来越多地用于预防和治疗真菌感染。接受 HSCT 的患者常出现肝功能障碍，这可能会影响临床是否开始使用伏立康唑的决策。我们对 2005 年 1 月至 2008 年 2 月期间接受>2 个连续剂量伏立康唑治疗的所有成人和儿科 HSCT 受者进行了回顾性研究。临床肝毒性定义为治疗医生将肝酶升高（即使是轻度升高）归因于伏立康唑的肝毒性，并导致停止使用伏立康唑。生化肝毒性定义为一种或多种肝酶升高至正常值上限的 3 倍以上，或如果基线异常，则升高至基线值的 3 倍以上。评估的肝酶包括天冬氨酸转氨酶、丙氨酸转氨酶、碱性磷酸酶和总胆红素。简单和多元逻辑回归用于定义肝功能障碍的风险。Wilcoxon 符号秩检验用于评估使用伏立康唑前后肝功能检查值的差异。200 例患者中有 68 例（34%）在使用伏立康唑时出现肝毒性。伏立康唑治疗的中位时间为 72 天（范围 1-804 天）。51 例（75%）患者发生生化肝毒性；17 例（25%）患者发生临床肝毒性。35 例（51%）肝毒性患者需要停止治疗。在简单逻辑回归中，急性移植物抗宿主病（GVHD）是肝毒性的一个危险因素，而接受 T 细胞耗竭的同种异体移植物则具有保护作用。在多元逻辑回归中，急性 GVHD（P=0.002）仍然具有显著性。没有因伏立康唑而导致肝功能衰竭或死亡的病例。在接受异基因 HSCT 的患者队列中，使用伏立康唑时肝毒性的发生率为 34%。一般来说，肝功能障碍是轻微和可逆的。在有侵袭性真菌感染高风险的 HSCT 受者中，使用伏立康唑监测似乎是安全的。
